Addressing Foodborne Threats To Health

Addressing Foodborne Threats to Health: Policies,
Practices, and Global Coordination, Workshop

Summary
Forum on Microbial Threats
ISBN: 0-309-65457-2, 304 pages, 6 x 9, (2006)
This free PDF was downloaded from:
http://www.nap.edu/catalog/11745.html
Visit the National Academies Press online, the authoritative source for all books from the
National Academy of Sciences, the National Academy of Engineering, the Institute of
Medicine, and the National Research Council:
• Download hundreds of free books in PDF
• Read thousands of books online, free
• Sign up to be notified when new books are published
• Purchase printed books
• Purchase PDFs
• Explore with our innovative research tools
Thank you for downloading this free PDF. If you have comments, questions or just want
more information about the books published by the National Academies Press, you may
contact our customer service department toll-free at 888-624-8373, visit us online, or
send an email to [email protected].
This free book plus thousands more books are available at http://www.nap.edu.
Copyright © National Academy of Sciences. Permission is granted for this material to be

shared for noncommercial, educational purposes, provided that this notice appears on the
reproduced materials, the Web address of the online, full authoritative version is retained,
and copies are not altered. To disseminate otherwise or to republish requires written
permission from the National Academies Press.
Addressing Foodborne Threats to Health: Policies, Practices, and Global Coordination, Workshop Summary
ADDRESSING
FOODBORNE THREATS
TO HEALTH
Policies, Practices, and
Global Coordination
Workshop Summary

Board on Global Health
Copyright © National Academy of Sciences. All rights reserved.

THE NATIONAL ACADEMIES PRESS 500 Fifth Street, N.W. Washington, DC 20001
NOTICE: The project that is the subject of this report was approved by the Governing
Board of the National Research Council, whose members are drawn from the councils of
the National Academy of Sciences, the National Academy of Engineering, and the Insti-
tute of Medicine.
This project was supported by the American Society for Microbiology; Burroughs
Wellcome Fund; Defense Threat Reduction Agency; GlaxoSmithKline; Infectious Dis-
ease Society of America; Lawrence Livermore National Laboratory; Merck Company
Foundation; Pfizer; Sanofi Pasteur; U.S. Department of Health and Human Services’ Na-
tional Institutes of Health, National Institute of Allergy and Infectious Diseases, Centers
for Disease Control and Prevention, and Food and Drug Administration; U.S. Department
of Defense’s Global Emerging Infections Surveillance and Response System and Walter
Reed Army Institute of Research; U.S. Department of Homeland Security; U.S. Depart-
ment of State; and U.S. Department of Veterans Affairs. Any opinions, findings, conclu-
sions, or recommendations expressed in this publication are those of the author(s) and do
not necessarily reflect the view of the organizations or agencies that provided support for
this project.
International Standard Book Number-10 0-309-10043-7 (Book)

International Standard Book Number-13 978-0-309-10043-4 (Book)
International Standard Book Number-10 0-309-65457-2 (PDF)
International Standard Book Number-13 978-0-309-65457-9 (PDF)
Additional copies of this report are available from the National Academies Press, 500
Fifth Street, N.W., Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-
3313 (in the Washington metropolitan area); Internet, http://www.nap.edu.
For more information about the Institute of Medicine, visit the IOM home page at:
www.iom.edu.
Copyright 2006 by the National Academy of Sciences. All rights reserved.
Printed in the United States of America.
The serpent has been a symbol of long life, healing, and knowledge among almost all
cultures and religions since the beginning of recorded history. The serpent adopted as a
logotype by the Institute of Medicine is a relief carving from ancient Greece, now held by
the Staatliche Museen in Berlin.
COVER: A detailed section of a stained glass window 21″ × 56″ depicting the natural
history of influenza viruses and zoonotic exchange in the emergence of new strains was
used to design the front cover. Based on the work done at St. Jude Children’s Research
Hospital supported by American Lebanese Syrian Associated Charities (ALSAC) and the
National Institute of Allergy and Infectious Diseases (NIAID). Artist: Jenny Hammond,
Highgreenleycleugh, Northumberland, England.

“Knowing is not enough; we must apply.

Willing is not enough; we must do.”
—Goethe
Advising the Nation. Improving Health.

The National Academy of Sciences is a private, nonprofit, self-perpetuating society of

distinguished scholars engaged in scientific and engineering research, dedicated to the
furtherance of science and technology and to their use for the general welfare. Upon the
authority of the charter granted to it by the Congress in 1863, the Academy has a mandate
that requires it to advise the federal government on scientific and technical matters. Dr.
Ralph J. Cicerone is president of the National Academy of Sciences.
The National Academy of Engineering was established in 1964, under the charter of the
National Academy of Sciences, as a parallel organization of outstanding engineers. It is
autonomous in its administration and in the selection of its members, sharing with the
National Academy of Sciences the responsibility for advising the federal government. The
National Academy of Engineering also sponsors engineering programs aimed at meeting
national needs, encourages education and research, and recognizes the superior achieve-
ments of engineers. Dr. Wm. A. Wulf is president of the National Academy of Engineering.
The Institute of Medicine was established in 1970 by the National Academy of Sciences
to secure the services of eminent members of appropriate professions in the examination
of policy matters pertaining to the health of the public. The Institute acts under the respon-
sibility given to the National Academy of Sciences by its congressional charter to be an
adviser to the federal government and, upon its own initiative, to identify issues of medical
care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of
Medicine.
The National Research Council was organized by the National Academy of Sciences in
1916 to associate the broad community of science and technology with the Academy’s
purposes of furthering knowledge and advising the federal government. Functioning in
accordance with general policies determined by the Academy, the Council has become the
principal operating agency of both the National Academy of Sciences and the National
Academy of Engineering in providing services to the government, the public, and the
scientific and engineering communities. The Council is administered jointly by both Acad-
emies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Wm. A. Wulf are chair
and vice chair, respectively, of the National Research Council.
www.national-academies.org

FORUM ON MICROBIAL THREATS

STANLEY M. LEMON (Chair), School of Medicine, University of Texas
Medical Branch, Galveston
MARGARET A. HAMBURG (Vice-chair), Nuclear Threat Initiative/Global
Health & Security Initiative, Washington, D.C.
P. FREDERICK SPARLING (Vice-chair), University of North Carolina,
Chapel Hill
DAVID W. K. ACHESON, Center for Food Safety and Applied Nutrition,
Food and Drug Administration, Rockville, Maryland
RUTH L. BERKELMAN, Emory University, Center for Public Health
Preparedness and Research, Rollins School of Public Health, Atlanta,
Georgia
ROGER G. BREEZE, Centaur Science Group, Washington, D.C.
STEVEN J. BRICKNER, Pfizer Global Research and Development, Pfizer
Inc., Groton, Connecticut
GAIL H. CASSELL, Eli Lilly & Company, Indianapolis, Indiana
RALPH L. ERICKSON, Global Emerging Infections Surveillance and
Response System, Department of Defense, Silver Spring, Maryland
MARK B. FEINBERG, Merck Vaccine Division, Merck & Co., West Point,
Pennsylvania
J. PATRICK FITCH, Battelle Memorial Institute, Livermore, California
DARRELL R. GALLOWAY, Medical S&T Division, Defense Threat
Reduction Agency, Ft. Belvoir, Virginia
S. ELIZABETH GEORGE, Biological and Chemical Countermeasures
Program, Department of Homeland Security, Washington, D.C.
JESSE L. GOODMAN, Center for Biologics Evaluation and Research, Food
and Drug Administration, Rockville, Maryland
EDUARDO GOTUZZO, Instituto de Medicina Tropical–Alexander von
Humbolt, Universidad Peruana Cayetano Heredia, Lima, Peru
JO HANDELSMAN, College of Agricultural and Life Sciences, University of
Wisconsin, Madison
CAROLE A. HEILMAN, Division of Microbiology and Infectious Diseases,
National Institute of Allergy and Infectious Diseases, National Institutes of
Health, Bethesda, Maryland
DAVID L. HEYMANN, Polio Eradication, World Health Organization,
Geneva, Switzerland
PHIL HOSBACH, New Products and Immunization Policy, Sanofi Pasteur,
Swiftwater, Pennsylvania
JAMES M. HUGHES, Global Infectious Diseases Program, Emory
University, Atlanta, Georgia
STEPHEN A. JOHNSTON, Arizona BioDesign Institute, Arizona State
University, Tempe, Arizona
GERALD T. KEUSCH, Boston University School of Medicine and Boston
University School of Public Health, Massachusetts

RIMA F. KHABBAZ, National Center for Preparedness, Detection and

Control of Infectious Diseases, Centers for Disease Control and Prevention,
Atlanta, Georgia
LONNIE J. KING, Center for Zoonotic, Vectorborne, and Enteric Diseases,
Centers for Disease Control and Prevention, Atlanta, Georgia
GEORGE W. KORCH, United States Army Medical Research Institute for
Infectious Diseases, Ft. Detrick, Maryland
JOSHUA LEDERBERG, The Rockefeller University, New York
LYNN G. MARKS, Medicine Development Center, GlaxoSmithKline,
Collegeville, Pennsylvania
MARY McBRIDE, Science and Technology Chemical and Biological National
Security Program, Lawrence Livermore National Laboratory, Livermore,
California
STEPHEN S. MORSE, Center for Public Health Preparedness, Columbia
University, New York
MICHAEL T. OSTERHOLM, Center for Infectious Disease Research and
Policy, School of Public Health, University of Minnesota, Minneapolis
GEORGE POSTE, Arizona BioDesign Institute, Arizona State University,
Tempe
DAVID A. RELMAN, Stanford University, Palo Alto, California
GARY A. ROSELLE, Central Office, Veterans Health Administration,
Department of Veterans Affairs, Washington, D.C.
JANET SHOEMAKER, Office of Public Affairs, American Society for
Microbiology, Washington, D.C.
BRIAN J. STASKAWICZ, Department of Plant and Microbial Biology,
University of California, Berkeley
TERENCE TAYLOR, International Council for the Life Sciences,
Washington, D.C.
Liaisons
ENRIQUETA C. BOND, Burroughs Wellcome Fund, Research Triangle Park,
North Carolina
NANCY CARTER-FOSTER, Program for Emerging Infections and HIV/
AIDS, U.S. Department of State, Washington, D.C.
EDWARD McSWEEGAN, National Institute of Allergy and Infectious
Diseases, National Institutes of Health, Bethesda, Maryland
Staff
EILEEN CHOFFNES, Forum Director
KIM LUNDBERG, Research Associate
ALISON MACK, Science Writer
KATE SKOCZDOPOLE, Research Associate
vi

BOARD ON GLOBAL HEALTH

Margaret Hamburg (Chair), Consultant, Nuclear Threat Initiative,
Washington, D.C.
George A.O. Alleyne, Director Emeritus, Pan American Health Organization,
Washington, D.C.
Yves Bergevin, Department of Child and Adolescent Health and Development,
World Health Organization, Geneva, Switzerland
Donald Berwick, Clinical Professor of Pediatrics and Health Care Policy,
Harvard Medical School, and President and Chief Executive Officer,
Institute of Healthcare Improvement, Boston, Massachusetts
Jo Ivey Boufford (IOM Foreign Secretary), Professor, Robert F. Wagner
School of Public Service, New York University, New York
David R. Challoner, Vice President for Health Affairs, Emeritus, University of
Florida, Gainesville
Ciro de Quadros, Director of International Programs, Sabin Vaccine Institute,
Washington, D.C.
Sue Goldie, Associate Professor of Health Decision Science, Department of
Health Policy and Management, Center for Risk Analysis, Harvard
University School of Public Health, Boston, Massachusetts
Richard Guerrant, Thomas H. Hunter Professor of International Medicine and
Director, Center for Global Health, University of Virginia School of
Medicine, Charlottesville
Gerald Keusch, Assistant Provost for Global Health, Boston University School
of Medicine, and Associate Dean for Global Health, Boston University
School of Public Health, Massachusetts
Jeffrey Koplan, Vice President for Academic Health Affairs, Emory
University, Atlanta, Georgia
Sheila Leatherman, Research Professor, University of North Carolina School
of Public Health, Chapel Hill
Michael Merson, Anna M. R. Lauder Professor, Dean of Public Health, and
Chair, Department of Epidemiology and Public Health, Yale University
School of Medicine, New Haven, Connecticut
Mark L. Rosenberg, Executive Director, the Task Force for Child Survival
and Development, Emory University, Decatur, Georgia
Philip Russell, Professor Emeritus, Bloomberg School of Public Health, Johns
Hopkins University, Baltimore, Maryland
Staff
Patrick Kelley, Director
Allison Brantley, Senior Program Assistant
vii


Reviewers
This report has been reviewed in draft form by individuals chosen for their
diverse perspectives and technical expertise, in accordance with procedures ap-
proved by the NRC’s Report Review Committee. The purpose of this indepen-
dent review is to provide candid and critical comments that will assist the institu-
tion in making its published report as sound as possible and to ensure that the
report meets institutional standards for objectivity, evidence, and responsiveness
to the study charge. The review comments and draft manuscript remain confiden-
tial to protect the integrity of the deliberative process. We wish to thank the fol-
lowing individuals for their review of this report:
Johanna Dwyer, D.Sc., Frances Stern Nutrition Center, Tufts–New England
Medical Center
Craig Hedberg, Ph.D., Division of Environmental and Occupational Health,
University of Minnesota
Terence Taylor, International Council for the Life Sciences, Washington,
D.C.
Mary Wilson, M.D., Department of Population and International Health,
Harvard University
The review of this report was overseen by Floyd Bloom, M.D., Professor
Emeritus, Department of Neuropharmacology, The Scripps Research Institute,
and Melvin Worth, M.D., Scholar-in-Residence, National Academies, who were
responsible for making certain that an independent examination of this report was
carried out in accordance with institutional procedures and that all review com-
ments were carefully considered. Responsibility for the final content of this re-
port rests entirely with the authoring committee and the institution.
ix


Preface
The Forum on Emerging Infections was created in 1996 in response to a

request from the Centers for Disease Control and Prevention (CDC) and the Na-
tional Institutes of Health (NIH). It was established by the Institute of Medicine
(IOM) to provide structured opportunities for leaders from government, academia,
and industry to meet and examine issues of shared concern regarding research,
prevention, detection, and management of emerging or reemerging infectious dis-
eases. In pursuing this task, the Forum provides a venue to foster the exchange of
information and ideas, identify areas in need of greater attention, clarify policy
issues by enhancing knowledge and identifying points of agreement, and inform
decision makers about science and policy issues. The Forum seeks to illuminate
issues rather than resolve them directly; for this reason, it does not provide advice
or recommendations on any specific policy initiative pending before any agency
or organization. Rather, its strengths are embodied in the diversity of its member-
ship and the contributions of individual members expressed throughout the ac-
tivities of the Forum. In September 2003, the Forum changed its name to the
Forum on Microbial Threats.
ABOUT THE WORKSHOP

In December 2004, at a press conference called to announce his departure as
Secretary of the Department of Health and Human Services (DHHS), Tommy
Thompson raised both concern and controversy when he remarked that he could
not understand why terrorists had not yet attacked our food supply “because it is
xi

xii PREFACE
so easy to do.”1 Three days later, the Food and Drug Administration (FDA) an-
nounced the last in a series of four food safeguards mandated under the Bio-
preparedness Act of 2002.2 Although these provisions improve the FDA’s ability
to intercept and track the origins of food that is suspected to pose a threat to
health, they cannot prevent contamination. Biological and chemical agents can
be—and have been—introduced, both accidentally and deliberately, at many vul-
nerable points along the farm-to-table food chain.
Foodborne agents have been estimated to cause approximately 76 million
illnesses, 325,000 hospitalizations, and 5,200 deaths in the United States each
year.3 More than 250 different foodborne diseases, including both infections and
poisonings, have been described, according to the CDC.4 The U.S. Department of
Agriculture (USDA) estimates costs associated with medical expenses and losses
in productivity due to missed work and premature deaths from five major types
of foodborne illnesses (Campylobacter, Escherichia coli O157:H7, Shiga toxin-
producing strains of E. coli, Listeria monocytogenes, and Salmonella) at $6.9
billion annually.5 This figure likely represents the tip of the iceberg, as it does not
account for the broad spectrum of foodborne illnesses or for their wide-ranging
repercussions for consumers, government, and the food industry.
The potential impact on human health of deliberate adulteration of food can
be estimated by extrapolation from the many documented examples of uninten-
tional outbreaks of foodborne disease, some of which have sickened hundreds of
thousands of people and killed hundreds.6 Given the wide variety of potential
chemical and biological adulterants that can be introduced at many vulnerable
points along the food supply continuum, contaminating food is perhaps one of the
easiest means to intentionally distribute these agents. Although the many possi-
bilities for foodborne bioterrorism cannot be specifically prevented, strategic
preparations for surveillance, diagnosis, outbreak investigation, and medical re-
sponse could mitigate foodborne threats of any origin.
To examine issues critical to the protection of the nation’s food supply, the
Institute of Medicine’s Forum on Microbial Threats hosted a public workshop on
October 25 and 26, 2005, in Washington, D.C. The presentations and discussions
1Branigin W, Allen M, Mintz J. 2004 (December 3). Tommy Thompson resigns from HHS: Bush
asks Defense Secretary Rumsfeld to stay. Washington Post. [Online]. Available: http://www.
washingtonpost.com/wp-dyn/articles/A31377-2004Dec3.html [accessed May 6, 2006].
2Gardner A. 2004 (December 6). U.S. Moves to Further Protect Food Supply. [Online]. Available:
http://www.healthfinder.gov/news/newsstory.asp?docID=522737 [accessed June 27, 2006].

3Mead PS, Slutsker L, Dietz V, McCraig LF, Bresee JS, Shapiro C, Griffin PM, Tauxe RV. 1999.
Food-related illness and death in the United States. Emerging Infectious Diseases 5(5):607–625.
4CDC. 2005. Foodborne Illness. [Online]. Available: http://www.cdc.gov/ncidod/dbmd/diseaseinfo/
foodborneinfections_g.htm#foodbornedisease [accessed June 27, 2006].

5Vogt DU. 2005. Food Safety Issues in the 109th Congress. CRS Report RL31853 Washington,
D.C.: The Library of Congress.

6Sobel J. 2005. Food and beverage sabotage. In: Pilch RF, Zilinskas RA, Ed. Encyclopedia of
Bioterrorism Defense. New York: Wiley-Liss, Inc. Pp. 215–220.

PREFACE xiii
of the workshop were structured to explore the existing knowledge and unan-
swered questions indicated by (but not limited to) the following topics:
• The globalization of the U.S. food supply
• The spectrum of microbial threats to food
• Case studies of food threats
• The organization of food safety systems
• Costs and benefits of reporting foodborne threats: the case of bovine
spongiform encelphalopathy (BSE)
• Surveillance for foodborne illness
ACKNOWLEDGMENTS
The Forum on Microbial Threats and the IOM wish to express their warmest
appreciation to the individuals and organizations who gave their valuable time to
provide information and advice to the Forum through their participation in this
workshop. A full list of presenters can be found in Appendix A.
The Forum is indebted to the IOM staff who contributed during the course of
the workshop and the production of this workshop summary. On behalf of the
Forum, we gratefully acknowledge the efforts led by Eileen Choffnes, director of
the Forum; Kim Lundberg, research associate; and Kate Skoczdopole, research
associate, who dedicated much effort and time to developing this workshop’s
agenda, and for their thoughtful and insightful approach and skill in translating
the workshop proceedings and discussion into this workshop summary. We would
also like to thank our science writer, Alison Mack, for her thoughtful and insight-
ful approach and skill in translating the workshop proceedings and discussion
into this workshop summary.
Finally, the Forum also thanks the sponsors that supported this activity. Fi-
nancial support for this project was provided by the U.S. Department of Health
and Human Services’ National Institutes of Health, National Institute of Allergy
and Infectious Diseases, Centers for Disease Control and Prevention, and Food
and Drug Administration; U.S. Department of Defense’s Global Emerging In-
fections Surveillance and Response System, Walter Reed Army Institute of Re-
search, and Defense Threat Reduction Agency; U.S. Department of State;
U.S. Department of Veterans Affairs; U.S. Department of Homeland Security;
Lawrence Livermore National Laboratory; American Society for Microbiology;
Sanofi Pasteur; Burroughs Wellcome Fund; Pfizer; GlaxoSmithKline; Infectious
Disease Society of America; and the Merck Company Foundation. The views
presented in this workshop summary report are those of the editors and workshop
participants and are not necessarily those of the funding organizations.
Stanley M. Lemon, Chair

P. Frederick Sparling, Vice-chair
Margaret A. Hamburg, Vice-chair


Contents
SUMMARY AND ASSESSMENT 1

Addressing Foodborne Threats to Health: Policies, Practices, and
Global Coordination, 1
Organization of the Workshop Summary, 2
The Spectrum of Foodborne Threats, 3
The U.S. Food System: Globalized, Efficient, and Vulnerable, 4
Food Safety Oversight, 6
Accidental Foodborne Disease, 9
Foodborne Attacks: Scenarios and Consequences, 11
Surveillance of Foodborne Threats to Health, 14
Reporting Foodborne Threats: The Case of BSE, 19
Research and Policy Opportunities, 23
References, 26
1 THE U.S. FOOD SYSTEM 31

Overview, 31
The Food Supply and Biodefense: The Next Frontier of the
Food Safety Agenda, 32
Michael T. Osterholm, Ph.D.
The U.S. Food Supply—How Changing Demographics and
Consumer Demand Pose New Challenges for Food Safety, 43
Craig W. Henry, Ph.D.
References, 50
xv

xvi CONTENTS
2 FOOD SAFETY OVERSIGHT 53

Overview, 53
The U.S. Food Safety System, 54
John Bailar, M.D., Ph.D.
Food Safety Threats—International Coordination, 57
Jørgen Schlundt, Ph.D.
References, 67
3 INVESTIGATING FOODBORNE THREATS 70

Overview, 70
The Burden of Illness Associated with Foodborne Threats to Health,
and the Challenge of Prevention, 72
Robert V. Tauxe, M.D., M.P.H.
The Ongoing Saga of U.S. Outbreaks of Cyclosporiasis Associated
with Imported Fresh Produce: What Cyclospora cayetanensis
Has Taught Us and What We Have Yet to Learn, 85
Barbara L. Herwaldt, M.D., M.P.H.
Surveillance and Investigation of a Large Statewide Cyclospora
Foodborne Disease Outbreak Involving an Imported
Stealth Ingredient, 115
Roberta Hammond, Ph.D. and Dean Bodager, R.S., D.A.A.S., M.P.A.
Hepatitis A Outbreaks from Green Onions, 125
Beth P. Bell, M.D., M.P.H. and Anthony E. Fiore, M.D., M.P.H.
References, 133
4 BIOTERRORISM AND THE FOOD SUPPLY 141
Overview, 141
The Threat Against Milk: Just One of Many, with More to Come, 142
Clay Detlefsen, M.B.A., Esq.
Botulinum Toxin: The Linkage with Bioterrorism, 150
Milton Leitenberg, M.S.
The Food and Drug Administration’s Approach to Food Defense, 168
David W. K. Acheson, M.D.
References, 174
5 SURVEILLANCE OF THE FOOD SUPPLY 177

Overview, 177
Systems to Detect Microbial Contamination of the Food Supply, 178
John M. Besser, M.S.
The Consumer Complaint Monitoring System: Enhancing
Discovery and Mitigation of Foodborne Threats to
Health Through Pattern Surveillance and Multiple-Attribute
Algorithms, 189
CDR Kimberly Elenberg, M.S., R.N. and Artur Dubrawski, Ph.D.
References, 192

CONTENTS xvii
6 REPORTING FOODBORNE THREATS: THE CASE OF

BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) 195
Overview, 195
Prions and the Safety of the Food Supply, 196
Stanley B. Prusiner, M.D.
Surveillance and Prevention of vCJD and BSE: The Australian
Perspective, 206
Steven Collins, M.D.
BSE as a Case Study of Public Health and the Public Good, 212
Maura Ricketts, M.D., M.H.Sc., F.R.C.P.C.
Incentives and Disincentives for Disease Surveillance and
Reporting: The BSE Case Study, 221
Will Hueston, D.V.M., Ph.D.
References, 227
7 RESEARCH AND POLICY OPPORTUNITIES 232

Overview, 232
Animal Health at the Crossroads, 233
Committee on Assessing the Nation’s Framework for
Addressing Animal Diseases
Priorities for Research in Food Defense, 247
Francis F. Busta, Ph.D., Shaun Kennedy, B.S.E., and
Julie Ostrowsky, M.Sc.
References, 253
APPENDIXES
A Agenda 255
B Acronyms 259
C Forum Member Biographies 263


Tables and Figures
TABLES
1-1 Food Categories with the Fastest Growing Global Sales and Growth Rate
Between 2003 and 2004, 44
1-2 Food Expenditure Patterns Among Selected Countries, 45
1-3 Food Expenditure Patterns Among Selected Countries, Food Share of
Total Expenditures, 45
1-4 Food Expenditure Patterns Among Selected Countries, Bread and
Cereals, 49
1-5 Food Expenditure Patterns Among Selected Countries, Meat and
Seafood, 49
1-6 Food Expenditure Patterns Among Selected Countries, Dairy and
Eggs, 49
1-7 Food Expenditure Patterns Among Selected Countries, Oils and
Fats, 50
1-8 Food Expenditure Patterns Among Selected Countries, Fruits and
Vegetables, 50
1-9 Food Expenditure Patterns Among Selected Countries, Sugar and
Confectionary, 50
1-10 Grocery Shopper Trends for 2005, 46
1-11 Trends in Proportion of Shoppers Who Purchased Organic Food Within
the Past Six Months, 47
2-1 Overlap in Federal Food Safety Oversight, 56
xix

xx TABLES AND FIGURES
3-1 Foodborne Pathogens in the United States, 73

3-2 Some New Pathogen-Food Combinations Characterized During Outbreak
Investigations in the United States, 80
3-3 Cyclospora cayetanensis, and Cyclosporiasis: Perspectives and Status as
of April 2006, 104
3-4 Characteristics of Foodborne Outbreaks and Investigations:
Challenges, Opportunities, Approaches, and Advances, in General
and Specific to Outbreaks of Cyclosporiasis Associated with Imported
Fresh Produce, 107
3-5 Goals of Investigations of Foodborne Outbreaks: Challenges,
Opportunities, Approaches, and Advances, in General and
Specific to Outbreaks of Cyclosporiasis Associated with
Imported Fresh Produce, 111
3-6 Factors that Have Complicated Efforts to Communicate About
Foodborne Outbreaks of Cyclosporiasis, 114
3-7 Selected History, Cyclospora Outbreaks, and Vehicles: Florida,
National, and International, 117
3-8 Cyclospora Clusters, Florida 2005: Range of Dates of Exposure,
Dates of Onset, Confirmed and Probable Cases, 118
3-9 Source and Distribution of Cluster X Hepatitis A Virus Sequences,
September–December 2003 and January 2002–August 2003, 130
5-1 Networks and Resources for Food Safety, 179

5-2 Comparison of Food Monitoring and Disease Surveillance, 181
5-3 Comparison of Disease Surveillance Approaches, 184
6-1 Cases of Transmissible Spongiform Encephalopathies (TSE)

Reported to the Australian National CJD Registry (ANCJDR),
January 1, 1970 Through June 30, 2005, 210
6-2 The Functions of Public Health, 214
6-3 Functions and Core Programs, 214
6-4 Activity Map for vCJD, 215
6-5 Health Protection and the Management of an Outbreak, 215
6-6 Controlling BSE, 219
7-1 National Center for Food Protection and Defense Research

Initiatives, 250
FIGURES
1-1 Speed of global travel in relation to world population, 33
1-2 The problem: Global food systems, 36
1-3 Identifying the source of food in a global system is challenging, 37-38

TABLES AND FIGURES xxi
1-4 Food expenditures as a share of disposable personal income, United

States, 1974–2003, 39
2-1 The WHO International Food Safety Authorities Network (INFOSAN):

Set-up of focal points for information sharing, 65
2-2 The WHO International Food Safety Authorities Network (INFOSAN):
Potential communication lines for national INFOSAN Emergency
Contact Points, 66
3-1 Reported outbreaks of foodborne diseases, 1990–2004, United

States, 76
3-2 Reported incidence of Listeria monocytogenes infections and reported
outbreaks of listeriosis, United States, 1986–2004, 82
3-3 Reported outbreaks of E. coli O157 infections, United States,
1982–2002, 82
3-4 Generic and Cyclospora-specific challenges in bridging the chasm
between disease and prevention and control, 89
3-5 Sporulation of Cyclospora cayetanensis oocysts, 93
3-6 Epidemiology curve by week of onset, Florida 2005 Cyclospora
outbreak, 119
3-7 Laboratory-confirmed and probable cases of cyclosporiasis by state of
residence, March–June 2005, Cyclospora outbreak, Florida, 121
3-8 Laboratory-confirmed and probable cases of cyclosporiasis by
Florida county of residence, March–June 2005, Cyclospora outbreak,
Florida, 122
3-9 Comparison of hepatitis A viral sequences among individuals with
hepatitis A from northern Mexico (Border Infectious Disease Surveillance
[BIDS] Project), 2002–2003; outbreak-related surveillance, October–
December 2003; and six U.S. sentinel county sites, January 2002–August
2003, 127
3-10 Date of illness onset among restaurant patrons, September–November,
2003; n = 590, 128
4-1 U.S. domestic airline passengers, 143
6-1 Reported frequency of food consumption, odds ratio of vCJD cases

versus general population controls, 208
6-2 BSE and vCJD outbreak development in the UK; Epidemic curve of BSE
in Europe, 216
7-1 Interactions of emerging infectious diseases (EIDs) with a continuum that

includes wildlife, domestic animal, and human populations, 237


Summary and Assessment
ADDRESSING FOODBORNE THREATS TO HEALTH:

POLICIES, PRACTICES, AND GLOBAL COORDINATION
Secretary of the Department of Health and Human Services (HHS), Tommy
Thompson raised both concern and controversy when he remarked that he could
not understand why the terrorists had not yet attacked our food supply “because it
is so easy to do” (Branigin et al., 2004). Although to date the United States has
been spared such a disaster, the many documented examples of unintentional
outbreaks of foodborne disease—some of which have sickened hundreds of thou-
sands of people, and killed hundreds—provide a grim basis for estimating the
impact of deliberate food adulteration (Sobel, 2005). Due to the wide variety of
potential chemical and biological agents that could be introduced at many vulner-
able points along the food supply continuum, contaminating food is considered
an especially simple, yet effective, means to threaten large populations.
Intentional adulteration is not the only reason to be concerned about the safety
of the U.S. food supply, however. Accidental foodborne illness already causes an
estimated 76 million illnesses, 325,000 hospitalizations, and 5,200 deaths in the
United States each year (Mead et al., 1999). The U.S. Department of Agriculture
(USDA) estimates costs associated with medical expenses and losses in produc-
tivity due to missed work and premature deaths from five major types of food-
borne illnesses (Campylobacter, E. coli O157:H7, Shiga toxin-producing strains
of E. coli, Listeria monocytogenes, and Salmonella) at $6.9 billion annually (Vogt,
2005). This figure likely represents the tip of the iceberg, as it does not account

2 ADDRESSING FOODBORNE THREATS TO HEALTH
for the broad spectrum of foodborne illnesses or for their wide-ranging repercus-
sions for consumers, government, and the food industry.
Although specific preventions cannot be mounted against the many possi-
bilities for foodborne bioterrorism, strategic preparations to reduce vulnerability
to foodborne illness—and to anticipate and address the medical, social, and eco-
nomic consequences—could mitigate foodborne threats to health, whatever their
origin. To explore the nature and extent of such threats, possibilities for reducing
their impact, and obstacles to this goal, the Forum on Microbial Threats of the
Institute of Medicine (IOM) convened the workshop Foodborne Threats to
Health: The Policies and Practice of Surveillance, Prevention, Outbreak Investi-
gations, and International Coordination on October 25 and 26, 2005. Workshop
participants discussed the threat spectrum and burden of disease associated with
foodborne illness and the role that increasing globalization of food production
and distribution plays in the transmission of foodborne disease. Participants also
reviewed existing research, policies, and practices concerning foodborne threats
in order to identify unmet needs, challenges, and opportunities for improving
food safety systems, surveillance, and emergency response.
ORGANIZATION OF THE WORKSHOP SUMMARY

This workshop summary report is prepared for the Forum membership in the
name of the editors as a collection of individually authored papers and commen-
tary. Sections of the workshop summary not specifically attributed to an indi-
vidual reflect the views of the editors and not those of the Forum on Microbial
Threats, its sponsors, or the IOM. The contents of the unattributed sections are
based on the presentations and discussions that took place during the workshop.
The workshop summary is organized within chapters as a topic-by-topic de-
scription of the presentations and discussions. Its purpose is to present lessons
from relevant experience, delineate a range of pivotal issues and their respective
problems, and put forth some potential responses as described by the workshop
participants.
Although this workshop summary provides an account of the individual pre-
sentations, it also reflects an important aspect of the Forum philosophy. The work-
shop functions as a dialogue among representatives from different sectors and
presents their beliefs on which areas may merit further attention. However, the
reader should be aware that the material presented here expresses the views and
opinions of the individuals participating in the workshop and not the delibera-
tions of a formally constituted IOM study committee. These proceedings summa-
rize only what participants stated in the workshop and are not intended to be an
exhaustive exploration of the subject matter or a representation of consensus
evaluation.

THE SPECTRUM OF FOODBORNE THREATS

Ensuring the safety of food is a long-standing and critical objective of public
health. The estimate that millions of Americans—whose food is among the safest
on earth—are sickened by tainted food each year attests to the need to further
safeguard our food supply, while the mounting threat of terrorism lends this mis-
sion a particular urgency. As a first step in assessing the spectrum of threats to the
U.S. food supply, speakers and participants in the workshop reviewed a broad
range of foodborne pathogens and poisons that are known to endanger human
health. They also noted the dangers inherent in nonhuman pathogens that can
harm crops or livestock, and along with them, the economic vitality of communi-
ties as small as farms and as large as nations.1
According to the Centers for Disease Control and Prevention (CDC), more
than 250 different foodborne illnesses (including both infections and poison-
ings) have been described to date (CDC, 2005a). The list of major foodborne
pathogens expands each year; the most recent update, presented by speaker
Robert Tauxe, names 20 bacterial species, half of which have been identified
within the past three decades, along with five viruses, five parasites, and prions,
nearly all of which were identified after 1975 (see Chapter 3). Many of these
pathogens, including most of those recently identified, have animal reservoirs—
a factor that has likely contributed to their emergence, as with other zoonoses
(infections or diseases transmitted from vertebrate animals to humans). These
include avian influenza, severe acute respiratory syndrome (SARS), and “mad
cow disease” (bovine spongiform encephalopathy or BSE; see subsequent dis-
cussion and Chapter 6).
Presenter Lonnie King observed that conditions favoring the transmission of
zoonoses are at an all-time high, as are the scope, scale, and implications of such
outbreaks. These include diseases that, while limited to livestock, have poten-
tially devastating economic consequences (e.g., foot-and-mouth disease) as well
as emerging infections that threaten humans (NRC, 2005). The direct and indirect
economic impacts associated with the 2001 outbreak of foot-and-mouth disease
among cattle and sheep in the United Kingdom has been estimated to be $25
billion, a figure that includes loss of tourism revenues, compensation to affected
farmers, trade impacts, and downstream effects on associated agribusiness (e.g.,
slaughterhouses, auctions, transport companies, and food processors) and con-
sumer prices (Breeze, 2004; Chalk, 2005). Crops are also currently under siege
by exotic, emergent, and pesticide-resistant pathogens; workshop participants
noted in passing that economically important crops represent targets for
bioterrorism (NRC, 2002). Although plant pathogens do not pose a significant
public health threat, their presence could trigger trade embargoes with severe
1It should be noted that not all foodborne illness is caused by an infection, not all foodborne disease
causes diarrhea, and not all foodborne disease is acute. The cause of foodborne disease is often unde-
fined, and, in many cases, the pathogens that cause them are not detected by routine laboratory tests.

consequences, particularly for those rural communities that depend on income

from export of the affected crops (Cook, 2005).
Although discussions of food safety often focus on infectious disease threats,
several workshop participants remarked that harmful chemicals represent an even
greater risk to the food supply than those posed by biologic agents, given the
huge number of potential chemical adulterants and the difficulty of detecting
them in foods and/or eliminating them from the food chain (see Osterholm in
Chapter 1 and Busta in Chapter 7). In Michigan, for example, the contamination
of 200 pounds of ground beef with insecticide containing nicotine by a disgruntled
supermarket employee sickened 111 people, including 40 children, in 2003 (CDC,
2003a). In 1985, approximately 1,000 people were poisoned by eating water-
melon tainted with the highly toxic pesticide aldicarb, which was not registered in
the United States for use on melons, and which had been linked to several prior
episodes of food poisoning resulting from its intentional or inadvertent misappli-
cation (CDC, 1986). Although such deliberate or incidental acts of adulteration
are thought to account for a minute percentage of foodborne illness, they illus-
trate the potential for future catastrophe.
THE U.S. FOOD SYSTEM:

GLOBALIZED, EFFICIENT, AND VULNERABLE
Food production and distribution for the developed world takes place across
vast and intricate global networks. In the United States, thousands of different
food items—many of them produced in other countries—pass quickly through an
elaborate system of processors, distributors, and purveyors, to a public with in-
creasingly broad tastes and immense purchasing power. This “farm-to-fork” con-
tinuum is an extraordinarily complicated industrial infrastructure. However, the
system that has brought us increasingly cheaper food in greater variety carries
increased risks associated with foodborne illness, whether accidental, incidental,
or intentional (see Osterholm in Chapter 1).
Over the past decade, the annual output of the U.S. agricultural sector has
consistently surpassed $1 trillion (USDA, 2006a). Agriculture accounts for 13
percent of the U.S. gross domestic product and employs 18 percent of the nation’s
workforce (USDA, 2005a). During fiscal year 2005, the nation’s agricultural ex-
ports, at $62.4 billion, exceeded agricultural imports by $4.7 billion (USDA,
2006b). The United States is also a major importer of food, bringing in more than
75 percent of its fresh fruits and vegetables and more than 60 percent of its sea-
food (Hedberg et al., 1994; Khan et al., 2001). Between 2000 and 2004, the United
States imported significantly greater amounts of nearly every class of commodity
(Henry, 2005; see Henry in Chapter 1).
Currently more than 130,000 foreign food facilities—a number that closely
approximates the number of domestic facilities—have registered with the Food
and Drug Administration (FDA) as required under the Public Health Security and

Bioterrorism Preparedness and Response Act of 2002 (FDA, 2002). It cannot

be assumed that domestically produced food is more “wholesome” or less vul-
nerable to adulteration than imported products; sanitary standards at some U.S.
food production facilities may be vastly inferior to others in foreign sites (see
Osterholm in Chapter 1).
Most foreign and domestic foods are transported across the country from
central facilities. Meat served in American homes has typically traveled 1,000
miles from its farm of origin to the ultimate point of consumption (Chalk, 2004).
If that meat happens to be a take-out hamburger, it could contain as many as 300
different ingredients, each with a distinct supply chain leading from a farm of
origin to the restaurant where it was prepared (Osterholm, 2005). Food distribu-
tion systems permit the rapid delivery of perishable goods, provide just-in-time
restocking of nonperishable items, and take advantage of economies of scale
(Sobel, 2005). These strategies, along with improvements in production and pro-
cessing, have contributed to a substantial decline in food expenditures as a per-
centage of disposable personal income in the United States, from more than 13.5
percent in the mid-1970s to near 10 percent by 1998. Dr. Craig W. Henry (see
Chapter 1) noted that a similar trend on a global scale appears in data from the
USDA’s Economic Research Service, which indicates that the average percent-
age of income spent on major food groups had declined by approximately 3 per-
cent between 1997 and 2003 in all but the wealthiest countries (USDA, 2005b).
The efficient and widespread distribution of food permits the equally rapid trans-
mission and propagation of foodborne illness. This situation can delay recogni-
tion of an outbreak and impede identification of adulterated food, as illustrated in
recent case studies of foodborne outbreaks discussed below and detailed in Chap-
ter 3. Even more challenging, the U.S. food supply offers countless opportunities
for intentional harm (Osterholm, 2005):
• Prefarm inputs include cattle feed, agricultural chemicals such as fertil-

izers and pesticides, and water supplied for irrigation.
• Farming practices include intensive animal production (zoonoses), the
raising of animals and crops in close proximity (fecal contamination of plant
products), and corporate farming (products are widely distributed).
• Transportation is critical to maintaining the U.S. food supply.
• Processing encompasses the preparation of myriad foods in thousands of
locations around the globe, any of which represent potential targets for sabotage.
• Distribution occurs with such rapidity and over such great distances that
it resembles aerosol release. In the case of some products, a terrorist could as-
sume overnight delivery of an adulterant to many thousands, if not millions, of
people—a product that would be difficult to detect and remove from the market
before considerable harm was done.
• Retail includes both groceries and prepared food: a huge and complex
system of outlets for an equally vast array of foods, provided by a largely low-

paid and transient workforce. This is particularly the case in restaurants, which
account for nearly half of all U.S. food expenditures.
As income levels in developing countries continue to rise, it is expected that

global food consumption patterns—and, concomitantly, food production and dis-
tribution methods—increasingly will resemble those of developed countries
(Regmi et al., 2001). Worldwide demand for high-quality animal protein contin-
ues to grow rapidly. A recent study estimates that global consumption of meat
will increase by over 50 percent between 1997 and 2020 and will nearly double in
developing countries during the same period. Almost all of the increased demand
is expected to be met through expanded production of poultry, pork, and beef
(Rosegrant et al., 2001). The globalization of the world’s food supply will expose
a greater proportion of its people to emerging and reemerging foodborne disease
and contamination (Buzby, 2001). Meanwhile, in developed countries such as the
United States, many consumers seek food that is not only appealing to the palate,
but that is also safe, convenient, and produced or marketed in accord with their
values (see Henry in Chapter 1). Although consumer demand may, over time,
encourage the food industry to increase their investment in ensuring food safety,
a number of workshop participants expressed the view that additional measures
must be taken, and taken quickly, to address key vulnerabilities in the U.S. food
supply.
FOOD SAFETY OVERSIGHT

The globalized food supply presents considerable difficulties to agencies
charged with ensuring food safety. Conference presentations and discussions re-
vealed opportunities and barriers to meeting these challenges in the United States,
as well as at the international level, through the efforts of the World Health Orga-
nization (WHO) and other non-governmental organizations.
The U.S. Food Safety System

At least 15 federal agencies are responsible for implementing the more than
30 laws that direct food inspection in the United States (GAO, 2004, 2005a). As
a reflection of their respective budgets, four agencies—USDA, FDA, Environ-
mental Protection Agency (EPA), and the National Marine Fisheries Service
(NMFS)—play central roles in overseeing the food safety “system.” In 2003,
these agencies combined spent about $1.7 billion and employed nearly 15,000
people (full-time equivalents) to inspect food manufacturing, processing, and stor-
age facilities; conduct research and develop methods to reduce the prevalence of
foodborne pathogens; assess risks posed by various food contaminants; and edu-
cate industry and the public on ways to mitigate or minimize foodborne illnesses
(GAO, 2005b).

To coordinate food safety activities across jurisdictional boundaries, federal

agencies have entered into more than 70 agreements that specify how these dis-
parate agencies carry out their missions in a more or less “coordinated” fashion
(GAO, 2005a, 2005b). In many instances, however, the agencies either do not
fully implement or do not enforce these agreements, resulting in considerable
waste, confusion, and inefficiencies. In recent years, the Government Account-
ability Office (GAO, formerly the General Accounting Office) has documented
many such problems resulting from the fragmented, balkanized nature of the fed-
eral food safety system and has recommended the streamlining of relevant stat-
utes, as well as consolidation of all food safety activities into a single agency with
a single mission (GAO, 2004, 2005b). Indeed, over the past six decades, more
than 21 similar proposals have advocated a reorganization of the federal food
safety system (Vogt, 1998).
Such calls for reform were amplified by a 1998 report of the Institute of
Medicine and National Research Council (NRC) that recommended the integra-
tion of food safety oversight into a single, independent agency (IOM/NRC, 1998).
John Bailar, the chairman of the study committee that prepared this report, dis-
cussed the committee’s findings at the workshop (see Chapter 2). The committee
determined that no federal agency holds food safety as its primary mission and
that this absence of focused leadership—which extends to the state and local
level—results in inadequate surveillance, inconsistent and archaic regulations,
insufficient resources, limited consumer knowledge, and poor adherence to even
the minimum food safety standards now in place (Bailar, 2005).
Bailar noted that a similar set of circumstances led to the creation of the
Environmental Protection Agency in 1970. Yet, despite the weight of the evi-
dence for the food safety report’s findings and the clarity of its recommendations,
little progress toward implementation has been made in the seven years since its
publication. Speaking from personal experience, Bailar attributed this lack of ac-
tion to three possible factors: bureaucratic inertia, turf battles among agencies
currently responsible for ensuring food safety, and resistance to change of any
sort by the food industry. Workshop participants noted that the reorganization of
food safety at the federal level could also benefit state and local food safety sys-
tems, many of which mirror the disorganization of federal jurisdictions. In dis-
cussion, some participants considered this a critical connection, because state and
local officials perform many activities essential to food safety, such as the inspec-
tion of food-processing plants and surveillance for foodborne disease.
At the time of the workshop, proposals for reforming the federal food safety
system were under consideration by legislators in both the House and Senate;
each would create a single independent U.S. food safety agency to oversee in-
spections, enforcement, and standard setting (DeLauro, 2005). The Senate bill,
known as the Safe Food Act of 2005 (U.S. Senate, 2005), takes into account many
of the aforementioned IOM/NRC report’s recommendations (Smith-DeWaal,
2005), as well as recent GAO findings describing reforms undertaken by other

wealthy countries (Canada, Denmark, Ireland, Germany, the Netherlands, New

Zealand, and the United Kingdom) that consolidated their food safety activities
except foodborne disease surveillance (Schlundt, 2005) into a single agency
(GAO, 2005a). Although these changes have proved both challenging and costly,
government officials and other stakeholders in these countries report that re-
organization has made their food safety systems more effective or efficient
(GAO, 2005a).
Global Approaches to Ensuring Food Safety

Even the most sophisticated food safety programs cannot eliminate all risk of
foodborne illness. The global nature of much of the world’s food supply and the
reality that safety cannot be “tested into” food necessitate the establishment of a
coherent, risk-based, international system for preventing foodborne disease, ac-
cording to speaker Jørgen Schlundt (see Chapter 2), director of the food safety
program of the WHO. Schlundt maintained that such an international foodborne
disease prevention system should focus on identifying vulnerabilities in the food
chain and the most effective preventive measures that can be taken to ad-
dress them.
Establishing food safety systems in resource-poor countries will be challeng-
ing, as many of them lack the basic infrastructure upon which food safety de-
pends. Yet the achievement of this goal is increasingly urgent, not only because
food exports from developing countries are on the increase, but also to address
the recent introduction into developing countries of debilitating foodborne patho-
gens, such as Salmonella and Campylobacter, from the better-prepared industri-
alized world (Schlundt, 2005). WHO, in collaboration with the Food and Agri-
culture Organization (FAO) of the United Nations, has responded to this need by
conducting risk assessments of foodborne illness and supporting training and ca-
pacity building for countries attempting to establish and meet risk-based stan-
dards for food safety (WHO, 2002a,b). This effort aims to help developing coun-
tries create efficient and appropriate food safety systems from the ground up that
incorporate elements of successful systems in developed countries, Schlundt said.
WHO/FAO recommendations on the necessary elements of an effective na-
tional food safety program also served as the basis for a set of food safety guide-
lines developed for consumer organizations around the world by the Center for
Science in the Public Interest (CSPI, 2006). As described at the workshop by
CSPI food safety director Caroline Smith DeWaal, the recently published guide-
lines focus on eight essential elements for national food safety programs:
1. Food laws and regulations

2. Foodborne disease surveillance and investigation systems
3. Food control management
4. Inspection services

5. Recall and tracking systems

6. Food monitoring laboratories
7. Information, education, communication, and training
8. Funding and affordability of the national food safety program
Timely communication is critical to protecting the food supply, particularly

at the international level. The International Food Safety Authorities Network
(INFOSAN), established in 2004 by WHO and FAO, links officials responsible
for food safety in 144 nations (INFOSAN, 2006). These officials receive food
safety information from the network and disseminate it in their countries; they
also alert the network to incidents of foodborne illness of international signifi-
cance. When such emergencies occur, the WHO Global Outbreak Alert and Re-
sponse Network (GOARN), which played a central role in the global response to
SARS, is poised to respond (IOM, 2004; Schlundt, 2005). Under the recently
revised international health regulations, due to take effect in 2007, countries with
confirmed outbreaks of infectious disease that pose a threat beyond their borders
are required to alert WHO. Governments of affected countries are responsible for
determining whether an outbreak constitutes an international disease emergency,
and in the case that such an emergency exists, for informing WHO once the prob-
lem ceases to be a threat. However, Schlundt noted, international health regula-
tions grant WHO the right to overrule a national government that is not sharing
information about a disease outbreak with any country that could potentially be
affected by such an emergency.
ACCIDENTAL FOODBORNE DISEASE

Over the past two decades, cases of accidental foodborne disease reported to
the CDC have outstripped incidents of intentional food adulteration by approxi-
mately 10,000 to 1, according to speaker Robert Tauxe (see Chapter 3). Although
the rarity of criminal food tampering may be reassuring, this statistic also high-
lights the regularity—and to a certain extent the “ordinariness” of accidental
foodborne illness, even in a wealthy nation. In addition to morbidity and mortal-
ity, the burden of foodborne illness borne by the industrialized world includes
medical expenses, losses in productivity due to missed work and premature
deaths, and trade embargoes against affected products as well as reduced profits.
Consumer anxiety sparked by the contamination of a specific food brand or item
can negatively affect entire agricultural sectors or industries (Tauxe, 2005). In
developing countries, where food safety presents far greater challenges, foodborne
disease is a fact of daily life and a significant cause of death due to diarrheal
illness (WHO, 2002a,b).
The true incidence of food contamination in the United States is unknown.
Epidemiologists believe that many affected people do not seek medical attention;
moreover, foodborne disease is difficult to diagnose. “Unknown agents” account

for 81 percent of foodborne illnesses and hospitalizations in the United States and
64 percent of such deaths (Mead et al., 1999). Detecting a foodborne outbreak is
even more difficult, as illustrated by the single largest salmonella outbreak in the
United States, which occurred in 1994 (Osterholm, 2005; see Osterholm in Chap-
ter 1). In that episode, approximately 224,000 people across a large area of the
United States contracted salmonellosis from ice cream that became contaminated
following pasteurization (Hennessy et al., 1996; Sobel et al., 2002). Because only
about 1.5 percent of the thousands of people presumed to have been infected
actually reported symptoms, epidemiological analysis was necessary to deter-
mine the source of the pathogen. The following case studies presented at the
workshop illustrated additional challenges inherent in the recognition and inves-
tigation of food-associated outbreaks of infectious disease.
Cyclosporiasis from Imported Produce

Speaker Barbara Herwaldt recalled that little was known about the biology or
epidemiology of the coccidian parasite Cyclospora cayetanensis when in the mid-
1990s, large, multistate outbreaks of gastroenteritis began to occur (see Chap-
ter 3). Cyclospora is endemic in many tropical and subtropical countries and had
previously been identified in persons with AIDS and in Western travelers to de-
veloping countries (Herwaldt, 2000, 2005). Although effective treatment for
cyclosporiasis is available, most laboratories lack the tools and expertise neces-
sary for accurate diagnosis of this foodborne parasite. Herwaldt and colleagues
traced the initial U.S. outbreaks of cyclosporiasis to Guatemalan raspberries, a
“stealth” food often consumed as a garnish, but rarely listed on menus. Some
food safety experts initially questioned whether these outbreaks could have been
caused by an obscure organism borne by a mere garnish, but Herwaldt and co-
workers’ conclusion was confirmed when additional outbreaks occurred much as
they had predicted.
Several types of fresh produce, including mesclun (a mixture of young salad
greens) and basil, have been vehicles for cyclosporiasis outbreaks. Dean Bodager
described an ongoing investigation of an outbreak that occurred in Florida in
early 2005 (see Chapter 3). As is typical in many foodborne outbreaks, a large
number of sporadic case clusters occurred over an extended period of time (four
months, in this case). The investigation, triggered by reports of an unusually
large number of infections detected by a private lab, involved health departments
in Florida’s 67 counties and in 28 other affected states, the three different state
agencies that regulate food in Florida, and two federal agencies—the CDC, and
the FDA. The investigators now believe that imported basil, served in an upscale
restaurant, harbored the parasite. Such investigations constitute the best method
to identify foodborne pathogens and their sources, discover how they entered the
food supply, and prevent similar outbreaks from occurring in the future,
Herwaldt noted.

The development of preventive measures will require a better understanding

of an organism Herwaldt (2005) described as “a mystery, wrapped in an enigma,
served on a bed of imported produce.” In the meantime, public health authorities
must consider the potential of seemingly unrelated cases of cyclosporiasis (among
other potentially foodborne illnesses) as indicators of outbreaks and pursue them
to their sources through timely and thorough investigation.
Hepatitis A from Imported Green Onions

Although the pathogen involved is far better characterized than Cyclospora,
investigations of foodborne illness caused by hepatitis A virus (HAV) present a
similar array of challenges. Speaker Beth Bell described a series of outbreaks in
late 2003, including some 600 people who ate in the same Pennsylvania restau-
rant over a four-day period (CDC, 2003b; Wang and Moran, 2004; see Chapter
3). This outbreak was detected when an alert clinician reported to his local health
department that he had identified 10 cases of HAV within a few days, as com-
pared with 1 case of hepatitis A in the entire previous year. Six of these recent
cases had reported eating in two separate groups at the same restaurant. A case-
control study suggested that all of the customers who became ill had eaten salsa
containing raw green onions that had been imported from four farms in Mexico,
where hepatitis A is endemic; the FDA subsequently banned imports from these
farms. In response to these events, Mexico established a mandatory food safety
program.
This process revealed several opportunities for improving the safety of the
food supply, much as did the previously discussed investigations of cyclosporiasis
outbreaks. Molecular methods for HAV detection hastened tracing the cases back
to their source, but a more sensitive surveillance program could reveal an out-
break consisting of more sporadic cases, including those that occur in other
countries (Bell, 2005). Preventive measures taken on the farm, such as providing
access to adequate sanitary facilities for field workers and using clean water for
irrigation and for the rinsing of harvested produce, could also have mitigated this
outbreak. Finally, as Bell observed, simply telling the story of the outbreak can
increase the public health community’s awareness of this and other food safety
issues.
FOODBORNE ATTACKS: SCENARIOS AND CONSEQUENCES

Despite the comparative rarity and mildness of previous incidents of inten-
tional food adulteration, little imagination is required to conceive the possibility
of a major attack featuring the U.S. food supply. Workshop participants consid-
ered accounts of intentional foodborne illness, as well as likely scenarios for food
adulteration with both biological and chemical agents at vulnerable points in the
U.S. food supply chain. These discussions revealed needs that must be addressed

to reduce the potential for such attacks and to mitigate their consequences should
they occur.
Incidents of intentional food adulteration reviewed at the workshop included
the following:
• The 1984 contamination of an Oregon salad bar with Salmonella typhi-

murium by members of the Rajneesh religious cult, who intended to sway an
election by incapacitating voters. A limited “trial run” of their plan sickened more
than 700 people (Torok et al., 1997).
• The intentional infection of 12 employees by a coworker who left pastries
tainted with Shigella dysenteriae in their break room at a large Texas medical
center laboratory in 1996 (Kolavic et al., 1997).
• Several incidents in China in which food products were contaminated with
rat poison by business competitors (Osterholm, 2005). In 2001, 120 people were
sickened after being poisoned by the owners of a noodle factory (Death sentence,
2002a). In 2002, a similar incident took place when a snack store owner spiked a
competitor’s breakfast foods with rat poison resulting in the deaths of at least 38
people and causing over 300 to become seriously ill (Death sentence, 2002a,b).
The consequences of these and other actual foodborne attacks pale in com-
parison with the potential human (and/or animal) morbidity, mortality, and socio-
economic consequences that could unfold from an intentional act of adulteration
targeting the U.S. food supply chain (Breeze, 2004; Chalk, 2005). A thwarted
attempt at such an event, or even a credible hoax, would probably have severe
economic repercussions for growers and processors of the affected foods, given
previous consumer reaction to perceived threats such as BSE in beef (see subse-
quent discussion and Chapter 6) or the ripening agent Alar in apples.2
2Alar (Uniroyal’s brand name for the chemical daminozide) was sprayed on apples as a ripening
agent to regulate fruit growth and color and to simplify harvest. Registered with the FDA in 1963,
Alar was removed from the U.S. market by its manufacturer in 1989 in response to safety concerns.
The alarm was raised by media reports of a study by the Natural Resources Defense Council that
implicated Alar as a dangerous carcinogen, especially in children. U.S. apple sales and prices plum-
meted and the EPA moved to ban Alar; Uniroyal pulled its product from the market before the ban
could take effect. Years later, the extent to which Alar constituted a public health threat continues to
be debated. Some organizations, most notably the industry-funded American Council on Science and
Health, contend that the Alar “scare” was unfounded. Others, including the Consumers Union, con-
tend that Alar poses a significant public health risk according to government standards, thus the
EPA’s actions were appropriate. For a more in-depth discussion of this issue see, Ashton L. 1999
(February 28). Alar scare 10 years past, but food safety debate goes on. Yakima Times [online] (ex-
cerpts.) Available: http://www.ecologic-ipm.com/APyw22899.html; Environmental Working Group.
1999. Ten years later, myth of ‘Alar scare’ persists. [Online] Available: http://www.ewg.org/reports/
alar/alar.html; and, Wikipedia, accessed March 4, 2006. Daminozide. Available: http://
en.wikipedia.org/wiki/Alar.

Food could provide an extremely effective vehicle for delivery of a variety of

pathogens, such as anthrax (Osterholm, 2005), as well as for noninfectious, chemi-
cal agents including biological toxins (e.g., botulinum toxin) and poisons (e.g.,
cyanide, dioxin) directly to humans (Khan et al., 2001). To identify the likeliest
combinations of foods and adulterants that might be vulnerable, the FDA em-
ploys risk management protocols, described by speaker David Acheson and de-
tailed in Chapter 4. Characteristics of high-risk food products include large batch
size, short shelf life (which implies rapid turnover), the potential for uniform
mixing of a contaminant into the food, and a production process that would per-
mit the agent to be added, undetected, in sufficient quantities for it to be effective
(see also Osterholm in Chapter 1). As Acheson and other workshop participants
noted, however, no food can be considered risk free, either with regard to inten-
tional or accidental adulteration. The FDA uses these food vulnerability assess-
ments to develop guidance documents and training for state and local regulatory
officials and the food industry, to focus the agency’s emergency response plan-
ning, and to set research priorities.
Many workshop participants expressed concern about a range of potential
attackers of the U.S. food supply from al-Qaeda and other foreign nonstate actors,
to radical animal rights groups, to homegrown “lone wolf” perpetrators. The tran-
sient nature of the food industry workforce is particularly worrisome, according
to Osterholm, who noted the ease with which members of terrorist groups could
be employed within food-processing companies and obtain “insider knowledge”
of the vulnerable “choke points” in the production process.
Botulinum Toxin in Milk: A Possible Bioterrorism Scenario

Three workshop presentations (see Acheson, Leitenberg, and Detlefsen in
Chapter 4) addressed a single, highly publicized scenario for foodborne terror-
ism: the intentional contamination of the U.S. milk supply with botulinum toxin.
A May 2005 New York Times op-ed essay on this subject by Lawrence Wein
(2005) raised heated controversy as to the appropriateness of its publication, as
well as the accuracy of its conclusion that milk represents “a uniquely valuable
medium for a terrorist” (Leitenberg and Smith, 2005). Six weeks later, the contro-
versy was further fueled by the delayed publication of a peer-reviewed paper
(Detlefsen, 2005; Wein and Liu, 2005) in the Proceedings of the National Acad-
emy of Sciences (Alberts, 2005). Based on a mathematical model of a “cows-to-
consumers supply chain,” the authors predicted that “if terrorists can obtain
enough toxin, and this may well be possible, then rapid distribution and con-
sumption [will] result in several hundred thousand poisoned individuals if detec-
tion from early symptoms is not timely.”
Discussants Milton Leitenberg and Clay Detlefsen disputed several claims
made by Wein and Liu. Leitenberg identified what he considered were numerous
inaccuracies and improperly sourced citations in their work; he also questioned

the ability of terrorist groups such as al-Qaeda to prepare botulinum toxin accord-
ing to the “Jihadi manual” mentioned in Wein’s op-ed essay, since it requires
such technology as a refrigerated cold room, a vacuum refrigerated ultracentri-
fuge, and a mouse colony. Detlefsen argued that the dairy industry, in partnership
with the U.S. government, have taken extensive measures to ensure the security
of the milk supply following the terrorist attack of September 11, 2001. These
efforts included the determination that higher pasteurization temperatures can be
used to denature type A botulinum toxin while retaining milk’s familiar flavor
and texture. Many milk producers have already adopted this practice, Detlefsen
explained, but because it is voluntary, it is not universal.
David Acheson presented the FDA’s analysis of the milk production process
and recommendations for improving its biosecurity. These include greater aware-
ness of the threat posed by bioterrorism, locks on vulnerable production and stor-
age facilities, thermal destruction of pathogens, and the development of cost-
effective tools for the surveillance and mitigation of multiple agents. That Wein
and Liu may have overstated a specific threat of foodborne bioterrorism and un-
derstated the preparations in place against it does not contradict the argument,
made by several workshop participants, that the food supply must be protected
without unduly burdening industry or frightening the public.
Food Safety vs. Food Biosecurity

The early detection of foodborne disease, resulting either from accidental
contamination (food safety) or from deliberate attack (food biosecurity), demands
sensitive surveillance systems for communicable disease at both local and na-
tional levels, and it depends on close cooperation and communication among
clinicians, laboratories, and public health officials (WHO, 2002c). The particu-
lars of these needs—for the organization of food safety systems, surveillance,
reporting, and response to foodborne disease outbreaks—are discussed in greater
detail below and in contributions to Chapters 2 and 5–7.
Preventing or mitigating the impact of deliberate food adulteration requires
greater attention to such threats on the part of the food industry, according to
workshop participants. Industrial food safety standards focus on accidental
foodborne disease, a relatively common occurrence with mild to moderate impact
on the average affected individual; bioterrorism, by contrast, is a rare, potentially
high-impact event. This distinction increases the already daunting challenge of
ensuring food safety, of balancing the risk of harm against the cost of protection,
and of implementing and paying for cost-effective safeguards.
SURVEILLANCE OF FOODBORNE THREATS TO HEALTH

Two categories of tools and practices are used to detect threats to the food
supply: farm-to-table food safety systems and human disease surveillance (Besser,

2005). Although theoretically capable of providing primary prevention, farm-to-

table systems—which include food pathogen monitoring, animal disease surveil-
lance, the testing of food during processing and distribution, and the analysis of
consumer complaints of adulterated food—can be insensitive because of typi-
cally low pathogen loads in contaminated food, according to speaker John Besser
(see Chapter 5). The presence of foodborne pathogens, symptoms of foodborne
illness, and illness-related behaviors in humans are comparatively sensitive indi-
cators of foodborne outbreaks, but usually take so long to be recognized that they
afford only secondary prevention. Several workshop presentations discussing the
benefits, limitations, and accomplishments of specific food and disease surveil-
lance tools sparked discussion on obstacles to timely foodborne threat detection
and how such challenges might be overcome.
Monitoring Food Safety from Farm to Fork

In framing his description of food surveillance—which focused on microbial
threat agents—speaker Robert Buchanan noted its key role in verifying the effec-
tiveness of food safety systems, as well as in preventing foodborne disease. How-
ever, he observed, effective food surveillance requires a clear understanding of its
strengths and limitations, and the simultaneous use of complementary preventive
strategies and public health surveillance methods. The acquisition of food sur-
veillance data occurs through the same multi-step process of sampling and analy-
sis regardless of whether the potential contamination is likely to be intentional or
accidental. Thanks to major advances in detection technology over the last de-
cade, several methods can now be used to identify food contaminants in “real
time”—a relative term in the food industry, measured by the length of time the
monitoring agency has to act upon detecting contamination. For a product that
can remain in a warehouse for two weeks after it is tested for safety, “real time” is
13 days; for perishable products such as fruits, vegetables, and milk, “real time”
is nearly instantaneous.
Considerably less research has gone into improving sampling methods for
food surveillance, which Buchanan characterized as the heart of the surveillance
process. An effective sampling plan takes into account the probability of finding
a contaminated sample, known as the defect rate. Given the ability of very small
numbers of certain microbes to cause foodborne illness, the detection rate for
many foods is miniscule. The odds of detecting contamination in these cases can
be increased by taking more samples, larger samples, or by focusing on the like-
liest trouble spots in the food chain, Buchanan said. Targeted “smart” sampling
techniques can be further adapted to provide information, such as baseline con-
tamination rates, that cannot be determined by traditional batch testing methods.
In addition to the defect rate, the cost and effectiveness of any food surveillance
protocol depends upon the degree of confidence required to ensure safety.

Analyzing Consumer Complaints

Speaker Kimberly Elenberg described a new tool used by the USDA’s Food
Safety and Inspection Service (FSIS) to rapidly track and analyze consumer com-
plaints regarding adulterated food (see Chapter 5). The analytical component of
the Consumer Complaint Monitoring System (CCMS), called Emerging Patterns
in Food Complaints (EPFC), employs computational methods to detect patterns
in complaints received by CCMS—data that are too voluminous and complex for
the human mind to grasp. EPFC examines reports of such “adverse food events”
as foreign objects in food and symptoms of illness for mathematical patterns
associated with foodborne outbreaks. The system includes decision trees that can
identify likely chemical or microbial contaminants from symptom descriptions
and onset times, Elenberg explained.
Recent tests demonstrate that EPFC can resolve faint signals amid the flood
of noisy data it encounters, permitting it to generate useful alerts based on fewer
adverse reports than would be required to obtain a similarly reliable result by
other means, including typical syndromic surveillance methods. For example,
when presented with historical data, the system immediately identified a food-
borne E. coli outbreak that had originally taken two weeks of skilled analysis to
identify. In the future, Elenberg and colleagues hope to greatly expand the appli-
cation of their analytical methods, and eventually to enable the real-time integra-
tion of data on animal, plant, and human disease.
Public Health Surveillance

As defined by speaker Robert Tauxe, public health surveillance is “the moni-
toring of health events in humans, linked to action.” Information gained from
public health surveillance is used to measure the magnitude and burden of
foodborne illness, to identify outbreaks, and to evaluate the impact of prevention
and control efforts. In the United States, authority to conduct public health sur-
veillance rests with state governments. Surveillance data is derived from a num-
ber of different sources including: complaints from citizens to local health depart-
ments; formal reporting systems for diseases deemed notifiable; reports from
physicians and laboratories to various jurisdictions upon the identification of cer-
tain specific diseases, as required by law; microbial strains referred to state public
health laboratories for characterization; and reports of outbreaks under investiga-
tion. Although voluminous, these data are highly heterogeneous and typically of
limited quality.
Since 1996, public health surveillance in the United States has been substan-
tially strengthened through the establishment of standard notifiable disease re-
porting in all 50 states, as well as the creation of FoodNet, PulseNet, and the
electronic food outbreak reporting system known as eFORS (CDC, 2003c; Tauxe,
2005). FoodNet is an active surveillance system that collects data about sporadic
cases of foodborne illness, as it is diagnosed (CDC, 2006; see Tauxe in Chapter

3). It is composed of 10 sentinel sites that collectively sample 14 percent of the

U.S. population; these sites are operated jointly by state health departments, the
FDA, and the USDA under the aegis of the CDC Emerging Infections Program.
Information derived from FoodNet is used to estimate the burden of foodborne
illness and to monitor epidemiological trends in foodborne disease. FoodNet also
serves as a platform for conducting specialized studies of emerging pathogens.
PulseNet, the national molecular subtyping network for bacterial foodborne
pathogens, is a digital repository for the genetic fingerprints of several pathogen
strains, collected by state and some city public health laboratories and managed
by the CDC (CDC, 2005b; see Tauxe in Chapter 3). The analysis and compari-
son of such fingerprints has greatly improved outbreak detection and investiga-
tion, particularly when contaminated foods are widely distributed and the attack
rate is low, such as in the previously discussed case of nationally distributed ice
cream. A complex multistate outbreak investigation generally follows such a dis-
covery. PulseNet currently monitors five foodborne pathogens—Escherichia coli
O157:H7, Salmonella, Shigella, Listeria, and Campylobacter—and more are ex-
pected to be added, as are increasing numbers of molecular subtypes of patho-
gens found throughout the food chain, in addition to those isolated from people
with foodborne disease. Global networks for foodborne disease surveillance typi-
cally focus on human pathogens, but some programs monitor animals as well.
These include the WHO Salmonella surveillance network—Global Salm-Surv
(WHO, 2006) and Med-Vet-Net (Med-Vet-Net, 2005), a project of the European
Union that examines foodborne infections of both humans and livestock, with a
special emphasis on zoonoses (King, 2005). Global Salm-Surv, which now also
covers other pathogens including Campylobacter, has accumulated data for
565,000 human and 102,000 nonhuman isolates, Jørgen Schlundt noted.
Surveillance of Foodborne Outbreaks

Approximately 1,200 outbreaks of foodborne disease are reported to the CDC
each year, each of which, on average, affects 20 to 30 people (Tauxe, 2005).
Better surveillance results in more outbreaks being detected, which in turn in-
creases the possibility of preventing future outbreaks, Tauxe explained. Research
on foodborne outbreaks leads to targeted prevention strategies for known and
emerging pathogens on an ongoing basis. Although most outbreak investigations
occur after the fact, they enable public health authorities to discover new combi-
nations of foods and pathogens, identify gaps in the food safety system, and to
develop new processes and regulations that improve the safety of the food supply.
This process of continual improvement has been expedited by eFORS, a
system by which local or state health departments report foodborne outbreaks to
the CDC via a Web-based interface (CDC, 2003c). Diffuse outbreaks continue to
challenge surveillance systems, however. An outbreak of foodborne disease that
occurs among 250 people within a one-block radius is easily detected, Tauxe

observed, but if the same number of people fell ill across the United States, only
a highly sophisticated surveillance system could discern the “signal” of such an
outbreak from the “background noise” of unrelated, sporadic cases of foodborne
illness.
Progress and Roadblocks

FoodNet data reveal that incidences of some foodborne diseases have de-
clined since the network’s advent (Tauxe, 2005). Since baselines were estab-
lished in 1996–1998, cases of Campylobacter have dropped by 31 percent, List-
eria by 40 percent, E. coli by 42 percent, and there has been a marginal but
statistically significant decrease in Salmonella cases. Control of E. coli O157:H7
in ground beef has improved, although it is not yet adequate, as is the control of
Campylobacter in poultry, Salmonella in eggs, and Listeria monocytogenes in
processed meats, Tauxe noted; control remains elusive for multi-drug resistant
Salmonella in ground beef, a wide array of different pathogens and different prob-
lems in produce, and Vibrio in raw shellfish.
A variety of constraints that limit the effectiveness of foodborne disease sur-
veillance will not be easily overcome, workshop participants acknowledged. Chief
among these is that detection largely depends upon people getting ill; sometimes
this occurs after a long period of incubation, further complicating the determina-
tion of an outbreak’s source. People often delay seeking medical attention, after
which considerable time may elapse before a physician or a laboratory can render
a diagnosis, and even more time for a public health laboratory to determine its
subtype—a necessity for recognizing the “signal” of a diffuse outbreak. Once
such an outbreak is suspected, investigators must trace the contaminant to its
source. For some foods with many unsourced components, such as ground beef,
this task is nearly impossible to perform, Tauxe said.
Improving Foodborne Threat Surveillance

Several opportunities for enhancing foodborne disease surveillance identi-
fied by workshop participants included the following:
• Increase the capacity and resources of regulatory agencies for skilled trace-
back of food contaminants.
• Decrease the anonymity of foods to make them more readily traceable.
• Provide the resources necessary to bring every state up to the highest cur-
rent standards of foodborne disease epidemiology, and create a national network
capable of real-time surveillance.
• Expand molecular subtyping to include a broader variety of pathogens,
fingerprinting pathogens derived from foods and livestock in real time, and link-
ing these subtypes to those in human databases.

• Use faster, automated methods for fingerprinting and the detection of ill-
ness clusters (the CDC is currently evaluating several such methods).
• Expand global and regional networks for foodborne disease surveillance,
and in particular increase funding for PulseNet, which has already expanded into
Canada, Europe, Asia, and Latin America (Besser, 2005; Tauxe, 2005).
Having reflected on the inherent benefits and limitations of the various ap-
proaches for detecting and investigating foodborne illness, workshop participants
affirmed the need for multiple, integrated surveillance systems. The value of such
systems was demonstrated in the 2005 recalls of ice cream, packaged salad, and
juice based on PulseNet findings (Besser, 2005). Increasingly sensitive detection
methods are blurring the line between outbreaks and sporadic cases of foodborne
disease, according to Besser, making real-time surveillance of foodborne illness
an achievable goal.
REPORTING FOODBORNE THREATS: THE CASE OF BSE

Among all the resources brought to bear on the control of foodborne illness,
time is perhaps the most precious. The rapid reporting of foodborne threats is
therefore essential to reducing the burden of foodborne illness, but it also carries
inevitable and significant costs to individuals, industry, and national economies.
Initial costs such as the value of lost production and expenses associated with the
destruction and containment of contaminated and potentially adulterated prod-
ucts (which in some cases translates into acres of crops or herds of livestock) are
easily appreciated and often compensated—in which case those costs are often
borne by taxpayers.
A variety of indirect costs can also result from outbreaks of foodborne ill-
ness, not all of which are incurred by the producer of the affected food. These
include the loss of export markets due to restrictions on products associated with
disease threats, loss of consumer confidence and market share (which may extend
to related products that have never been contaminated), and multiplier effects on
businesses and individuals with economic ties to the affected products, from food
processors and distributors to business owners and nonfarm workers who serve
farming communities (Chalk, 2005; Monke, 2005).
The balance of costs and benefits associated with reporting foodborne threats
is clearly illustrated by the recent and ongoing global experience with the neuro-
logical disease of BSE. After Canada announced the discovery of BSE in cattle in
May 2003, farm-level prices for Canadian beef declined by nearly half. Beef
prices in the United States remained very strong until December of that year,
when a cow with BSE was discovered within its borders; although U.S. beef
prices did not fall as far as Canada’s, a trade model developed at Kansas State
University estimated the total BSE-associated loss incurred by the U.S. beef in-

dustry in 2004 at more than $3.2 billion (Coffey et al., 2005; Hanrahan and
Becker, 2005; Monke, 2005).
Although the United States and Canada have clearly incurred substantial costs
associated with the reporting of BSE, the benefits of the initial report and ongoing
investigation in the United Kingdom were demonstrated nearly a decade later,
when the disease was linked with a human variant of Creutzfeldt-Jakob disease
(vCJD) (Brown et al., 2001). The establishment of a causal association between
BSE and vCJD has led to the establishment of a variety of infection control and
surveillance measures, as well as efforts to determine the extent of the vCJD
epidemic for the purpose of public health planning. However, it is clear that the
disincentives for reporting BSE, discussed below, still greatly outweigh the in-
centives for doing so. Through a series of presentations, workshop participants
explored the biology of BSE and its implications for food safety, international
perspectives on BSE surveillance and prevention, and public health lessons
learned from this disease, and its consequences.
BSE Biology and Food Safety Implications

A member of the family of diseases known as transmissible spongiform en-
cephalopathies (TSEs, also known as prion diseases), BSE was first identified in
1986 in the United Kingdom and has since been detected in 26 countries (GAO,
2005c). In the early 1980s, speaker Stanley Prusiner proposed that the pathogens
that cause two TSEs— Creutzfeldt-Jakob disease (CJD) and scrapie, a disease of
sheep—consist entirely of an “infectious” change in the conformation of a pro-
tein that he termed the prion (Prusiner, 2004). Researchers have since learned that
in addition to scrapie and CJD, prions apparently cause BSE and its human vari-
ant, vCJD, as well as chronic wasting disease in deer and elk (see Chapter 6).
Scientists have also discovered that the prion protein is encoded in the ge-
nome of every animal studied to date and is expressed, in its normal form, in
nerve cells. Prion disease arises when a prion protein in an abnormal, disease-
causing conformation induces normal prion proteins to refold (Prusiner, 2004,
2005). Abnormal prion proteins form complexes that resist heat, radiation, and
chemicals that would destroy viruses and other pathogens. These complexes build
up in nerve cells, causing them to rupture, and producing the characteristic plaques
(masses of protein) and vacuoles (microscopic holes) found in the brains of ani-
mals with TSEs. Prion diseases may be of spontaneous, infectious, or inherited
origin; in the case of BSE, both spontaneous and infectious cases appear to have
occurred. Because prion diseases have incubation periods that can exceed 40 years
and are invariably fatal, no exposure to prions should be considered acceptable,
Prusiner argued (Prusiner, 2005).
In his workshop presentation, Prusiner described the experimental evidence
for this model of TSE etiology and efforts to develop rapid, low-cost diagnostic
tests for BSE (see Chapter 6). Some recently developed tests are able to detect

sufficiently low levels of disease-causing prions in brain tissue to permit the iden-
tification of infected but asymptomatic cattle within hours of slaughter. A far
better—and as yet unrealized—alternative would detect minute amounts of ab-
normal prions in the blood and urine of live animals, including humans.
International Perspectives on BSE and vCJD

Speakers Steven Collins, an Australian expert on BSE and vCJD, and Maura
Ricketts, a Canadian authority on prion diseases, shared their perspectives on the
response to these health threats (see Chapter 6). As a preface to his remarks,
Collins described an epidemic of the prion disease kuru in the Eastern Highlands
of Papua, New Guinea. The disease, recognized in the 1950s, has since been
linked with the practice of ritualistic cannibalism, which was successfully out-
lawed 50 years ago. Nevertheless, cases are still occasionally diagnosed, suggest-
ing that there may be no finite incubation period for kuru (and perhaps for other
TSEs as well). Despite its low transmissibility compared to microbial infections,
kuru produced high mortality rates in villages where the disease was endemic.
The disease is now thought to be nearly eliminated.
Collins recalled the false reassurance offered in the early years of the BSE
epidemic by the lack of documented evidence for the animal-to-human transmis-
sion of the related disease, scrapie, which had been recognized for more than a
century. Under this mistaken assumption, approximately 200 million infected
cattle reached the human food chain during the epizootic (Collins, 2005). In 1996,
a researcher at the National CJD Surveillance unit in Edinburgh recognized a
case of CJD of an unusual form now known as vCJD; preliminary research soon
suggested a link between vCJD and BSE. Based on this experience, Collins said,
it should be assumed that all TSEs are capable of breaching species barriers; thus,
it is now important to determine whether chronic wasting disease has been trans-
mitted from deer to humans.
To date, 158 cases of vCJD have been diagnosed in the United Kingdom
(Collins, 2005). The mean age at onset is 26 years. Two presymptomatic cases
may be linked to blood transfusions, raising the possibility that a much larger
population than initially thought is at risk of developing vCJD, despite appear-
ances that the epidemic is declining. Australia has conducted surveillance for all
human forms of TSEs since 1996, taking a variety of approaches described in
detail by Collins in Chapter 6. To date, no probable or definite case of vCJD has
been diagnosed in Australia, nor has any endogenous case of BSE or scrapie
been found.
In the course of describing the Canadian response to BSE and vCJD, detailed
in her contribution to Chapter 6, Ricketts emphasized the social and political
forces that shaped the public health response to this threat. Although far from
cautious in their individual behaviors, the Canadian public clearly dreaded vCJD
and supported the expenditure of $18 billion per year for protection from the

disease. Ricketts conjectured that this support was driven in part by public out-
rage against agricultural and food companies that reaped huge profits selling prod-
ucts that made unsuspecting consumers ill.
Trade-based economies resist the disclosure of threats to public health and
the adoption of preventive measures due to their short-term costs, Ricketts ob-
served. Thus government support for disease prevention and surveillance is es-
sential; however, it is often difficult to obtain because the affected country must
acknowledge that it has a foodborne disease problem.
Lessons from BSE

Speaker Wil Hueston, of the Center for Animal Health and Food Safety at
the University of Minnesota, shared insights gained from 16 years of involve-
ment with BSE and the interface between animal and human health. He distilled
this experience into the following seven lessons, summarized here and discussed
in detail in Chapter 6:
1. Detecting a new animal disease is extremely difficult, for a host of

reasons ranging from the fact that animal disease is typically diagnosed and treated
on the farm, where sick animals are usually sold, eaten, or buried, to the lack of
support for the diagnosis of emerging animal diseases.
2. Recognizing BSE in a low-incidence country (such as the United
States) is difficult, because most countries use passive surveillance and confuse
the absence of evidence for the disease with evidence for its absence. There are
huge disincentives for expanding national surveillance, however: it is expensive
to do, and it increases the potential for economic losses if BSE is discovered
before there is a plan in place to address it.
3. Most farmers are honest, but disincentives for reporting BSE greatly
outweigh incentives. Possible incentives for reporting BSE, such as treatment or
the certification of herds (rather than nations) as BSE-free, do not exist, while
controls mandated by the government raise the cost of production in an economy
that values cheap food. At the same time, producers that report BSE lose the
market for their product and face costs associated with investigation, destruction,
and disposal of infected animals.
4. Testing can become an end unto itself unless its purpose is clarified;
even then, it is not a panacea. It must be backed up with animal and public health
measures to reduce the burden of disease.
5. Effective protective measures focus on reducing the risk of infectious
disease, not the presence or absence of disease in a country. Trade bans do not
work because infectious diseases can cross any border.
6. Opportunity costs. Every dollar spent on BSE is not available to address
other threats to human and animal health. The cost of BSE testing is currently
disproportionate to its public health benefit.

7. High health status is a curse because, once attained, the impetus for
maintaining a public health infrastructure is lost.
Hueston also presented a series of actions that could be taken to address key
issues raised by BSE and that are generally applicable to improving the response
to infectious disease. They included the following:
• Surveillance strategies that reflect purpose and scientific validity, as well

as the recognition that no single strategy fits all circumstances;
• Incentives for reporting disease, rather than regulatory demands;
• To gain a better understanding of the sociology and psychology of disease
reporting and compliance, greater collaboration among biological, medical, and
social scientists;
• Replacement of the nationalistic, “zero-risk” paradigm of infectious dis-
ease response with global risk management and science-based regulation; and
• Recognizing that all animal health issues are potential public health is-
sues, an emphasis on transdisciplinary approaches to all animal diseases (not just
zoonoses).
RESEARCH AND POLICY OPPORTUNITIES

Previously noted workshop presentations and discussions addressed the role
of food safety oversight, surveillance, and reporting in protecting the food sup-
ply. Additional research and policy opportunities for reducing foodborne threats
were raised in subsequent workshop presentations on animal health, food de-
fense, and food safety science. The emphasis on risk assessment in the latter
presentation provides a framework for addressing several key challenges to food
safety, as well as opportunities for protecting the food supply, identified by work-
shop participants.
Animal Health at the Crossroads

Following closely on the discussion of BSE and its implications for food
safety, Lonnie King’s presentation highlighting the recently published NRC re-
port, Animal Health at the Crossroads (2005), magnified and reinforced partici-
pants’ understanding of the critical linkage between animal and human health.
The report, summarized in Chapter 7, used case studies of key animal diseases to
evaluate existing prevention and detection systems and identify opportunities and
barriers to their improvement. Many of the report’s findings directly address the
reduction of foodborne illness, including the identification of the following needs:
• Greater collaboration and integration between public health and animal

health officials and between biomedical and veterinary research communities;

• New technologies and scientific tools to detect, diagnose, and prevent

animal diseases and zoonoses;
• Expanding and strengthening the animal health laboratory network;
• Global systems that prevent, detect, and diagnose known and emerging
disease threats to animal and public health; and
• The improved and expanded use of predictive, risk-based tools and mod-
els to develop strategies to address health threats.
Food Protection and Defense

In contrast to earlier discussion stressing the importance of a unified effort to
detect and respond to both accidental and deliberate foodborne threats, speaker
Frank Busta focused on research needs and opportunities that, while they might
also reduce accidental foodborne illness, are specifically directed toward reduc-
ing and mitigating attacks on the food supply. This is the purpose of the National
Center for Food Protection and Defense (NCFPD), which Busta directs at the
University of Minnesota. The NCFPD pursues this goal through a series of strat-
egies, including the rapid and accurate detection of attacks, the minimization of
consequences, and the rapid implementation of recovery measures.
The research needs identified by Busta, detailed in his contribution to Chap-
ter 7, involve tools and technologies necessary to answer key questions prompted
by a foodborne attack. Sampling, detection, and tracing technologies can help
determine how an attack was staged and what agent was involved. Studies of
decontamination and disposal methods can indicate how to protect public health
and food workers from the threat agent. Risk communication and economic re-
search can inform optimum approaches to recovery from a foodborne attack. Such
information is currently being pursued by many different agencies, and could be
collected, coordinated, and shared—rather than duplicated—through the estab-
lishment of a multidimensional database, Busta noted.
Food Safety Science

Contending that food safety “is an intellectual concept, not an inherent bio-
logical property of a substance,” speaker Sanford Miller noted the profound in-
fluence of such nonscientific issues as politics, economics, and social values on
perceptions of risks to the food supply. The clear identification of foodborne
threats and the accurate estimation of the risks they present require a new ap-
proach; Miller has collected these functions into a new academic discipline that
he calls food safety science. This nascent field integrates nutrition, microbiology,
toxicology, molecular biology, genetics, functional biology, and conventional
food science and brings these sciences to bear on the problem of ensuring a safe
food supply.

Miller, along with several other workshop participants, emphasized the im-
portance of risk assessment to the strategic protection of the food supply. “We all
feel comfortable talking about science,” he observed, “but the moment comes
when science has to be translated into risk and risk has to be translated into public
policy. That is when we run into trouble, because we as scientists don’t really
understand that process and its dynamics.” A case in point, one participant noted,
is the common pursuit of food safety and security, a goal for which risk assess-
ment provides the intellectual underpinning (Taylor, 2005).
Assessing Needs and Opportunities

The following summary comprises needs and policy opportunities for re-
ducing foodborne threats to health that were most frequently mentioned by work-
shop participants. In the spirit of the discussion that followed Miller’s presenta-
tion, the items below can be most appropriately viewed through the lens of risk
assessment. That paradigm is the key to appropriately prioritizing needs and
anticipating the cost-effectiveness of research and policy opportunities to en-
hance food safety and biosecurity (protection of the food supply from deliberate
adulteration).
1. Prevention:
a. Create positive incentives for safe food production; encourage in-
dustry to recognize and address vulnerabilities, either through regu-
lation or through market forces.
b. Organize responsibilities for food safety and biosecurity oversight
into a single independent government agency (but maintain surveil-
lance separately; see below).
c. Build capacity to support food safety in developing countries.
d. Manage risks with the understanding that zero risk cannot be
achieved.
e. Adopt multilevel (domestic) and coordinated (global) approaches to
protecting the food supply.
2. Detection:
a. Improve the cost-effectiveness of surveillance by focusing on the
greatest or most likely risks.
b. Use common agencies, mechanisms, and resources to address acci-
dental and deliberate foodborne illness.
c. Make all food products more traceable, less anonymous.
d. Separate surveillance from food safety oversight to permit objective
evaluation of protective measures.
e. Emphasize coordination, communication, and collaboration among
local, state, federal, and international food safety authorities.

3. Response:
a. Create incentives for reporting apparent and actual threats to the food
supply.
b. Coordinate animal and public health responses to foodborne
outbreaks.
c. Use validated risk-based approaches for mitigating foodborne
threats.
4. Research:
a. Investigate the biology and natural history of emerging foodborne
pathogens such as Cyclospora and prions.
b. Examine the ecology of foodborne diseases to inform the integration
of animal and health surveillance.
c. Advance techniques for real-time surveillance of foodborne threats
to health.
d. Define the role of water as a source of foodborne illness.
5. Policy opportunities:
a. Create interdisciplinary animal-public health programs.
b. Conduct training programs in food safety for public health officials
in developing countries, veterinarians, and the animal health
community.
c. Strengthen and integrate laboratory networks that diagnose food-
borne and animal diseases.
d. Enhance communication and collaboration among all geographic
levels, all scientific and medical disciplines, and all public and pri-
vate sectors, toward the common goal of safe food.
REFERENCES
Alberts B. 2005. Modeling attacks on the food supply. Proceedings of the National Academy of
Sciences 102(28):9737–9738.
Bailar J. 2005 (October 26). Session V: Who Is Responsible for Ensuring the Wholesomeness of the
Food Supply? Domestic and International Perspectives. Presentation at the Forum on Microbial
Threats Workshop Meeting, Foodborne Threats to Health: The Policies and Practices of Sur-
veillance, Prevention, Outbreak Investigations, and International Coordination, Washington,
D.C., Institute of Medicine, Forum on Microbial Threats.
Bell B. 2005 (October 25). Session III: The Food Supply “Threat Spectrum”—Case Studies: Cyclo-
sporiasis in Imported Produce—Hepatitis A from Imported Green Onions. Presentation at the
Forum on Microbial Threats Workshop Meeting, Foodborne Threats to Health: The Policies and
Practices of Surveillance, Prevention, Outbreak Investigations, and International Coordination,
Washington, D.C., Institute of Medicine, Forum on Microbial Threats.
Besser J. 2005 (October 25). Session IV: What Are the Tools and Technologies for “Real Time”
Surveillance of the Food Supply for Conventional and Unconventional Adulterants? Presenta-
tion at the Forum on Microbial Threats Workshop Meeting, Foodborne Threats to Health: The
Policies and Practices of Surveillance, Prevention, Outbreak Investigations, and International
Coordination, Washington, D.C., Institute of Medicine, Forum on Microbial Threats.

Branigin W, Allen M, Mintz J. 2004 (December 3). Tommy Thompson resigns from HHS: Bush asks
Defense Secretary Rumsfeld to stay. Washington Post. [Online]. Available: http://www.
washingtonpost.com/wp-dyn/articles/A31377-2004Dec3.html [accessed April 27, 2006].
Breeze R. 2004. Agroterrorism: Betting far more than the farm. Biosecurity and Bioterrorism: De-
fense Strategy, Practice, and Science 2(4):1–14.
Brown P, Will RG, Bradley R, Asher DM, Detwiler L. 2001. Bovine spongiform encephalopathy and
variant Creutzfeldt-Jakob disease: Background, evolution, and current concerns. Emerging In-
fectious Diseases 7(1):6–16.
Buzby JC. 2001. Effects of food-safety perceptions on food demand and global trade. In: Regmi A,
Ed. Changing Structure of Global Food Consumption and Trade. WRS-01-1. Washington, D.C.:
Economic Research Service. Pp. 55–66.
CDC (Centers for Disease Control and Prevention). 1986. Aldicarb food poisoning from contami-
nated melons—California. Morbidity and Mortality Weekly Report 35(16):254–258.
CDC. 2003a. Nicotine poisoning after ingestion of contaminated ground beef—Michigan, 2003.
Morbidity and Mortality Weekly Report 52(18):413–416.
CDC. 2003b. Hepatitis A outbreak associated with green onions at a restaurant—Monaca, Pennsylva-
nia, 2003. Morbidity and Mortality Weekly Report 52(47):1155–1157.
CDC. 2003c. Foodborne Outbreak Response and Surveillance Unit. [Online]. Available: http://
www.cdc.gov/foodborneoutbreaks [accessed May 3, 2006].
CDC. 2005a. Foodborne Illness. Division of Bacterial and Mycotic Diseases. [Online]. Available:
http://www.cdc.gov/ncidod/dbmd/ diseaseinfo/foodborne infections_g.htm#foodborne disease
[accessed April 27, 2006].
CDC. 2005b. PulseNet Homepage. [Online]. Available: http://www.cdc.gov/pulsenet/ [accessed May
3, 2006].
CDC. 2006. FoodNet–Foodborne Diseases Active Surveillance Network Homepage. [Online]. Avail-
able: http://www.cdc.gov/foodnet/ [accessed May 3, 2006].
Chalk P. 2004. Hitting America’s Soft Underbelly: The Potential Threat of Deliberate Bio-
logical Attacks Against the U.S. Agricultural and Food Industry. Santa Monica, CA: RAND
Corporation.
Chalk P. 2005. The U.S. agricultural system: A target for al-Qaeda? Terrorism Monitor 3(5):4–6.
Coffey B, Mintert J, Fox S, Schroeder T, Valentin L. 2005. The Economic Impact of BSE on the U.S.
Beef Industry: Product Value Losses, Regulatory Costs, and Consumer Reactions. [Online].
Available: http://www.oznet.ksu.edu/library/agec2/mf2678.pdf [accessed May 4, 2006].
Collins S. 2005 (October 26). Session VI: What Are the Incentives and Disincentives Associated with
Disease/Contamination Reporting? Impacts on Human Health and International Trade—BSE
as a “Case Study”? Presentation at the Forum on Microbial Threats Workshop Meeting,
Foodborne Threats to Health: The Policies and Practices of Surveillance, Prevention, Outbreak
Investigations, and International Coordination, Washington, D.C., Institute of Medicine, Forum
on Microbial Threats.
Cook J. 2005 (June 28). Session I: Threats to Crops. Presentation at the Forum on Microbial Threats
Working Group Meeting, Food Supply Terrorism as a Biosecurity Issue: Assessing the Problem
and the Ethical Considerations of Infectious Disease Research and Surveillance, Washington,
CSPI (Center for Science in the Public Interest). 2006. Safe Food International. [Online]. Available:
http://safefoodinternational.org/guidelines_for_consumer_ organizations 20050727.pdf [ac-
cessed May 3, 2006].
Death sentence for China poisoning. 2002a (September 30). BBC News. [Online]. Available: http://
news.bbc.co.uk/2/hi/asia-pacific/2287801.stm [accessed April 26, 2006].
Death sentence over Chinese poisonings. 2002b (September 30). CNN News. [Online]. Available:
http://edition.cnn.com/2002/WORLD/asiapcf/east/09/30/china.poison/ [accessed May 4, 2006].

DeLauro R. 2005 (May 17). Testimony before the House Government Reform Subcommittee on the
Federal Workforce and Agency Organization oversight hearing on “Question: What Is More
Scrambled Than an Egg? Answer: The Federal Food Inspection System.” [Online]. Available:
http://www.hhs.gov/asl/testify/t050517.html [accessed July 6, 2006].
Detlefsen C. 2005. Dairy industry vigilant in addressing food security. Cheese Market News 25(22):1.
FDA (Food and Drug Administration). 2002. The Bioterrorism Act of 2002. [Online]. Available:
http://www.fda.gov/oc/bioterrorism/bioact.html [accessed May 3, 2006].
GAO (Government Accountability Office). 2004. Federal Food Safety and Security System: Funda-
mental Restructuring Is Needed to Address Fragmentation and Overlap. GAO-04-588T. Wash-
ington, D.C.: GAO.
GAO. 2005a. Overseeing the U.S. Food Supply: Steps Should Be Taken to Reduce Overlapping In-
spections and Related Activities. GAO-05-549T. Washington, D.C.: GAO.
GAO. 2005b. Oversight of Food Safety Activities: Federal Agencies Should Pursue Opportunities to
Reduce Overlap and Better Leverage Resources. GAO-05-213. Washington, D.C.: GAO.
GAO. 2005c. Mad Cow Disease: FDA’s Management of the Feed Ban Has Improved, but Oversight
Weaknesses Continue to Limit Program Effectiveness. GAO-05-101. Washington, D.C.: GAO.
Hanrahan C, Becker GS. 2005 (March 10). Mad Cow Disease and U.S. Beef Trade. CRS report
RS21709. Washington, D.C.: Library of Congress.
Hedberg CW, MacDonald KL, Osterholm MT. 1994. Changing epidemiology of foodborne disease:
A Minnesota perspective. Clinical Infectious Diseases 18(5):671–680.
Hennessy TW, Hedberg CW, Slutsker L, White KE, Besser-Wiek JM, Moen ME, Feldman J, Coleman
WW, Edmonson LM, MacDonald KL, Osterholm MT. 1996. A national outbreak of Salmonella
enteritidis infections from ice cream. The Investigation Team. New England Journal of Medi-
cine 334(20):1281–1286.
Henry C. 2005 (October 25). Session I: The Current U.S. Food Supply. Presentation at the Forum on
Microbial Threats Workshop Meeting, Foodborne Threats to Health: The Policies and Practices
of Surveillance, Prevention, Outbreak Investigations, and International Coordination, Washing-
ton, D.C., Institute of Medicine, Forum on Microbial Threats.
Herwaldt BL. 2000. Cyclospora cayetanensis: A review, focusing on the outbreaks of cyclosporiasis
in the 1990s. Clinical Infectious Diseases 31(4):1040–1057.
Herwaldt BL. 2005 (October 25). Session III: The Food Supply “Threat Spectrum”—Case Studies:
Cyclosporiasis in Imported Produce—Fresh Basil. Presentation at the Forum on Microbial
INFOSAN (International Food Safety Authorities Network). 2006. INFOSAN Homepage. World
Health Organization. [Online]. Available: http://www.who.int/foodsafety/fs_management/
infosan/en/ [accessed May 3, 2006].
IOM (Institute of Medicine). 2004. Learning from SARS. Washington, D.C.: The National Academies
Press.
IOM/NRC (National Research Council). 1998. Ensuring Safe Food from Production to Consumption.
Washington, D.C.: National Academy Press.
Khan AS, Swerdlow DL, Juranek DD. 2001. Precautions against biological and chemical terrorism
directed at food and water supplies. Public Health Reports 116(1):3–14.
King L. 2005 (October 25). Session VII: Threat Reduction Research and Policy Opportunities. Pre-
sentation at the Forum on Microbial Threats Workshop Meeting, Foodborne Threats to Health:
The Policies and Practices of Surveillance, Prevention, Outbreak Investigations, and Interna-
tional Coordination, Washington, D.C., Institute of Medicine, Forum on Microbial Threats.
Kolavic SA, Kimura A, Simons SL, Slutsker L, Barth S, Haley CE. 1997. An outbreak of Shigella
dysenteriae type 2 among laboratory workers due to intentional food contamination. Journal of
the American Medical Association 278(5):396–398.

Leitenberg M, Smith G. 2005 (June 17). “Got toxic milk?”: A rejoinder. Federation of American
Scientists. Available: http://www.fas.org/sgp/eprint/milk.html [accessed May 3, 2006].
Mead PS, Slutsker L, Dietz V, McCaig LF, Bresee JS, Shapiro C, Griffin PM, Tauxe RV. 1999. Food-
related illness and death in the United States. Emerging Infectious Diseases 5(5):607–625.
Med-Vet-Net. 2005. Med-Vet-Net Homepage. Available: http://www.medvetnet.org/cms/ [accessed
May 3, 2006].
Monke J. 2005. Agroterrorism: Threats and Preparedness. CRS Report RL32521. Washington, D.C.:
The Library of Congress.
NRC. 2002. Countering Agricultural Bioterrorism. Washington, D.C.: The National Academies Press.
NRC. 2005. Animal Health at the Crossroads: Preventing, Detecting, and Diagnosing Animal Dis-
eases. Washington, D.C.: The National Academies Press.
Osterholm M. 2005 (October 25). Session II: The Food Supply “Threat Spectrum.” Presentation at
the Forum on Microbial Threats Workshop Meeting, Foodborne Threats to Health: The Policies
and Practices of Surveillance, Prevention, Outbreak Investigations, and International Coordina-
tion, Washington, D.C., Institute of Medicine, Forum on Microbial Threats.
Prusiner S. 2004. Detecting mad cow disease. Scientific American 291(1):86–93.
Prusiner S. 2005 (October 25). Session VI: What Are the Incentives and Disincentives Associated with
Disease/Contamination Reporting? Impacts on Human Health and International Trade—BSE
as a “Case Study”? Presentation at the Forum on Microbial Threats Workshop Meeting,
Regmi A, Deepak MS, Seale JL Jr., Berstein, J. 2001. Cross-country analysis of food consumption
patterns. In: Changing Structure of Global Food Consumption and Trade. Regmi A, Ed. Market
and Trade Economics Division, Economic Research Service, U.S. Department of Agriculture,
Agriculture and Trade Report. WRS-01-1. Pp. 14–22.
Rosegrant, M, Paisner, MS, and Meijer, S. 2001. Long term prospects for agriculture and the resource
base. Rural Development Strategy Background Paper No. 1. Washington, D.C.: The World
Bank. P. 150.
Schlundt J. 2005 (October 26). Session V: Who Is Responsible for Ensuring the Wholesomeness of the
Food Supply? Domestic and International Perspectives. Presentation at the Forum on Microbial
Smith-DeWaal C. 2005 (October 26). Session V: Who Is Responsible for Ensuring the Wholesome-
ness of the Food Supply? Domestic and International Perspectives. Comment from a rep-
resentative of the Center for Science in the Public Interest at the Forum on Microbial Threats
Workshop Meeting, Foodborne Threats to Health: The Policies and Practices of Surveillance,
Prevention, Outbreak Investigations, and International Coordination, Washington, D.C., Insti-
tute of Medicine, Forum on Microbial Threats.
Sobel J. 2005. Food and beverage sabotage. In Encyclopedia of Bioterrorism Defense, RF Pilch and
RA Zilinskas, Eds. New York: Wiley-Liss, Inc. Pp. 215–220.
Sobel J, Khan AS, Swerdlow DL. 2002. Threat of a biological terrorist attack on the U.S. food supply:
The CDC perspective. Lancet 359(9309):874–880.
Tauxe R. 2005 (October 25). Session II: The Food Supply “Threat Spectrum.” Presentation at the
Taylor T. 2005 (October 26). Session VII: Threat Reduction Research and Policy Opportunities.
Comment from a Forum member at the Forum on Microbial Threats Workshop Meeting,

Torok T, Tauxe RV, Wise RP, Livengood JR, Sokolow R, Mauvais S, Birkness KA, Skeels MR,
Horan JM, Foster LR. 1997. A large community outbreak of salmonellosis caused by inten-
tional contamination of restaurant salad bars. Journal of the American Medical Association
278(5):389–395.
USDA (U.S. Department of Agriculture). 2005a. National Agriculture Statistics Service: Workforce
Plan for FY 2005–2009. Available: http://www.nass.usda.gov/About_Nass/Strategic_Plan/
nassworkforceplanfy2005.pdf [accessed April 26, 2006].
USDA. 2005b. Global Food Markets: International Consumer and Retail Trends. Economic Re-
search Service. Available: http://www.ers.usda.gov/briefing/globalfoodmarkets/consumer.htm
[accessed May 3, 2006].
USDA. 2006a. Agricultural Outlook: Key Statistical Indicators. Economic Research Service Avail-
able: http://www.ers.usda.gov/publications/AgOutlook/AOTables/ [accessed April 27, 2006].
USDA. 2006b. Foreign Agricultural Trade of the United States: Monthly Summary. Economic Re-
search Service. Available: http://www.ers.usda.gov/Data/FATUS/MonthlySummary.htm [ac-
cessed April 27, 2006].
U.S. Senate. 2005. Safe Food Act of 2005. 109th Congress. S. 729. Introduced April 6, 2005. Sponsor:
Sen. Richard Durbin. Co-sponsor: Sen. Hillary Clinton. Available: http://www.govtrack.us/con-
gress/bill.xpd?bill=s109-729 [accessed May 3, 2006].
Vogt DU. 1998. Food Safety: Recommendations for Changes in the Organization of Federal Food
Safety Responsibilities, 1949–1997. Congressional Research Service. Washington, D.C.: Li-
brary of Congress.
Vogt DU. 2005. Food Safety Issues in the 109th Congress. Congressional Research Service. Wash-
ington, D.C.: The Library of Congress.
Wang MJ, Moran GJ. 2004. Update on emerging infections: News from the Centers for Disease
Control and Prevention. Annals of Emergency Medicine 43(5):660–663.
Wein L. 2005 (May 30). Got toxic milk? New York Times, Op-Ed Section.
Wein LM, Liu Y. 2005. Analyzing a bioterror attack on the food supply: The case of botulinum toxin
in milk. Proceedings of the National Academy of Sciences 102(28):9984–9989.
WHO (World Health Organization). 2002a. WHO Global Strategy for Food Safety. Geneva: WHO.
Available: http://www.who.int/foodsafety/publications/general/global_strategy/en/ [accessed
May 3, 2006].
WHO. 2002b. Food Safety and Foodborne Illness. Available: http://www.who.int/mediacentre/
factsheets/fs237/en/ [accessed May 3, 2006].
WHO. 2002c. Terrorist Threats to Food. Geneva: WHO. Available: http://www.who.int/foodsafety/
publications/general/en/terrorist.pdf [accessed May 3, 2006].
WHO. 2006. Global Salm-Surv (GSS) Homepage. Available: http://www.who.int/salmsurv/en/ [ac-
cessed May 3, 2006].

The U.S. Food System
OVERVIEW
Aside from the prospect of terrorism, the U.S. food supply is vulnerable to
myriad threats. As Dr. Michael Osterholm observes in the first contribution to
this chapter, unintentional foodborne illness kills thousands of people each year
in this country and sickens millions more. The vastness and complexity of mod-
ern food production provides abundant opportunity for contamination; consider,
for example, the intricate path from farm to table taken by processed food prod-
ucts, comprising multiple ingredients from around the world. At the same time,
the breadth and swiftness of modern food distribution networks make outbreaks
of foodborne illness difficult to detect and all but impossible to contain, as illus-
trated by the histories of several recent foodborne outbreaks.
Intentionally adulterated food could be delivered to thousands, perhaps mil-
lions, of Americans within days. Osterholm notes that such an outright attack on
the food supply could cause higher morbidity and mortality, and a far greater
economic impact, than is associated with all-too-common outbreaks of accidental
foodborne illness. Although most previous acts of foodborne terrorism have in-
volved local attacks staged by lone perpetrators, Osterholm argues that the rela-
tive ease by which food could be used to harm societies and economies, as well as
individuals, necessitates the development of effective measures to prevent, de-
tect, and respond to potential bioterrorist attacks to the food system. In the course
of this process, policy makers will need to assess the risks and benefits of pos-
sible safeguards and consider how the costs of safer foods will be borne by the
food industry and, ultimately, the public.
31

The benefits of modern food production and distribution, which balance the
aforementioned risks, are considered in the second paper in this chapter. Dr. Craig
Henry demonstrates that increasingly globalized and sophisticated food supply
chains have afforded cheaper food for much of the world’s population. He also
discusses consumer and demographic trends that affect the food supply, includ-
ing growing global demand for products that are not only tasty, convenient, and
inexpensive, but safe as well.
THE FOOD SUPPLY AND BIODEFENSE:

THE NEXT FRONTIER OF THE FOOD SAFETY AGENDA
Michael T. Osterholm, Ph.D.1
The interface between the international food supply system and terrorism has
the potential to produce a catastrophic impact on both the health of consumers
and the availability of and confidence in specific food products.
Former Secretary of Health and Human Services Tommy Thompson ob-
served upon his resignation in 2004, “I, for the life of me, cannot understand why
the terrorists have not, you know, attacked our food supply, because it is so easy
to do” (Branigin et al., 2004). A few months later, Michael Chertoff, Secretary of
Homeland Security, said that he “didn’t want to get up in public and say the sky is
falling if it is not falling,” and stated that he was going to be “realistic and sen-
sible and serious about the kinds of trade-offs that we have to consider when we
are making decisions about protecting ourselves.” Although superficially contra-
dictory, I would argue that these two remarks are consistent. They reflect the
recognition that, four years after September 11, 2001, we cannot guarantee the
safety of everyone and everything within our borders. We have to make critical
decisions about which critical components of our everyday world to accord prior-
ity in protection or in response should an attack occur. I believe that the security
of our food supply must be at the top of such a list.
Lester Crawford, a former commissioner of the Food and Drug Administra-
tion (FDA), said in 2002, “To conclude that the use of food as an instrument of
terror is unlikely would be looking at the world of today through the prism of the
past. The terror of these times is based on a different note on a different scale.”
The occurrence of unintentional foodborne illness already kills thousands of
people each year in this country and sickens millions more. However, an inten-
1Director, Center for Infectious Disease Research and Policy; Associate Director, Department
of Homeland Security National Center for Food Protection and Defense; Professor, University of
Minnesota.

THE U.S. FOOD SYSTEM 33
tional terrorist attack on the food supply is likely to have very different ramifica-
tions in terms of morbidity and mortality, and a far greater economic impact than
unintentional foodborne illness.
The Food System

Figure 1-1, which depicts key global trends between 1850 and the present,
places our food system in a historical context. The right vertical axis shows the
number of days required to circumnavigate the globe; in 1850 it took approxi-
mately one year to accomplish an around-the-world trip; by 1950 that same feat
could be accomplished in less than 48 hours. Although the time to circumnavi-
gate the world has been essentially the same since 1950, we now move substan-
tially more people and goods around the world today than we did even 30 years
ago. The left vertical axis shows the world’s population in billions; in the past
century the world population has grown from less than 1 billion to more than 6.5
billion people. The commensurate growth in need for protein and carbohydrate
has important implications for the origins of food and its patterns of consumption.
FIGURE 1-1 Speed of global travel in relation to world population.

SOURCE: Murphy and Nathanson (1994). Reprinted with permission from Elsevier.

Today’s global food system constitutes the world’s most complicated indus-
trial infrastructure. The following framework identifies the major components of
the food supply and highlights their vulnerability to intentional harm:
• Pre-farm inputs include cattle feed, agricultural chemicals such as fertil-

izers and pesticides, and water supplied for irrigation.
• Farming practices include intensive animal production (zoonoses2), the
raising of animals and crops in close proximity (fecal contamination of plant
products), and corporate farming (products are widely distributed). The recent
introduction of foot-and-mouth disease in Great Britain serves as an example of
the severe effects upon the food supply that can result from a disease that is
limited to livestock.
• Transportation is critical to maintaining the U.S. food supply. This was
clearly illustrated when, in response to Hurricane Katrina, the Federal Emergency
Management Agency (FEMA) requested that private fleet refrigerated trucks lo-
cate themselves in several holding areas in the impacted states of Louisiana and
Mississippi so they could be used if needed for cold storage of human bodies and
food and ice. Although a limited number of independent truckers—the main mov-
ers of goods from wholesale to retail grocery stores—answered the call, a major
shortage of overland transportation occurred, resulting in an interruption of the
food supply when food failed to be delivered from processors to retail locations.
• Processing encompasses the preparation of myriad foods in thousands of
locations around the globe, any of which represents potential targets for sabotage.
• Wholesale distribution occurs with such rapidity and over such great
distances that the process resembles an aerosol release. In the case of some prod-
ucts, a terrorist could assume overnight delivery of an adulterant to many thou-
sands, if not millions, of people—a product that would be difficult to detect and
remove from market before considerable harm was done.
• Retail includes both groceries and prepared food: a huge and complex
system of outlets for an equally vast array of foods, provided by a largely low-
paid and transient workforce. This is particularly the case in restaurants, which
account for nearly half of all U.S. food expenditures. Most foodborne attacks to
date have occurred at this level, or thereafter at the point of consumption.
The Global Food Supply

The global nature of the U.S. food supply adds further layers of complication
to the farm-to-table framework, thereby magnifying concerns for its safety. The
U.S. agricultural sector annually produces more than $1 trillion dollars in eco-
2Zoonoses is defined as “diseases of non-human animals that may be transmitted to man or may be
transmitted from man to non-human animals.” (http://cancerweb.ncl.ac.uk/cgi-bin/omd?zoonoses).

nomic activity. Agriculture accounts for 13 percent of the U.S. gross domestic
product and employs more than 16 percent of the nation’s workforce (USDA,
2005a). In 2004, the nation’s agricultural exports, at $62.3 billion, exceeded agri-
cultural imports by $9.6 billion.
The United States is also a major importer of food. Currently, the number of
foreign food facilities that have registered with the FDA as required under the
Biopreparedness Act of 2002—more than 130,000—outnumbers the number of
domestic registrations. Figure 1-2 shows the main regions from which the United
States imports significant amounts of several key foods. The supply of these foods
may be disrupted by a variety of factors, including variables rarely considered in
the United States, such as political instability or the interruption of electrical
power. It is also important to note that domestically produced food is no less
vulnerable to adulteration than imported products. As Figure 1-3 demonstrates,
sanitary standards at some U.S. food production facilities are vastly inferior to
others in foreign sites.
The global food supply exemplifies cost containment, with the result that
food in the United States and throughout much of the world has become increas-
ingly cheaper. Figure 1-4 shows that while the United States spent an increasing
amount of money on food over the past two decades, the percentage of disposable
income represented by food expenditures has fallen dramatically over the same
period. The expectation of inexpensive food as part of the global just-in-time
economy means that there is little resiliency in our food supply, however. Food
once stored in warehouses for weeks or months is now shipped overnight, around
the world, a situation that makes it difficult to detect a contaminated product and
remove it from commerce before it is widely consumed; thus today’s food recall
typically documents last week’s outbreak.
For a terrorist, the number of foods that move from “farm to fork” within
days to weeks represents an opportunity. In many instances, an adulterated
food could be guaranteed overnight delivery to thousands, if not millions, of
Americans.
Previous Outbreaks and Attacks

The single largest outbreak of salmonellosis documented in the United States
to date stands as an example of the potential of a foodborne illness to occur among
many thousands of consumers before it is detected. In 1994, ice cream mix pro-
duced in a Minnesota plant was shipped before final freezing and packaging as a
pasteurized product in trucks that had previously carried raw egg mix without
being adequately cleaned. There were more than 200,000 cases of illness among
those who ate the ice cream (Hennessy et al., 1996).
As is typical in foodborne outbreaks, humans serve as the bioassay for con-
tamination. Routine enteric disease surveillance conducted by the Minnesota
Department of Health identified an increased occurrence of cases of Salmonella

36
FIGURE 1-2 The problem: Global food systems.

SOURCE: Osterholm (2005).

37
FIGURE 1-3 Identifying the source of food in a global system is challenging.

USA? PERU? MEXICO?
Where is this?
CHILE?
SOURCE: Sholl (2005).

38
USA? PERU? MEXICO?

Where is this?
CHILE?
FIGURE 1-3 Continued.

14 9.0
Food Expenditures in Trillions of Dollars

13.5 8.0
% Disposable Income
13 7.0
12.5 6.0
12 Percent 5.0
11.5 Expenditures 4.0
11 3.0
10.5 2.0
10 1.0
74 77 80 83 86 89 92 95 98 2001
Year
FIGURE 1-4 Food expenditures as a share of disposable personal income, United States,
1974–2003.
SOURCE: Adapted from USDA (2004).
serotype enteritidis infection. An epidemiologic investigation led to the identifi-

cation of Salmonella serotype enteritidis contamination in selected lots of ice
cream. Epidemiologic data provided the only indication that ice cream was the
vehicle, as the bacterium was found in less than two percent of samples tested.
Nevertheless, despite the low attack rate, a large number of people were sickened
because of the large volume of contaminated ice cream. An intentional attack
would probably feature higher concentrations of such an agent, with predictably
devastating consequences.
To date intentional foodborne attacks have not produced a major catastrophe.
Instead, they have been largely localized events, staged by individuals. For ex-
ample, a postgraduate student in parasitology scattered his roommate’s food with
the roundworm Ascaris suum; four persons became seriously ill, and two suffered
respiratory failure (Phills et al., 1972). Although Ascaris is not an agent of par-
ticular concern, this example reminds us that many individuals have access to
infectious and noninfectious adulterants that could easily be added to many foods.
A well-known incident occurred in Oregon, in 1984, when members of the
Rajneesh religious cult contaminated a salad bar with Salmonella, causing 751
illnesses (Torok et al., 1997). This attack was actually a limited “trial run” of a
plan to sway an election by incapacitating voters.
In 1996, a disgruntled Texas lab worker intentionally contaminated pastries

with Shigella dysenteriae and left them for her coworkers to eat. Twelve people
became infected (Kolavic et al., 1997); the culprit was ultimately sentenced to 20
years in prison (Ex-lab worker, 1998).
As the following examples illustrate, chemical contamination of the food
supply may pose an even much greater risk than many biologic agents:
• In Holland and Germany, in 1978, a dozen children were hospitalized

after citrus fruit from Israel was intentionally contaminated with mercury (Khan
et al., 2001).
• In China, in 2001, 120 people became ill after specific food products were
laced with rat poison by makers of competing products (Death sentence, 2002a).
In 2002, a similar rat poisoning incident killed at least 38 people and made more
than 300 seriously ill (Death sentence, 2002a, 2002b).
• In Michigan, the contamination of 200 pounds of ground beef with insec-
ticide containing nicotine by a disgruntled employee in a supermarket sickened
111 people, including 40 children (CDC, 2003).
Foodborne Attack Scenarios

Terrorists could achieve mass human casualties by adding a class A bio-
terrorism agent such as botulinum toxin during the processing or transportation of
a variety of vulnerable foods. This is not an artificial scenario, given the previ-
ously described account of milk adulteration. It is of grave concern to analysts
who have researched its possibility and projected consequences, some of whom
feel that such attack scenarios should not be publicly discussed.
Economic disruption is a likely outcome of any foodborne attack, and it could
be achieved without directly harming humans by spreading pathogens specific to
livestock (e.g., foot-and-mouth disease) or crops (e.g., soybean rust). Such dis-
eases could have critical implications for the food supply system. Economic con-
sequences would also likely result from mass anxiety, which could be generated
with a credible hoax that targeted popular food products or a popular restaurant.
Previous incidents have shown that consumers react intensely to the mere sugges-
tion that a food has been or will be contaminated and may extrapolate an isolated
incident of contamination to a nationwide scale.
An ideal food or beverage vehicle for a foodborne terrorism attack would
have the following characteristics:
• It would be produced in such a way that a perpetrator would have the

ability to adulterate it beyond control steps that would eliminate or disable the
potential agent. Although food processes such as heat treatment are designed to
deactivate pathogens, most do not specifically target chemical contaminants.
• It would be a large volume of a widely distributed product, allowing the
agent to be disseminated to the largest possible population.

• It would be able to preserve the agent’s potency until it is consumed.

• It would be a product that is rapidly distributed and consumed, thus un-
likely to be detected until considerable damage is done.
• The product would be consumed disproportionately by high-risk popula-
tions (e.g., children or the elderly).
In addition to Clostridium botulinum (botulism) and its toxin, biological

agents for such attacks could include Bacillus anthraces (anthrax) and other en-
teric bacterial species. Gastrointestinal anthrax represents a relatively effective
foodborne weapon; while not as deadly as its aerosol counterpart, it can result in
significant morbidity, mortality, and economic disruption. Although only 22 cases
of anthrax occurred in this country in 2001, those cases resulted in a dramatic
impact on the U.S. postal system; even a few cases of food-related anthrax in a
single food commodity would do the same, if not more. At the same time, com-
mon enteric bacterial species, such as Salmonella, could produce mass illness, as
demonstrated by the previous example of the Rajneesh cult attack Such an out-
break may not be recognized as an attack, and therefore fail to cause panic
and fear.
Chemical adulterants pose an even greater risk to the food supply than many
biologic agents. A vast number of potentially deadly chemicals could be intro-
duced into a number of widely distributed foods, to devastating effect.
Food Biosecurity
In recent years in the United States, food biosecurity has traditionally been
defined as the development of effective measures to prevent, detect, and respond
to potential bioterrorist attacks to the food system. However, it is important to
recognize a more essential, global definition of food biosecurity: the availability
of sufficient food. While the United States attempts to protect its food supply
from bioterrorism, we must also bear in mind that security for much of the world
is compromised by the lack of an adequate food supply.
The World Health Organization (WHO) in a 2002 document entitled Terror-
ist Threats to Food (WHO, 2002) concluded that the early detection of disease
resulting from covert food terrorism requires sensitive surveillance systems for
communicable disease at the local and national levels, with close cooperation and
communication among clinicians, laboratories, and public health officials. These
conclusions apply to food safety in general, not just protection against deliberate
attacks, reinforcing the need for a comprehensive system for foodborne disease
surveillance.
Detecting and responding to an act of foodborne terrorism will depend on the
type of agent, the efficiency of the attack, and the geographic distribution of
cases. If an attack produces a few unusual, distinctive cases, it is more likely to be

detected than one that sickens many people with a common foodborne illness. A
large number of acute cases of foodborne illness, clustered by time and location,
will trigger an immediate response. However, it may take weeks to recognize an
epidemic of foodborne disease: from the time the contaminated food is eaten until
symptoms appear; from the time a person seeks medical attention until the results
of a stool sample can be interpreted; from the time public health officials receive
laboratory results until case interviews can be conducted.
Improving systems for food defense requires us to decide how we determine
what constitutes acceptable risk, as well as what measures best serve the public
good. Today, the U.S. food industry emphasizes food safety, which is not the
same thing as food biosecurity. For example, a standard tool for identifying po-
tential sources of foodborne illness, called Hazard Analysis and Critical Control
Point (HACCP) (FDA, 2006), focuses on exposures that are reasonably likely to
occur, regardless of impact. Bioterrorism, while an extremely rare event, would
be expected to have a severe impact.
Should food producers be required, or merely encouraged, to invest resources
in protecting their products against the risk of terrorism? Are food defense sys-
tems public goods that warrant public support? They are unlikely to yield mea-
surable benefits to a company. Representatives from the food industry have stated
that they would prefer legislative requirements for such safeguards, so that every
company bears the same burden as its competitors. Under such conditions, food
defense would be treated as a cost of doing business. No such regulation has yet
been formally proposed, nor has the level of “tolerable risk” been defined, except
to note that risk cannot be entirely eliminated. However, it is clear that an effec-
tive response to the threat of foodborne terrorism requires collaboration and
greater efficiency among the federal agencies responsible for food safety and for
transportation, as well as among state and local health departments.
Despite all we know about the potential for various agents to cause foodborne
illness, we do not know the identity of tomorrow’s terrorist today. He or she
could be a member of an animal liberation group who is working in a food-
processing plant, waiting for an opportunity to act. An unbalanced individual
with expertise in microbiology could be planning to stage a small-scale attack
with an infectious agent just to see what happens. An international terrorist orga-
nization could be readying an attack. That is why Paul Wilkinson, from the Cen-
tre for the Study of Terrorism and Political Violence, said more than a decade
ago, “Fighting terrorism is like being a goalkeeper. You can make a hundred
brilliant saves, but the only shot that people remember is the one that gets past
you” (Wilkinson, 1992).

THE U.S. FOOD SUPPLY—

HOW CHANGING DEMOGRAPHICS AND CONSUMER DEMAND
POSE NEW CHALLENGES FOR FOOD SAFETY
Craig W. Henry, Ph.D.3, 4
Food Products Association
Summary
When purchasing food, U.S. consumers consider a variety of product at-
tributes, including taste, convenience, cost, and safety. Increasingly, this is true
around the world, as consumers seek to purchase high-quality, safe foods.
Regardless of income, families in countries around the world are spending
less on food as a percentage of total expenditures, as they benefit from the lower
cost of food production and increased competition in the retail marketplace. How-
ever, the fact remains that lower-income families, on average, spend approxi-
mately 2.5 times more on food as a percent of total expenditures than do higher-
income families. Conversely, higher-income families spend more on meat and
seafood products than do lower-income families.
Process attributes related to the manner in which a food is grown, raised,
processed, and marketed are becoming increasingly important to consumers glo-
bally. For example, there is a growing demand for “organically” grown food
products, particularly in the United States and Europe.
The food purchased and consumed in the United States increasingly is im-
ported. From 2000 to 2004, food imports into the United States increased sub-
stantially, with meat, fresh fruit, and vegetables leading in sales growth.
Demographic changes in the United States are reflected by the marketplace.
For example, the number of single-parent households in the United States contin-
ues to grow. By 2030, it is anticipated that only 17 percent of U.S. households
will be single-earner married couples, with almost 30 percent of households
headed by unmarried individuals. With more households where both parents work
and more single-parent households in the future, less time will be available for
meal preparation.
Clear, concise, and accurate information must be communicated among the
United States and countries around the world to help ensure compliance with
regulatory requirements. Additionally, stakeholders must coordinate the approach
to addressing threats such as mad cow disease and avian influenza. Only through
3Senior vice president of Scientific and Regulatory Affairs.

4The Food Products Association (FPA) is the largest trade association serving the food and bever-
age industry in the United States and worldwide. FPA’s laboratory centers, scientists, and profes-
sional staff provide technical and regulatory assistance to member companies and represent the food
industry on scientific and public policy issues involving food safety, food security, nutrition, con-
sumer affairs, and international trade.

a collaborative effort and the proper allocation of resources can the United States
and other countries meet the challenge of ensuring a safe, abundant, and nutri-
tious world food supply.
Global Consumption Trends

Gathering accurate and up-to-date statistics on global food consumption
trends is challenging. However, using statistics from a number of sources—in
particular, information compiled and published by the Food Marketing Institute
(FMI)—allows us to examine some emerging trends regarding global food con-
sumption (Tables 1-1 through 1-3).
It is clear that some “health-oriented” foods—such as soy-based drinks and
yogurt beverages—have enjoyed substantial growth during this period. Demo-
graphics certainly play an important role in food expenditures. The U.S. Depart-
ment of Agriculture (USDA) report for March 2005 provided excellent insight
into global buying habits. First, we see the predominant income groups in a vari-
ety of countries (Table 1-2). Following the breakdown of income groups, we see
the food expenditure patterns among the selected countries (Table 1-3).
Although food expenditures have declined for all income groups, the decline
is more pronounced for the low-income group. Tables 1-4 through 1-9 provide
more insight into the type of foods being purchased by the various levels of in-
come (see Annex 1-1).
If we look at the trends as far as a summary of this is concerned, between
1997 and 2003 there is a clear decline of 2.5 percent of income spent on the major
food groups. However, the question remains, why are the costs of food expendi-
tures declining? More efficient production, leading to lower food prices, and/or
increased competition in the retail food marketplace likely have had an impact.
Certainly, the global food industry has done an excellent job of enhancing effi-
ciencies related to farming practices and food production.
TABLE 1-1 Food Categories with the Fastest Growing

Global Sales and Growth Rate Between 2003 and 2004
Categories with Fastest Growing Sales Growth Rate 2003–2004 (%)
Soy-based drinks 31
Drinkable yogurts 19
Eggs 14
Cereal, muesli, fruit bars 10
Sports energy drinks 10
All others 6–9
SOURCE: Nielson (2004).

TABLE 1-2 Food Expenditure Patterns Among Selected Countries

High Upper Middle Lower Middle Low Income
Japan Mexico Colombia Ukraine
United States Czech Republic Russia Indonesia
United Kingdom Hungary Romania India
Germany Chile Bulgaria Vietnam
France Brazil Morocco
Singapore South Africa Philippines
South Korea Turkey China
SOURCE: USDA (2005b).
Data indicates that growing wealth in countries around the world is creating
a growing demand for food attributes beyond taste and cost. Worldwide, we see
growth in consumer demand for foods with various attributes, such as the in-
creased demand for soy-based drinks. Convenience and safety are another two
key attributes that are having a growing effect on consumer buying habits.
According to the FMI’s Grocery Shopper Trends for 2005, single men and
women without children, account for 25 percent of the 81.9 million working
households in the United States. Since 1940, single-parent families have doubled
and now account for 16 percent of the households in the United States. The issue
is: who is buying and who is preparing meals in our domestic economy? Married
couples with and without children account for 37 percent of U.S. households. By
2030 it is expected that 17 percent of households with married couples will have
a single earner. Forty-five percent will be dual-earner married couples, and 30
percent will be unmarried individuals. Single-parent households will exceed 18
percent (FMI, 2005).
In the United States, female “bread winners” are far more common today
than in the past. Twenty percent of U.S. households currently are supported by a
single female earner. This equates to close to 3.6 million or 8 percent of all the
total current working households. This results in fewer adults at home with a
primary focus on family care and meal preparation. In turn, this creates a change
in how meals are prepared and, subsequently, creates time constraints for meal
TABLE 1-3 Food Expenditure Patterns Among Selected

Countries, Food Share of Total Expenditures
1997 (%) 2003 (%)
High-income average 11.7 11.1
Upper-middle income average 22.2 19.5
Lower-middle income average 35.4 32.0
Low-income average 41.7 38.3

preparations. Let’s consider how meals are actually sourced and prepared within
the home. Surprisingly only 1.5 evening meals per week are consumed away
from home. Thirty-nine percent of the shoppers, on a weekly average, eat out less
than once per week. On the weekly average, 15 percent of single mothers eat at
fast food restaurants at least three times a week. Let us look at the various sources
of food for the U.S. household (Table 1-10).
Ninety-two percent of households eat home-cooked meals one or more times
a week; 79 percent eat home-cooked meals at least three times a week. This indi-
cates that a significant percentage of the time, people are preparing their meals at
home. An equal number, 22 percent, eat at least one meal a week at either a fast-
food or full-service restaurant. And nearly a quarter of U.S. households eat at
least one “ethnic” meal at home or at a restaurant each week; Chinese and Mexi-
can cuisine have become part of the mainstream America diet. Grocery Shopper
Trends for 2005 also indicates that income, age, region, residence, and ethnicity
affect food buying decisions.
The NPD Group recently released findings from its 20th Annual Report on
Eating Patterns in America (NPD Group, 2006). It is interesting to see what has
changed over the past 20 years. Today, 53 percent of consumers say they try to
avoid snacking as opposed to 71 percent in 1985. The annual number of main
meals skipped per person rose from 102 in 1985 to 114 in 2005. Meals cooked in
microwave ovens doubled from 10 percent in 1985 to 20 percent today. To me,
this is surprising, in that I would have expected it would have been a much higher
increase than just a doubling.
Clearly, saving time is important for most consumers. What has the food
industry done to respond to consumer demand for more convenient but still good-
tasting foods? Joy Zacharia, associate editor of Cooking Light magazine, says
consumers are taking advantage of prewashed salads, precut and washed veg-
etables, pork tenderloins and boneless, skinless chicken breast and thighs.
Consumers in developed countries around the world increasingly look for
convenient, high-quality foods that are safe. There is also a growing market for
foods perceived to support healthy lifestyles. The food industry continues to de-
velop and market new products to meet evolving consumer demands.
TABLE 1-10 Grocery Shopper Trends for 2005

1 or More At Least 3
Times/Week (%) Times/Week (%)
Eat home-cooked meals at home 92 79
Eat out at fast-food establishments 22 5
Dine out at full-service restaurants 22 4
Purchase items at gourmet coffee shops 7 3
Eat ethnic meals at home or out 24 6
SOURCE: FMI (2005).

TABLE 1-11 Trends in Proportion of Shoppers Who Purchased

Organic Food Within the Past Six Months
Number of Organic Foods Purchased 2000 (%) 2003 (%) 2004 (%)
None 47 50 48
One or two categories 24 24 26
Three or four categories 16 15 14
Five or more categories 13 11 12
Total 100 100 100
SOURCE: FMI et al. (2004).
Demand for Organic Foods

In recent years, there has been conflicting conclusions regarding the trends in
organic food consumption. The Organic Trade Association (OTA) states that the
organic industry grew by 20 percent and attained $10.8 billion in sales in 2003
(OTA, 2003). However, according to FMI et al. (2004) organic food sales have
remained steady (Table 1-11).
The organic market survey of 2005 indicates 37 percent of U.S. shoppers
expressed an interest in buying organic fruits and vegetables, 24 percent are inter-
ested in or have bought organic cereals and breads, and 23 percent either pur-
chased or would purchase organic packaged foods. Interestingly, 18 percent of
consumers surveyed indicated they would be interested in purchasing organic
meats, but this product line has grown by only 5 percent since 2000. Apparently,
the organic demand for meats is driven by availability. Shoppers indicate that, if
there was a greater availability of organic meats, they would take advantage of it.
Going forward, we are likely to see steadily increasing demand for organic food
and other foods with attributes related to health or a healthy lifestyle.
Global Demographics
Research by the American Enterprise Institute (AEI) indicates that, to sustain
the current global population, every woman must bear 2.1 children (Eberstadt,
2004). Nearly half of the developed world has birth rates below that figure. In the
United States, population growth is being fueled by immigration and by a higher
birth rate for minorities.
Another factor to take into consideration regarding global demographics is
the male-to-female ratio. Today more boys than girls are being born. The popula-
tions of most nations have an average of 105 boys for every 100 girls born. This
imbalance is particularly pronounced in nations such as China (with 121 boys
born for every 100 girls) and India (with 126 boys born for every 100 girls).
AEI research also indicates that HIV and AIDS are definitely affecting mor-
tality rates in a number of countries, which has the potential to affect global food
demand in the future.

What about the U.S. workforce and the ratio of workers to retirees? In 1950,
the United States had 16 workers for every retiree. In 2005, that number is down
to three workers for every retiree, which poses enormous challenges for contin-
ued funding of the Social Security system and its benefits to retired workers. This
issue is even more pronounced in other countries. For example, in Italy it is pro-
jected that there will be 0.7 active workers for each retiree by 2030. This indicates
there is a very serious economic problem on the horizon.
According to the USDA Economic Research Service, in the last three de-
cades we have seen a tremendous growth in food sales worldwide. In the pro-
cessed food area, sales are now $3.2 trillion, or about three-fourths of the total
world food sales. However, we have not seen significant overall growth in global
trade during the same time period. For most countries, the vast majority of pro-
cessed food consumed is produced within that country.
This is not true for the United States. Between 2000 and 2004, U.S. food
imports significantly increased by 29 percent, according to the USDA Foreign
Agriculture Service, with meat, fresh vegetables, and fruits leading this growth.
Without question, U.S. consumers have become accustomed to having year-round
access to fresh produce. We must pay very close attention to the production and
the quality of such products as they come through our system.
Food Safety
Food is handled at multiple points throughout the food chain, from farm to
fork. This is a factor on an international basis that must be addressed to meet
customer and regulatory requirements. Look at most seafood products as an ex-
ample. It is typical to have oceangoing vessels with full processing and even
packaging capability. The product is handled in one particular area on the vessel
and then shipped for further processing, potentially in two or more countries,
before the finished product actually reaches the retail market. This creates a chal-
lenge that needs to be considered as far as food safety and quality are concerned.
Imported food products meet consumer demand for varied foods—including
fresh fruits and vegetables year-round. Ensuring the safety of imported foods is
an absolute priority for the U.S. food industry. When it comes to imported foods,
vigilance, verification, and validation of sound food safety systems and practices
is a necessary part of doing business.
Verifying that food safety systems in countries around the world are equiva-
lent to those in the United States is an important aspect of ensuring that the foods
sold in the United States are safe, be they imported or domestically produced.
This can be a challenge. For example, in 2004 U.S. meat inspectors reported that
meat facilities in France do not meet USDA food safety sanitation standards, and
therefore banned the sale of processed meats from France in the United States. In
2005, Brazil voluntarily suspended meat exports to the United States for similar
reasons.

Proper allocation of resources to enhance food safety is paramount. All stake-

holders need to work together in addressing the challenges that lie before the
United States and the global community. Mad cow disease and the potential emer-
gence of pandemic avian flu are just two examples of those challenges. Only if
we apply the appropriate collaborative effort, and certainly the proper allocation
of resources, are we going to make progress in addressing the key food safety
challenges facing the United States and the global community.
ANNEX 1-1
Countries, Bread and Cereals
1997 (%) 2003 (%)

Countries, Meat and Seafood
1997 (%) 2003 (%)

Countries, Dairy and Eggs
1997 (%) 2003 (%)


Countries, Oils and Fats
1997 (%) 2003 (%)

Countries, Fruits and Vegetables
1997 (%) 2003 (%)

Countries, Sugar and Confectionary
1997 (%) 2003 (%)
REFERENCES
ACNielsen. 2004. What’s Hot Around the Globe: Insights on Growth in Food and Beverages 2004.
[Online]. Available: http://www2.anielsen.com/reports/documents/2004_whatshot_food-
bev.pdf [accessed April 14, 2006].
Branigin W, Allen M, Mintz J. 2004 (December 3). Tommy Thompson resigns from HHS: Bush asks
Defense Secretary Rumsfeld to Stay. The Washington Post. [Online]. Available: http://www.
washingtonpost.com/wp-dyn/articles/A31377-2004Dec3.html [accessed August 2, 2006].
CDC (Centers for Disease Control and Prevention). 2003. Nicotine poisoning after ingestion of con-
taminated ground beef—Michigan, 2003. Morbidity and Mortality Weekly Report 52(18):
413–416.
Chertoff M. 2005 (March 17). Homeland security chief to shift from “sky is falling” approach. New
York Times. P. A21.

Crawford LM. 2002 (September 6). A Conversation on Food Safety and Global Security. Secretary’s
Open Forum, Department of State, Washington, D.C. [Online]. Available: http://www.fda.gov/
oc/speeches/2002/state0906.html [accessed June 28, 2006].
Death sentence for China poisoning. 2002a (September 30). BBC News. [Online]. Available: http://
news.bbc.co.uk/2/hi/asia-pacific/2287801.stm [accessed April 26, 2006].
Death sentence over Chinese poisonings. 2002b (September 30). CNN News. [Online]. Available:
http://edition.cnn.com/2002/WORLD/asiapcf/east/09/30/china.poison/ [accessed May 4, 2006].
Eberstadt N. 2004 (August 20). Four Surprises in Global Demography. Washington, D.C.: AEI.
[Online]. Available: http://www.aei.org/publications/pubID.21076,filter.all/pub_detail.asp [ac-
cessed June 28, 2006].
Ex-lab worker tainted food. 1998 (September 12). Houston Chronicle. P. A48.
FDA (Food and Drug Administration). 2006. Hazard Analysis and Critical Control Point. Available:
http://www.cfsan.fda.gov/~lrd/haccp.html [accessed May 5, 2006].
FMI (Food Marketing Institute). 2005. Grocery Shopper Trends for 2005. [Online]. Available: http:/
/www. fmi.org/ [accessed April 14, 2006].
FMI, Prevention Magazine, and Rodale, Inc. 2004. The organic market. Ch. 4 In: Shopping for Health:
Making Sense of Nutrition News and Health Claims. Washington, D.C.: The Food Marketing
Institute. Pp. 55–62.
cine 334(20):1281–1286.
Kolavic SA, Kimura A, Simons SL, Slutsker L, Barth S, Haley CE. 1997. An outbreak of Shigella
Murphy FA, Nathanson N. 1994. The emergence of new virus diseases: An overview. Seminars in
Virology 5(2):87–102.
NPD Group. 2006. NPD Group Homepage. [Online]. Available: http://www.npdfoodworld.com/
foodServlet? nextpage=pr_body.html&content_id=2228 [accessed April 14, 2006].
Osterholm MT. 2005. (October 25). Session I: The Current U.S. Food Supply. Presentation at the
OTA (Organic Trade Association). 2003. Organic Trade Association Homepage. [Online]. Available:
http://www.ota.com/index.html [accessed April 14, 2006].
Phills JA, Harrold AJ, Whiteman GV, Perelmutter L. 1972. Pulmonary infiltrates, asthma and eosino-
philia due to Ascaris suum infestation in man. New England Journal of Medicine 286(18):
965–970.
Sholl J. 2005 (June 28). Session III: Vulnerabilities of the Ready to Eat Food Supply. Pictures taken
by Jeff Sholl and presented at the Forum on Microbial Threats Working Group Meeting, Food
Supply Terrorism as Biosecurity Issue—Assessing the Problem and the Ethical Considerations
of Infectious Disease Research and Surveillance (slide 31), Washington, D.C., Institute of Medi-
cine, Forum on Microbial Threats.
Torok TJ, Tauxe RV, Wise RP, Livengood JR, Sokolow R, Mauvais S, Birkness KA, Skeels MR,
Horan JM, Foster LR. 1997. A large community outbreak of salmonellosis caused by intentional
contamination of restaurant salad bars. Journal of the American Medical Association 278(5):
389–395.

USDA (U.S. Department of Agriculture). 2004. Food CPI, Prices and Expenditures: Food Expendi-
tures by Families and Individuals as a Share of Disposable Personal Income. Economic
Research Service. [Online]. Available: http://www.ers.usda.gov/Briefing/CPIFoodAnd
Expenditures/data/table7.htm [accessed July 25, 2006].
USDA. 2005a. National Agriculture Statistics Service: Workforce Plan for FY 2005–2009. [Online].
Available: http://www.nass.usda.gov/About_Nass/Strategic_Plan/nassworkforceplanfy2005.pdf
USDA. 2005b. Global Food Markets: International Consumer and Retail Trends. [Online]. Avail-
able: http://www.ers.usda.gov/Briefing/ globalfoodmarkets/consumer.htm [accessed April 14,
2006].
WHO (World Health Organization). 2002. Terrorist Threats to Food: Guidelines for Establishing
and Strengthening Prevention and Response Systems. [Online]. Available: http://www.who.int/
foodsafety/publications/fs_management/terrorism/en/ [accessed April 28, 2006].
Wilkinson P. 1992 (September 1). British Scholar, author on terrorism. The Daily Telegraph. [Online].
Available: http://www.bartleby.com/66/25/64725.html [accessed May 5, 2006].

Food Safety Oversight
OVERVIEW
In the United States, the oversight of food safety at the national level pres-
ently involves at least 12 agencies,1 of which 4 predominate: the U.S. Department
of Agriculture (USDA), the Food and Drug Administration (FDA), the Environ-
mental Protection Agency (EPA), and the National Marine Fisheries Service.
Many of the more than 70 agreements intended to coordinate food safety activi-
ties among federal agencies are not fully implemented or enforced, resulting in
considerable waste, confusion, and inefficiency. Therefore, it is not surprising
that over the past six decades more than 20 proposals have advocated a reorgani-
zation of the federal food safety system. Prominent among these calls for reform
was a 1998 report of the Institute of Medicine (IOM) and National Research
Council (NRC), entitled Ensuring Safe Food from Production to Consumption
that recommended the integration of food safety oversight into a single, indepen-
dent agency (IOM/NRC, 1998). In the first paper in this chapter, Dr. John Bailar,
chairman of the study committee, discusses the committee’s findings and consid-
ers why little progress has been made toward implementing the report’s recom-
mendations in the seven years since its publication.
1The major federal agencies involved include: the Agricultural Marketing Service, the Animal and
Plant Health Inspection Service, the Agricultural Research Service, the Cooperative State Research,
Education and Extension Service, the Economic Research Service, the Food Safety and Inspection
Service, and the Grain Inspection, Packers, and Stockyards Administration of the United States De-
partment of Agriculture; the Centers for Disease Control and Prevention, the Food and Drug Admin-
istration, and the National Institutes of Health of the Department of Health and Human Services; the
National Marine Fisheries Service of the Department of Commerce; and the Environmental Protec-
tion Agency.
53

The subsequent contribution by Dr. Jørgen Schlundt, director of the food

safety program of the World Health Organization (WHO), offers a global per-
spective on the burden of foodborne illness and progress toward the development
of international systems to respond to foodborne outbreaks. WHO has assumed a
central role in global food safety through its organization of Global Salm-Surv, a
network linking Salmonella surveillance efforts in 141 countries, and the Interna-
tional Food Safety Authorities Network (INFOSAN), which disseminates infor-
mation related to food safety. Pending forthcoming revisions to the international
health regulations due to take effect in 2007, WHO will serve as the hub of a
global system for reporting public health emergencies including foodborne illness.
Although each country needs to defend its food supply from deliberate con-
tamination, Schlundt maintains that these efforts should be undertaken as part of
a comprehensive food safety agenda that extends to the international level. The
WHO Global Strategy for Food Safety takes a largely preventive approach, com-
bining surveillance, communication among all stakeholders, and rapid response
to foodborne outbreaks. Rather than rely on food testing to intercept contami-
nated products, the inherent inefficiency of which Schlundt demonstrates, WHO
seeks to build capacity for safe food production and outbreak detection and alert,
particularly in developing countries in recognition of their increasing contribu-
tion to global food trade.
THE U.S. FOOD SAFETY SYSTEM

John Bailar, M.D., Ph.D.2
Professor Emeritus, University of Chicago
The focus of my remarks to the Forum on Microbial Threats was the 1998
report entitled Ensuring Safe Food from Production to Consumption (IOM/NRC,
1998). That report was issued by a committee assembled jointly by the Institute
of Medicine and the National Research Council, which I chaired, and which in-
cluded at least three participants in this workshop: Lonnie King, Sanford Miller,
and Michael Osterholm. My brief presentation, summarized below, described the
long-recognized need for a complete overhaul of the U.S. food safety system,
including the integration of widely scattered responsibilities for food safety over-
sight into a single, independent federal agency.
How the System Falls Short

The problems that must be addressed by the U.S. food safety system were
discussed in detail in several workshop presentations (see Summary and Assess-
2Scholar in Residence, The National Academies.

FOOD SAFETY OVERSIGHT 55
ment, as well as Osterholm in Chapter 1, Tauxe in Chapter 3). Briefly, they in-
clude the tens of millions of cases, the thousands of deaths, and the billions of
dollars lost every year because of foodborne illness, as well as the possibility of
deliberate harm to our food system. To address these challenges, we have a food
safety system that involves at least 12 different agencies (of which four have
major responsibilities) that conduct monitoring, surveillance, inspection, en-
forcement, outbreak management, research, and education. These agencies work
under a total of 35 food safety-related statutes and more than 50 interagency
agreements and working groups; they report to a total of 28 House and Senate
committees. A variety of federal-state programs, international treaties and agree-
ments, and voluntary programs are also involved in ensuring food safety.
Clearly, there is an absence of focused leadership in food safety oversight.
The federal agencies that share responsibility for food safety are poorly inte-
grated, as are federal, state, and local food safety agencies. Moreover, each fed-
eral agency with food safety responsibilities has other missions that are generally
regarded as more important. This situation has numerous and serious repercus-
sions: surveillance of known, existing problems is inadequate; food safety stan-
dards are inconsistent, uneven, and archaic; resources available for food safety
are lacking; consumers have limited knowledge about food safety; and there is
poor adherence to even the minimum food safety standards currently in place.
The lack of integration and clear leadership among federal agencies respon-
sible for food safety is demonstrated in Table 2-1, which lists the various offices
and agencies involved in ensuring the safety of various food categories and con-
taminants through monitoring and surveillance, risk assessment, research, inspec-
tion and enforcement, and education. None of the four major elements of food
safety—type of hazard, food category, nature of activity, or program responsibil-
ity—lines up with any of the others. Is anyone surprised that foodborne illness
remains so common? Overlap occurs for every specific function listed in the table
(e.g., four offices and three different agencies are responsible for risk assessment
in seafood). Inconsistencies appear in each column; for example, in several cases,
agencies responsible for monitoring and surveillance for a given commodity are
not responsible for risk assessment, and some of these agencies in turn differ
from those involved in research, inspection, enforcement, and education. Look-
ing across the rows in Table 2-1, the group of agencies sharing responsibility for
a function in one commodity (e.g., inspection of fruits and vegetables) does not
match the agencies responsible for the same function in another commodity (e.g.,
inspection of seafood).
Reorganizing the U.S. Food Safety System

Prominent among the recommendations made in Ensuring Safe Food from
Production to Consumption seven years ago is the following statement:

56
TABLE 2-1 Overlap in Federal Food Safety Oversight
Selected Food Products Food Contaminants
Grain, Rice
Fruits and Eggs & Meat & & Related Imported Animal Drugs Pesticide
Vegetables Dairy Products Egg Products Poultry Seafood Commodities Foods & Feeds Residues
CDC; CDC; CDC; CDC; CDC; CDC; CDC, CFSAN CDC; CDC;
CFSAN/FDA CFSAN & CFSAN/FDA; CFSAN/FDA; CFSAN/FDA; CFSAN/FDA & ORA/FDA; CVM/FDA; FSIS/USDA;
CVM/FDA AMS/USDA USDA: FSIS, NMFS/NOAA FSIS/USDA FSIS/USDA; CFSAN/FDA

ERS APHIS
CFSAN/FDA; CFSAN; ARS & USDA: ARS, CFSAN/FDA; ARS/USDA; Same as CVM/FDA; OPPTS/EPA;
ARS/USDA CVM/FDA; FSIS/USDA; CSREES, NMFS/NOAA; CFSAN/FDA domestic food ARS/USDA/ USDA: AMS,
ARS/USDA ORACBA; FSIS, ERS, ARS/USDA products APHIS ARS, ERS,
CFSAN/FDA ORACBA; NASS
CFSAN/FDA
CFSAN, CFSAN; CFSAN/FDA; USDA: ARS, CVM & ARS, Same as CFSAN & ORD/EPA;
NCTR/FDA; CVM/FDA, ARS/USDA CSREES CFSAN/FDA; CSREES/ domestic food CVM/FDA; CSREES &
ARS, CSREES & CSREES NMFS/NOAA; USDA; products ARS & ARS/USDA;
CSREES/ ARS/USDA CSREES & CFSAN/FDA CSREES/ CFSAN/FDA
USDA ARS/USDA USDA
CFSAN & CFSAN, ORA, FSIS/USDA; FSIS/USDA; ORA & GIPSA/USDA; FSIS/USDA; ORA & USDA:FSIS,
ORA/FDA & CVM/FDA FDA: CVM, CFSAN & CFSAN/FDA; ORA & CFSAN & CVM/FDA; AMS/ FDA:
CFSAN & CVM/FDA NMFS/NOAA CFSAN/FDA ORA/FDA FSIS/USDA; CFSAN,
ORA APHIS CVM, & ORA;
OECA/EPA
CFSAN/FDA; CFSAN/FDA; CFSAN/FDA; USDA: FSIS, CFSAN/FDA; CSREES, CSREES, CSREES, CFSAN/FDA;

CSREES, CSREES, FSIS & CSREES, CSREES, ARS/USDA; ARS/FDA; ARS/USDA; FSIS &
ARS/USDA ARS/USDA CSREES, ARS, ERS, ARS/USDA; CFSAN/FDA CFSAN/FDA CVM/FDA CSREES,
ARS/USDA ORACBA; NMFS/NOAA ARS/ USDA
CFSAN/FDA
NOTE: Acronym list is provided in Appendix B.

SOURCE: IOM/NRC (1998).

Congress should establish, by statute, a unified and central framework for man-
aging food safety programs, one that is headed by a single official and which has
the responsibility and control of resources for all federal food safety activities,
including outbreak management, standard-setting, inspection, monitoring, sur-
veillance, risk assessment, enforcement, research, and education (IOM/NRC,
1998).
This committee was not the first body to call for such reform. At that time, we
knew of nearly 20 commissions, committees, and studies dating back to 1949
that had made similar recommendations (Vogt, 1998); more recently, the Gov-
ernment Accountability Office (GAO) has taken up this issue (GAO, 2004,
2005a,b). However, I would like to emphasize one of the important points that
came out of our report: the need to have an independent agency, one that will not
be influenced by competing priorities within agencies where the work of ensur-
ing food safety is currently carried out.
I will conclude with a personal observation as to why, despite the many calls
for reorganization, our food safety system remains fragmented and inadequate. I
believe that the following three reasons lie at the heart of this problem:
1. Bureaucratic inertia—It will take time, effort, and money to implement

the major reorganization that has been recommended.
2. Turf battles—Federal agencies and congressional committees that cur-
rently oversee various aspects of food safety do not want to give up funds, per-
sonnel positions, authorities, and responsibilities.
3. Industrial inertia—Regulated industries have adapted to the present sys-
tem and its constraints. Companies do not welcome change, even when it is in the
public interest.
Although none of these obstacles constitutes an acceptable excuse for post-

poning needed reform, they clearly must be overcome in order to create the uni-
fied, independent federal program that is needed to truly ensure the safety of the
U.S. food supply.
FOOD SAFETY THREATS—INTERNATIONAL COORDINATION

Jørgen Schlundt, Ph.D.3
World Health Organization
Summary
Food safety relates to both human health and economic development. Coun-
tries all over the world are affected by a range of diseases related to food, in effect
3Director, Department of Food Safety, Zoonoses and Foodborne Diseases.

causing a very significant disease burden that seems to have been on the rise in
both developed and developing countries over the most recent decades. Outbreaks
of foodborne diseases most often originate in natural or accidental contamination
events, but the potential for intentional contamination of the food chain is present,
as documented by previously recorded—although relatively minor—such out-
breaks. The developments towards a more global food market underlines that it is
in the best interest of all countries to strengthen the international capacity for
foodborne outbreak alert and response. Such capacity is built most efficiently
through unified systems dealing with all forms of outbreak—intentional as well
as unintentional. The role of the WHO is to provide advice on strengthening
national systems to prevent and respond to foodborne outbreaks, including inten-
tional contamination events. The WHO is in a unique position to coordinate exist-
ing international systems for public health disease surveillance and emergency
response. The revised WHO International Health Regulations provides the legal
platform for all countries to declare public health emergencies of international
concern. The WHO INFOSAN offers a system for alert action and response to
public health emergencies involving food, related to both intentional and uninten-
tional contamination events.
Existing Foodborne Disease Burden

Food safety is an important public health problem that relates to both human
health and economic development (WHO, 2002a). Countries all over the world
are affected by a range of diseases related to food, in effect causing a very signifi-
cant disease burden that seems to be increasing both in developed and developing
countries.
Food safety problems can cause a number of different diseases, from rela-
tively mild cases of food poisoning to deadly infections and cancer. Diarrheal
diseases—almost all caused by food- or waterborne microbial pathogens—are
leading causes of illness and death in less developed countries, killing an esti-
mated 1.8 million people annually at the global level (WHO, 2005). Even in
developed countries it is estimated that up to one-third of the population is af-
fected by microbiological foodborne disease each year (Mead et al., 1999). The
majority of the pathogens causing this significant disease burden are now consid-
ered to be zoonotic pathogens. The occurrence of some of these zoonotic patho-
gens seems to have increased significantly over recent years.
Although a significant fraction of diarrhea is caused by food, this still only
constitutes part of the total foodborne disease burden. Other parts of the burden
relate to a number of important, and often more chronic, diseases caused by not
only microorganisms but also chemical contaminants in our food. The disease
burden related to chemical contaminants and chemical constituents in our food is
very difficult to estimate, but it is likely that this part of the total burden could be
as big as the microbiological burden.

The reporting of foodborne disease is typically based on the number of labo-

ratory confirmed cases, only representing a fraction of the real cases. The factor
between reported and real cases is called the underreporting factor. Few thorough
epidemiological estimations of the national underreporting factor have been made,
but there are significant variations in the factor presented. One example of such
variation is that for salmonellosis the factors can vary from 3.2 fold from a study
in the United Kingdom (Wheeler et al., 1999) to 38 fold from a study in the
United States (Mead et al., 1999). It is not easily evaluated whether differences in
the underreporting factor between countries is a reflection of real differences in
the performance of health systems or a reflection of differences in methodology
used to estimate the factor.
Although some national foodborne disease surveillance systems mainly col-
lect information on the number of outbreaks and the number of cases involved in
the outbreaks, for most foodborne diseases the majority of cases are sporadic.
Surveillance systems must include measures to estimate also the sporadic part of
the foodborne disease burden. New, active surveillance systems are likely in the
future to blur the difference between what has traditionally been referred to as
outbreaks and sporadic cases. The possibility of comparing types of pathogens
(e.g., pulsed-field gel electrophoresis typing) isolated from human cases in a broad
national system enables the linking of cases, previously considered single or spo-
radic in nature, and present them as part of an outbreak spread over a larger
geographical area (Gerner-Smidt et al., 2005). It is thus likely that our under-
standing of the relative importance of outbreaks and sporadic cases will change in
the near future.
As a result of the increased global trade in food it is also likely that outbreaks
covering larger areas and affecting several countries will be recognized in larger
numbers in the future. Surveillance of foodborne diseases provides information
for action. The use of laboratory data in surveillance enables the identification of
pathogens and the potential sources of infection. In the future, integrated surveil-
lance including human data as well as animal- and food-monitoring data can also
provide the basis for preventive action along the entire food chain. In 2000, WHO
initiated the Global Salm-Surv, which provides targeted efforts to national typing
laboratories, and the sharing and analysis of such results has recently lead to the
recognition of trade and foreign travel as factors related to the international emer-
gence of certain Salmonella serotypes as well as to multicountry outbreaks of
Salmonella (WHO, 2006).
The Global Salm-Surv network builds laboratory and epidemiological ca-
pacity for integrated laboratory-based foodborne disease surveillance. The net-
work presently has almost 900 members from 141 countries. The Global
Salm-Surv maintains a database that in its first five-year period (2000–2004)
recorded 565,042 isolates from humans and 102,113 nonhuman isolates
(mainly from food).

As an integral part of foodborne disease surveillance there is a need to enable

precise and timely information sharing between countries of outbreak-related data.
At the global level such systems do not yet exist, but WHO efforts related to the
new International Health Regulations and the newly formed INFOSAN should be
seen in this light. These initiatives will be described further in Chapter 4.
Deliberate Contamination of Food: Recent Concern—Old Problem

The “deliberate contamination of food” is sometimes used synonymously
with food terrorism or food bioterrorism. Food terrorism is defined as an act or
threat of deliberate contamination of food for human consumption with chemical,
biological, or radionuclear agents for the purpose of causing injury or death to
civilian populations and/or disrupting social, economic, or political stability.
Threats from terrorists, criminals, and other antisocial groups who target the safety
of the food supply are already a reality. During the past two decades, WHO mem-
ber states have expressed concern about the possibility that chemical and biologi-
cal agents and radionuclear materials might deliberately be used to harm civilian
populations. In May 2002, the 55th World Health Assembly (WHA) adopted a
resolution that expressed serious concern about threats against civilian popula-
tions by deliberate use of biological, chemical, or radionuclear agents (WHO,
2002b). It noted that such agents can be disseminated via food, and the WHA
requested the Director General to provide tools and support to member states,
particularly developing countries, in strengthening their national systems.
In the past food supplies have often been contaminated deliberately, histori-
cally during military campaigns and, more recently, to terrorize or otherwise in-
timidate civilian populations (Khan et al., 2001). Deliberate contamination of
food by chemical, biological, or radionuclear agents can occur at any vulnerable
point along the food chain, from farm to table, depending on both the food and
the agent. For example, in 1984, members of a religious cult contaminated salad
bars in the United States with Salmonella typhimurium, causing 751 cases of
salmonellosis. The attack appeared to be a trial run for a more extensive attack
intended to disrupt local elections. The cult was also in possession of strains of
Salmonella typhi, the causative organism of typhoid fever, a severe invasive ill-
ness (Torok et al., 1997).
The impact on human health of the future deliberate contamination of food
can be estimated by extrapolation from the many documented examples of unin-
tentional outbreaks of foodborne disease. The largest, best-documented incidents
include an outbreak of S. typhimurium infection in 1985, affecting 170,000 people,
caused by contamination of pasteurized milk from a dairy plant in the United
States (Ryan et al., 1987). An outbreak of hepatitis A associated with consump-
tion of clams in Shanghai, China, in 1991 affected nearly 300,000 people and
may be the largest foodborne disease incident in history (Halliday et al., 1991). In
1994, an outbreak of S. enteritidis infection from contaminated pasteurized liquid

ice cream that was transported as a premix in tanker trucks caused illness in
224,000 people in 41 states in the United States (Hennesy et al., 1996). In 1996,
about 8,000 children in Japan became ill, including some deaths, with Escheri-
chia coli O157:H7 infection from contaminated radish sprouts served in school
lunches (Mermin and Griffin, 1999).
Episodes of foodborne illness caused by chemicals have also been reported
in the published literature. The chemicals that can contaminate food include pes-
ticides, mycotoxins, heavy metals, and other acutely toxic chemicals. In perhaps
one of the most deadly incidents, over 800 people died and about 20,000 were
injured, many permanently, by a chemical agent present in cooking oil sold in
Spain in 1981 (WHO, 1983). In 1985, 1,373 people in the United States reported
becoming ill after eating watermelon grown in soil treated with aldicarb (Green
et al., 1987).
There are also many examples of outbreaks resulting from imported foods.
In 1989, staphylococcal food poisoning in the United States was associated with
eating mushrooms that had been canned in China (Levine et al., 1996). Outbreaks
of cyclosporiasis in the United States in 1996 and 1997 were linked to consump-
tion of Guatemalan raspberries (Herwaldt and Ackers, 1997). In the early 1990s
epidemiological investigations of an increased human incidence of Salmonella
berta in England and Wales was traced to chicken imported from Denmark
(Threlfall et al., 1992).
In general, contamination of food may also have enormous economic impli-
cations. In an effort to damage Israel’s economy in 1978, some citrus fruit ex-
ported to several European countries was contaminated with mercury, leading to
significant trade disruption. In 1998, a company in the United States recalled 14
million kilograms of frankfurters and luncheon meats potentially contaminated
with Listeria, resulting in a total cost of approximately US$50–70 million (CDC,
1999). An outbreak of E. coli O157:H7 infection in the United States in 1997
resulted in the recall of 11 million kilograms of ground beef (CDC, 1997). The
crisis in Belgium in which dioxin-contaminated meat and dairy products were
recalled around the world demonstrates not only the extensive costs to individual
countries, but also the extent of disruption of global trade that can be caused by
this type of incident (WHO, 2004a). From October 1996 to November 2002, 139
cases of variant Creutzfeldt-Jakob Disease have been reported globally, mainly in
the United Kingdom, and most likely linked to exposure through food to the
causative “agent” of bovine spongiform encephalopathy (BSE) in cattle (WHO,
2002c). Consequent consumer concern about consumption of meat has had a sig-
nificant long-term impact on meat production in many countries.
In less developed countries, the economic consequences of major food con-
tamination events could—in addition to human suffering and costs—also affect
development and exacerbate poverty as well as food availability. Likewise the
loss of export earnings can be very substantial both as a result of substantiated as
well as unsubstantiated import restrictions. The lost revenues from food (espe-

cially fish) exports as a result of the 1991 cholera epidemic in Peru has been
estimated to be US$700 million (Motarjemi, 1993). In a less well documented
case, fish import restrictions in the European Union were upheld for a significant
period of time following the publication of reports of cholera in East Africa,
resulting in significant economic losses.
Prevention and Response Systems

All countries must have basic systems to prevent or deter deliberate contami-
nation of their food supplies and, if attacked, to respond rapidly to minimize the
health, economic, and other effects of such contamination.
However, counterterrorism should be seen as only one aspect of a broader,
comprehensive food safety program in national and global contexts. WHO and a
number of member states have addressed this issue with strategies to reduce the
increasing burden of foodborne illness. The WHO Global Strategy for Food
Safety, endorsed in January 2002 by the WHO executive board, comprises a pre-
ventive approach to food safety, with increased surveillance and more rapid re-
sponse to outbreaks of foodborne illness. This approach could substantially ex-
pand the abilities of member states to protect the safety of their food supplies
against natural and accidental threats and provides a framework for addressing
terrorist threats to food.
Food production systems have become longer and more complicated over
the latest decades. These changes in the way food is produced, processed, dis-
tributed, and sold have occurred at the same time as rapidly expanding interna-
tional trade, the emergence of new transboundary food scares, greater inter-
national travel, and changing consumer preferences—all serving to draw new
attention to the importance and challenge of ensuring food safety at the interna-
tional level.
The recognition of the source and potential intention behind an outbreak or
contamination event will in many cases only be possible at a very late stage.
Although deliberate contamination presents a special set of issues, the same de-
tection and response systems need to tackle outbreaks or contamination events
whether the event is intentional or unintentional. Sensible precautions, coupled
with strong surveillance and response capacity, constitute the most efficient and
effective way of countering all such emergencies, including deliberate contami-
nation of food.
For both developed and developing countries, guidance is needed to
strengthen surveillance, preparedness, and response systems to meet the threat of
any food safety emergency. Unfortunately, the tragic events in the United States
on September 11, 2001, have focused a new angle to the debate of food safety:
the issue of bioterrorism or other forms of intentional contamination of food.
Agricultural production systems and food-processing facilities are potentially at
risk. Efforts towards prevention should be integrated in existing systems, for ex-

ample critical points for control should be defined within existing Hazard Analy-
sis and Critical Control Point (HACCP) systems. Likewise existing surveillance
and monitoring systems for foodborne disease and food contamination should be
expanded to include the threats related to potential intentional contamination.
This integrated approach would result in activities supporting the general food
safety efforts instead of detracting from them.
Strengthening of such integrated systems and programs will both increase a
country’s capacity to reduce the increasing burden of foodborne illness and help
to address the threat of intentional food contamination. It is important to reiterate
that any intentional contamination event would probably always initially be con-
sidered as a natural or unintentional event, and that such events must therefore be
managed on the food side through one, coherent system with relevant links to
other authorities (police, intelligence services, etc.) in case of suspicious events.
Prevention, although never completely effective, is the first line of defense.
The key to preventing food terrorism is establishment and enhancement of exist-
ing food safety management programs and implementation of reasonable security
measures—not the setting up of new separate systems potentially detracting from
existing efforts and scarce resources.
Prevention is best achieved through a cooperative effort between govern-
ment and industry, given that the primary means for minimizing food risks lie
with the food industry. Policy advice should be aimed at strengthening existing
emergency alert and response systems by improving links with all the relevant
agencies and with the food industry. This multistakeholder approach will
strengthen disease outbreak surveillance, investigation capacity, preparedness
planning, effective communication, and response (WHO, 2002d).
There is a growing realization that existing systems for food animal produc-
tion in many countries do not correspond to the prevalent food control systems
that are often centered around efforts at the slaughter house. The importance of
small-holder production systems and animal markets has been clearly outlined,
especially in an Asian context and in relation to recent outbreaks of highly patho-
genic H5N1 avian influenza. A recent WHO report underlines the need for WHO
and countries to improve current regulatory frameworks related to the marketing
of live birds and other animals for food, including guidance applicable in devel-
oping countries (WHO, 2004b). Again the links between countries through in-
creased food trade should be recognized, as should the need for timely interna-
tional information sharing and coordinated response.
A growing share of the food consumed in industrialized countries today
comes from developing and transition countries, and this trend is likely to inten-
sify in the future. Clearly, it is in the best interest of us all to strengthen the
capacity of the public and private sector in developing countries to produce food
that meets international safety and quality standards. Consumers and importers in
industrialized countries stand to benefit from increased access to an affordable,
diverse, and safe supply of food products. Developing countries will benefit from
access to new markets and greater foreign exchange earnings through trade.

International Preparedness
Contrary to popular beliefs the effect of food control systems based on test-
ing is not very efficient. The reason for this relates to the fact that for many food
types the prevalence of pathogens potentially causing disease can be very low.
Salmonella in eggs causes a very large proportion of the human salmonellosis
cases in most countries. Nevertheless, the prevalence of Salmonella-positive eggs
is often 1:1,000 or even down to 1:10,000. In effect, you would therefore have to
test a very large number of eggs to have any chance to find positive eggs, and the
effect of removing such (few) eggs from the market is negligible. Even for foods
with higher prevalence of pathogens, control based on testing is inefficient, and
the main positive effect of such systems lies in a potential for (economic) punish-
ment leading to changes in the production systems. For example, it is likely that
the classification of enterohemorrhagic Escherichia coli as an adulterant in the
United States and the resulting economic disasters for certain producers found to
be in violation could have resulted in changes in the production systems leading
to the avoidance of some of the previous problems. However, in many of these
cases it is difficult to measure objectively the effect of such strategies as these
problems are often affected by many different factors at the same time.
Since test-and-eliminate strategies are often not very efficient, it follows that
prevention of outbreaks solely based on border control in most cases will not
provide the level of protection sought after. New—and more efficient—food
safety systems try to focus on preventative efforts as close to the source as pos-
sible, such as in industrial production settings through the introduction of HACCP
systems. Because many food contamination events have international implica-
tions and because a significant fraction of food for consumption in many coun-
tries are imported, it follows that the most efficient way for any country to pre-
vent intentional or unintentional foodborne outbreaks is to strengthen food safety
in the country of origin and to ensure efficient international systems for outbreak
alert and necessary response. A result of the global food market is that we now
have a joint interest in building capacity to prevent and detect foodborne out-
breaks in all countries through relevant international mechanisms.
In general, the need for international exchange of experience and scientific
information in the food safety area is evident. The recent 2nd Global Forum for
Food Safety Regulators in Bangkok, Thailand, is an example of such exchange of
experience with a view of building efficient food safety capacity in all countries
(FAO/WHO, 2004). Based on the outcome of this meeting the newly established
INFOSAN, hosted by WHO, will continue a real-time interaction between the
food safety authorities of the world (WHO, 2004c).
INFOSAN is intended to be an information network for the dissemination of
important information about global food safety issues. INFOSAN members (of
which each country can have several) receive information notes on current issues
of interest for food safety authorities. Recent examples of information note sub-

jects include avian influenza, Enterobacter sakazakii in powdered infant formula,

acrylamide in food, antimicrobial-resistant Salmonella, and evaluation of geneti-
cally modified food. The INFOSAN focal points are expected to disseminate
INFOSAN information to interested parties and stakeholders in their country, as
appropriate. INFOSAN focal points may be located in several ministries, such as
ministries of health, commerce, agriculture, and trade (see Figure 2-1).
A new emergency arm of the INFOSAN network (INFOSAN Emergency)
will enable timely sharing of information and coordinated response in the case of
major international foodborne outbreaks or food contamination events (WHO,
2004c). INFOSAN Emergency contact points are expected to function as two-
way action points for emergency information. They should alert relevant food
safety authorities within their country to foodborne disease outbreaks or food
contamination events of international public health significance as reported to
them by INFOSAN Emergency. And they should convey to the network informa-
tion of national outbreaks or contamination events with a potential to become
international events. Only one INFOSAN Emergency contact point has been re-
quested per country in order to facilitate rapid and reliable communication with
governments in cases where timeliness is critical. Potential future incidents in-
volving deliberate contamination with international implications would likely be
communicated through INFOSAN Emergency.
Relevant past examples of international food-related events that could have
benefited from an international system for information sharing include the
Chernobyl accident in the former Soviet Union (1986), the BSE outbreak and ban
WHO International INFOSAN Network
INFOSAN INFOSAN INFOSAN INFOSAN INFOSAN

Focal point Focal point Focal point Focal point Focal point
in in in in in
Agriculture Health Food Safety Trade other
Sector Sector Authority Sector Sectors
FIGURE 2-1 The WHO International Food Safety Authorities Network (INFOSAN):
Set-up of focal points for information sharing.
SOURCE: INFOSAN (2005).

on feeding materials in the United Kingdom (1996), and the dioxin contamina-
tion of animal-derived food in Belgium (1997).
Since its inception in October 2004, INFOSAN Emergency has been involved
in 11 verification events and sent out 3 notifications alerting from 5 to 32 coun-
tries on issues of potential international importance. These issues include pow-
dered infant formula contaminated with Salmonella, orange juice contaminated
with Salmonella, and pork contaminated with Streptococcus.
Clear, rapid, reliable, and authoritative information on food emergencies is
the essential basis not only for prevention and response measures but also main-
taining consumer confidence in the food supply. INFOSAN Emergency will be
activated only during major international incidents involving the imminent risk
of serious injury or death to consumers. INFOSAN Emergency contact points
will be expected to accept some notification and response responsibility and to
facilitate the communication of urgent messages during food safety emergencies.
Figure 2-2 presents an example of how this may be structured in a country. Be-
cause of the potential sensitivity of the information exchanged, communication
on this network would be considered confidential.
Other
WHO WHO Global Outbreak Alert & Response Network (GOARN) networks
Regional for
chemicals
& and
Country radiological
Offices WHO INFOSAN Emergency Network materials
National Outbreak National INFOSAN Emergency

Alert & Response Contact Point
System
Foodborne disease
Communications Linkages
surveillance & • Recall & tracing systems
Rapid intelligence, investigation systems • Food import/export inspection
i.e. pharmaceutical • Food control laboratories
usage information • Industry alert systems
& poison control • Agriculture alert systems
centers • Food safety risk assessment
• Food technology expertise
• Food contaminant monitoring
• Other sectors
FIGURE 2-2 The WHO International Food Safety Authorities Network (INFOSAN):
Potential communication lines for national INFOSAN Emergency Contact Points.
SOURCE: INFOSAN (2005).

INFOSAN Emergency will be closely linked to the alert-and-response ac-

tivities of WHO and will be—to the extent necessary—functioning in support of
the new international health regulations (WHO, 2004d). These regulations stipu-
late the international rules for sharing information on certain infectious diseases.
The existing rules have up until now only covered yellow fever, cholera, and
plague, enabling (and demanding) international exchange of information of out-
breaks of such diseases. Responding to a realization that many internationally
important disease incidents involve other responsible agents, including new agents
such as the SARS virus, the need for a revision of international health rules was
formulated in the WHA several years ago. The new rules propose the extension
of the WHO coordinated public health emergency system to include all public
health emergencies of international concern, which has been defined to also in-
clude foodborne emergencies or emergencies involving zoonotic diseases. Be-
cause of the legal framework of the regulations, there is no need for national
ratification, and they will enter into force for all 192 WHO member states in June
2007.4 All WHO member states will be obliged to declare public health emergen-
cies of international concern to the WHO.
WHO’s international systems to minimize impact on public health of inter-
national incidents, including the international health rules, INFOSAN, and other
networks related to chemical and radiological incidents basically exist to do the
following:
• Rapidly detect any international incident;

• Respond in a timely fashion to international emergencies; and
• Decide and inform on the termination of emergency situations.
The systems therefore require:
• Capacity for efficient information gathering and rapid communication;

• Capacity to verify and make decisions;
• Procedures to respond and capacity to assist; and
• Basic platforms of national preparedness with international links.
REFERENCES
CDC (Centers for Disease Control and Prevention). 1997. Escherichia coli O157:H7 infections asso-
ciated with eating a nationally distributed commercial brand of frozen ground beef patties and
hamburgers: Colorado, 1997. Morbidity and Mortality Weekly Report 46(33):777–778.
CDC. 1999. Update: Multi-state outbreak of listeriosis—United States, 1998–1999. Morbidity and
Mortality Weekly Report 47(51/52):1117–1118.
4In May 2006, the WHA in a resolution agreed to: “Call upon Member States to comply immedi-
ately, on a voluntary basis, with provisions of the International Health Regulations (2005) considered
relevant to the risk posed by avian influenza and pandemic influenza.”

FAO/WHO (Food and Agriculture Association and the World Health Organization). 2004. Second
FAO/WHO Global Forum of Food Safety Regulators—A Forum Dedicated to Sharing Experi-
ences in Management of Food Safety. [Online]. Available: http://www.foodsafetyforum.org/
global2/index_en.asp [accessed April 10, 2006].
GAO (Government Accountability Office). 2004. Federal Food Safety and Security System: Funda-
mental Restructuring is Needed to Address Fragmentation and Overlap. GAO-04-588T. Wash-
ington, D.C.: GAO.
GAO. 2005a. Overseeing the U.S. Food Supply: Steps Should be Taken to Reduce Overlapping In-
spections and Related Activities. GAO-05-549T. Washington, D.C.: GAO.
GAO. 2005b. Oversight of Food Safety Activities: Federal Agencies Should Pursue Opportunities to
Reduce Overlap and Better Leverage Resources. GAO-05-213. Washington, D.C.: GAO.
Gerner-Smidt P, Kincaid J, Kubota K, Hise K, Hunter SB, Fair MA, Norton D, Woo-Ming A,
Kurzynski T, Sotir MJ, Head M, Holt K, Swaminathan B. 2005. Molecular surveillance of shiga
toxigenic Escherichia coli O157 by PulseNet USA. Journal of Food Protection 68(9):1926–
1931.
Green MA, Heumann MA, Wehr HM, Foster LR, Williams LP Jr, Polder JA, Morgan CL, Wagner
SL, Wanke LA, Witt JM. 1987. An outbreak of watermelon-borne pesticide toxicity. American
Journal of Public Health 77(11):1431–1434.
Halliday ML, Kang LY, Zhou TK, Hu MD, Pan QC, Fu TY, Huang YS, Hu SL. 1991. An epidemic
of hepatitis A attributable to the ingestion of raw clams in Shanghai, China. Journal of Infec-
tious Diseases 164(5):852–859.
Hennesy TW, Hedberg CW, Slutsker L, White KE, Besser-Wiek JM, Moen ME, Feldman J, Coleman
WW, Edmonson LM, MacDonald KL, Osterholm MT. 1996. National outbreak of Salmonella
enteritidis infections from ice cream. New England Journal of Medicine 334(20):1281–1286.
Herwaldt BL, Ackers ML. 1997. An outbreak in 1996 of cyclosporiasis associated with imported
raspberries. Cyclospora Working Group. New England Journal of Medicine 336(22):1548–1556.
INFOSAN (International Food Safety Authorities Network). 2005. International Food Safety Au-
thorities Network. [Online]. Available: http://www.who.int/foodsafety/fs_management/infosan
_0705_en.pdf [accessed April 20, 2006].
IOM/NRC (Institute of Medicine/National Research Council). 1998. Ensuring Safe Food from Pro-
duction to Consumption. Washington, D.C.: National Academy Press.
Levine WC, Bennet RW, Choi Y, Henning KJ, Rager JR, Hendricks KA, Hopkins DP, Gunn RA,
Griffin PM. 1996. Staphylococcal food poisoning caused by imported canned mushrooms. Jour-
nal of Infectious Diseases 173(5):1263–1267.
Mermin JH, Griffin PM. 1999. Public health in crisis: Outbreaks of Escherichia coli O157:H7 in
Japan. American Journal of Epidemiology 150(8):797–803.
Motarjemi Y. 1993. Health and development aspects of food safety. Archiv für Lebensmittelhygiene
44(2):35–41.
Ryan CA, Nickels MK, Hargrett-Bean NT, Potter ME, Endo T, Mayer L, Langkop CW, Gibson C,
McDonald RC, Kenney RT, Puhr ND, McDonnell PJ, Martin RJ, Cohen ML, Blake PA. 1987.
Massive outbreak of antimicrobial-resistant salmonellosis traced to pasteurized milk. Journal of
Threlfall EJ, Hall ML, Ward LR, Rowe B. 1992. Plasmid profiles demonstrate that an upsurge in
Salmonella berta in humans in England and Wales is associated with imported poultry meat.
European Journal of Epidemiology 8(1):27–33.
Torok T, Tauxe RV, Wise RP, Livengood JR, Sokolow R, Mauvais S, Birkness KA, Skeels MR,
Horan JM, Foster LR. 1997. A large community outbreak of Salmonella caused by intentional

389–395.
Vogt DU. 1998. Food Safety: Recommendations for Changes in the Organization of Federal
Food Safety Responsibilities, 1949–1997. CRS Report 93-955. Washington, D.C.: Library of
Congress.
Wheeler JG, Sehti D, Cowden JM, Wall PG, Rodrigues LC, Tompkins DS, Hudson MJ, Roderirick
PJ. 1999. Study of infectious intestinal disease in England: Rates in the community, presenting
to general practice, and reported to national surveillance. The Infectious Intestinal Disease Study
Executive. British Medical Journal 318(7190):1046–1050.
WHO (World Health Organization). 1983. Toxic Oil Syndrome: Mass Food Poisoning in Pain. Re-
port of a WHO meeting, Madrid, Spain, May 21–25, 1983. Copenhagen: WHO Regional Office
for Europe.
WHO. 2002a. WHO Global Strategy for Food Safety: Safer Food for Better Health. Food Safety
Issues Series. [Online]. Available: http://www.who/int/foodsafety/publications/general/global
_strategy/en/ [accessed April 10, 2006].
WHO. 2002b. World Health Assembly Resolution (WHA55.16): Global Public Health Response to
Natural Occurrence, Accidental Release or Deliberate Use of Biological and Chemical Agents
or Radionuclear Material That Affect Health. [Online]. Available: http://www.who.int/gb/
ebwha/pdf_files/WHA55/ewha5516.pdf [accessed April 10, 2006].
WHO. 2002c. Fact Sheet No. 180 on variant Creutzfeldt-Jakob Disease (Rev. November 2002).
Geneva: WHO.
WHO. 2002d. Terrorist Threats to Food: Guidance for Establishing and Strengthening Prevention
and Response Systems, Food Safety Issues Series. Geneva: WHO.
WHO. 2004a. Sixth Futures Forum on Crisis Communication. Report of a WHO meeting, Reykjavik,
Iceland, May 10–11, 2004. Copenhagen: WHO Regional Office for Europe.
WHO. 2004b. Food safety. In: The Work of WHO in the Western Pacific Region, Report of the Re-
gional Director, 1 July 2003–30 June 2004. Manila, Philippines: WHO. Pp. 80–83.
WHO. 2004c. INFOSAN: International Food Safety Authorities Network. [Online]. Available: http:
//www.who/int/foodsafety/fs_management/infosan/en/ [accessed April 10, 2006].
WHO. 2004d. IHR: International Health Regulations. [Online]. Available: http://www.who.int/csr/
ihr/en/ [accessed April 10, 2006].
WHO. 2005. World Health Report 2005. Annexes by Country. [Online]. Available: http://www.who.
int/whr/2005/en/ [accessed April 10, 2006].
WHO. 2006. WHO Global Salm-Surv Progress Report (2000–2005): Building Capacity for
Laboratory-Based Foodborne Disease Surveillance and Outbreak Detection and Response.
Geneva: WHO.

Investigating Foodborne Threats
OVERVIEW
Foodborne illness is estimated to affect more than 76 million people in the
United States each year, resulting in 325,000 hospitalizations and 5,200 deaths,
but its true incidence is unknown (Mead et al., 1999). Because foodborne disease
is difficult to diagnose, the vast majority of these illnesses and more than half of
such deaths are attributed to “unknown agents” (Mead et al., 1999). The annual
cost of medical expenses and productivity losses associated with the five most
prevalent, diagnosable foodborne illnesses is nearly $7 billion (Vogt, 2005).
Many people with symptoms of foodborne illness do not seek medical atten-
tion, further contributing to underdiagnosis. These circumstances, in addition to
the rapid distribution of food on both a national and global scale, make it nearly
impossible to detect even a large foodborne outbreak in time to limit its impact;
see, for example, the description of the 1994 Salmonella outbreak in ice cream,
described by Osterholm in Chapter 1. Most often, outbreak investigations occur
after the fact. However, as the papers in this chapter illustrate, findings from
outbreak investigations enable public health authorities to identify new foodborne
pathogens, trace their entry into the food chain, and thereby reveal opportunities
to improve food safety.
The first contribution to this chapter, by Robert Tauxe of the Centers for
Disease Control and Prevention (CDC), provides an overview of the foodborne
threat spectrum and the practices of public health surveillance by which these
microbes, and the burden of disease they cause, have become known. Tauxe ex-
plores several recent advancements in this field, including the development of
information networks for foodborne disease surveillance (see also Besser in Chap-
70

INVESTIGATING FOODBORNE THREATS 71
ter 5) and enhanced outbreak investigations, and their probable link to recent
reductions in cases of several major foodborne diseases.
Despite these improvements, the processes of outbreak detection and investi-
gation remain highly challenging, as illustrated in the case studies that make up
the remainder of this chapter. The first two papers, by Barbara Herwaldt of the
CDC and Roberta Hammond and Dean Bodager of the Florida Department of
Health, describe their experiences investigating a relatively new foodborne threat:
the coccidian parasite Cyclospora cayetanensis. Little was known about the or-
ganism when, in the mid-1990s, large, multistate outbreaks of gastroenteritis were
recognized. Herwaldt and public health colleagues eventually traced these out-
breaks to raspberries from Guatemala, where Cyclospora infection is endemic.
Several other types of fresh produce have also been identified as vehicles for
cyclosporiasis outbreaks. Herwaldt analyzes the challenges presented by food-
borne outbreaks (in general, as well as the specific difficulties associated with C.
cayetanensis) and draws important lessons for the future of public health.
In the subsequent paper, Hammond and Bodager describe the complexities
of a recent C. cayetanensis investigation. Triggered by an early 2005 report from
a private lab of an unusually large number of infections, the investigation ulti-
mately involved county health departments throughout Florida, three different
state agencies that regulate food in Florida, and two federal agencies: the CDC
and the Food and Drug Administration (FDA). The investigators determined that
imported basil provided the vehicle for the parasite; like raspberries, basil is a
“stealth” ingredient that many people do not recognize or (because such foods are
often served as garnishes) easily forget. Such accounts illustrate the importance
of examining seemingly unrelated cases of apparent foodborne illnesses as indi-
cators of outbreaks and pursuing them to their sources through timely and thor-
ough investigation.
The pathogen discussed in the chapter’s final contribution, the hepatitis A
virus (HAV), is far better characterized than Cyclospora, yet its investigators are
faced with a similar array of challenges. This paper, by workshop speaker Beth
Bell and Anthony Fiore of the CDC, describes a series of hepatitis A outbreaks in
late 2003 that included the largest such outbreak reported in the United States. It
involved over 600 patrons of a single Pennsylvania restaurant, and ultimately led
the FDA to ban imports from the Mexican farms that grew the tainted green
onions that caused the outbreak. Investigators were aided by molecular methods
for HAV detection (comparable methods do not exist for Cyclospora), but Bell
and Fiore note several characteristics of routine hepatitis A surveillance and of
the infection itself that continue to hinder its detection and control. The authors
conclude that foodborne HAV infection (and those of other enteric pathogens)
may be best prevented on the farm by reducing the contamination of produce with
fecal material.
Taken as a whole, the papers in this chapter demonstrate both the crucial
importance and the daunting difficulty of conducting foodborne outbreak investi-

gations. The success of such investigations depends to a large extent on public

and private laboratories that must have adequate resources if they are to quickly
and accurately detect threats to our food supply. Indeed, Tauxe observes that
future advancements in the detection and investigation of foodborne illness are
less likely to be achieved through technical innovation than through the strength-
ening of public health infrastructure.
THE BURDEN OF ILLNESS ASSOCIATED WITH FOODBORNE

THREATS TO HEALTH, AND THE CHALLENGE OF PREVENTION
Robert V. Tauxe, M.D., M.P.H.1
Centers for Disease Control and Prevention2
Few human endeavors are more complex than the constant, daily, and varied
effort to produce and prepare the foods we eat. The many cultural traditions and
changing tastes introduce new foods and food-making processes to growing popu-
lations around the world. As a result, the foodborne diseases that follow the con-
tamination of the food supply with any of a large number of microbes and toxins
present similarly evolving challenges. A new foodborne disease may emerge
when a previously unknown pathogen appears in a reservoir related to the food
supply or when transmission through a new foodborne pathway is documented
for a known pathogen. When a new foodborne disease appears, there is a natural
history to the challenge, starting with first detection and description; the develop-
ment of means to diagnose and treat the new infection; investigations into the
sources, reservoirs, and transmission pathways; and finally prevention stratagems
that improve to the point that the disease no longer presents an important prob-
lem. Each of the many known foodborne diseases is somewhere on this progres-
sion, and more are likely to be appreciated in the future. The spectrum of
foodborne diseases is a dynamic range of threats.
An array of bacterial, viral, and parasitic pathogens that cause foodborne
infections are currently recognized as public health problems in the United States.
Among these, an important number have only been recognized as foodborne
pathogens in the last three decades (Table 3-1). Some were first detected as patho-
gens in recent times and may represent the evolution of new combinations of
virulence properties. For example, E. coli O157:H7, not detected at all before the
1970s and first recognized as a cause of human illness in 1982, became a major
foodborne disease with a recognized bovine reservoir on several continents by
the 1990s (Griffin and Tauxe, 1991). This pathogen evolved from precursors with
1Captain, U.S. Public Health Service; Chief of Foodborne and Diarrheal Diseases Branch, Division
of Bacterial and Mycotic Diseases, National Center for Infectious Diseases.

2The findings and conclusions in this manuscript have not been formally disseminated by CDC and
should not be construed to represent any agency determination or policy.

TABLE 3-1 Foodborne Pathogens in the United States

Bacteria Viruses
Bacillus cereus Norovirus*
Brucella Rotavirus*
Campylobacter* Astrovirus*
Clostridium botulinum Hepatitis A
Clostridium perfringens*
Enterobacter sakazakii* Parasites
E. coli O157:H7* Anisakis
E. coli non-O157 STEC* Cryptosporidium*
E. coli other diarrheogenic* Cyclospora*
Mycobacterium bovis Giardia lamblia*
Salmonella Typhi Toxoplasma*
Salmonella nontyphoidal Trichinella
Shigella
Staphylococcus aureus Prions
Streptococcus Bovine encephalopathy agent*
Vibrio cholerae, toxigenic (O1 and O139)*
Vibrio vulnificus*
Vibrio parahaemolyticus*
Yersinia enterocolitica*
NOTE: Pathogens characterized as foodborne within the last 30 years are indicated with an asterisk.
SOURCE: Tauxe (2005); Adapted from Tauxe (2002).
far less pathogenic potential as the result of several phage-induced mutations

(Wick et al., 2005). Though the timing of these modifications remains unproven,
several have noted that mobilization of phages and of other transferable genetic
elements could be linked to exposure to antimicrobial agents (Zhang et al., 2000;
LeFebvre et al., 2005) and therefore perhaps linked to relatively recent changes in
agriculture. Another recent example is the emergence of an entirely new toxi-
genic serotype of Vibrio cholerae with epidemic potential. This serotype, O139,
first appeared in 1992 in India, and spread rapidly through much of South and
Southeast Asia where it was transmitted through water and food (Hoge et al.,
1996). This serotype appears to have evolved as the result of a horizontal transfer
of the genes that produce the O-antigen, possibly from another Vibrio, into sev-
eral strains of the dominant strain of epidemic toxigenic V. cholerae O1 (Faruque
et al., 2003).
Other pathogens were recognized as human pathogens well before they were
linked to foodborne transmission. For example, Listeria monocytogenes, first de-
scribed as a cause of severe invasive infections in humans in the 1930s, was first
linked to foodborne transmission in 1981 in an outbreak associated with cole
slaw (Schlech et al., 1983), and more recently it was documented to be primarily
foodborne (Slutsker et al., 2000). Campylobacter jejuni, described as a cause of
invasive infection in immunocompromised hosts in the 1950s, was shown in 1977

to be a common enteric pathogen in normal hosts; the importance of foodborne

transmission was established by 1980 (Blaser et al., 1983). The more recent ob-
servations of the parasite Cyclospora cayetanensis show how a pathogen that was
geographically restricted to remote and third-world locations may leap to the
forefront as a new food safety challenge, as summarized elsewhere in this report.
This means that the new and emerging foodborne pathogens observed elsewhere
in the world are of substantial interest and may offer a view into our future. The
recent reports of outbreaks of Yersinia pseudotuberculosis associated with lettuce
in Finland and of hepatitis E infection associated with swine in Japan are worthy
of our attention (Nuorti et al., 2004; Yazaki et al., 2003).
Still others represent the recrudescence of foodborne challenges long brought
under control, as changing tastes and patterns of trade reintroduce pathogens to
the public that we last saw as a significant problem many decades ago. Souvenir
seafood brought back in suitcases led to foodborne cholera in New Jersey in the
1990s (Finelli et al., 1992). The recent appearance of bovine tuberculosis in New
York City may be a result of the rapid shipment of homemade cheeses from Latin
America, made traditionally with unpasteurized milk (CDC, 2005a). The specter
of an intentional attack on the population through the food supply has added other
pathogens—new and old—to the list of potential threats (Sobel et al., 2002).
We can anticipate new challenges to continue to emerge. A robust and flex-
ible public health surveillance system is an important part of how we will detect,
characterize, and ultimately prevent these new challenges.
Public Health Surveillance

Public health surveillance is conducted to define the magnitude and burden
of a disease that needs public health action, to identify and investigate outbreaks
so that control measures can be rapidly implemented and issues in need of further
research swiftly identified, and to measure the impact of control and prevention
efforts. The public health surveillance of infections that are likely to be foodborne
now includes a substantial list of pathogens whose diagnosis is to be reported to
public health authorities, and a new set of national networks for characterizing
the pathogens and the illnesses they cause. The recent improvements in surveil-
lance have been summarized in detail in a recent Institute of Medicine (IOM)
publication (IOM/NRC, 2003). The following is a brief sketch of some of the
improvements.
The primary authority for surveillance rests with the state health departments,
which gather information from cities and counties and operate most of the public
health laboratories. State and local notifiable diseases laws request or require
clinicians and laboratories to report specific infections and to refer isolates of
some pathogens to the public health laboratory for further characterization. These
laws also typically require the reporting of unusual clusters or outbreaks of dis-
ease. In addition, many jurisdictions maintain complaint lines, to which concerned

citizens may directly report illnesses or observations they think may need public
health attention. Some food testing occurs in the course of routine inspections and
as part of process monitoring within food production. This testing may also pro-
vide some information about the status of the food supply, though its purpose is
usually the ongoing verification of process control, not safety testing of each lot.
Since 1996, the public health surveillance system for foodborne diseases has
been strengthened in several ways. Several diseases were added to the standard
notifiable disease reporting system, including non-O157 Shiga toxin-producing
E. coli, hemolytic uremic syndrome, Cyclospora cayetanensis, and Listeria
monocytogenes. The routine public health serotyping of Salmonella and Shigella
was strengthened by the production and distribution of new antisera and training
in their use; now new DNA sequence-based methods are being developed for
more rapid identification of the serotype of Salmonella (McQuiston et al., 2004).
Public health monitoring of antimicrobial resistance in several enteric bacterial
pathogens has been implemented in parallel with monitoring of resistance in the
same pathogens isolated from animals and foods, leading to the identification of
such hazards as fluoroquinolone-resistant Campylobacter jejuni and multi-drug
resistant strains of Salmonella enteriticas serotype Typhimurium and Salmonella
enteriticas serotype Newport (Holmes and Chiller, 2004).
The reporting of outbreaks of foodborne diseases from local and state health
departments has been improved by standardized and rapid reporting via the
Internet and the Electronic Foodborne Outbreak Reporting System (CDC, 2005d).
Enhanced surveillance, including a new collection form and improved close-out
procedures doubled the number of foodborne outbreaks reported to more than
1,200 outbreaks each year (Figure 3-1). Now the Electronic Foodborne Outbreak
Reporting System has changed an old and slow paper-based system into a more
rapid reporting that makes it likely that a cluster of similar outbreaks occurring in
several parts of the country at once will be detected and flagged, and also increas-
ing the utility of the surveillance data to track trends in specific foodborne out-
break categories.
PulseNet, CDC’s national network for subtyping foodborne bacterial patho-
gens, has been implemented in all 50 states and a growing number of large city
health departments, as well as in the laboratories of the food regulatory agencies
at the U.S. Department of Agriculture (USDA) and the FDA (Gerner-Smidt et al.,
2006). This network relies on the submission of isolates of E. coli O157:H7,
Listeria monocytogenes, Salmonella, and other bacterial pathogens from clinical
laboratories to the public health laboratory, where the DNA “fingerprint” is de-
termined using pulsed-field gel electrophoresis. Automated comparison of the
digitized DNA pattern with the growing state and national database can swiftly
identify strains (and therefore cases) that might be related, detecting clusters
spread across multistate jurisdictions that might otherwise have been missed com-
pletely. In the 1960s, Salmonella serotyping transformed surveillance for that
organism by increasing the signal-to-noise ratio and making it possible to pick

1600 Enhanced surveillance

Paper forms
1400
1200 Web-based (EFORS)
1000
Outbreaks
800
600
400
200
0
1990 1992 1994 1996 1998 2000 2002 2004
Year
FIGURE 3-1 Reported outbreaks of foodborne diseases, 1990–2004, United States.
SOURCE: Adapted from CDC (2006b).
out outbreaks of one serotype from the background noise of all salmonellosis
(CDC, 1965). Now PulseNet provides an additional specificity, with a generally
applicable tool for identifying clusters of infections that are likely to be related,
even within a single closely-related serotype such as E. coli O157:H7, or within
individual Salmonella serotypes. PulseNet test protocols have now been devel-
oped for seven bacterial foodborne pathogens, as well as for Yersinia pestis and
F. tularensis.
PulseNet protocols have now been adopted in Canada, Japan, Australia and
other countries and are the heart of international networks for surveillance in
Europe, Asia and the Pacific, and Latin America (Swaminathan et al., 2006). This
will enhance our own prevention capacity. For example, in 2004, public health
laboratories in Japan detected a small cluster of E. coli O157:H7 infections in
Okinawa that they linked to consuming ground beef from the commissary at a
U.S. military base there, and an indistinguishable E. coli was detected in ground
beef in Japan, which came from the United States (CDC, 2005b). The notification
by Japan led to recall of 90,000 pounds of ground beef shipped to the military and
other institutions in the United States. The same strain was also identified in two
persons in the United States who did eat beef the origin of which was not trace-
able, and who would not otherwise have been linked.
In the future, routine usage of multilocus variable number tandem repeat
assays or other sequence based-methods in state health department laboratories
will further refine the speed and precision of the network. However, the promise

of real-time results is more dependent on resources, rather than technology, in-

cluding the vital participation of the private clinical laboratory sector to refer
strains rapidly to the public health laboratory and on the laboratory support within
the state health department to run the tests swiftly.
Another major advance in foodborne surveillance has been FoodNet, the ac-
tive sentinel site surveillance system for foodborne illness (Allos et al., 2004).
While PulseNet enhances the ability of all states to detect clusters and investigate
outbreaks, FoodNet is focused on developing standard and detailed surveillance
data on sporadic (nonoutbreak-associated cases) in 10 sites around the country,
now representing 14 percent of the U.S. population. Though sporadic cases are
far more common than those that are associated with outbreaks, they receive far
less attention in general. Active surveillance means that the health department
regularly contacts the clinical laboratories to collect reports of what has been
diagnosed, rather than relying on the laboratories to report them. In addition
FoodNet conducts specialized surveys of the clinical laboratories, of the general
population, and of other groups to obtain measures of the frequency of gastroen-
teritis in general, of specific diagnostic tests, and other measures important to
interpreting surveillance data. Data from FoodNet have been critical to refining
the overall estimates of the burden of foodborne disease and to tracking trends in
specific infections over time. For example, between 1996 and 2004, FoodNet
documented a 42 percent decline in diagnosed E. coli O157 infections, decreas-
ing to 0.9 per 100,000 in the year 2004; a 40 percent decline in Listeria infec-
tions; and a 31 percent decline in Campylobacter infections (CDC, 2005c). With
case-control and other studies, FoodNet also defines the association between in-
fections and specific foods, contributing to the attribution of the burden of spe-
cific infections to foods. Increasingly, FoodNet serves as a platform for develop-
ing and evaluating improved public health surveillance and investigative and
prevention strategies.
Estimating the Burden of Foodborne Diseases

The health burden of an infection includes the morbidity it causes, the hospi-
talization and other medical care that results, and the mortality, among other mea-
sures. Estimating this burden for a given pathogen means going beyond the re-
ported cases. To contribute a reported case, the person must become ill, must seek
medical care, the physician must ask for a laboratory test, the patient must pro-
vide a specimen for diagnostic study, the specimen must yield evidence of the
pathogen, and the case must be reported. Slippage at each point means that the
diagnosed cases are likely to represent only a small fraction of the cases that
actually occur. Other measures of severe infection, such as hospital discharge
summary records and cause of death as reported on death certificates, may be
used to estimate the total number of hospitalizations and deaths due to acute
enteric disease, but these measures significantly underreport specific infections,

as laboratory diagnoses may often not be reflected in the discharge or death cer-
tificate coding. In 1999, we published a report estimating the actual acute health
burden of foodborne disease in the United States (Mead et al., 1999).
These estimates were assembled from a variety of data collected by FoodNet
and other sources. FoodNet population surveys measure the number of cases of
acute gastroenteritis that actually occur and the proportion of these that seek care
and are cultured (Herikstad et al., 2002). The FoodNet clinical laboratory surveys
measure the likelihood that a specimen will be routinely tested for say, Salmo-
nella or Campylobacter or E. coli O157 (Voetsch et al., 2004a). This information
can then be used to amplify the number of cases that are diagnosed and reported;
in this way FoodNet estimated that there are actually 38 cases of salmonellosis
for every one that is diagnosed and reported (Voetsch et al., 2004b). FoodNet
data also provide the number of diagnosed salmonellosis cases that lead to hospi-
talization and the number that lead to death. Doubling that number to account for
cases that were not cultured provides a conservative estimate of the total number
of hospitalizations and deaths. Using similar data and assumptions, the incidence
of other infections under surveillance by FoodNet can also be estimated, and by
use of a uniform set of assumptions and expert opinion it is possible to estimate
the overall burden of known enteric infections at some 39 million infections per
year (Mead et al., 1999).
The next step was to estimate the proportion of these infections that are trans-
mitted through food, rather than through water, direct contact with ill children, or
other pathways. The estimated proportion of infections that are transmitted
through foods varied by pathogen, and in sum was 38 percent. Thus, of 39 million
enteric infections estimated to be caused by the known enteric pathogens,
16 million were attributed to food. A curious observation is that the estimate of
acute enteric illness developed pathogen by pathogen (annual incidence of
39 million cases) is substantially less than the total amount of acute gastroenteri-
tis in the population estimated by population survey (annual incidence of
211 million cases) (Mead et al., 1999). This “diagnostic gap” suggests that there
are more pathogens yet to be discovered (Tauxe, 2002). The fraction of these
other cases not accounted for by known pathogens that might be attributed to
food is not directly measurable. The authors of the 1999 estimate chose 38 per-
cent, the summary statistic for the known pathogens, as the best point estimate of
what it might be for the other acute illnesses not accounted for by known patho-
gens. The final estimate, 76 million illnesses, 323,000 hospitalizations, and 5,000
deaths, refers to the year 1997. This comprehensive estimate is now being revised
in a similar stepwise approach, starting with the measurement of the overall bur-
den of acute gastroenteritis and with more refined and pathogen-specific ap-
proaches to the estimates of unreported illness.
There are other ways of measuring the burden of unreported illness. In the
United Kingdom, the Intestinal Infectious Diseases study empanelled a group of
citizens who recorded their symptoms prospectively and provided stool speci-

mens for even mild cases of diarrheal illness (Wheeler et al., 1999). The Dutch
SENSOR study followed a similar strategy, working with a group of sentinel
general practitioners and their patients (de Wit et al., 2001). Both European ap-
proaches depended on the national healthcare system itself to provide a popula-
tion-based framework, and both were sufficiently expensive that they have not
been repeated. There are also measures of burden other than simple counts of
cases, hospitalizations, and deaths. For example, the health-related costs for the
principal bacterial foodborne pathogens (Salmonella, Campylobacter, E. coli
O157, other Shiga-toxin-producing E. coli, and Listeria monocytogenes) have
been estimated to be $6.9 billion (ERS, 2000). The cost to society associated with
the estimated number of deaths that were not attributed to known etiologies could
be as high as $17 billion, underlining the need for further refinement of this sector
of the estimate (Frenzen, 2004). Inclusion of the postinfectious sequelae in the
estimate can also greatly increase the economic burden. A detailed model devel-
oped for Campylobacter in the Netherlands included the burden of postinfectious
arthritides and Guillain-Barre syndrome and measured the burden in disability-
adjusted life years; this estimate indicated that a greater burden was due to the
sequelae, rather than the acute illness (Havelaar et al., 2005). The industry costs
of disrupted trade and development that can be occasioned by foodborne illness
can be enormous, though they usually do not appear on the public health ledger.
The costs of antimicrobial resistance associated with foodborne exposures have
also not been estimated, but they might include the cost of illness caused by
resistant foodborne pathogens and the costs related to the spread of transmissible
resistance genes that are present in commensal organisms in the food supply,
from which they may transfer to human pathogens.
Prevention of Emerging Foodborne Threats:

The Importance of the Outbreak Investigation
The prevention of foodborne diseases in general is a complex effort, involv-
ing many different actors along the chain of production from the farm to food
service. There are many different pathogens involved, almost none of which are
vaccine preventable in the final consumer. Educating consumers, food handlers,
and producers about their role in preventing foodborne disease is important, but
not sufficient. Contamination of food can occur at many points from farm to
table. Often the key to prevention is to understand those mechanisms of contami-
nation well enough to prevent them, before the food reaches the final consumer.
Investigation of contamination events, and especially investigation of outbreaks,
is critical to understanding the mechanisms of contamination. Prevention often
means reengineering food processes and policies for safety, usually with a focus
on a specific food and/or pathogen.
The foodborne outbreak investigation is thus a major driver for enhancing
overall food safety. When an outbreak is detected, the first priority is to learn

enough to prevent further cases from occurring in the current outbreak. However,
it is also an opportunity to learn something new, and to open research agendas
with impact far beyond the one outbreak. Many foodborne pathogens were first
identified in the course of an outbreak investigation. A new combination of patho-
gen and food may be revealed that needs further study by food scientists, animal
and plant pathologists, as well as medical researchers. Just as the National Trans-
portation Safety Board investigates a plane crash thoroughly after the fact to learn
how to prevent similar ones, careful investigation even after an outbreak is over
can define gaps in the system, stimulate further specific research, and indicate the
needs for new processes or regulations. New combinations of specific pathogens
and foods identified by outbreak investigations have been critical to guiding re-
search and prevention (see Table 3-2).
As the surveillance systems that we use in the United States have been en-
hanced in the last 10 years, we have observed a change in the number and nature
of outbreaks detected. This is a paradox of surveillance: making surveillance bet-
ter often reveals more of the problem, so that the actual public health burden
appears worse. For example, as noted above, the number of foodborne outbreaks
reported through the Electronic Foodborne Outbreak Reporting System doubled
following relatively simple improvements in process and participation. PulseNet
has caused a more substantial change in the nature of the outbreaks detected. By
increasing the signal-to-noise ratio for specific pathogen subtypes, PulseNet
makes it far more likely that geographically diffuse outbreaks will be detected.
Those diffuse outbreaks are particularly instructive.
PulseNet has had a profound impact on the kind of outbreaks that have been
detected because the nature of the outbreaks detected depends critically on the
methods used to detect them. If outbreaks only come to the attention of public
health when concerned citizens, physicians, or healthcare facilities report them,
then only large and locally apparent outbreaks are likely to be detected. These
TABLE 3-2 Some New Pathogen-Food Combinations Characterized During

Outbreak Investigations in the United States
Pathogen Food
E. coli O157 Beef, apple cider, and sprouts
Salmonella serotype Enteritidis Eggs, broilers, and almonds
Salmonella Poona Cantaloupe
Multidrug resistant Salmonella Newport Ground beef and raw milk cheese
Salmonella Javiana, Newport, and Tomatoes
Braenderup
Listeria monocytogenes Sliced luncheon turkey, hot dogs, and Mexican queso
fresco
Cyclospora Raspberries and basil
Norovirus Raw oysters, salads, and sliced luncheon meats
Hepatitis A Strawberries and green onions

classic point source outbreaks often affect a single group of people in a single
town or city, following a single meal, with a substantial attack rate. Investigating
this outbreak proceeds with local authority, and the food-handling problems that
are identified are often local in scope. Although important, these investigations
may have greatest impact at the local level.
The use of molecular subtyping to compare strains across many jurisdictions
has revealed an entirely different kind of outbreak in which a dispersed group of
persons who do not know each other are affected at the same time with the same
infecting organism in many different locations. In this scenario, no local listening
post may perceive more than a few cases, and the local increase is often not
apparent against the background of cases. Although each individual case may
appear to be sporadic, the outbreak may in fact be very large but dispersed. Inves-
tigating these dispersed scenario outbreaks requires the coordinated efforts of
many health authorities acting in concert and pooling the information. Though
difficult to detect and to investigate, the findings of these outbreaks can be of
particular importance. The dispersion may well reflect a contamination event high
in the food’s chain of production, not just a problem in the final kitchen. Identify-
ing that event can instruct the industry and regulatory authorities about a flaw in
the system that was previously unappreciated. Correcting it can lead to lasting
and generalized protection across the country.
This means that improved detection and investigation can serve to probe the
safety of the food production system at several levels. These investigations, pro-
viding information about gaps in the food safety system, drive the cycle of pre-
vention faster and reduce the overall number of infections. The results of en-
hanced prevention can be seen in the recent declines in the incidence of infections
with Listeria monocytogenes and E. coli O157, the two pathogens tracked most
intensively by PulseNet. Following the institution of PulseNet surveillance for
Listeria monocytogenes, there was an important increase in the number of out-
breaks detected (Figure 3-2). Many of these were related to processed meats,
focusing prevention efforts on that sector; incidence declined to an all time low of
2.7 per million in 2004, a drop of 40 percent since the baseline period 1996–1998
(CDC, 2005c). The incidence of E. coli O157 infections began to decrease sharply
after 2002, as the repeated investigations of pulsed-field gel electrophoresis clus-
ters focused attention on more specific controls at the level of ground beef. By
2004, the incidence of E. coli O157 infections as measured in FoodNet had
dropped 42 percent since the baseline period of 1996–1998, and was 0.9 per
100,0000, below the goals set by Healthy People 2010. It is doubtful that such
progress would have been made without PulseNet.
The most recent outbreak surveillance information published for E. coli
O157:H7 also illustrates how improved surveillance can first produce a sharp
increase in reported outbreaks, followed by a drop as better prevention strategies
take effect (Figure 3-3) (Rangel et al., 2005). In the 1980s, E. coli O157 out-
breaks of infection were rare, perhaps because the pathogen itself was less com-

10 Single state outbreak

PulseNet begins
Cases per million population
9 subtyping
Multistate outbreak
8 Listeria
7 Healthy People
6 2010 Goal
5
4
3
2
1
0
'86 '89 '90 '91 '92 '93 '94 '95 '96 '97 '98 '99 '00 '01 '02 '03 '04
Year
FIGURE 3-2 Reported incidence of Listeria monocytogenes infections and reported out-
breaks of listeriosis, United States, 1986–2004.
SOURCES: Adapted from Tappero et al. (1995); CDC (2006a,b).
50
PulseNet for
45 E. coli O157
40
E. coli O157 became nationally notifiable
35
30 Large western
states outbreak
25
20
15
10
0
1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002
FIGURE 3-3 Reported outbreaks of E. coli O157 infections, United States, 1982–2002.
SOURCE: Rangel et al. (2005).

mon, but also because it was not likely to be diagnosed or reported. Washington,
the first state to make it a notifiable condition, did so in 1988. After the large
Western states outbreak of 1993, centered in Washington, many other states made
it notifiable, and it became nationally notifiable in 1994. At the same time, an
education effort targeting clinical laboratories promoted simple laboratory screen-
ing for the pathogen. It is not surprising that the number of reported outbreaks
jumped to more than 30 in 1994, and then began to decline, as many in the fast-
food industry and homes changed burger cooking procedures to avoid under-
cooking. In 1996–1997, in the first FoodNet case-control study of sporadic E. coli
O157:H7 infections, eating burgers at a fast-food restaurant was no longer associ-
ated with illness, though it had been in earlier studies (Kassenborg et al., 2004).
Following the launch of PulseNet, the number of reported outbreaks more than
doubled again in 1998, and since then has generally trended downwards as other
prevention measures have been enacted. As noted above, the biggest decrease
may have happened after 2002, after new procedures to reduce the contamination
of ground beef were implemented, though the impact of those on E. coli O157:H7
outbreaks has not yet been summarized in print.
Constraints and Limitations on Using Outbreaks

to Drive Control and Prevention
Detecting and investigating foodborne outbreaks triggers public health inter-
vention, but as a prevention system, this has built in delays. Most obviously, it is
not activated until after people are exposed, become ill, and the outbreak is de-
tected. Often the outbreak is actually over by the time it is detected, making the
outbreak investigation itself a blunt instrument for achieving control over single
brief exposures to contamination. There are biology-dependent delays, like the
incubation period between the moment of exposure and the onset of symptoms,
which can vary from less than a day for some pathogens to several weeks for
others. Delays in diagnosis may depend on when the typical patient feels suffi-
ciently ill to consult a physician and on how long the laboratory tests take to yield
a diagnosis. Signal delay depends on the time it takes to accumulate enough cases
in one database to be detectable as a distinct cluster and may be longer if cases are
more dispersed. There are also the resource-dependent delays that depend criti-
cally on support that surveillance gets in the private and public sectors. Clinical
laboratories may batch isolates for shipment to the public health laboratory to cut
shipping costs, adding delays. The speed of testing strains in public health labora-
tories also depends on the available resources. Interviewing cases and tracing
implicated foods back to their sources depends on the availability of trained and
supported investigative staff, for whom this is part of their core work duties, not a
distraction from the “real” work they must accomplish.
Many state and local health departments lack sufficient capacity to effec-
tively investigate outbreaks. For example, in a recently published survey of state

health departments, 88 percent reported there were barriers to more active case
finding, and 30 percent reported that they lacked adequate epidemiological staff
to conduct investigations. Outbreaks go uninvestigated for a number of reasons,
the most common of which are delayed notification (83 percent of those respon-
dents) and lack of staff (67 percent). Many state public health laboratories are
also understaffed and under supported, making real-time testing of submitted
strains difficult and leaving them with little surge capacity for emergencies
(APHL, 2003).
Pooling Resources
The fundamental ability to detect and investigate outbreaks is critical to the
response to any new threat, be it intentional or natural in origin. In the only two
intentional foodborne attacks involving bacterial infectious agents in recent expe-
rience in the United States, local and state health departments detected and re-
sponded to outbreaks as a matter of course; it was not recognized at the outset that
the events were intentional in origin (Torok et al., 1997; Kolavic et al., 1997).
Some states have recognized that robust public health surveillance is a fundamen-
tal part of protecting the public health against both natural and intentional events,
and the infusion of new resources to strengthen the response to bioterror threats
has improved surveillance and response capacity in general. However, in many
others, bioterror response resources have lured staff and attention away from the
traditional activities of public health, leaving those systems weaker than before.
Yet actual foodborne bioterror events remain remarkably rare. During the last 25
years, two have been documented, while during this same time, applying the
recent Electronic Foodborne Outbreak Reporting System number of 1,200 food-
borne outbreaks a year, there were an estimated 30,000 nonintentional foodborne
outbreaks. Like firefighters in a firehouse restricted to arson fires, the dedicated
squad will have to practice its skills in drills and table top exercises, while their
less well-equipped and perhaps less well-paid colleagues put out all the fires,
which must occur before the fire can be determined to be arson or not.
Enhancing Foodborne Outbreak Investigations

Despite the many constraints, the response to foodborne outbreak investiga-
tions can be improved substantially. Expanding routine subtyping to a greater
number of isolates and different pathogens may help drive prevention faster and
more broadly. Faster and more automated subtyping methods, including
sequenced-based methods for both bacteria and viruses, need to be deployed as
the cost and complexity of sequencing equipment decreases. Cluster detection
can be speeded by providing the resources for swift transport and real-time test-
ing rather than batch processing. Routine case interviews can be made more swift
and standardized, and they can be integrated with control interviews to make

investigation rapid. Improving the record keeping necessary for accurate tracing
of foods to their sources, and increasing the skilled capacity in the state and na-
tional regulatory agencies to perform such investigations would speed that criti-
cal phase of investigations. Fingerprinting the pathogens isolated from foods and
food animals in real time and linking those data with the human isolate database
would make it possible to rapidly generate hypotheses about potential sources.
Expanding the capacity for surveillance in other countries around the world
and expanding regional and global surveillance networks to detect and investi-
gate outbreaks can enhance the detection of foodborne threats at home and abroad
(Tauxe and Hughes, 1996).
Conclusion
Enhancing foodborne surveillance, outbreak detection and response means
better public health. Outbreaks will continue to occur, and people will continue to
get ill, but with effective response, these unfortunate events can drive prevention.
FoodNet is providing better data to measure trends and burden of illness and to
determine sources of sporadic infections. PulseNet, the new network for molec-
ular subtyping, is blurring the line between obvious outbreaks and apparently
sporadic cases, and it is probing more deeply into the safety of the entire food
system. Investigating and learning from the outbreaks is critical to achieving con-
tinuous improvement in food safety. As the public health system is likely to be
the first responders in the event of an intentional attack, as well as for the far more
frequent unintentional outbreaks, having a more robust and effective response is
better for the public protection in either event.
THE ONGOING SAGA OF U.S. OUTBREAKS OF CYCLOSPORIASIS

ASSOCIATED WITH IMPORTED FRESH PRODUCE:
WHAT CYCLOSPORA CAYETANENSIS HAS TAUGHT US AND
WHAT WE HAVE YET TO LEARN
Barbara L. Herwaldt, M.D., M.P.H.3
. . . For disease will peer up over the hedge

of health, with only its eyes showing . . .
For there will be computers
For there will be hard data and they will be hard
to understand
3Medical Epidemiologist in the Division of Parasitic Diseases.

4The findings and conclusions in this manuscript have not been formally disseminated by the CDC
and should not be construed to represent any agency determination or policy.

For the trivial will trap you and the important escape you
For the Committee will be unable to resolve the question
For there will be the arts
and some will call them
soft data
whereas in fact they are the hard data
by which our lives are lived . . .
—John Stone (Stone, 2004)
Prologue: An Ongoing Tale of Two Settings,

Viewed from Multiple Perspectives
Cyclospora cayetanensis infection is endemic in many resource-poor and
middle-income countries (Bern et al., 1999, 2000; Herwaldt, 2000; Lopez et al.,
2003; Ortega et al., 1993). The United States, a resource-rich consumer country,
has unwittingly imported this foreign, enigmatic parasite along with fresh pro-
duce that has been linked to outbreaks of cyclosporiasis. From the U.S. perspec-
tive, the unforeseen emergence of this microscopic pathogen has evolved into an
ongoing tale of large foodborne outbreaks, which have entailed crossing jurisdic-
tional borders and working with foreign governments, produce growers, and trade
organizations (CDC, 1998, 2004; Herwaldt, 2000; Herwaldt et al., 1997, 1999;
Ho et al., 2002; Lopez et al., 2001).
The parasite C. cayetanensis, which was christened in 1994 (Ortega et al.,
1994), and the precedent-setting series of outbreaks of cyclosporiasis continue to
be sources of fascination, frustration, challenges, and learning opportunities for
the persons, agencies, industries, and governments they have directly or indi-
rectly affected. The parasite and various aspects of the outbreaks (e.g., coordina-
tion of multisite investigations, interactions with foreign sources of implicated
produce, regulatory responses when the mode of contamination is unknown, im-
pacts on international trade) have been and continue to be subjects of case studies
(Calvin, 2003; Jackson, 2006; Powell, 1998), including a U.S. Senate hearing in
1998 entitled The Safety of Food Imports: From the Farm to the Table: A Case
Study of Tainted Imported Fruit (U.S. Senate, 1998) and this case study, which
was presented in part at the IOM’s October 2005 workshop on food safety.5
This case study—in which the parasite and the U.S. outbreaks are viewed
with a wide-angle lens that includes public health, societal, and historical con-
texts—focuses on food for thought (e.g., perspectives, principles, and issues for
the public health community to ponder) rather than detailed commentary about
foodborne threats to health or comprehensive review of the outbreaks of cyclo-
5Forum on Microbial Threats. 2005 (October 25–26). “Foodborne Threats to Health: The Practice
and Policies of Surveillance, Prevention, Outbreak Investigations, and International Coordination,”

Washington, D.C.

sporiasis. In the text of the article, selected details about the parasite and the
outbreaks are included for illustrative purposes, such as to underscore lessons
learned, relearned, or yet to be learned and to highlight common themes (e.g.,
challenges intrinsic to emerging pathogens). Supplemental details and perspec-
tive are provided in figures (Figure 3-4, Figure 3-5) and tables (Tables 3-3 through
3-6, which may be found at the end of this article in Annexes 3-1 through 3-4).
Table 3-4 and Table 3-5 represent attempts to list and dissect the elements of
foodborne outbreaks and investigations to demonstrate what various ingredients
add to the mix (e.g., the challenges, opportunities, and approaches if the etiologic
agent is an enigmatic parasite).6
Investigating the initial outbreaks in the 1990s would have been even more
difficult than it was if Cyclospora and cyclosporiasis had emerged in the United
States as complete unknowns. The fact that they did not reflects the contributions
and astute observations of relatively few persons with expertise in parasitology
and tropical medicine, in diverse places such as Papua New Guinea, Peru, and
Nepal (Ashford, 1979; Hoge et al., 1995; Ortega et al., 1993, 1994). Their efforts
culminated in fundamental scientific and medical advances, described in articles
published seemingly just in the nick of time. Through studies in Peru, the confu-
sion about the identity of the organism was resolved: it is not a species of blue-
green algae (cyanobacteria); it is a coccidian parasite, the first and only species in
the Cyclospora genus known to infect humans (Ortega et al., 1993, 1994). In a
placebo-controlled clinical trial in Nepal, the antimicrobial combination of
trimethoprim-sulfamethoxazole was demonstrated to be highly effective treat-
ment of cyclosporiasis (Hoge et al., 1995), the first and only such therapy to have
been documented (Table 3-3, Annex 3-1).
Unfortunately, the parasitologists were not prophets: the experts were as sur-
prised as the novices by the unpredicted U.S. emergence of C. cayetanensis and
by the unprecedented association between a parasite and large, common-source
foodborne outbreaks. Although other enteric parasites are known to be transmis-
sible by contaminated food, nothing remotely comparable to the widespread, re-
current outbreaks of cyclosporiasis has been documented in the United States for
any other parasite. The first of the series of major eruptions of C. cayetanensis on
the international scene occurred in the spring of 1996, after premonitory rum-
blings earlier in the decade (Herwaldt, 2000; Huang et al., 1995; Koumans et al.,
6Table 3-4 and Table 3-5, which are complementary, have the same column headings—i.e., out-
breaks/investigations in general, the etiologic agent C. cayetanensis, fresh produce vehicles, and for-
eign sources. In Table 3-4, which focuses on the characteristics of outbreaks/investigations, the row
headings distinguish outbreaks/investigations in general and outbreaks with various characteristics
(i.e., large, multisite, concurrent, recurrent, seasonal, and associated with high attack rates). In Table
3-5, which focuses on the goals of outbreak investigations, the row headings distinguish the processes
of identifying food vehicles, their sources, sites/modes of contamination, and control measures. Addi-
tional perspectives about the scientific and communication challenges highlighted in Table 3-4 and
Table 3-5 are provided in Table 3-3 and Table 3-6, respectively.

1998). The eruption in 1996 took the form of a large (>1,000 reported cases7),
multinational outbreak of cyclosporiasis in two countries, the United States and
Canada, that was linked to a third country, Guatemala, where the epidemiologi-
cally implicated raspberries were grown (Herwaldt et al., 1997).
The modus operandi of this pathogen in the United States as the etiologic
agent of outbreaks has not changed during the subsequent decade, although the
repertoire of food vehicles and sources has expanded beyond raspberries from
Guatemala to include assorted types of fresh produce from several middle-in-
come countries (Table 3-4, Annex 3-2; Table 3-5, Annex 3-3). The saga of out-
breaks appears to have evolved into an interminable tome, with no end in sight.
Its inscrutable chief character, C. cayetanensis, a unicellular (protozoan) parasite,
continues to wreck havoc, surprise, outsmart, baffle, and bewilder us (Table 3-3,
Annex 3-1). As discussed in this article, Cyclospora epitomizes the challenges
intrinsic to addressing obscure pathogens that appear, seemingly out of nowhere,
including how and why the challenges translate into difficulties investigating and
preventing outbreaks and communicating among health professionals, the gen-
eral public, and the produce industry. The scientific unknowns and political over-
tones are among the factors that have complicated efforts to communicate and
collaborate (see Tables 3-4 through 3-6, Annexes 3-2 through 3-4).
Cyclospora, the U.S. outbreaks of cyclosporiasis, and their aftermaths have
affected physical, economic, and communal health in exporter and importer na-
tions (Calvin, 2003; Herwaldt, 2000; Jackson, 2006; Powell, 1998) (Table 3-6,
Annex 3-4). The need to invest resources to investigate the outbreaks has resulted
in increased recognition of and interest in this parasite and its effects on the per-
sons, products, and places where Cyclospora infection is endemic. The extent to
which the heightened awareness will stimulate long-term investments in multi-
disciplinary, multilingual research activities; the research will solve remaining
mysteries about this elusive pathogen, its quirky human hosts, and their micro-
and macrohabitats; and the increased knowledge will be translated into wisdom,
vision, and sustainable, effective, transnational prevention and control measures
remains to be seen and recorded. The potential for additional scientific advances
to have positive ripple effects that extend beyond Cyclospora and cyclosporiasis
is high.
7Although the true magnitude of the outbreak in North America in 1996 is unknown, 1,465 cases of
cyclosporiasis were reported (including 1,270 [87 percent] in the United States, in 20 states and the
District of Columbia), which dwarfed the total number of cases previously documented worldwide
(Herwaldt et al., 1997). In the raspberry-associated outbreak in 1997, the case count was 1,012 (in-
cluding 981 [97 percent] in the United States, in 17 states and the District of Columbia) (Herwaldt et
al., 1999). The total number of reported cases in the series of outbreaks in North America from 1995–
2005 exceeds 4,000. The admonition to remember that cases occur in real persons bears repeating
(Baron, 1985). As expressed by a physician to the medical students she mentors: “. . . you have not
finished your work until you have taken care of the patient, not just the problem” (Treadway, 2006).

Challenges in Addressing Public Health Issues in General

and Foodborne Outbreaks of Cyclosporiasis in Particular
Addressing public health issues, even ostensibly straightforward matters, can
be difficult in part because of competing demands for scarce resources. The chal-
lenges are compounded for chronic issues such as foodborne cyclosporiasis that
are associated with confounding complexities and unknowns. Figure 3-4 and the
text in this section of the article represent attempts, replete with mixed meta-
phors, to place the challenges in perspective by depicting and describing the ele-
ments of a support structure for a public health bridge between disease and pre-
vention and control. The goal (i.e., to bridge the chasm between disease and
prevention and control), the base on which the support structure for the bridge is
built (i.e., the public health infrastructure), and the societal and historical con-
texts for public health activities are not unique to cyclosporiasis.
Building and maintaining a structurally sound, science-grounded bridge are
challenging (i.e., are uphill struggles, as depicted by the angle of the bridge). The
instability and vulnerability of the base (soil) are major impediments. The infra-
FIGURE 3-4 Generic and Cyclospora-specific challenges in bridging the chasm between
disease and prevention and control.
SOURCE: B. Herwaldt and D. Juranek, CDC, Division of Parasitic Diseases, April 2006
(see Acknowledgments).

structure is portrayed as underground (unseen), overburdened, stretched, atro-

phied, eroded, and diverted. The impoverished infrastructure includes the residual
resources of all types, at all tiers (e.g., local, state, federal) of the public health
system. Core infrastructure constraints can be appreciated through the lens of an
analogy, in which the public health system is viewed as an internal combustion
engine, subject to the laws of thermodynamics (see footnote for details).8 Revital-
izing the infrastructure will require commitment, concerted effort, and coordina-
tion from and among all tiers of the public health system, as well as great wisdom
and vision, archetypical eroded, diverted elements.
Addressing foodborne cyclosporiasis entails adding more loads to the over-
burdened infrastructure in the form of the support elements for the public health
bridge between disease and prevention and control. The elements are depicted as:
• a foundation stone, which symbolizes the importance of addressing fun-

damental constraints intrinsic to emerging pathogens; and
• pathogen and vehicle pillars (support columns), which symbolize the
needs to address the superimposed challenges specific to the type of pathogen
(the unique peculiarities of the coccidian parasite C. cayetanensis [Table 3-3,
Annex 3-1]) and the types of food vehicles (not just fresh produce, but imported
produce served in inconspicuous ways, such as garnishes [Table 3-4, Annex 3-2;
Table 3-5, Annex 3-3]).
A multidimensional, complex web of interactions is depicted by the checker-

board pattern under the bridge. Although the concept of pathogen-vehicle inter-
actions is highlighted, additional types of interactions (synergisms, antagonisms,
collaborations, feedback loops) among the elements of the support structure for
the bridge, the infrastructure, and society at large are germane (Table 3-4, Annex
3-2; Table 3-5, Annex 3-3). The fact that the parasite C. cayetanensis is emerging
while parasitologists are becoming an endangered species is an ironic example of
a negative pathogen-infrastructure interaction.
The public health infrastructure is further stretched and strained if the chal-
lenges associated with emerging pathogens must be addressed in the context of
emergencies (the extraordinary demands associated with large, multisite out-
breaks [Table 3-4])—i.e., if a base of scientific knowledge about the pathogen
8Within the public health system (engine), resources (internal energy) are constantly being con-
sumed (e.g., scarce financial and personnel resources are becoming scarcer), regardless of whether the
system is idling or moving an agenda and whether the direction of the movement is forward or back-
ward. Although resources can be converted from one type or state to another (e.g., from dollars to
devices and from federal to state programs), as well as redistributed, recycled, and diverted, they
cannot be created de novo; acquisition of new resources requires infusions from, or collaborations
with, other systems. The positive spin on the need for outside input is that it provides opportunities for
invaluable perspective and reality checks.

and databases for outbreaks must be created concurrently and on the fly. If the
infrastructure withstands the cumulative burden of many converging stresses,
outbreak investigations, in concert with basic and applied research activities, pro-
vide opportunities to solve mysteries through scientific advances and to identify
and reinforce weak elements in the public health system (Buchanan, 1997; Hall,
1997; Tauxe, 1997) (see Table 3-4, Annex 3-2; Table 3-5, Annex 3-3). The yin of
outbreaks can be partially converted into yang, by translating challenges into
opportunities into advancements in science and the public good.
Challenges in Addressing Emerging Pathogens,

Parasites, and Cyclospora cayetanensis
Emerging Pathogens
The challenges intrinsic to emerging pathogens—particularly to newly de-
scribed orphan microbes without close relations—include many constraints, all
of which did or still apply, to varying degrees, to C. cayetanensis, the quintessen-
tial emerging pathogen (Table 3-3, Annex 3-1). The constraints include:
• lack of fundamental knowledge about the biology of the organism (e.g.,

life cycle) and therefore the epidemiology of infection (e.g., modes of transmis-
sion), which translate into difficulties predicting the behavior of the organism
(e.g., responses to environmental stimuli), determining the pertinent questions to
include in epidemiologic surveys, and evaluating the plausibility of competing
hypotheses in outbreak investigations (Tables 3-4 through 3-6, Annexes 3-2
through 3-4);
• lack of competence and expertise among specialists (e.g., parasitologists),
let alone lack of general knowledge and familiarity among other health profes-
sionals and lay persons (i.e., the little known by supposed experts is not widely
known or readily accessible);
• lack of tools (e.g., analytic methods, techniques to propagate viable or-
ganisms, decontamination strategies); and
• lack of research materials (e.g., ample quantities/isolates of the organism).
The handicaps can be restated and classified in such categories as ignorance

(“don’t have a clue but wish I knew”), uncertainty (“not sure and might be
wrong”), unpredictability (“wouldn’t even hazard a guess”), unfamiliarity (“don’t
ask me”), and unavailability (“urgently need but don’t have”), further modified
by the likelihood the formidable obstacles can be overcome in the foreseeable
future.

Parasites, Including Cyclospora cayetanensis

Many of these constraints apply to parasites, even to those not considered
emerging pathogens per se. For example, as a broad generalization, health profes-
sionals and lay persons are less knowledgeable about and familiar with parasites
than bacteria. Addressing foodborne enteric parasites—particularly protozoa,
which include the coccidia C. cayetanensis and Cryptosporidium species9 (Table
3-3, Annex 3-1)—requires a paradigm shift. Although the statement that proto-
zoa are not bacteria is a truism, the ramifications of the fact that protozoa do not
behave like bacteria (e.g., do not multiply outside the host, in the environment, or
in food) have been difficult to communicate.
The scientific and communication challenges posed by foodborne outbreaks
of cyclosporiasis have been exacerbated by the different characteristics and be-
haviors of the major enteric coccidia (Table 3-3, Annex 3-1). An example of a
fundamental biologic difference with epidemiologic ramifications is that Crypto-
sporidium oocysts (the environmental stage of coccidia) in freshly excreted stool
are infective, whereas Cyclospora oocysts are not; they must mature (sporulate)
outside the host to become infective, which is thought to require days to weeks
under favorable environmental conditions (Table 3-3, Annex 3-1; Figure 3-5).
The identified differences between Cyclospora and Cryptosporidium species in
the realms of what is known about them underscore the potential risks of extrapo-
lating from the knowns about Cryptosporidium species to fill gaps in knowledge
about Cyclospora. The persistence of many enigmas about C. cayetanensis re-
flects the elusive search for pertinent model systems, the paucity of Cyclospora
oocysts available for research purposes, and the pathogen’s short recorded his-
tory, as recounted below.
Challenges Entailed in Discovering and Classifying

Cyclospora cayetanensis (1977–1994)
Reverberating Themes
Portions of the chronicle of the (re)discovery and (re)classification of the
pathogen christened C. cayetanensis in 1994 are retold and dissected here to un-
derscore recurring themes in the ongoing saga of cyclosporiasis, including com-
mon themes for emerging pathogens. Examples of such themes include the im-
portance of:
• distinctions between signals and noise and the difficulties encountered in

detecting and identifying previously undescribed, nondescript, rare signals (e.g.,
9In this article, the terminology “Cryptosporidium species” refers to C. hominis/parvum.

Graphic Illustration
2 sporocysts
4 sporozoites
sporulation
Microscopy
(DIC)
(undifferentiated cytoplasm) ( fully differentiated)
FIGURE 3-5 Sporulation of Cyclospora cayetanensis oocysts. Unsporulated and sporu-

lated C. cayetanensis oocysts are shown in graphic illustrations (top) and photographs
(bottom), as viewed by differential interference contrast (DIC) microscopy, a specialized
type of microscopy that markedly accentuates morphologic features (Herwaldt, 2000).
Persons infected with Cyclospora shed immature, unsporulated oocysts (8–10 µm in diam-
eter), which are thought to require days to weeks in favorable environmental conditions to
sporulate and become infective (Ortega et al., 1993) (Table 3-3, Annex 3-1).
SOURCE: B. Herwaldt and D. Juranek, CDC, Division of Parasitic Diseases, April 2006
(see Acknowledgments).
pathogens, outbreaks, contaminated produce) in complex mixtures of noise (e.g.,

stool specimens, surveillance data, salads);
• careful observations by trained, experienced persons (e.g., clinicians,
laboratorians, epidemiologists), who, at a minimum, realize they are seeing some-
thing that is or might be unusual and know where to turn for help and confirma-
tion (Table 3-3, Annex 3-1; Table 3-4, Annex 3-2);
• basic skills (e.g., looking, seeing, watching, waiting, counting, thinking,
writing, reading);
• basic materials (e.g., stool specimens for diagnostic purposes and oocysts
for research purposes [Table 3-3, Annex 3-1]); and
• basic tools (e.g., microscopes for detecting oocysts and telephones for
expeditious reporting of cases and potential outbreaks of cyclosporiasis).

Distinguishing Signals and Noise: Detecting Parasites Amidst the Sea of

Specks in Stool Specimens
Detection and identification of protozoa, even those already known to be
pathogens, by light-microscopic examination of stool specimens, is labor inten-
sive and challenging. When viewed by light microscopy, stool specimens appear
to be seas of specks; environmental samples have even more specks, lures, and
pathogen imposters. Determining which of the specks are or might be parasites is
difficult, especially if methods for highlighting or tagging the pertinent specks
are unavailable (Table 3-3, Annex 3-1). Cyclospora oocysts (8–10 µm in diam-
eter) can easily be missed; the oocysts in freshly excreted stool (i.e., those seen by
clinical microbiologists) are unsporulated, with undifferentiated, nondescript cy-
toplasm and typically are shed at low levels (Table 3-3, Annex 3-1; Figure 3-5)
(Herwaldt, 2000).
The Ashford and Ortega Chapters

In retrospect,10 the first three described cases of C. cayetanensis infection
were detected in 1977 and 1978, by Ashford, a British parasitologist working in
Papua New Guinea (Ashford, 1979). If someone without Ashford’s extraordinary
eye for detail and parasitologic expertise had looked through the oculars of the
microscope during “routine stool examination” of the patients’ specimens, the
presence and importance of the odd, “scanty” structures in the specimens almost
assuredly would have been missed or dismissed. Ashford’s discovery is all the
more remarkable because techniques that facilitate detection and identification of
this organism were not yet available (Table 3-3, Annex 3-1).
Explicitly listing the steps (ingredients) entailed in Ashford’s discovery is
illustrative.
• He took the time to examine the stool specimens (i.e., he had to “look” to
be able to “see”).
• He found/saw the “scanty” structures (unsporulated oocysts) in the sea of
specks (i.e., he detected the “signal” despite the “noise”).
• He took note of them and realized that they were microbes, not debris
(i.e., he both “saw” and “perceived”).
• He recognized that they were unusual (“distinct”) (i.e., he had sufficient
experience to distinguish “usual/typical” from “unusual/atypical”).
• He recognized that they had features suggestive of coccidian oocysts (i.e.,
he had sufficient knowledge to begin to categorize the structures).
10Some aspects of the Cyclospora chronicle are clear only if viewed through the retrospectoscope,
which underscores the importance of reevaluating conclusions (e.g., from ongoing and prior outbreak
investigations [Table 3-4]), as additional data and insights become available.

• He monitored the structures to see whether they would sporulate (i.e., he

knew how to test the hypothesis that they were coccidian oocysts and had suffi-
cient interest to do so).
• He did not yield to the temptation to discard the specimens before sporu-
lation finally was demonstrable (at 8 days in 1 case and 11 in another).
• He recognized his limitations: he could not discern, with confidence, the
number of sporozoites (i.e., two) in each of the two sporocysts in a sporulated
oocyst and realized that his tally (i.e., four) might be (and was) incorrect.
• He understood the ramifications of his limitations: he could not place the
organism in a genus or christen it because precise counts of the numbers of sporo-
zoites and sporocysts, not best guesses, are required for taxonomic classification
of coccidia by traditional morphologic criteria.11
• But he also recognized the importance of publishing his observations,
with conservative conclusions, which he did in 1979, in the Annals of Tropical
Medicine and Parasitology, in an article entitled “Occurrence of an undescribed
coccidian in man in Papua New Guinea” (Ashford, 1979).
Ashford’s report (signal) about the anonymous organism he noticed was vir-
tually unnoticed (undetected) for over a decade,12 as, presumably, the organism
had been for much longer. The Ashford chapter in this chronicle raises the first in
a series of laments (e.g., “if onlys” and “what ifs”). Whether and how the course
of Cyclospora history would have been different, if Ashford had chosen a differ-
ent title or journal for his article or had worked in an ideal world, without real-
world constraints, are subjects for fairy tales rather than nonfiction; in fairy tales,
pathogens would emerge with passports that included their pedigrees and profiles
(e.g., personal and family names, vital statistics, travel histories), as well as high-
resolution photographs of their key morphologic features.
The subsequent accomplishments of parasitologists Ortega and colleagues
are also remarkable. They surmounted hurdles whose height and importance can
be fully appreciated only by parasitologists. In the 1980s and early 1990s, while
studying Cryptosporidium infection in Peru, they noticed what appeared to be a
“big Cryptosporidium” species. Fortunately, they were not content with initial
impressions (the organism is not a Cryptosporidium species), just as Ashford had
not been content with best guesses (his best guess about the number of sporozo-
ites per sporocyst would have resulted in misplacement of the microbe in the
11The miscount, although understandable (i.e., because of the configuration of the crescent-shaped
sporozoites [Figure 3-5]), was not a minor matter. The difference between two sporozoites in each
of two sporocysts and four sporozoites per sporocyst represents the difference between the
Cyclospora and Isospora genera, respectively. Cryptosporidium species have four naked sporozo-
ites (no sporocysts).
12Searching the medical literature for potentially relevant articles about anonymous organisms is
difficult.

Isospora genus). Ortega and colleagues were able to demonstrate sporulation/

excystation of the structures they noticed and to determine, with confidence, the
morphologic features of a sporulated oocyst (Figure 3-5), which enabled them to
place the organism in the Cyclospora genus and to debunk speculations about its
identity (e.g., a cyanobacterium-like body).13
They described their observations in 1993, in The New England Journal of
Medicine, in a seminal article entitled “Cyclospora species: A new protozoan
pathogen of humans” (Ortega et al., 1993), unaware of Ashford’s report 14 years
earlier in a tropical medicine journal (Ashford, 1979). Ashford read (detected)
Ortega’s article in 1993 and realized that it described the organism he had cor-
rectly categorized as a coccidian parasite but had been unable to classify by ge-
nus. In 1994, in an article in which Ortega and colleagues officially christened the
organism as Cyclospora cayetanensis (Table 3-3), Ashford’s contributions from
back in the 1970s, from Papua New Guinea, were cited (Ortega et al., 1994).
The Incalculable Value of Cadres of Experts

The chronicle of the discovery and classification of C. cayetanensis under-
scores the importance of cultivating and retaining cadres of persons with
specialized—sometimes seemingly old-fashioned—skills, tools, and depth and
breadth of expertise: the expertise includes uncanny abilities to straddle decades,
even centuries (e.g., to have historical memory and perspective but not be teth-
ered to the past, and to be comfortable with both morphologic and molecular
data); to ponder imponderables; and to see and connect microscopic dots
(specks). Protecting and safeguarding brain trusts (i.e., preventing brain drains
and diversions) is much easier and wiser than attempting to register and recover
lost treasures. The key roles played by parasitologists, skilled in the fine arts of
light microscopy and morphologic identification and classification of parasites,
exemplified by their predecessor Antoni van Leeuwenhoek,14 cannot be over-
emphasized. Their contributions not only were prerequisites for the subsequent
advances in the realm of molecular biology (Orlandi et al., 2002, 2003; Relman
13Yet another twist in the tale was reported in the mid 1990s. Phylogenetic analyses, based on one
gene (i.e., the small subunit ribosomal RNA gene), showed that C. cayetanensis is as closely related
to some species of a different genus of coccidia—namely, the Eimeria genus—as some Eimeria
species are to each other (Herwaldt, 2000; Relman et al., 1996). The biologic implications of this
finding are unknown, but the ramifications for testing environmental samples are clear. Although, to
date, no Eimeria species have been shown to be human pathogens, because they are prevalent in
animals, environmental samples should be analyzed with techniques that distinguish C. cayetanensis
from Eimeria species, not just other Cyclospora species. By traditional taxonomic (morphologic)
criteria, Eimeria oocysts have four sporocysts (Cyclospora oocysts have two), each of which contains
two sporozoites.
14Antoni van Leeuwenhoek (1632–1723), Dutch microscopist extraordinaire.

et al., 1996; Steele et al., 2003; Varma et al., 2003; Verweij et al., 2003) but
continue to be essential (e.g., to date, molecular techniques cannot distinguish
unsporulated and sporulated oocysts).
Challenges Associated with Detecting and Investigating

the First Three Documented U.S. Outbreaks (1990 and 1995)
The accounts of the first three documented U.S. outbreaks of cyclosporiasis,
which occurred in 1990 and 1995, underscore the understandable difficulties in-
trinsic to investigating outbreaks when little is understood about the etiologic
agent (e.g., potentially pertinent questions and hypotheses are not considered or
rigorously explored). All three of these outbreaks were detected because of un-
usual circumstances: stool specimens from the index case-patients were exam-
ined in clinical microbiology laboratories in which techniques that facilitate de-
tection of Cyclospora were used routinely in parasitologic examinations (Table
3-3, Annex 3-1).
The Outbreak in Illinois in 1990: Waterborne or Foodborne?

The first documented U.S. outbreak occurred in a physicians’ dormitory in
Illinois, in the summer of 1990, before the confusion about the identity of the
organism had been resolved. The irresolvable uncertainty about whether the out-
break was waterborne, as it then was thought to be (Huang et al., 1995), or
foodborne (Herwaldt, 2000) represents another in the series of laments related to
Cyclospora. Although the outbreak was exceptional regardless of whether it was
waterborne or foodborne, not knowing the mode or vehicle of transmission trans-
lates into missed opportunities to generate and explore hypotheses and to distin-
guish the exceptional that did occur from that which did not.
If the outbreak was waterborne (i.e., associated with fixing a water pump
and refilling storage tanks in a penthouse area of the dormitory) (Huang et al.,
1995), it represents the only described U.S. waterborne outbreak of cyclo-
sporiasis, the means by which the water supply could have become contami-
nated are unclear, and the median incubation period (i.e., two days) was unchar-
acteristically short for common-source outbreaks of cyclosporiasis and enteric
protozoan diseases in general (Herwaldt, 2000). If the outbreak was foodborne,
it was associated with a meal in late June, the median incubation period was
characteristically long (i.e., eight days [Table 3-3, Annex 3-1]), the food vehicle
is unknown (details about the ingredients of food items, including a fruit salad,
and food-specific attack rates were not obtained), it was the first in a long series
of documented U.S. foodborne outbreaks of cyclosporiasis, and it preceded the
next described foodborne outbreaks by five years.

The Outbreaks in New York and Florida in 1995:

Harbingers of the Subsequent Foodborne Outbreaks?
In 1995, two potentially related outbreaks were detected: one associated with
a country club in New York in May–June and the other with two social events in
Florida in May (Herwaldt, 2000; Koumans et al., 1998). In retrospect, at least one
if not both of these outbreaks in 1995 presaged the raspberry-associated out-
breaks that were documented in 1996, 1997, 1998 (Canada), and 2000 (Table 3-4,
Annex 3-2; Table 3-5, Annex 3-3) (Herwaldt, 2000). The outbreak in New York
in 1995, like the outbreak in Illinois in 1990, was initially thought to be water-
borne (i.e., associated with consumption of water from coolers on a golf course).
However, reevaluation of the data for the outbreak in New York, prompted by the
subsequent foodborne outbreaks, indicated that the outbreak might have been
associated with fruit, possibly raspberries (Herwaldt, 2000). Probably not coinci-
dentally, New York and Florida—states with clinicians, laboratorians, and epide-
miologists knowledgeable about cyclosporiasis—were the first of the total of 20
states to report cases in the multinational outbreak in 1996 linked to Guatemalan
raspberries (Herwaldt, 2000).15
Evolving and Persisting Challenges Associated with

the Next Era of Outbreaks of Cyclosporiasis:
From Harbingers (in 1990 and 1995) to Sonic Booms (1996–2005)
The ongoing saga of cyclosporiasis has evolved from harbingers to serial,
large outbreaks, detected during many of the seasons and most of the years in the
subsequent decade (1996–2005). Despite the preparedness exercises with the har-
binger outbreaks in 1990 and 1995, we16 knew little about the biology of Cyclo-
spora or the epidemiology of cyclosporiasis in 1996, when confronted with a
large outbreak (1,465 reported cases), which included 55 clusters of cases (i.e., 55
15The positive ripple effects of training received by one person who trains others can continue for
years. In Florida, microbiology staff in a community hospital had dutifully examined stool specimens
for Cyclospora ever since a training course in the spring of 1992 (i.e., before the organism had been
christened), despite detecting only two cases of infection, in persons returning from overseas travel,
during the ensuing three years (Koumans et al., 1998). In June 1995, the laboratory staff detected and
reported the index cases of the outbreak in 1995. The staff subsequently trained laboratorians from
other hospitals in the county and a state laboratory to examine stool specimens for Cyclospora. The
state of Florida added cyclosporiasis to its list of reportable diseases in July 1995. Laboratory and
epidemiologic staff in Florida continue to play central roles in detecting and investigating outbreaks
of cyclosporiasis associated with imported fresh produce (e.g., mesclun lettuce from Peru in 1997 and
basil from Peru in 2005) (Herwaldt, 2000; also see the section in this chapter by R. Hammond and D.
Bodager).
16The words we and our are used to include all potentially relevant persons and agencies, without
any explicit or implicit focus on the author’s roles.

minioutbreaks associated with social and other events). In retrospect, the out-
break in 1996 can be viewed as the first course of what has become an ongoing
curriculum of difficult challenges and learning opportunities: a progressive din-
ner with assorted types of fresh produce, nontraditional exports from several
middle-income countries (e.g., raspberries and snow peas from Guatemala,
mesclun lettuce from Peru, basil from Peru and Mexico17).
Selected details about some of the outbreaks are provided, for illustrative
purposes, in the text and tables. As noted in the prologue, Table 3-4 and Table 3-
5 provide matrices for listing and dissecting the ingredients of outbreaks and
investigations. Examples of challenges, opportunities, approaches, societal con-
texts and trends, scientific advances, and lessons (re)learned, codified, and yet to
be learned are included as well. The outbreaks and their impacts, particularly the
series of outbreaks linked to Guatemalan raspberries, are discussed in detail in
other articles and case studies (Calvin, 2003; CDC, 1998, 2004; Herwaldt, 2000;
Herwaldt et al., 1997, 1999; Ho et al., 2002; Jackson, 2006; Lopez et al., 2001;
Powell, 1998; U.S. Senate, 1998).
The Complementary Needs for, and Values of, “One/Few” and “Many”:
Quality and Quantity
A reverberating theme in this narrative is the potential importance of “one/
few” (e.g., one oocyst detected in one stool specimen by one laboratorian; one
commonality noted among a few reported cases of infection; one harbinger, clue,
or outlier), which can have a positive impact (e.g., the one reported case could be
the index case of an otherwise unrecognized multicluster outbreak) or a negative
impact (e.g., a red herring misinterpreted as evidence). Missed oocysts and cases
translate into missed outbreaks and learning opportunities and into anxious pa-
tients with un(mis)diagnosed cases of infection treated with ineffective therapies
(Table 3-3, Annex 3-1; Table 3-6, Annex 3-4).
A complementary theme is the value of “many” (e.g., the unmet research
need for large quantities of oocysts [Table 3-3, Annex 3-1] and the epidemiologic
benefits of outbreaks with many cases and clusters of cases [Table 3-4, Annex 3-
2]). Large, multicluster outbreaks, such as the outbreaks in 1996 and 1997—
although challenging to investigate and coordinate and potentially devastating for
17The examples are those that can be provided with confidence (i.e., these vehicles and sources
were definitively implicated in investigations of U.S. outbreaks). The evidence for other vehicles and
sources (e.g., blackberries from Guatemala, in various years including 1999, and raspberries from
Chile, in an outbreak during late December 2001 through early January 2002) was not definitive
because of the typical types of constraints (Herwaldt, 2000; Jackson, 2006). For example, only one
cluster of cases was documented for the outbreak in the winter of 2001/2002 (i.e., no opportunities to
triangulate among clusters were available); the evidence that the raspberries that were eaten—which
were grown in Chile—were the vehicle of infection was suggestive but not definitive.

the affected persons, producers, economies, and societies (Table 3-6, Annex 3-
4)—can be blessings in disguise. Such outbreaks can translate into opportunities
to compile compelling epidemiologic evidence to implicate food vehicles and
sources (e.g., Guatemalan raspberries) and, ultimately, to learn to prevent con-
tamination and transmission. Geographically dispersed, multicluster outbreaks
provide opportunities (Table 3-4, Annex 3-2; Table 3-5, Annex 3-3), such as:
• to circumvent limitations in knowledge about plausible modes and ve-

hicles of transmission and to overcome limitations of individual clusters of cases
(e.g., by triangulating among the clusters and events to identify the common
themes in the mixtures of produce vehicles and potential sources);18
• to determine where food vehicles became contaminated (e.g., if the source
is the only commonality in the distribution system of a widely dispersed vehicle);
• to generate hypotheses about modes by which the vehicle became con-
taminated at its source (e.g., use of contaminated agricultural water); and
• therefore, to identify and implement potentially effective control mea-
sures (i.e., to translate science into action).
Recurrent outbreaks (e.g., the series of outbreaks linked to Guatemalan rasp-

berries), despite of and because of the challenges they pose, also provide opportu-
nities (Table 3-4, Annex 3-2; Table 3-5, Annex 3-3), such as:
• to (re)test hypotheses and to strengthen already compelling epidemiologic

evidence (e.g., through the investigation of the raspberry-associated outbreak in
the spring of 1997, which was uncannily similar to the outbreak in 1996 [Herwaldt
et al., 1997, 1999]);
• to complement compelling epidemiologic evidence with confirmatory
laboratory data (e.g., as was done in 2000 in the investigation of the last docu-
mented outbreak linked to Guatemalan raspberries because frozen leftovers of
the implicated food item—a wedding cake—were found and analytic methods
for this complex food matrix were developed [Ho et al., 2002] [Table 3-5, An-
nex 3-3]); and
• to assess the (in)effectiveness of control measures implemented in the
past and to pause to reevaluate how to proceed (e.g., in the spring of 1998, in an
inadvertent intervention trial, the United States did not import fresh Guatemalan
raspberries, whereas Canada did and experienced an outbreak [CDC, 1998;
Powell, 1998] [Table 3-4, Annex 3-2]).
18Epidemiologic and traceback investigations of produce-associated outbreaks would be greatly
simplified, if meals and food items included a maximum of one type of fresh produce, if aliquots of
such items were frozen for potential future analytic testing, and all pertinent receipts were saved.

Large and recurrent outbreaks (signals) are blessings in disguise in other

ways as well: they get attention in ways that subtle signals do not. Dismissed
cases (signals) in distant lands (i.e., cases not considered “our problem”) can
ultimately translate into sonic booms so loud (U.S. outbreaks so large) that they
cannot be ignored (Table 3-4, Annex 3-2). They serve as piercing wake-up calls
about the vulnerability of our food supply in general and fresh produce in particu-
lar, including the need to bring parasites and parasitologists to the food safety and
science tables. These wake-up calls can spur the growth of some good fruits, as
discussed below.
Detecting and Classifying Slow-Growing Fruits

Various types of slow-growing fruits pertain to the narrative and illustrate
yet again the yin and yang of the chronicle of Cyclospora. Certain principles are
evident. The unexpected not only occurs but occurs in unforeseen ways and
places, at unpredicted times, and with unanticipated effects. The fruits of invest-
ments in research, foreign technical assistance, the U.S. public health system, and
outbreak investigations might not be evident for years, might not meet expecta-
tions (e.g., unfulfilled hopes for trickle-down benefits of investments in particular
aspects of the public health infrastructure), or might not resemble the seeds that
were intentionally or unwittingly planted.
We remain indebted to the astute scientists whose years of investments
yielded timely fruits. Because of them we faced the outbreaks of cyclosporiasis
knowing that the etiologic agent is a coccidian parasite, which slowly matures
(i.e., has a long extrinsic maturation period), and knowing how to treat cases of
cyclosporiasis, which can be slow to resolve (Ashford, 1979; Hoge et al., 1995;
Ortega et al., 1993, 1994) (Table 3-3, Annex 3-1). The scientists did not invest in
their research activities with foreknowledge that Cyclospora would emerge as it
did, that the return on their investments would be large, and that U.S. investiga-
tors and patients would be among the beneficiaries. The fact that we could pluck
the fruits of their years of labors should not be taken for granted.
Some of the U.S. outbreaks of cyclosporiasis, most notably the series of out-
breaks associated with Guatemalan raspberries, represent a different type of slow-
growing fruit of different types of labors and investments in the 1980s. Un-
intended fruits of good intentions to address an economic problem (i.e., to
strengthen the economies of countries such as Guatemala by decreasing their
reliance on traditional export crops) ripened in the 1990s, when markedly in-
creased volumes of raspberries, a nontraditional export crop, were flown from
South to North (Herwaldt, 2000; Jackson, 2006; U.S. Senate, 1998). Unintended
fruits came in the form of widely dispersed outbreaks of cyclosporiasis, which
had economic consequences not only for raspberry growers in Guatemala (i.e.,
the raspberry business essentially went out of business) but also for collaterally

affected growers and suppliers of various types of fresh produce in countries

including the United States (Calvin, 2003; Herwaldt, 2000; Jackson, 2006).
It would be overly simplistic to consider the good intentions in the 1980s
misguided or shortsighted and to classify the fruits noted in the 1990s and there-
after as bad.19 The outbreaks and investigations have spurred the growth and
maturation of various types of good fruits, with various beneficiaries. Examples
of ripening good fruits (Table 3-4, Annex 3-2; Table 3-5, Annex 3-3) include the
ongoing processes of:
• increasing knowledge and competence (e.g., increasing understanding of

the clinical spectrum and manifestations of Cyclospora infection and developing
training tools to strengthen capacity related to parasitic diseases in general and
cyclosporiasis in particular); and
• developing, using, evaluating, and improving various generic and
Cyclospora-specific tools (e.g., diagnostic techniques for clinical specimens, ana-
lytic methods for food and environmental samples, surveillance systems, epide-
miologic survey instruments, protocols for traceback and farm investigations,
control measures).
In addition, the translation of the outbreaks into piercing wake-up calls about the
vulnerability of our food supply in general and fresh produce in particular has
been associated with maturing fruits, with industry-wide ramifications. The out-
breaks of cyclosporiasis linked to fresh produce have added to the critical mass of
data from other such outbreaks (Table 3-4, Annex 3-2) to help sharpen the focus
of the food-safety lens on produce vehicles in the United States and abroad. In
short, good science takes time but already has yielded profits that extend beyond
this particular unicellular pathogen and include science-grounded food safety
guidelines and policies (e.g., “Good Agricultural Practices” for produce).
Epilogue: The Saga Is Ongoing, More Work Needs to Be Done,

and the Workers and Resources Are Few
The work is not done just because the organism (i.e., C. cayetanensis) has
been classified by genus and christened, one highly effective therapy for cyclo-
sporiasis has been identified, our abilities to detect and investigate cases and out-
breaks have markedly improved, and specific produce vehicles and sources have
been identified in some of the outbreak investigations. Cyclospora did not grace-
fully exit after its dramatic entrance, nor has it fully emerged from obscurity into
19In 2004, the saga of cyclosporiasis circled back to Guatemala, when an outbreak was linked to
snow peas, another nontraditional export crop (CDC, 2004).

clarity. Despite scientific advances at the margins, Cyclospora remains largely

veiled in mystery; we remain plagued by fundamental unknowns and by funda-
mental constraints as we seek to convert unknowns into knowns (Table 3-3, An-
nex 3-1). Our ability to prevent contamination of produce and thereby to prevent
what we have been investigating (i.e., foodborne outbreaks) would be markedly
improved by increased understanding of the biology of Cyclospora and the epide-
miology of cyclosporiasis.
The lack of commitment to and the paucity of resources for the long-term
investments—i.e., marathons not sprints—needed to solve the many remaining
mysteries are disconcerting, especially because the ramifications of our igno-
rance and the collateral benefits of the advances to date are palpable. If for no
other reason than self-interest (e.g., to avoid the actual and opportunity costs of
investigating serial outbreaks), the need to decipher Cyclospora’s enigmatic code
is evident. Cracking the code of a microbe as hardy and resilient as Cyclospora—
e.g., identifying decontamination strategies that kill or remove the pathogen with-
out damaging delicate fresh produce—almost assuredly would have far-reaching
positive ripple effects for food safety.
One of the reverberating themes in the saga of this parasite is that the invest-
ments of “few” (e.g., the parasitologists’ mite) can result in large proceeds. Fortu-
nately, some doggedly persistent scientists are continuing to poke and prod
Cyclospora, despite the paucity of resources and oocysts, with the expectation
that ultimately it will excyst its secrets. These resilient investigators emulate the
parasite’s uncanny abilities to survive in austere microniches and to resist the
pressures and stresses in harsh macroenvironments. Relatively few persons de-
serve the credit for the fact that Cyclospora and cyclosporiasis did not emerge in
the United States as complete unknowns. In the future, which, by definition, is
unknown, relatively few persons may deserve the credit for identifying and imple-
menting an exit strategy for this inscrutable pathogen and for writing the last
chapter of the chronicle of cyclosporiasis, which now appears to have no end
in sight.
Acknowledgments
I am indebted to the countless persons who have contributed in various ways
to the marathon investigations of the U.S. outbreaks of cyclosporiasis. I reluc-
tantly acknowledge that Cyclospora, which has defined the seasons of more than
a decade of my life, has been a worthy opponent. Special thanks to my CDC
colleague, Dr. Dennis D. Juranek, for his innumerable, invaluable insights and
for his artistic contributions, most notably to Figure 3-4 and Figure 3-5.

ANNEX 3-1
104
TABLE 3-3 Cyclospora cayetanensis and Cyclosporiasis: Perspectives and Status as of April 2006
Qualifier Perspective Comments (related issues are addressed in multiple comments from various perspectives)
No No history (i.e., only a short The parasite C. cayetanensis was recently identified (first described in the late 1970s, in Papua New Guinea),
recorded history) classified in the Cyclospora genus in 1993, and christened with the species name “cayetanensis” in 1994; the
name was derived from that of a Peruvian university where key studies about this parasite had been conducted.
No precedent C. cayetanensis is the first/only species in the Cyclospora genus known to infect humans, not merely another
species in a genus known to include human pathogens.
No fulfillment of Koch’s Human volunteer studies have not been successful, nor have attempts to infect animals with homologous spp.
postulates (e.g., Papio anubis [olive baboon] with Cyclospora papionis).a In contrast: human volunteer studies have been
successful for some other enteric protozoa, including Cryptosporidium spp.
No infective oocysts in Infected persons shed immature, unsporulated oocysts, which must sporulate in the environment (i.e., outside
freshly excreted stool the host) to become infective (Figure 3-5; see below regarding extrinsic maturation period). In contrast: other
protozoa—e.g., oocysts of Cryptosporidium spp. and cysts of G. intestinalis and E. histolytica—are fully
mature/infective when shed in stool.
No risk, if consume Consumption of Cyclospora oocysts (e.g., in contaminated food) that have not yet sporulated poses no risk;
noninfective oocysts direct person-to-person (fecal-oral) transmission is highly unlikely.
No known hosts besides No natural or experimental infection of wild, domestic, or laboratory animals with C. cayetanensis per se
humans (versus other Cyclospora spp.) has been unequivocally documented; no animal models have been identified
(e.g., to study the pathogenesis of infection).

No means to assess infectivity No direct methods to assess infectivity of Cyclospora oocysts have been identified; sporulation and excystation
are indicators of viability and indirect measures of infectivity. The applicability to Cyclospora of data about
the effects of various conditions/stimuli on other coccidia is unknown (Table 3-5).
No multiplication, except in C. cayetanensis oocysts do not multiply in the environment; humans are the only known amplifying hosts, and
infected humans no in vitro cultivation systems have been developed.

No means to maintain isolates No means to maintain viable isolates have been identified (e.g., cryopreservation, serial passage in animals).
No established means for No PulseNet-equivalent exists (e.g., to link seemingly unrelated cases of infection); potential means for
strain differentiation molecular typing/strain differentiation are being explored.
No treatment alternatives No highly effective alternatives to trimethoprim-sulfamethoxazole therapy have been identified.
Not Not responsive to empiric The fact that therapy for cyclosporiasis differs from therapies for amebiasis, giardiasis, cryptosporidiosis, and
antimicrobial therapy some bacterial infections underscores the importance of diagnosing infection rather than treating empirically.
Not included in routine Specimens submitted for testing for ova and parasites usually are not examined for Cyclospora unless
parasitologic testing of stool specifically requested.b
Not enough oocysts for Acquisition of oocysts is dependent on obtaining stool specimens from infected persons, which is difficult in
research purposes general, let alone obtaining voluminous fresh stools, with plentiful oocysts, for research purposes. The
constraints are compounded by the lack of methods for propagating/maintaining viable oocysts. Contrast: The
cumulative total number of C. cayetanensis oocysts obtained for research purposes is comparable to the
quantity of Cryptosporidium oocysts shed in a few days by an infected calf.a
Long Long extrinsic maturation The process of sporulation of Cyclospora oocysts (Figure 3-5) typically requires at least one week under
period in the environment favorable laboratory conditions. The effects of real-world conditions—in micro- and macroenvironments—on
the rate of sporulation and on the survival of unsporulated and sporulated oocysts are poorly understood.
Long survival in the The needs to survive long enough both to sporulate and to be ingested by a susceptible host suggest that
environment Cyclospora oocysts are quite hardy. Whether they are even more resistant to environmental stresses than
Cryptosporidium oocysts, which do not undergo exogenous sporulation, is unknown.

Long intrinsic incubation The median incubation period in common-source outbreaks typically is ~one week (i.e., relatively long,
period after ingestion of compared with the incubation periods for most nonparasitic enteric pathogens, which adds an insurmountable
infective oocysts biologic delay to existing system delays in detecting, reporting, and investigating cases and outbreaks).
continues
105
TABLE 3-3 Continued
106
Qualifier Perspective Comments (related issues are addressed in multiple comments from various perspectives)
Long duration of illness in Gastrointestinal illness can be protracted and can wax/wane in intensity, for weeks to months, with substantial
untreated persons without weight loss and persistent fatigue (i.e., not a trivial, brief illness). The parasite and host factors that influence
prior exposure to Cyclospora the manifestations/severity of infection are poorly understood.
Long duration of shedding Even asymptomatic persons can shed oocysts, and shedding can persist >one month after symptoms resolve.
Low Low infectious dose Although not yet confirmed by human volunteer studies, the infectious dose is presumed to be relatively low,
on the basis of data for other protozoa and from outbreak investigations (e.g., seemingly trivial exposures, such
as one berry/one bite, have resulted in Cyclospora infection).
Low-level shedding of Low-level shedding (~1–2 logs lower than for Cryptosporidium spp.) is commona and underscores the utility
oocysts, even by ill persons of sensitive recovery/detection methods (e.g., UV fluorescence microscopy, acid-fast staining, PCR).b
without prior exposure to
Cyclospora
aM. Arrowood, personal communication, CDC, Division of Parasitic Diseases, February 2006.
bBoth Cyclospora and Cryptosporidium oocysts are detectable with acid-fast staining. Cyclospora (not Cryptosporidium) oocysts are autofluorescent but are
not detected by immunoassays for cryptosporidial antigens (Herwaldt, 2000).
SOURCES: Alfano-Sobsey et al. (2004); Ashford (1979); Bern et al. (1999, 2000); CDC (1998, 2004); Connor et al. (1999); Dalton et al. (2004); Dixon (2003);
Dubey et al. (1998); Eberhard et al. (1999, 2000); Herwaldt (2000); Herwaldt et al. (1997, 1999); Ho et al. (2002); Hoge et al. (1995); Huang et al. (1995); Jones
et al. (2004); Kniel et al. (2002); Koumans et al. (1998); Lee and Lee (2001); Lopez et al. (2001); Orlandi et al. (2002, 2003); Ortega et al. (1993, 1994, 1997);
Relman et al. (1996); Robbins et al. (1988); Sathyanarayanan and Ortega (2004); Steele et al. (2003); Varma et al. (2003); Vermeij et al. (2003).

ANNEX 3-2
TABLE 3-4 Characteristics of Foodborne Outbreaks and Investigations: Challenges, Opportunities, Approaches, and
Advances, in General and Specific to Outbreaks of Cyclosporiasis Associated with Imported Fresh Produce
General issues for Food vehicles: fresh Food sources: foreign
Outbreaks and outbreaks caused by the produce (generic and countries (generic and
investigations etiologic agent Cyclospora-specific Cyclospora-specific
in general C. cayetanensis issues) issues)
(cluster of cases, (germ, bug, microbe, (crop, meal, dish, entrée, (garden, plot, farm,
epidemic, scourge, pathogen, contaminant, ingredient, garnish, cooperative, firm,
plague) adulterant, poisonous/ agricultural commodity) industry, conglomerate)
(evaluation, survey, deleterious substance) (neighbor, trade partner, Comments (generic and
study, research, inquiry, competitor, outsider, Cyclospora-specific
trial) alien, foreigner) issues)
Outbreaks and Consume resources Difficult to investigate Outbreaks of Outbreaks of Local, state, and federal (e.g.,
investigations outbreaks, especially in cyclosporiasis have been cyclosporiasis have been CDC, FDA) public health
in general Provide opportunities to the mid 1990s, when linked to fresh produce linked to foreign sources agencies have different (but
identify and solve little was known about (e.g., raspberries, (e.g., Guatemala, potentially complementary)
problems (e.g., through biology of Cyclospora snow peas, basil, Mexico, Peru). roles, responsibilities,
control and prevention and epidemiology of mesclun lettuce). capabilities, and cultures with
measures), increase cyclosporiasis Context/trends: respect to food safety
knowledge and expertise, Context/trends: Globalization of food (Table 3-6). Rather than
and identify priorities Cases, clues, harbingers, Increased consumption supply; perennial fare of homogenizing the differences
for basic and applied and outbreaks easily of fresh produce (not risk produce; decreased into a single institutional
research missed, dismissed, and free) and increased reliance of middle- approach to complex food
misinterpreted proportion of reported income countries on safety issues, the power of
(Table 3-3, Figure 3-5) U.S. foodborne outbreaks traditional export crops; multifaceted, multiagency

linked to fresh produce and rapid, widespread collaborations should be
distribution of perishable harnessed.
food
continues
107
TABLE 3-4 Continued
108

Outbreaks and outbreaks caused by the produce (generic and countries (generic and Comments (generic and
investigations etiologic agent Cyclospora-specific Cyclospora-specific Cyclospora-specific
in general C. cayetanensis issues) issues) issues)
Large Difficult to manage Even large outbreaks are Even ostensibly small Large outbreaks serve as Health professionals should
outbreaks ramifications of easily missed clues can facilitate wake-up calls about consider that ostensibly
protracted illness, (serendipitously identifying vehicle/ vulnerability of food isolated or unrelated cases
(important, outbreaks, and outbreak detected); if detected, source of large outbreaks. supply. could be part of outbreaks
major, investigations (including they cannot be ignored and should notify public
pandemic) actual and opportunity (must be investigated), Linkage of implicated health officials.
costs) which translates into food vehicles to foreign
increased recognition of sources adds layers of Cyclosporiasis has been
and knowledge about complexity, sensitivity, placed on the U.S. food-
this obscure pathogen. and skepticism safety agenda and became
(Table 3-6). nationally notifiable in 1998.
Multisite, Require multiagency, Difficult to conduct Commonly noted for Provide opportunities to Multisite outbreaks of
multicluster multidisciplinary investigations and fresh produce vehicles confirm that source is cyclosporiasis spurred
outbreaks collaboration and strong coordinate public health contaminated where they only commonality (e.g., development and
central coordination of messages if sites have were grown if no commonalities in improvement of various types
(scattered, the investigations and disparate levels of distribution system) of tools for conducting and
dispersed, public health messages expertise about this Opportunities to coordinating outbreak and
diffuse, emerging pathogen and triangulate particularly Opportunities to traceback investigations
extensive, Provide opportunities to diverse thresholds for helpful, if biologic and triangulate particularly (Table 3-5) and for increasing
widespread) triangulate among making public statements epidemiologic plausibility helpful, if >one possible knowledge and competence
multiple clusters of cases about preliminary of preliminary findings source of implicated related to parasitic diseases

(i.e., to look for data/conclusions unknown and if >one food vehicle (Table 3-5) (e.g., DPDx, a telediagnosis
commonalities, not just type of produce in meal project initiated in March
statistical significance), or food item (e.g., in a 1998 by the CDC’s of
to overcome limitations salad) (Table 3-5) Division Parasitic Diseases
of individual clusters [DPD]a).
Concurrent Provide fertile soil for Provide opportunities to Can be (and have been) Can be (and have been) No PulseNet-equivalent
outbreaks shortcuts in reasoning identify more vehicle- caused by different types caused by same type of exists for C. cayetanensis to
(i.e., heuristics), such as source combinations, of produce produce from different link seemingly unrelated
(simultaneous, presumption that cases/ which can translate into countries cases (Table 3-3).
synchronized, outbreaks are related clues for hypothesis
parallel, generation
separate)
Recurrent Provide fertile soil for Provide opportunities to Can be (and have been) Strengthened evidence Recurrence of outbreak
outbreaks heuristics (see above) reevaluate data from caused by same vehicle/ can decrease skepticism linked to Guatemalan
prior outbreaks, after source (e.g., Guatemalan about conclusions, raspberries in 1997 prompted
(repeated, Provide opportunities to biologic and raspberries), same especially those derived U.S. import alert for spring of
serial, reconsider control epidemiologic vehicle/different sources from epidemiologic data 1998; outcome of inadvertent
sequential, measures, to retest boundaries known (e.g., (e.g., basil from Mexico about outbreaks that do intervention trial (Canada but
frequent, hypotheses, and to plausible incubation and Peru), and different not make intuitive sense not the United States
persistent, reevaluate data from period and modes/ vehicles/same source (e.g., no smoking guns). imported raspberries and had
ongoing, current and past vehicles of transmission) (e.g., raspberries and an outbreak) strengthened
unrelenting) outbreaks (with iterative snow peas from conclusions, decreased
feedback loops and Guatemala, mesclun skepticism, and increased
midcourse corrections) to lettuce and basil from cooperation.
strengthen evidence and Peru)
conclusions
Seasonal No “off season” for “Off season” for a Seasonality of Cyclospora

outbreaks U.S. federal-level particular region infection provides
investigators: relevant provides time to unexplained clues; in
(cyclic, season differs among (re)assess risks and Guatemala, seasonality of
periodic, cyclosporiasis-endemic control measures. infection in humans overlaps

intermittent, source countries with spring export season.
regular,
predictable)
continues
109
TABLE 3-4 Continued
110

Outbreaks and outbreaks caused by the produce (generic and countries (generic and Comments (generic and
investigations etiologic agent Cyclospora-specific Cyclospora-specific Cyclospora-specific
in general C. cayetanensis issues) issues) issues)
Outbreaks Difficult to identify Common finding for Repeatedly noting high
with high uninfected persons, cyclosporiasis; combines attack rates in outbreaks
attack rates whose exposures can be two scenarios (i.e., of cyclosporiasis has
compared with those of widespread outbreaks strengthened presumption

(many hits, infected persons and local, event- that infectious dose is
strikes, associated clusters of relatively low (Table 3-3).
casualties) cases with high attack
rates)
NOTE: In the rows in the left column and in the headings of the other columns, bolded words are sterile words used by investigators and parenthetical italicized
words are related words with different denotations and connotations. Although many of the principles are generic (i.e., not Cyclospora specific), Cyclospora adds
layers of complexity to investigations of foodborne outbreaks in general and to those caused by imported fresh produce in particular; lack of familiarity with and
knowledge about the pathogen pervades all aspects of investigations, including the implicated source’s skeptical reaction to conclusions derived from epidemio-
logic data. Also see Table 3-5 and Table 3-6.
aSee link to DPDx: http://www.dpd.cdc.gov/DPDx.
SOURCES: Bern et al. (1999, 2000); Bruzzi (2006); Buchanan (1997); Calvin (2003); CDC (1998, 2004); Fraser (1987); Hall (1997); Herwaldt (2000); Herwaldt
et al. (1997, 1999); Ho et al. (2002); Hoffman et al. (2005); Huang et al. (1995); Jackson (2006); Jones et al. (2004); Koumans et al. (1998); Lopez et al. (2001);
Novotny (2006); Ortega et al. (1993); Powell (1998); Redelmeier (2005); Sivapalasingam et al. (2004); Sobel et al. (2002); Tauxe (1997).

ANNEX 3-3
TABLE 3-5 Goals of Investigations of Foodborne Outbreaks: Challenges, Opportunities, Approaches, and Advances, in
General and Specific to Outbreaks of Cyclosporiasis Associated with Imported Fresh Produce
outbreaks caused by produce (generic and countries (generic and
Outbreaks and the etiologic agent Cyclospora-specific Cyclospora-specific Comments (generic and
investigations in general C. cayetanensis issues) issues) Cyclospora-specific issues)
Identify Can be tedious, resource- Outbreaks of Notoriously difficult to Demonstration by CDC The pertinent pathogen and
vehicles intensive process; easy to cyclosporiasis have been identify produce vehicle, and FDA of Cyclospora/ produce characteristics that,
go astray or reach dead associated with various especially if >one type DNA in frozen leftovers among other factors, account
(associate, end fresh produce vehicles, served and no of implicated food (i.e., for particular pathogen-
determine, including ones opportunities to in food items containing produce combinations are
establish, link, uncommonly linked to triangulate (Table 3-4); Mexican basil [1999] and unknown.
implicate, cite, bacterial outbreaks (e.g., complexities Guatemalan raspberries
incriminate) raspberries, basil). compounded, if served [2000]) added laboratory Public health messages
in stealthy, confirmation to already must clearly distinguish
inconspicuous ways compelling epidemiologic among types of produce
(e.g., as garnishes), evidence. (e.g., the particular
not noted on menus or type of berry or lettuce).
in recipes
Identify/ Can be tedious, resource- Outbreaks of Perishable food Notoriously difficult to The need to retrace the paths
inspect intensive process; easy to cyclosporiasis have been typically is unavailable identify source of fresh of fresh produce all the way
sources lose trail back to source associated with for analytic testing; even produce, especially if back to foreign sources
permutations and if pertinent food and >one possible source spurred CDC-FDA
(see above; Even nonimplicated combinations of perfected analytic and noopportunities to collaboration to improve and

also: probe, producers (of the same vehicles, sources, and methods (unfazed by triangulate (Table 3-4) codify epidemiologic-based
inspect, or different types of seasons. complex matrices) are procedures and protocols for
charge, food) can be spurred to available, test results Food and environmental traceback investigations and
continues
111
112
TABLE 3-5 Continued


outbreaks caused by produce (generic and countries (generic and
Outbreaks and the etiologic agent Cyclospora-specific Cyclospora-specific Comments (generic and
investigations in general C. cayetanensis issues) issues) Cyclospora-specific issues)
incriminate, improve record keeping could be negative samples obtained during farm inspections.
indict) (e.g., for tracebacks and because of spotty farm inspections might
traceforwards), to contamination. not be helpful/relevant.
minimize collateral
damage.
Identify sites/ Contamination of widely Ability to trace back to U.S. investigators and Potential interrelationships
modes of distributed vehicles at source farms translates inspectors need official among food, water, and other
contamina- their source provides into opportunities to invitations to access elements of the ecosystem, as
tiona opportunities to probe generate hypotheses farms in foreign well as the complexities
entire food chain and to about modes of countries; if regulatory intrinsic to analytic testing of
identify and strengthen contamination; use of decisions are at stake, complex matrices (e.g., food
weak links. contaminated water (e.g., regulators might have items, environmental
in mixtures of substances easier access than samples) underscore need for

, sprayed onto produce) a researchers seeking to holistic, multidisciplinary
strong consideration for explore scientific collaborations.
at least some outbreaks hypotheses.
of cyclosporiasis
Identify, Control measures in Constraints related to Need increased International Outbreaks of cyclosporiasis
implement, acute setting (e.g., to Cyclospora (Table 3-3) understanding of collaboration essential: have strengthened the
and evaluate stop transmission) might have prompted use of pathways by which entails working with precedent to act (e.g., issue
control differ from those for other coccidia as oocyst-laden feces reach foreign governments, import alerts) on basis of
measures refractory problems and potential model systems water/food and responses producers, and trade compelling epidemiologic
(interventions those that can be (e.g., Toxoplasma gondii, of pathogens, produce, organizations; explaining data (i.e., spurred the
and prevention implemented when to assess attachment and and investigators to how and why specific transition from “What is
strategies)b insights from risk survival on various types various stimuli/stresses products and sources epidemiology?” to
assessments and of berries and response were implicated; and “Epidemiologic data can
, scientific advances can to gamma irradiation, addressing concerns suffice”).

be translated into and Eimeria acervulina, about trade barriers,
targeted actions. to study decontamination blunt (e.g., countrywide)
strategies). regulatory actions, and
criteria for lifting
, sanctions
NOTE: In the rows in the left column, bolded words are sterile words used by investigators and parenthetical italicized words are related words with different
denotations and connotations. Although many of the principles are generic (i.e., not Cyclospora specific), Cyclospora adds layers of complexity to investigations
of foodborne outbreaks in general and to those caused by imported fresh produce in particular; lack of familiarity with and knowledge about the pathogen pervades
all aspects of investigations, including the implicated source’s skeptical reaction to conclusions derived from epidemiologic data. Also see Table 3-4 (including the
parenthetical italicized words in the column headings) and Table 3-6.
aNOTE: For the bolded words in this row, the two sets of related words include: (1) problem, oversight, misconception, accident, error, mistake, failure,
transgression, violation; and (2) stool, feces, manure, filth, unsanitary conditions.
bNOTE: For the bolded words in this row, the two sets of related words include (1) suggestion, recommendation, guidance, standard, warning, alert, require-
ment, mandate, sanction, regulation, enforcement action; and (2) detain, interdict, refuse entry, embargo, ban.
SOURCES: Bern et al. (1999, 2000); Bruzzi (2006); Buchanan (1997); Calvin (2003); CDC (2004); Dixon (2003); Dubey et al. (1998); Frazer (1987); Hall (1997);
Herwaldt (2000); Herwaldt et al. (1997, 1999); Ho et al. (2002); Jackson (2006); Kniel et al. (2002); Koumans et al. (1998); Lee and Lee (2001); Lopez et al.
(2001); Orlandi et al. (2002, 2003); Ortega et al. (1993); Relman et al. (1996); Robbins et al. (1988); Sapers (2001); Sathyanarayanan and Ortega (2004); Sobel

et al. (2002); Steele et al. (2003); Tauxe (1997); Varma et al. (2003); Vermeij et al. (2003); Wan et al. (1998).
113
ANNEX 3-4
TABLE 3-6 Factors that Have Complicated Efforts to Communicate About
Foodborne Outbreaks of Cyclosporiasis
Factor Issues, Themes, and Examples
Disparate perspectives about:
Food Vehicle for trade/commerce, health/nourishment, or
pathogens; something to fertilize, handle, export/
import, sell/buy, eat, sample, investigate, or
regulate
Fresh produce Good market, good source of fiber/vitamins, or
good vehicle for pathogens; something
notoriously difficult to implicate, trace back to
its source, and examine (Table 3-5)
Health (poor health) Well-being (disease), strength (weakness), vitality
(lethargy), stability (instability)
Whose matters? Persons (e.g., patients, field workers), businesses,
trading partners, economies, societies
Knowledge (ignorance) Certainty (uncertainty, doubt), determination
(underdetermination, indetermination), truth
Evidence Anecdote, historical precedent, epidemiologic data,
laboratory results (Table 3-5)
Various measures of significance and severity:

Epidemiologic Magnitudes of P values; widths of confidence
intervals; numbers of reported cases in an
outbreak and person-hours required to
investigate the outbreak
Clinical Numbers of loose stools and lost days (e.g., days of
illness, hospitalization, unemployment,
uncertainty about diagnosis, treatment with
ineffective medications [Table 3-3])
Commercial Lost reputation/customers; numbers of unharvested
fields and unsold packages of produce
Different interpretations of words/terminologies/messages because of:

Use of foreign languages Epidemiology, parasitology, food/environmental
science, economics, international law,
bureaucratic jargon, idiomatic English, Spanish
Loss of nuances during translation Distinctions among: impossible, implausible,
potential, possible, probable, and proven; and
lack of samples, lack of evidence, and evidence
of absence (Table 3-5)
Different denotations in different contexts Culture, media, report, case, power, error,
sensitivity, collaboration, gaps/GAPs (“Good
Agricultural Practices”), sporulationa
Different resonances for diverse audiences Military metaphors (e.g., food threats/hazards,
safety/security, defense/protection, mobilization/
fortification, border control/surveillance, silver
bullets, smoking guns)

TABLE 3-6 Continued

Factor Issues, Themes, and Examples
Framing effects Classification as a “them-versus-us” blame game or
a “whodunit” mystery (e.g., a game of “Clue”
solved by “disease detectives”)
Lack of clarity What does “thoroughly wash” mean, and what
does it accomplish (for contaminated fresh
produce in general and Cyclospora-contaminated
produce in particular)?
NOTE: Also see Table 3-4 and Table 3-5, particularly the examples of sterile words used by investi-
gators and related words with different denotations and connotations.
aFor coccidian parasites, such as Cyclospora: maturation to an environmentally resistant infective
stage (Table 3-3, Figure 3-5); for spore-forming bacteria: conversion to an environmentally resistant
resting stage.
SOURCES: Baron (1985); Bruzzi (2006); Calvin (2003); Dixon (2003); Fraser (1987); Herwaldt
(2000); Jackson (2006); Novotny (2006); Powell (1998); Redelmeier (2005); Sapers (2001); U.S.
Senate (1998); Sivapalasingam et al. (2004); Stone (2004); Treadway (2006).
SURVEILLANCE AND INVESTIGATION OF A LARGE STATEWIDE

CYCLOSPORA FOODBORNE DISEASE OUTBREAK
INVOLVING AN IMPORTED STEALTH INGREDIENT
Roberta Hammond, Ph.D.20 and Dean Bodager, R.S., D.A.A.S., M.P.A.21
Florida Department of Health
Background
In mid-April 2005, a private laboratory reported a dozen cases of cyclo-
sporiasis to the Florida Department of Health (FDH), Bureau of Epidemiology
Surveillance Section. The total number of cases reported in 2004 for Florida was
nine. For reporting week 14 ending April 16 (the week the positive results were
received from the private lab) the average number of cyclosporiasis cases from
2003 to 2005 was 1.67. The number of cases up to week 14, 2005, was approxi-
mately 20 percent higher than normally expected (FDH, 2005a). By reporting
week 17, the percent increase was 162 percent, a clear indication of a possible
outbreak. Cases were reported from numerous counties with no initial apparent
geographical or temporal pattern. This article will discuss the methods of the
ensuing complex investigation, epidemiological findings, and recommendations
20Statewide Coordinator, Food and Waterborne Disease Program, Bureau of Community Environ-
mental Health.
21Central Regional Environmental Epidemiologist, Food and Waterborne Disease Program, Bureau
of Community Environmental Health.

for future investigations involving outbreaks of disease resulting from intentional

or unintentional contaminants of the United States food supply.
Methods
Epidemiology teams were formed at the state and affected county levels of
the FDH. The core statewide team consisted of epidemiologists from the Division
of Disease Control and the Division of Environmental Health. A statewide lead
investigator was established for this investigation using the established organiza-
tional position of Statewide Coordinator of Food and Waterborne Diseases. The
statewide team also consisted of information management personnel, public com-
munication experts, and administrators. Each assembled county health depart-
ment team comprised county epidemiologists, environmental health personnel,
and epidemiology nurses. Each of these teams also included regional food and
waterborne disease epidemiologists and/or Florida Epidemic Intelligence Service
epidemiologists. County health department administrators were also a very sup-
portive part of the county teams. As the investigation progressed, owners and
management of the numerous affected food service establishments became inte-
gral parts of the investigation, supplying the investigators with critical informa-
tion pertaining to product and patrons. The FDA, the CDC Division of Parasitic
Diseases, the Florida Department of Agriculture and Consumer Services, and the
Department of Business and Professional Regulation also provided valuable as-
sistance with consultation, formal traceback, investigation of food service facili-
ties, and farm investigation activities.
Laboratory analysis of clinical specimens originated with private laborato-
ries. Florida has had numerous previous experiences with Cyclospora outbreak
investigations and, due to prior misidentification issues, understood the necessity
of confirming the findings of private laboratories. Table 3-7 depicts a listing of
previous outbreaks in Florida, other states, and other countries. Thus a system
was set up whereby private laboratory results were sent to a single FDH coordina-
tor. The private laboratories were also asked to send their slides to the FDH Bu-
reau of Laboratories in Jacksonville for confirmation. Laboratory results were
provided daily, sometimes up to 30 per day or more. This process also allowed
for the opportunity to ensure completeness of information on cases. The FDH’s
lab confirmation coordinator provided information for out-of-state cases to the
CDC laboratory.
A web-based data collection system was inaugurated in order for individual
county health department epidemiology staff to directly enter case information
into a database for quick, real-time analysis. The web-based system is a module
designed for outbreak investigations that is part of Florida’s statewide electronic
reportable disease management system. The outbreak database included demo-
graphic and exposure variables and was monitored in real time by the lead inves-
tigator. Florida residents who were confirmed cases and entered into the web-

TABLE 3-7 Selected History, Cyclospora Outbreaks, and Vehicles: Florida,

National, and International
Year Location Vehicle
Florida
1996 Palm Beach County (primarily), multiple Raspberries
clusters, part of multistate outbreak
1997 Leon County Mesclun lettuce
1997 Orange County Mesclun lettuce
1999 Palm Beach County Undetermined (multiple fruits)
National
1990 Chicago Contaminated tap water
1996 Multistate Raspberries
1997 Multistate Raspberries
1997 N. Virginia/Baltimore/Washington, D.C. Fresh basil
2004 Pennsylvania Snow peas
International
1992 Nepal Untreated water
1998 Canada Raspberries
2005 Canada Fresh basil
SOURCE: FDH (2004); CDC (1996a,b; 1997a,b; 1998; 2004); Sterling and Ortega (1999).
based outbreak module automatically were also entered into the disease reporting
system.
Communication of outbreak investigation progress and current descriptive
data were electronically mailed regularly to appropriate FDH administration staff
and investigation team members as well as to other state agency partners. Routine
and timely updates were also posted on the FDH disease alert notification system,
EpiCom, which is accessible by external partners in addition to all department
staff. The CDC equivalent system, EpiX, was utilized for solicitation of out-of-
state cases and communication nationwide. Press releases were also employed as
needed, discussing the statewide number of cases, organism ecology, and meth-
ods of reducing risk of illness to the public.
The case definition for this outbreak investigation was a probable or con-
firmed case of Cyclospora infection, using the surveillance case definition, with
onset since March 1, 2005, in a resident of or visitor to Florida. The FDH surveil-
lance case defines a confirmed case as a clinically compatible case that is labora-
tory confirmed; the FDH defines a probable case as a clinically compatible case
that is epidemiologically linked to a confirmed case.
Investigation Summary
Dates of exposure in the clustered cases ranged from March 19 to May 15,
2005. Dates of onset in the clustered cases ranged from March 24 to June 24,

2005 (see Table 3-8). Dates of onset of both sporadic and clustered cases ranged
from March 1 to July 10, 2005 (see Figure 3-6). Predominant symptoms included
diarrhea (78.5 percent), fatigue (64 percent), and abdominal pain (61.8 percent)
(see Table 3-8). Over 75 percent of the cases were older than 40 years of age, 81
percent of the cases were Caucasian, 79 percent non-Hispanic, and 57 percent
were female. Each case was asked a series of risk factor questions including a
long list of various raw fruits and vegetables, other foods, and travel histories.
The widespread nature of the cases and the lack of any readily apparent common
food item was a strong indicator of a widely distributed food. The only weakly
significant preliminary risk factors were iceberg lettuce (OR = 2.94, 95% CI 1.17–
7.42; P < .02) and limes (OR = 8.54, 95% CI 1.13–64.79; P < .02). Initially all the
cases appeared to be sporadic, but eventually some clusters emerged (see Table
3-8). Investigation of three of these clusters, from Pinellas, Flagler, and Sarasota
Counties were used to determine the implicated food product. The Palm Beach
County and the Orange County cluster investigations had inconclusive results.
The first cluster to emerge was the Pinellas County cluster, associated with
consuming food at chain restaurant A. In this cluster, there was a total of 42 cases
(17 laboratory confirmed, 25 probable). The range of exposures was from April 1
to 2, 2005. The range of dates of onset was March 25–April 23, 2005. The impli-
cated menu item was herb-flavored oil used for bread dipping with the following
ingredients: olive oil, fresh basil, Italian parsley, rosemary, and fresh garlic (OR
= 52, 95% CI 8.99–300.78; P < .0000001411 Fischers exact). During the investi-
gation of the cluster associated with chain restaurant A, another small cluster
became apparent at a different chain restaurant owned by the same company. A
total of eight cases (four confirmed, four probable) was linked to this second
TABLE 3-8 Cyclospora Clusters, Florida 2005: Range of Dates

of Exposure, Dates of Onset, Confirmed and Probable Cases
County Exposure Onset Confirmed Probable
Pinellas # 1 4/1–4/2 3/25a–4/23 17 25
Pinellas # 2 4/1–4/9 4/5–4/18 7 7
Flagler 4/1–4/12 4/9–4/21 16 4
Sarasota # 1b 3/19–4/17 3/24–4/21 17 78
Palm Beach 4/10 4/13–4/18 4 7
Sarasota # 2 5/5–5/15 5/9–6/24 6 28
Orange 5/2–5/6 5/4–6/8 4 61
Totals 71 210
aThe 3/25 case is included due to presumed recall bias by the case as to when
symptoms began.
bIncludes a sporadic, community group that ate at the independent restaurant, plus
four subclusters that ate food catered from the same restaurant.
SOURCE: FDH (2005b).

Outbreak Epi Curve Weekly

120
101
100
84
80
80 74
61
Count
60
41 42
40 33
20
9 10
5 3
1 1 2 0 0 0 0 1
0
5
05
20 05
27 5
4/ 05
10 05
17 5
24 5
5/ 05
5/ 05
15 5
22 5
29 5
6/ 05
12 05
19 5
26 5
7/ 05
10 5
5
00
3/ 00
4/ 00
4/ 00
5/ 00
5/ 00
5/ 00
6/ 00
6/ 00
7/ 00
00
20
0
20
0
20
0
20
0
/2
/2
/2
/2
/2
/2
/2
2
/2
/2
/2
/2
/2
/2
2
/2
6/
3/
1/
8/
5/
3/
27
13
3/
2/
3/
3/
4/
6/
Date Onset
FIGURE 3-6 Epidemiology curve by week of onset, Florida 2005 Cyclospora outbreak.
NOTE: The epidemiology curve is by week of onset, thus the first case of March 1 oc-
curred during the week of February 27–March 5, 2005.
SOURCE: Florida Department of Health (2005b).
cluster. The implicated item in the second cluster was bread dipping oil mixed
with pesto. Both restaurants from different chains receive Italian parsley and fresh
basil from the same distributor.
The second cluster, in Flagler County, was associated with consuming food
at an independent restaurant. This cluster had a total of 20 cases (16 confirmed, 4
probable) with exposures ranging from April 1 to 12, 2005. The Flagler County
cluster investigation also implicated a flavored bread dipping oil with the follow-
ing ingredients: olive oil, fresh basil, fresh garlic, and parmesan cheese (OR = 27,
95% CI 2.29–534.3; P = .002).
The Sarasota County cluster is really five separate doctor’s offices whose
staffs were provided catered lunches from the same independent restaurant by
drug company representatives. There was an additional sporadic group associated
with eating at the same independent restaurant. Exposures ranged from March 19
to April 17, 2005, and dates of onset from March 24 to April 21, 2005. While no
single, statistically significant food item was identified, an ingredient can be im-
plicated through the food histories. All five medical groups were served a lunch
of meat wraps, vegetable wraps, and Greek salad, all with sun-dried tomato vin-
aigrette. The sporadic cases ate at the restaurant where Greek salad, Moroccan

salad, and cucumber salad were on the menu. The Greek salad, meat wrap, and
veggie wrap all contained sun-dried tomato vinaigrette with the following ingre-
dients: olive oil, balsamic vinegar, sun-dried tomatoes, fresh onions, salt and pep-
per, and fresh basil. The inability to generate a statistically significant food is
attributed to the lack of controls available for the case-control study, the sus-
pected food ingredient being in multiple menu items and lack of recall for food
histories.
A short questionnaire was administered to 35 confirmed Cyclospora cases
picked at random from the sporadic outbreak cases in various areas of the state to
assess fresh basil consumption habits. Five cases were selected from each of
seven areas. Questions were asked pertaining to exposure to herbed green salads,
basil, herbs, bruschetta, pesto, and pasta salads. There were also three questions
related to visiting Italian, Thai, and gourmet restaurants that commonly serve
dishes with fresh basil or fresh basil garnish. The frequencies of response to the
questions included two questions that had more than 50 percent of respondents
answering affirmatively. These were eating at Italian restaurants (64.7 percent)
and bread dipped in oil with fresh herbs (68.8 percent). An analysis of these two
variables showed significance in going to an Italian restaurant and having bread
dipped in olive oil with fresh herbs. The Fisher exact value was P = .03. Eighty-
one percent of the 31 cases who responded to both questions had visited an Ital-
ian restaurant where the practice of dipping bread was customary and where they
ate bread in this manner. The FDH, in consultation with epidemiologists at CDC
and FDA, requested a formal traceback of the fresh basil based on the signifi-
cance of the findings of the three disease cluster investigations and the random
case-control study.
Results
This disease outbreak was caused by Cyclospora cayetanensis, a single-celled
protozoan with symptoms of watery diarrhea, nausea, loss of appetite, abdominal
pain, fatigue, and weight loss. The case fatality rate is very low. The incubation
period is one to seven days, usually about one week, and the ensuing illness can
last anywhere from one to three weeks. Typical vehicles include raspberries, ba-
sil, lettuce, snow peas, and water. Though water has been implicated, 90 percent
of outbreaks of cyclosporiasis are foodborne. Cyclosporiasis is endemic in many
developing countries and is often associated with diarrhea in travelers to Asia, the
Caribbean, Mexico, and Peru (Heyman, 2004).
The implicated food item in this outbreak was fresh basil imported from
Peru, a widely distributed food ingredient used raw in many salads, sauces, and
garnishes (Food Track Inc., 2005). It has been called a “stealth” ingredient by
many because unless one knows the ingredients of a particular menu item, one
might not remember having eaten it. Anecdotal evidence from a visit to the impli-
cated farm in Peru indicates that farm conditions could have been conducive to

FIGURE 3-7 Laboratory-confirmed and probable cases of cyclosporiasis by state of resi-

dence, March–June 2005, Cyclospora outbreak, Florida.
opportunities for contamination of the basil. There was a total of 592 cases with
365 confirmed and 227 probable. The investigated illness clusters accounted for
71 confirmed and 210 probable cases (see Table 3-8). A total of 493 cases were
residents of Florida with 10 cases in Canadian residents and 89 residents of other
states, all having visited Florida during their exposure period. Refer to Figure 3-7
and Figure 3-8 for details on geographical distribution of cases nationwide and in
Florida. All out-of-state cases were visitors to Florida who were exposed in
Florida during their incubation period.
Conclusion
Due to the nature of this widely distributed stealth ingredient used raw in
many common foods, this outbreak was large and diffuse and the investigation
thereof was exceedingly complex, involving the entire Regional Environmental
Epidemiology Strike Team, the FDH Bureau of Laboratories, staff from the Bu-

FIGURE 3-8 Laboratory-confirmed and probable cases of cyclosporiasis by Florida

county of residence, March–June 2005, Cyclospora outbreak, Florida.

reau of Epidemiology and all county health departments who reported cases. The
FDH also collaborated with multiple partners in this outbreak investigation in-
cluding private laboratories who reported cases, the Florida Department of Busi-
ness and Professional Regulation, the Florida Department of Agriculture and
Consumer Services, the FDA, and the CDC’s Division of Parasitic Diseases.
It can be expected that similar or more spectacular disease outbreaks will be
seen in the future due to increased global distribution of foods (particularly stealth
ingredients such as basil), shifts in consumption towards raw consumption of
these ingredients, unusual ingredients and recipes, and the increased expectation
for availability for out-of-season produce from other countries. The importation
of foods from underdeveloped countries possibly with insufficient potable water
supplies and processing sanitation standards is also a significant factor in these
types of outbreaks. The potential for large outbreaks of this kind is great in Florida,
given the large population (18 million) and the estimated annual number of visi-
tors (74.5 million). The FDH continues to conduct surveillance for Cyclospora
cases along with other emerging and reportable pathogens in order to discover
outbreaks early in their occurrence so that their cause can be discovered and
further spread of illness can be prevented. FDA continues its ongoing efforts in
working with produce-exporting countries to ensure that produce exported to this
country is safe and free from disease (FDA, 1998, 2001, 2003c, 2004; DOT and
HHS, 1999).
Recommendations
Accurate laboratory analysis is critical in determining the etiological agent
and scope of any foodborne outbreak. It should be noted that in this particular
investigation only one clinical sample was initially misidentified as a crypto-
sporidium. It is imperative that public and private laboratories have the capability
to accurately detect and quantify emerging pathogens and threats to our food
supply as quickly as possible. These analytical and technical capabilities must
include all biological, chemical, natural, and intentional threats. Public health
laboratory systems need to facilitate and lead in this endeavor. Public funding
allocations must reflect these high priorities for detection of food safety threats. It
is also important for owners/managers and personnel at private laboratory con-
cerns to be educated on their important role with disease surveillance and out-
break investigations and “buy in” to the investigation and critical communication
processes and keep all staff apprised of this responsibility.
While the web-based system used for the data collection for cases for this
outbreak investigation was somewhat helpful in rapidly collecting data from a
wide geographical area, it was determined to have limited capabilities to collect
control data, perform multiple variate analysis easily, and be conducive to easy
manipulation of data for analysis. The limited flexibility of the design resulted in
duplication of investigation and analytical efforts during some phases of the

investigation. When designing and testing such elaborate systems, information

technologists and software designers should include epidemiologists and other
technical experts on the design and use. Scientists should also welcome and un-
derstand that programmers and data system designers should also be a part of the
planning process of responding to natural and man-made biological events. Re-
sources also need to be devoted and planned to include training of end users of
these types of systems.
It should be noted that Florida was able to successfully investigate this ex-
tremely large and complex outbreak using epidemiology, nursing, laboratory, and
environmental health personal within the existing organizational structures. Many
resources at the county and state level in multiple scientific disciplines have been
developed in the past 10–12 years that permitted this to happen. State and local
municipalities who have the responsibility to conduct the surveillance, investiga-
tion, and reporting of diseases, both natural and intentional, that negatively im-
pact public health must obtain funding to secure the human resources and de-
velop the expertise to respond to large-scale threats to human health.
Acknowledgments
The following people provided their extensive skills and expertise with the
successful investigation and reporting of this extremely large foodborne disease
outbreak: Kathleen Ward, R.S., M.S.E.H., Bureau of Community Environmental
Health; Mike Friedman, M.P.H., Bureau of Community Environmental Health;
Robin Terzagian, Bureau of Community Environmental Health; Janet Wamnes,
M.S., Bureau of Community Environmental Health; Juan Suarez, Bureau of Com-
munity Environmental Health; Carina Blackmore, Ph.D., D.V.M., Bureau of
Community Environmental Health; Richard Hopkins, M.D., M.P.H., Bureau of
Epidemiology; Joann Schulte, D.O., M.P.H., Bureau of Epidemiology; David
Beall, Ph.D., Bureau of Laboratories; Doc Kokol, Public Information Officer;
Lindsay Hodges, Public Information Officer; Maria Donnelly, M.S.P.H., Pinellas
County Health Department; Sue Heller, R.N., B.S.N., Pinellas County Health
Department; Hunter Zager, Pinellas County Health Department; Joe Zwissler,
Pinellas County Health Department; Rick Barrett, Pinellas County Health De-
partment; Kelly Granger, M.P.H., Hillsborough County Health Department;
Aimee Pragle, M.S., Nassau County Health Department; Andre Ourso, M.P.H.,
Volusia County Health Department; Quintin Clark, Sarasota County Health De-
partment; K. Eric Stutz, M.P.H., R.S., Sarasota County Health Department; Maria
Teresa Bonafonte, Ph.D., Palm Beach County Health Department; Dawn Ginzl,
M.P.H., Orange County Health Department; Bill Toth, M.P.H., Orange County
Health Department; Barbara Herwaldt, M.D., M.P.H., CDC, Division of Parasitic
Diseases.

HEPATITIS A OUTBREAKS FROM GREEN ONIONS

Beth P. Bell, M.D., M.P.H.22 and Anthony E. Fiore, M.D., M.P.H.23
During the fall of 2003, several distinct foodborne hepatitis A outbreaks oc-
curred, including the largest such outbreak reported in the United States (Amon et
al., 2005; Wheeler et al., 2005). In total, the outbreaks involved over 1,000 cases
and at least three deaths. Most cases resulted from exposures in a small number of
restaurants, with over 600 cases reported among patrons of a single restaurant in
Pennsylvania. In each outbreak, the implicated food item was green onions im-
ported from Mexico. As a result, the FDA imposed an import ban on green onions
from the farms potentially implicated in the outbreaks (FDA, 2003a).
The outbreak investigations demonstrate a new use of molecular surveillance
for hepatitis A virus (HAV) strains. Although green onions were implicated in
each outbreak, the timing of the outbreaks suggested that at least two separate
instances of green onion contamination occurred. This was the extent of the infor-
mation that could be gleaned from the epidemiologic investigation. A more de-
tailed understanding of the relationships among the outbreaks, gained by building
on ongoing molecular surveillance, informed the traceback and affected the course
of the ongoing investigations.
Features of Hepatitis A Virus Infection

Several key features of HAV infection provide the context for the outbreaks
and are relevant to any consideration of prevention strategies (Fiore, 2004). After
an incubation period that averages 28 days but can range from 15–50 days, HAV
infection can present in a number of different ways, ranging from asymptomatic
infection; to nonspecific symptoms such as nausea, abdominal pain, and fatigue;
to jaundice and other classical symptoms of acute hepatitis. The likelihood of
symptomatic infection and of jaundice is directly related to age; young children
with HAV infection are unlikely to have a clinical illness recognizable as acute
hepatitis. The period of communicability extends from about two weeks before
until about one week after jaundice occurs, and HAV can be excreted in very high
concentration in the stool of infected people (e.g., about 1 billion particles per
gram). HAV in organic material is stable in the environment at least for a period
of weeks.
22Division of Viral Hepatitis.

23Division of Viral Hepatitis.
24The findings and conclusions in this manuscript have not been formally disseminated by the CDC
and should not be construed to represent any agency determination or policy.

Molecular Surveillance
In the investigations described here, we used molecular subtyping to charac-
terize outbreak-related HAV strains as they became available and to explore their
relationship to each other and to strains identified in the context of ongoing mo-
lecular surveillance projects in the United States and Mexico. We use nested
reverse transcription polymerase chain reaction (RT-PCR) to amplify a 315 nucle-
otide segment at the VP1-2a junction of strains from persons with hepatitis A
onset between January 2002 and August 2003, collected through the six counties
comprising the Sentinel Counties Study of Acute Viral Hepatitis, and through the
Border Infectious Disease Surveillance (BIDS) Project, which operates along the
U.S.-Mexico border (Amon et al., 2005)
At the time the outbreak investigations began, this database included over
100 distinct sequences from over 500 individuals. Approximately 95 percent of
the distinct sequences, representing 99 percent of specimens, were genotype 1A
(Figure 3-9) (Amon et al., 2005). The majority of these distinct sequences formed
a single cluster, in which all sequences were >96 percent similar to each other
(cluster X). This cluster included sequences from all individuals identified through
the BIDS project, as well as from travelers to Mexico. Particular risk factors
predominated in other clusters, such as being a homosexual man or using illicit
drugs (Figure 3-9).
Outbreaks in Tennessee, North Carolina, and Georgia

The first series of outbreaks involved over 400 cases and occurred in Tennes-
see, North Carolina, and Georgia during August to September 2003 (Amon et al.,
2005). In Tennessee and North Carolina, investigations indicated that cases were
associated with one restaurant in each state, but the restaurants were unrelated to
FIGURE 3-9 Comparison of hepatitis A viral sequences among individuals with hepatitis
A from northern Mexico (Border Infectious Disease Surveillance [BIDS] Project), 2002–
2003; outbreak-related surveillance, October–December 2003; and six U.S. sentinel county
sites, January 2002–August 2003.
NOTE: Numbers in ( ) indicate the number of samples with an identical sequence identi-
fied from the same surveillance source. Bars are color coded according to the source of the
sample, or, for samples identified through sentinel counties surveillance, by the reported
hepatitis A risk factors. Multicolored bars indicate, by the size of each colored segment,
the proportion of individuals with an identical sequence reporting a hepatitis A risk fac-
tors, or with no identified risk factors. Abbreviations of countries of travel outside of
North America: PHI: Philippines; IND: Indonesia; EC: Ecuador; VEN: Venezuela. X rep-
resents a cluster of sequences >96 percent similar to one another.
SOURCE: Amon et al. (2005).


¶¶¶¶¶¶ ¶¶ ¶ (8)
¶¶¶¶ ¶ ¶¶¶¶ (15)
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
(174) SEQUENCE D
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
HAV SEQUENCE ANALYSIS ¶¶¶¶¶¶¶¶¶

¶¶¶¶¶¶¶¶¶
(153) SEQUENCE B
¶¶¶¶¶¶¶¶¶ (20)
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
(34) SEQUENCE A
¶¶¶¶¶¶¶¶¶
1/2002–12/2003 BIDS PROGRAM (n=78) ¶¶¶¶¶¶¶¶¶

¶¶ ¶¶¶¶¶¶¶ (4)
¶¶¶¶¶¶¶¶¶ (2)
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶ Northern Mexico Residents ¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶ (4)
10–12/2003 OUTBREAK SURVEILLANCE (n=394) ¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶ (4)
¶¶¶¶¶¶¶¶ Outbreak Sequences ¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶ Outbreak -related Sequences ¶¶¶¶¶¶¶¶¶

¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶ Other Sequences ¶¶¶¶¶¶¶¶¶

¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
1/2002 – 8/2003 SENTINEL COUNTIES (n=115) ¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶ Travel to Mexico/Guatemala ¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶ Travel Outside N. America ¶¶¶¶¶¶¶¶¶

¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶ Drug Use ¶¶¶¶¶¶¶¶¶

¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶ MSM ¶¶¶¶¶¶¶¶¶

¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶ No Identified Risk Factors ¶¶¶¶¶¶¶¶¶

¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
X ¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶ (4)
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶ (3)
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶ ¶¶ (25)
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶ (2)
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶ ¶¶¶ ¶¶¶ (4)
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶ (3)
¶¶¶¶¶¶¶¶¶ (6)
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶ VEN
¶¶¶ ¶¶¶¶¶¶ (9)
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶ PHI
¶¶¶¶¶¶¶¶¶ IND
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶ ¶¶¶¶ (2)
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
1A ¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶
¶¶¶ ¶¶¶ ¶¶¶ (17)
¶¶¶¶¶¶¶¶¶ (2)
¶¶¶¶¶¶¶¶¶
¶¶¶¶¶¶¶¶¶ EC
5% 4% 3% 2% 1% 0%


Number
Date
FIGURE 3-10 Date of illness onset among restaurant patrons, September–November

2003; n = 590. The dotted bars represent Tennessee (TN) cases, the hatched bars North
Carolina (NC) cases, the diagonal striped bars Georgia (GA) cases, and the solid bars
Pennsylvania (PA) cases.
SOURCE: Bell (2005).
each other. Ill food service workers identified in each outbreak had illness onset
concurrent with other cases, indicating that they could not have been sources of
the outbreaks. Most cases in Tennessee reported an onset of illness during the
first week in September. The peak in North Carolina was about a week later. In
Georgia, at least three restaurant-associated clusters were identified, but informa-
tion about many of the cases that shared the outbreak strain was incomplete. An
epidemiologic investigation of the largest of these clusters showed that dates of
onset were similar to those in North Carolina (Figure 3-10). Exposures at each
restaurant occurred primarily during a 10-day period in August, and green onions
were implicated as the source in case-control studies among restaurant patrons in
each state. In the case-control study in Tennessee, for example, green onions
were eaten by 98 percent of 57 case-patients and 46 percent of 204 control sub-
jects (OR = 65.5, 95% CI 8.9–482.5). The epidemiologic investigations were

conducted during late September and early October, and the FDA initiated
traceback investigations on October 9.
Sera obtained from outbreak-related cases in the three states yielded two
distinct outbreak strains (sequence A and B) (Figure 3-9). Sequence A was found
among restaurant patrons from Tennessee, and sequence B was found among
Georgia and North Carolina cases. Both sequences fell into cluster X, the same
cluster of strains that also included most strains identified among persons who
acquired illness in Mexico.
Pennsylvania Outbreak
In early November, as the epidemiologic investigations were winding down
and the traceback investigations were underway, an outbreak in Pennsylvania
occurred, eventually involving a total of more than 600 cases among patrons of a
single restaurant in Beaver County, including 13 employees who became ill at the
same time as patrons (Figure 3-10) (Wheeler et al., 2005). Over 80 percent of the
425 case-patients who reported eating only once at the implicated restaurant ate
there between October 3 and October 6, including 67 percent who dined on Octo-
ber 4 or October 5. The estimated attack rate for the four-day period was 17.9
percent, including an estimated 25 percent of diners on October 4 and 29 percent
of diners on October 5.
A case-control study among patrons at the restaurant included 181 cases and
89 controls. Five of the 121 menu items were associated with illness. Mild salsa
was eaten by 91 percent of case-patients and 35 percent of controls (OR 19.6,
95% CI 11.0–34.9) and was the only item eaten by more than 25 percent of case-
patients. Eating green onions, an ingredient in over 50 menu items, was reported
by 98 percent of case-patients and 58 percent of controls and was strongly associ-
ated with illness (OR 33.3, 95% CI 12.8–86.2). The final multivariate model
included age, eating mild salsa, and eating any other menu item containing green
onions.
Green onions arrived at the restaurant in bundles of six to eight onions each,
packed on ice in boxes. After unpacking into metal pans, they were stored in the
refrigerator for up to five days. When needed, bundles were rinsed with tap water,
the rubber band around the bundle was removed, and the onions were chopped
using an electric dicer. After chopping, they were refrigerated in plastic contain-
ers for up to two days.
Mild salsa, the menu item most strongly associated with infection, was pre-
pared in 40-quart batches. The restaurant prepared up to two batches each day,
and stored them for up to three days in the refrigerator. Each quart contained six
ounces of raw chopped green onions, equivalent to 10–16 whole green onions.
Of course a pressing question was the relationship, if any, of this outbreak to
the outbreaks that had occurred earlier in the fall. Molecular surveillance results
obtained to date had pointed to the likelihood of two separate instances of con-

tamination accounting for these earlier outbreaks. The outbreak strain from cases
associated with the Pennsylvania outbreak (sequence D, Figure 3-9) turned out to
be distinct from but closely related to the other outbreak strains, and fell into the
same cluster of Mexico-related strains. These findings established that the four
geographically separate but temporally related outbreaks represented at least three
distinct events.
Other States
Not all hepatitis A is foodborne, and a common question that arises in the
context of many foodborne hepatitis A outbreaks is the extent to which available
surveillance methods are sensitive enough such that outbreak-associated cases or
small clusters can be distinguished from “background” cases. This is particularly
relevant for outbreaks, such as those described here, that are associated with a
distributed food item, but in which the majority of cases are associated with expo-
sure at a restaurant. Another “first” accomplished in the context of these investi-
gations was an improvement in the sensitivity of surveillance by incorporating
molecular methods. Comparison of strains identified during the outbreak period
provided evidence that some apparently “sporadic” hepatitis A cases were indeed
foodborne. Specimens were requested from any cases that did not have an identi-
fied source of transmission. Of over 50 specimens submitted, a number were
identical to outbreak strains (Table 3-9) (Amon et al., 2005).
TABLE 3-9 Source and Distribution of Cluster X Hepatitis A Virus

Sequences, September–December 2003 (Outbreak Surveillance Specimens) and
January 2002–August 2003 (Sentinel Counties and Mexico [BIDS*]
specimens); n = 478
Cluster X
non-A, B, D Sequence A Sequence B Sequence D
(n = 73) (n = 54) (n = 154) (n = 197)
Outbreak surveillance TN – 32 – –
PA/OH/WV – – – 170
NC – – 10 –
GA – 1 122 –
Other 8 1 21 4
U.S. Sentinel Counties 23 – – 8
Mexico (BIDS)* 42 20 1 15
NOTE: TN, Tennessee; PA, Pennsylvania; OH, Ohio; WV, West Virginia; NC, North Carolina; GA,
Georgia. *BIDS—Border Infectious Diseases Surveillance System.
SOURCE: Amon et al. (2005).

Investigation of Farms
Findings of molecular surveillance were consistent with sources in Mexico,
as sequences matching each of the outbreak strains were identified from among
BIDS specimens (Table 3-9). Four farms, all located in northern Mexico, poten-
tially supplied the implicated restaurants, but no single farm could explain all
four outbreaks. These traceback results were consistent with the results of se-
quencing—three distinct strains were identified from outbreak-associated cases
in the four states.
Representatives from the FDA and CDC visited the farms in question (FDA,
2003b). The harvesting procedure included a lot of handling of the onions, which
were pulled from the ground by hand, after which the outer layer was peeled off,
the roots were removed, the onions were cut to a consistent size, and they were
banded into bunches. Packing involved spraying bunches with chlorinated water
as they passed on a conveyor belt, followed by loading into a cardboard box
which was topped with chipped ice. In the distribution network, boxes generally
were not handled between the farm and the restaurant destination. A number of
conditions on the farm were identified as areas of concern, including poor sanita-
tion, inadequate hand washing facilities, worker health and hygiene, the quality
of the water used in the fields at packing sheds, and the ice-making process.
However, no single practice or event was identified that could have explained the
outbreaks.
Because HAV has no animal host, the original source of green onion con-
tamination was a human infected with HAV and excreting the virus in stool. This
fecal contamination could occur in a number of ways. Adults with contaminated
hands could have touched the green onions during harvest or processing. Hepati-
tis A is endemic in Mexico, which means that the vast majority of the population
is infected during childhood, and most adults are immune (Tanaka, 2000). Hence
the majority of infections at any given time are occurring among children. Thus
likely sources of contamination of hands include sewage or feces from workers’
HAV-infected children. It is also possible that HAV-infected children were
present in the fields and contaminated the green onions directly. Direct contami-
nation of the growing areas by sewage is also possible.
Discussion
The outbreaks described here were investigated rapidly and tracebacks were
initiated early. However, a number of features of hepatitis A make detection and
control of foodborne hepatitis A difficult, and the results of these investigations
illustrate important areas of progress and remaining challenges (Fiore, 2004).
Because HAV contamination of foods can be focal and the virus remains viable
in the environment for months, cases can be both geographically and temporally
dispersed. These investigations demonstrate the benefits of wider and faster use

of molecular epidemiologic methods, both in outbreak investigations and in the

context of routine hepatitis A surveillance. Viral sequencing showed that four
geographically separate outbreaks that occurred in the fall of 2003 represented at
least three distinct events. Sequencing activities also improved the sensitivity of
surveillance to define the scope of the outbreaks, distinguish outbreak-related
from nonoutbreak-related cases, and identify evidence of sporadic unrecognized
foodborne transmission. Finally, viral sequencing supported the results of the
first traceback investigations and accelerated control efforts related to the out-
break in Pennsylvania.
The investigations also exemplify challenges in foodborne hepatitis A out-
break response that stem from characteristics of routine hepatitis A surveillance
and inherent aspects of the infection itself. Because cases reported through rou-
tine surveillance are not typically asked about foodborne exposures, the recogni-
tion of an unusual increase in the number of cases or of cases occurring among
those in an unusual demographic group serves to alert authorities to begin asking
about foodborne exposures as one potential common link among cases. However,
even with the most rapid response and investigation of clusters of cases, the long
incubation period of hepatitis A and inevitable delays in diagnosis and reporting
necessitate a considerable lag time between exposure and the earliest possible
detection of a foodborne outbreak. For example, the exposure that resulted in the
outbreak in Pennsylvania was occurring as cases associated with the previous
outbreaks were just being reported in the other states. Thus, even if a farm impli-
cated in the earlier outbreaks had been linked to a farm implicated in the Pennsyl-
vania outbreak, it is unlikely that even the most rapid of responses to the earlier
outbreaks could have averted the subsequent outbreak in Pennsylvania.
Green onions are emerging as a potential “problem” food, having been im-
plicated in at least two previous restaurant-associated hepatitis A outbreaks
(Dentinger et al., 2001; Datta et al., 2001). The vast majority of green onions
consumed in the United States are imported from Mexico, a country in which
hepatitis A is endemic (Calvin et al., 2004). They require extensive handling
during harvest and may be particularly difficult to clean. A pattern of focal, low-
level contamination in which possibly very few bunches were contaminated, may
make it difficult to detect transmission when it occurs.
The outbreak in Pennsylvania illustrates how conditions at the point of sale
can amplify an outbreak. A combination of factors probably contributed to this
outbreak’s size and high attack rate. The large number of diners who ate at the
restaurant during the days of peak exposure were all offered mild salsa, the food
item most strongly associated with illness. Preparation practices, such as rinsing
green onions while they are still bundled and chopping and storage methods that
allowed for cross-contamination, could also have contributed to the size of the
outbreak. Because of the high concentration of HAV in stool and the likely low
infectious dose, even a small amount of fecal contamination might result in many
hundreds of infectious doses. Although the 2005 Food Code includes a require-

ment that vegetables that are not subsequently cooked be washed, it does not
offer guidance about specific methods to prevent cross-contamination of produce
(HHS, 2005).
Progress has been made in developing methods to detect HAV in food, in-
cluding reproducible methods to detect the virus in “spiked” food samples and
produce washes (Shan et al., 2005). Although theoretically attractive, there are a
number of difficulties inherent in attempting to detect HAV in produce. The virus
does not multiply in foods, and the concentration may be quite low. However,
viral culture is not feasible, so there is a need to rely on RT-PCR techniques,
which may not perform consistently in the presence of complex food mixtures.
Further, RT-PCR cannot distinguish infectious HAV from noninfectious HAV
RNA. Even if these technical problems were solved, HAV detection in food is
unlikely to be of much practical use in the context of outbreak investigations for
a number of reasons. Perhaps most important, particularly in the case of produce,
is that the implicated item has almost invariably been consumed or discarded by
the time illness is occurring. Further, methods are not at a level of development as
of yet such that they can be scaled up to volumes needed to be reasonably sure
that contamination is not present, particularly given the low infectious dose. Fi-
nally, these currently available methods take days to complete.
Perhaps most important is prevention of HAV (and other enteric pathogens)
contamination of produce in the first place by preventing fecal contamination of
produce on the farm. Hepatitis A is endemic in Mexico, and while the precise
mechanism of transmission in the outbreaks described here could not be deter-
mined, control measures can be implemented that could prevent such outbreaks.
These include ensuring that field workers are healthy and have access to adequate
sanitary facilities and ensuring that water used to irrigate and rinse produce is not
contaminated with feces. Children are the source of most transmission of HAV in
rural communities in Mexico and much of the developing world, and children
should not be present in areas where food is harvested. Reduction in HAV trans-
mission among children in areas where produce is grown would further reduce
opportunities for contamination.
REFERENCES
Alfano-Sobsey EM, Eberhard ML, Seed JR, Weber DJ, Won KY, Nace EK, Moe CL. 2004. Human
challenge pilot study with Cyclospora cayetanensis. Emerging Infectious Diseases 10(4):
726–728.
Allos B, Moore M, Griffin P, Tauxe R. 2004. Surveillance for sporadic foodborne disease in the 21st
century: The FoodNet perspective. Clinical Infectious Diseases 38(Suppl 3):S115–S120.
Amon JJ, Devasia R, Xia G, Nainan OV, Hall S, Lawson B, Wolthuis JS, Macdonald PD, Shepard
CW, Williams IT, Armstrong GL, Gabel JA, Erwin P, Sheeler L, Kuhnert W, Patel P, Vaughan
G, Weltman A, Craig AS, Bell BP, Fiore A. 2005. Molecular epidemiology of foodborne hepa-
titis A outbreaks in the United States, 2003. Journal of Infectious Diseases 192(30):1323–1330.

APHL (Association of Public Health Laboratories). 2003. A Recipe for Stronger Food Safety Testing
Programs. [Online]. Available: http://www.aphl.org/docs/foodsafetyreport.pdf [accessed April
12, 2006].
Ashford RW. 1979. Occurrence of an undescribed coccidian in man in Papua New Guinea. Annals of
Tropical Medicine and Parasitology 73(5):497–500.
Baron RJ. 1985. An introduction to medical phenomenology: I can’t hear you while I’m listening.
Annals of Internal Medicine 103(4):606–611.
Bell B. 2005 (October). Session III: The Food Supply “Threat Spectrum”—Case Studies: Cyclo-
sporiasis in Imported Produce—Fresh Basil. Presentation at the Forum on Microbial Threats
Workshop Meeting, Foodborne Threats to Health: The Policies and Practice of Surveillance,
Prevention, Outbreak Investigations, and International Coordination. Washington, D.C., Insti-
tute of Medicine, Forum on Microbial Threats.
Bern C, Hernandez B, Lopez MB, Arrowood MJ, de Mejia MA, de Merida AM, Hightower AW,
Venczel L, Herwaldt BL, Klein RE. 1999. Epidemiologic studies of Cyclospora cayetanensis in
Guatemala. Emerging Infectious Diseases 5(6):766–774.
Bern C, Hernandez B, Lopez MB, Arrowood MJ, de Merida AM, Klein RE. 2000. The contrasting
epidemiology of Cyclospora and Cryptosporidium among outpatients in Guatemala. American
Journal of Tropical Medicine and Hygiene 63(5–6):231–235.
Blaser MJ, Taylor DN, Feldman RA. 1983. Epidemiology of Campylobacter jejuni infections. Epide-
miologic Reviews 5:157–176.
Bruzzi JF. 2006. The words count—radiology and medical linguistics. New England Journal of Medi-
cine 354(7):665–667.
Buchanan RL. 1997. Identifying and controlling emerging foodborne pathogens: Research needs.
Emerging Infectious Diseases 3(4):517–521.
Calvin L. 2003. Produce, food safety, and international trade: Response to U.S. foodborne illness
outbreaks associated with imported produce. In: Buzby J, Ed. International Trade and Food
Safety: Economic Theory and Case Studies. USDA, Economic Research Service, AER-828. Pp.
74–96.
Calvin L, Avendaño B, Schwentesius R. 2004. The Economics of Food Safety: The Case of Green
Onions and Hepatitis A Outbreaks. [Online]. Available: http://www.ers.usda.gov/publications/
vgs/nov04/VGS30501/ [accessed February 24, 2006].
CDC (Centers for Disease Control and Prevention). 1965. Proceedings:National Conference on Sal-
monellosis, March 11–13, 1964, Atlanta, Georgia: U.S. Department of Health, Education and
Welfare, Public Health Service, DHEW publication no. (PHS)1262. Pp. 1–217.
CDC. 1996a. Outbreaks of Cyclospora cayetanensis infection—United States, 1996. Morbidity and
Mortality Weekly Report 45(25):549–551.
CDC. 1996b. Update: Outbreaks of Cyclospora cayetanensis infection—United States and Canada,
1996. Morbidity and Mortality Weekly Report 45(28):611–612.
CDC. 1997a. Update: Outbreaks of cyclosporiasis—United States and Canada, 1997. Morbidity and
CDC 1997b. Outbreak of cyclosporiasis—Northern Virginia-Washington, D.C.-Baltimore, Maryland,
metropolitan area, 1997. Morbidity and Mortality Weekly Report 46(30):689–691.
CDC. 1998. Outbreak of cyclosporiasis—Ontario, Canada, May 1998. Morbidity and Mortality
Weekly Report 47(38):806–809.
CDC. 2004. Outbreak of cyclosporiasis associated with snow peas—Pennsylvania, 2004. Morbidity
and Mortality Weekly Report 53(37):876–878.
CDC. 2005a. Human tuberculosis caused by Mycobacterium bovis—New York City, 2001–2004.
Morbidity and Mortality Weekly Report 54(24):605–608.
CDC. 2005b. Escherichia coli O157:H7 infections associated with ground beef from a U.S. military
installation, Okinawa, Japan, February 2004. Morbidity and Mortality Weekly Report 54(2):
40–42.

CDC. 2005c. Preliminary FoodNet data on the incidence of infection with pathogens transmitted
commonly through food—10 sites, United States, 2004. Morbidity and Mortality Weekly Report
54(14):352–356.
CDC. 2005d. Foodborne Outbreak Response and Surveillance Unit. [Online]. Available: http://
www.cdc.gov/foodborneoutbreaks/outbreak_satistics/cdc_reported.htm [accessed January 16,
2006].
CDC. 2006a. FoodNet Homepage. [Online]. Available: http://www.cdc.gov/foodnet/ [accessed July
7, 2006].
CDC. 2006b. Electronic Foodborne Outbreak Reporting System (EFORS). [Online]. Available: http:
//www.cdc.gov/ [accessed July 7, 2006].
Connor BA, Reidy J, Soave R. 1999. Cyclosporiasis: Clinical and histopathologic correlates. Clinical
Infectious Diseases 28(6):1216–1222.
Dalton C, Goater AD, Burt JP, Smith HV. 2004. Analysis of parasites by electrorotation. Journal of
Applied Microbiology 96(1):24–32.
Datta SD, Traeger MS, Nainan OV, et al. 2001. Identification of a multi-state outbreak of hepatitis A
associated with green onions using a novel molecular epidemiologic technique [abstract 896].
In: Program and Abstracts of the 39th Annual Meeting of the Infectious Diseases Society of
America. Alexandria, VA: Infectious Disease Society of America.
Dentinger CM, Bower WA, Nainan OV, Cotter SM, Myers G, Dubusky LM, Fowler S, Salehi ED,
Bell BP. 2001. An outbreak of hepatitis A associated with green onions. Journal of Infectious
Diseases 183(8):1273–1276.
de Wit M, Koopmans M, Kortbeek L, Wannet WJ, Vinje J, van Leusden F, Bartelds AI, van
Duynhoven YT. 2001. SENSOR, a population-based cohort study on gastroenteritis in the Neth-
erlands: Incidence and etiology. American Journal of Epidemiology 154(7):666–674.
Dixon BR. 2003. The prevalence and control of foodborne protozoan parasites. In: Blais BW, Ed.
Current Challenges in Food Microbiology. Kerala, India: Trivandrum. Pp. 31–76.
DOT, HHS (Department of the Treasury, Department of Health and Human Services). 1999. Presi-
dential Initiative—Safety of Imported Food, Status Report, December 11. [Online]. Available:
http://www.foodsafety.gov/~dms/fs-impor.html [accessed April 13, 2006].
Dubey JP, Thayer DW, Speer CA, Shen SK. 1998. Effect of gamma irradiation on unsporulated and
sporulated Toxoplasma gondii oocysts. International Journal for Parasitology 28(3):369–375.
Eberhard ML, da Silva AJ, Lilley BG, Pieniazek NJ. 1999. Morphologic and molecular characteriza-
tion of new Cyclospora species from Ethiopian monkeys: C. cercopitheci sp.n., C. colobi sp.n.,
and C. papionis sp.n. Emerging Infectious Diseases 5(5):651–658.
Eberhard ML, Ortega YR, Hanes DE, Nace EK, Do RQ, Robl MG, Won KY, Gavidia C, Sass NL,
Mansfield K, Gozalo A, Griffiths J, Gilman R, Sterling CR, Arrowood MJ. 2000. Attempts to
establish experimental Cyclospora cayetanensis infection in laboratory animals. Journal of Para-
sitology 86(3):577–582.
ERS (Economic Research Service). 2000. Economics of Foodborne Disease: Estimating the Benefits
of Reducing Foodborne Disease. [Online]. Available: http://www.ers.usda.gov/briefing/Food
borneDisease/features.htm. [accessed April 13, 2006].
Faruque S, Sack D, Sack R, Colwell R, Takeda Y, Nair G. 2003. Emergence and evolution of Vibrio
cholerae O139. Proceedings of the National Academy of Sciences 100(3):1304–1309.
FDA (U.S. Food and Drug Administration). 1998. Multi-Year Research Strategy Under the Produce
and Imported Food Safety Initiative, September. [Online]. Available: http://www.foodsafety.
gov/~dms/fsrstrat.html [accessed April 13, 2006].
FDA. 2001. FDA Survey of Imported Fresh Produce, January 30. [Online]. Available: http://
www.cfsan.fda.gov/~dms/prodsur6.html [April 13, 2006].
FDA. 2003a. Import Alert #25-20: Detention without Physical Examination of Green Onions (Scal-
lions) from Specific Firms in Mexico. [Online]. Available: http://www.fda.gov/ora/fiars/ora_
import_ia2520.html [accessed April 13, 2006].

FDA. 2003b. FDA Statement: FDA Update on Recent Hepatitis A Outbreaks Associated with Green
Onions from Mexico. [Online]. Available: http://www.fda.gov/bbs/topics/NEWS/2003/NEW
00993.html [accessed February 27, 2006].
FDA. 2003c. FDA and CBP Bolster Safeguards on Imported Food, December 3. [Online]. Available:
http://www.cfsan.fda.gov/~lrd/fpbtamou.html [accessed April 12, 2006].
FDA. 2004. Prior Notice of Imported Food—Questions and Answers. 2nd ed. [Online]. Available:
http://www.cfsan.fda.gov/~pn/pnqagui2.html [accessed April 12, 2006].
FDH (Florida Department of Health). 2004. Bureau of Community Environmental Health, Food and
Waterborne Disease Program Annual Reports. [Online]. Available: http://www.doh.state.fl.us/
environment/community/foodsurveillance/annualreports.htm [accessed April 13, 2006].
FDH. 2005a. Bureau of Epidemiology, Weekly Morbidity Report, Week 14, Ending 4/9/05, Selected
Diseases and Conditions (Confirmed Cases Only). [Online]. Available: http://www.doh.
state.fl.us/disease_ctrl/epi/Disease_Table/2005_Weeks/dt_Week1420051.HTML [accessed
April 13, 2006].
FDH. 2005b. Statewide Cyclosporiasis Outbreak, Florida, March–June 2005, Final Report. January
20, 2006.
Finelli L, Swerdlow D, Mertz K, Ragazzoni H, Spitalny K. 1992. Outbreak of cholera associated with
crab brought from an area with epidemic disease. Journal of Infectious Diseases 166(6):
1433–1435.
Fiore AE. 2004. Hepatitis A transmitted by food. Clinical Infectious Diseases 38(5):705–715.
Food Track Inc. 2005 (August 20). Florida outbreak linked to fresh basil from a grower in Peru.
Outbreak Bulletin, Cyclospora—USA (Florida)—UD#18. Food Safety & Security Alerts.
Fraser DW. 1987. Epidemiology as a liberal art. New England Journal of Medicine 316(6):309–314.
Frenzen P. 2004. Deaths due to unknown foodborne agents. Emerging Infectious Diseases 10(9):1536–
1543.
Gerner-Smidt P, Hise K, Kincaid J, Hunter S, Rolando S, Hyytia-Trees E, Ribot EM, Swaminathan B;
Pulsenet Taskforce. 2006. PulseNet USA—5-year update. Foodborne Pathogens and Diseases.
3(1):9–19.
Griffin PM, Tauxe RV. 1991. The epidemiology of infections caused by Escherichia coli O157:H7,
other enterohemorrhagic E. coli, and the associated hemolytic uremic syndrome. Epidemiologic
Reviews 13:60–98.
Hall RL. 1997. Foodborne illness: Implications for the future. Emerging Infectious Diseases 3(4):
555–559.
Havelaar A, Nauta M, Mangen M-J. 2005. Costs and Benefits of Controlling Campylobacter in
the Netherlands. Bilthoven, the Netherlands: National Institute for Public Health and the
Environment.
Herikstad H, Yang S, Van Gilder T, Vugia D, Hadler J, Blake P, Deneen V, Shiferaw B, Angulo FJ.
2002. A population-based estimate of the burden of diarrhoeal illness in the United States:
FoodNet, 1996–1997. Epidemiology and Infection 129(1):9–17.
Herwaldt BL. 2000. Cyclospora cayetanensis: A review, focusing on the outbreaks of cyclosporiasis
in the 1990s. Clinical Infectious Diseases 31(4):1040–1057.
Herwaldt BL, Ackers ML, Cyclospora Working Group. 1997. An outbreak in 1996 of cyclosporiasis
associated with imported raspberries. New England Journal of Medicine 336(22):1548–1556.
Herwaldt BL, Beach MJ, Cyclospora Working Group. 1999. The return of Cyclospora in 1997: An-
other outbreak of cyclosporiasis in North America associated with imported raspberries. Annals
of Internal Medicine 130(3):210–220.
Heymann, DL. 2004. Control of Communicable Diseases Manual. 18th ed. Washington, D.C.: Ameri-
can Public Health Association. Pp. 141–142.
HHS (Department of Health and Human Services). 2005. Public Health Service Food Code. [Online].
Available: http://www.cfsan.fda.gov/~dms/fc05-toc.html [accessed February 24, 2006].

Ho AY, Lopez AS, Eberhart MG, Levenson R, Finkel BS, da Silva AJ, Roberts JM, Orlandi PA,
Johnson CC, Herwaldt BL. 2002. Outbreak of cyclosporiasis associated with imported raspber-
ries, Philadelphia, Pennsylvania, 2000. Emerging Infectious Diseases 8(8):783–788.
Hoffman RE, Greenblatt J, Matyas BT, Sharp DJ, Esteban E, Hodge K, Liang A. 2005. Capacity of
state and territorial health agencies to prevent foodborne illness. Emerging Infectious Diseases
11(1):11–16.
Hoge CW, Shlim DR, Ghimire M, Rabold JG, Pandey P, Walch A, Rajah R, Gaudio P, Echeverria P.
1995. Placebo-controlled trial of co-trimoxazole for Cyclospora infections among travellers and
foreign residents in Nepal. Lancet 345(8951):691–693.
Hoge CW, Bodhidatta L, Echeverria P, Deesuwan M, Kitporka P. 1996. Epidemiologic study of
Vibrio cholerae O1 and O139 in Thailand: At the advancing edge of the eighth pandemic.
American Journal of Epidemiology 143(3):263–268.
Holmes C, Chiller T. 2004. National antibiotic resistance monitoring system for enteric bacteria.
Emerging Infectious Diseases 10(11):2061.
Huang P, Weber JT, Sosin DM, Griffin PM, Long EG, Murphy JJ, Kocka F, Peters C, Kallick C.
1995. The first reported outbreak of diarrheal illness associated with Cyclospora in the United
States. Annals of Internal Medicine 123(6):409–414.
IOM/NRC (Institute of Medicine/National Research Council). 2003. The science of public health
surveillance. In: Scientific Criteria to Ensure Safe Food. Washington, D.C.: The National Acad-
emies Press. Pp. 28–68.
Jackson GJ. 2006. Inspection and investigation: Tools for detecting sources of food contamination
and preventing illness outbreaks. In: Schweitzer G, Zali MR, Jackson G, Eds. Food Safety and
Foodborne Disease Surveillance Systems: Proceedings of an Iranian-American Workshop.
Washington, D.C.: The National Academies Press. Pp. 24–54.
Jones JL, Lopez A, Wahlquist SP, Nadle J, Wilson M. 2004. Survey of clinical laboratory practices
for parasitic diseases. Clinical Infectious Diseases 38(Suppl 3):198–202.
Kassenborg H, Hedberg C, Hoekstra R, Evans MC, Chin AE, Marcus R, Vugia DJ, Smith K, Ahuja
SD, Slutsker L, Griffin PM, Emerging Infections Program FoodNet Working Group. 2004. Farm
visits and undercooked hamburgers as major risk factors for sporadic Escherichia coli O157:H7
infection: Data from a case-control study in 5 FoodNet sites. Clinical Infectious Diseases
38(Suppl 3):S271–S278.
Kniel KE, Lindsay DS, Sumner SS, Hackney CR, Pierson MD, Dubey JP. 2002. Examination of
attachment and survival of Toxoplasma gondii oocysts on raspberries and blueberries. Journal
of Parasitology 88(4):790–793.
Kolavic S, Kimura A, Simons S, Slutsker L, Barth S, Haley C. 1997. An outbreak of Shigella
Koumans EH, Katz DJ, Malecki JM, Kumar S, Wahlquist SP, Arrowood MJ, Hightower AW,
Herwaldt BL. 1998. An outbreak of cyclosporiasis in Florida in 1995: A harbinger of multistate
outbreaks in 1996 and 1997. American Journal of Tropical Medicine and Hygiene 59(2):
235–242.
Lee MB, Lee E-H. 2001. Coccidial contamination of raspberries: Mock contamination with Eimeria
acervulina as a model for decontamination treatment studies. Journal of Food Protection
64(11):1854–1857.
LeFebvre B, Diarra M, Giguere K, Roy G, Michaud S, Malouin F. 2005. Antibiotic resistance and
hypermutability of Escherichia coli O157 from feedlot cattle treated with growth-promoting
agents. Journal of Food Protection 68(11):2411–2419.
Lopez AS, Dodson DR, Arrowood MJ, Orlandi PA, da Silva AJ, Bier JW, Hanauer SD, Kuster RL,
Oltman S, Baldwin MS, Won KY, Nace EM, Eberhard ML, Herwaldt BL. 2001. Outbreak of
cyclosporiasis associated with basil in Missouri in 1999. Clinical Infectious Diseases 32(7):
1010–1017.

Lopez AS, Bendik JM, Alliance JY, Roberts JM, da Silva AJ, Moura IN, Arrowood MJ, Eberhard
ML, Herwaldt BL. 2003. Epidemiology of Cyclospora cayetanensis and other intestinal para-
sites in a community in Haiti. Journal of Clinical Microbiology 41(5):2047–2054.
McQuiston J, Parrenas R, Ortiz-Rivera M, Gheesling L, Brenner F, Fields P. 2004. Sequencing and
comparative analysis of flagellin genes fliC, fljB, and flpA from Salmonella. Journal of Clinical
Microbiology 42(5):1923–1932.
Novotny TE. 2006. US Department of Health and Human Services: A need for global health leader-
ship in preparedness and health diplomacy [editorial]. American Journal of Public Health
96(1):11–13.
Nuorti J, Niskanen T, Hallanvuo S, Mikkola J, Kela E, Hatakka M, Fredriksson-Ahomaa M,
Lyytikainen O, Siitonen A, Korkeala H, Ruutu P. 2004. A widespread outbreak of Yersinia
pseudotuberculosis O:3 infections from iceberg lettuce. Journal of Infectious Diseases 189(5):
766–774.
Orlandi PA, Chu D-MT, Bier JW, Jackson GJ. 2002. Parasites and the food supply. Food Technology
56(4):72–81.
Orlandi PA, Carter L, Brinker AM, da Silva AJ, Chu D-M, Lampel KA, Monday SR. 2003. Targeting
single-nucleotide polymorphisms in the 18S rRNA gene to differentiate Cyclospora species
from Eimeria species by multiplex PCR. Applied and Environmental Microbiology 69(8):4806–
4813.
Ortega YR, Sterling CR, Gilman RH, Cama VA, Diaz F. 1993. Cyclospora species: A new protozoan
pathogen of humans. New England Journal of Medicine 328(18):1308–1312.
Ortega YR, Gilman RH, Sterling CR. 1994. A new coccidian parasite (Apicomplexa: Eimeriidae)
from humans. Journal of Parasitology 80(4):625–629.
Ortega YR, Nagle R, Gilman RH, Watanabe J, Miyagui J, Quispe H, Kanagusuku P, Roxas C, Ster-
ling CR. 1997. Pathologic and clinical findings in patients with cyclosporiasis and a description
of intracellular parasite life-cycle stages. Journal of Infectious Diseases 176(6):1584–1589.
Powell D. 1998. Risk-based regulatory responses in global food trade: Guatemalan raspberry imports
into the U.S. and Canada, 1996–1998. Conference on Science, Government, and Global Mar-
kets: The State of Canada’s Science-Based Regulatory Institutions, Carleton Research Unit of
Innovation, Science and Environment, Ottawa, October 1–2, 1998. Pp. 1–15.
Rangel J, Sparling P, Crowe C, Griffin P, Swerdlow D. 2005. Epidemiology of Escherichia coli
O157: H7 outbreaks, United States, 1982–2002. Emerging Infectious Diseases 11(4):603–609.
Redelmeier DA. 2005. The cognitive psychology of missed diagnoses. Annals of Internal Medicine
142(2):115–120.
Relman DA, Schmidt TM, Gajadhar A, Sogin M, Cross J, Yoder K, Sethabutr O, Echeverria P. 1996.
Molecular phylogenetic analysis of Cyclospora, the human intestinal pathogen, suggests that it
is closely related to Eimeria species. Journal of Infectious Diseases 173(2):440–445.
Robbins JA, Sjulin TM, Rasmussen HP. 1988. Scanning electron microscope analysis of drupelet
morphology of red raspberry and related Rubus genotypes. Journal of the American Society of
Horticultural Science 113(3):474–480.
Sapers GM. 2001. Efficacy of washing and sanitizing methods for disinfection of fresh fruit and
vegetable products. Food Technology and Biotechnology 39(4):305–311.
Sathyanarayanan L, Ortega Y. 2004. Effects of pesticides on sporulation of Cyclospora cayetanensis
and viability of Cryptosporidium parvum. Journal of Food Protection 67(5):1044–1049.
Schlech WF III, Lavigne PM, Bortolussi RA, Allen AC, Haldane EV, Wort AJ, Hightower AW,
Johnson SE, King SH, Nicholls ES, Broome CV. 1983. Epidemic listeriosis—evidence for trans-
mission by food. New England Journal of Medicine 308(4):203–206.

Shan XC, Wolffs P, Griffiths MW. 2005. Rapid and quantitative detection of hepatitis A virus from
green onion and strawberry rinses by use of a real-time reverse transcriptase-PCR. Applied
Environmental Microbiology 71(9):5624–5626.
Sivapalasingam S, Friedman CR, Cohen L, Tauxe RV. 2004. Fresh produce: A growing cause of
outbreaks of foodborne illness in the United States, 1973 through 1997. Journal of Food Protec-
tion 67(10):2342–2353.
Slutsker L, Evans MC, Schuchat A. 2000. Listeriosis. In: Scheld W, Craig W, Hughes J, Eds. Emerg-
ing Infections 4. Washington, D.C.: American Society for Microbiology Press. Pp. 83–106.
Sobel J, Khan AS, Swerdlow DL. 2002. Threat of a biological terrorist attack on the US food supply:
Steele M, Unger S, Odumeru J. 2003. Sensitivity of PCR detection of Cyclospora cayetanensis in
raspberries, basil, and mesclun lettuce. Journal of Microbiology Methods 54(2):277–280.
Sterling CR, Ortega YR. 1999. Cyclospora: An enigma worth unraveling. Emerging Infectious Dis-
eases 5(1):48–53.
Stone J. 2004. “Gaudeamus Igitur” [poem]. In: Stone, Music from Apartment 8: New and Selected
Poems. Baton Rouge: Louisiana State University Press.
Swaminathan B, Gerner-Smidt P, Ng LK, Lukinmaa S, Kam KM, Rolando S, Gutierrez EP, Binsztein
N. 2006. Building PulseNet International: An interconnected system of laboratory networks to
facilitate timely public health recognition and response to foodborne disease outbreaks and
emerging foodborne diseases. Foodborne Pathogens and Diseases 3(1):36–50.
Tanaka J. 2000. Hepatitis A shifting epidemiology in Latin America. Vaccine 18(Suppl 1):S57–S60.
Tappero J, Schuchat A, Deaver K, Mascola L, Wenger J. 1995. Reduction in the incidence of human
listeriosis in the United States: Effectiveness of prevention efforts? Journal of the American
Medical Association 273(14):1118–1122.
Tauxe RV. 1997. Emerging foodborne diseases: An evolving public health challenge. Emerging In-
Tauxe RV. 2002. Emerging foodborne pathogens. International Journal of Food Microbiology 78(1–
2):31–41.
Tauxe RV. 2005 (October 25). Session II: The Food Supply “Threat Spectrum.” Presentation at the
Tauxe RV, Hughes JM. 1996. International investigation of outbreaks of foodborne disease. British
Medical Journal (Clinical Research Ed.) 313(7065):1093–1094.
Torok TJ, Tauxe RV, Wise RP, Livengood JR, Sokolow R, Mauvais S, Birkness KA, Skeels MR,
Horan JM, Foster LR. 1997. A large community outbreak of salmonellosis caused by intentional
389–395.
Treadway K. 2006. Heart sounds. New England Journal of Medicine 354(11):1112–1113.
U.S. Senate, Permanent Subcommittee on Investigations of the Committee on Governmental Affairs.
1998. The Safety of Food Imports: From the Farm to the Table: A Case Study of Tainted Im-
ported Fruit. 105th Cong., 2nd Sess., Senate Hearing 105-516 (Part II). July 9, 1998.
Varma M, Hester JD, Schaefer FW, Ware MW, Lindquist HDA. 2003. Detection of Cyclospora
cayetanensis using a quantitative real-time PCR assay. Journal of Microbiology Methods
53(1):27–36.
Verweij JJ, Laeijendecker D, Brienen EAT, van Lieshout L, Polderman AM. 2003. Detection of
Cyclospora cayetanensis in travellers returning from the tropics and subtropics using micros-
copy and real-time PCR. International Journal of Medical Microbiology 293(2–3):199–202.

Voetsch A, Angulo F, Rabatsky-Ehr T, Shallow S, Cassidy M, Thomas SM, Swanson E, Zansky SM,
Hawkins MA, Jones TF, Shillam PJ, Van Gilder TJ, Wells JG, Griffin PM, Emerging Infections
Program FoodNet Working Group. 2004a. Laboratory practices for stool-specimen culture for
bacterial pathogens, including Escherichia coli O157:H7 in the FoodNet sites, 1995–2000. Clini-
cal Infectious Diseases 38(Suppl 3):S190–S197.
Voetsch AC, Van Gilder TJ, Angulo FJ, Farley MM, Shallow S, Marcus R, Cieslak PR, Deneen VC,
Tauxe RV, Emerging Infections Program FoodNet Working Group. 2004b. FoodNet estimate of
the burden of illness caused by nontyphoidal Salmonella infections in the United States. Clinical
Infectious Diseases. 38(Suppl 3):S127–S134.
Vogt DU. 2005. Food Safety Issues in the 109th Congress. Washington, D.C.: Library of Congress,
Congressional Research Service.
Wan J, Wilcock A, Coventry MJ. 1998. The effect of essential oils of basil on the growth of Aeromonas
hydrophila and Pseudomonas fluorescens. Journal of Applied Microbiology 84(2):152–158.
Wheeler JG, Sethi D, Cowden JM, Wall PG, Rodrigues LC, Tompkins DS, Hudson MJ, Roderick PJ.
1999. Study of infectious intestinal disease in England: Rates in the community, presenting to
general practice, and reported to national surveillance. The Infectious Intestinal Disease Study
Executive. British Medical Journal 318(7190):1046–1050.
Wheeler C, Vogt TM, Armstrong GL, Vaughan G, Weltman A, Nainan OV, Dato V, Xia G, Waller K,
Amon J, Lee TM, Highbaugh-Battle A, Hembree C, Evenson S, Ruta MA, Williams IT, Fiore
AE, Bell BP. 2005. An outbreak of hepatitis A associated with green onions. New England
Journal of Medicine 353(9):890–897.
Wick L, Qi W, Lacher D, Whittam T. 2005. Evolution of genomic content in the stepwise emergence
of Escherichia coli O157:H7. Journal of Bacteriology 187(5):1783–1791.
Yazaki Y, Mizuo H, Takahashi M, Nishizawa T, Sasaki N, Gotanda Y, Okamoto H. 2003. Sporadic
acute or fulminant hepatitis E in Hokkaido, Japan, may be food-borne, as suggested by the
presence of hepatitis E virus in pig liver as food. Journal of General Virology 84(Pt 9):2351–
2357.
Zhang X, McDaniel A, Wolf L, Keusch G, Waldor M, Acheson D. 2000. Quinolone antibiotics in-
duce Shiga toxin-encoding bacteriophages, toxin production, and death in mice. Journal of In-

Bioterrorism and the Food Supply
OVERVIEW
Each of the three papers collected in this chapter address a different aspect of
a single, highly publicized scenario for foodborne terrorism: the intentional con-
tamination of the U.S. milk supply with botulinum toxin, as described in a May
2005 New York Times op-ed essay by Lawrence Wein (Wein, 2005). The article
sparked an intense debate about the possible security risk it posed, a controversy
that was fueled in subsequent weeks by the delayed publication of a peer-
reviewed paper by Wein and a coauthor (Wein and Liu, 2005) in the Proceedings
of the National Academy of Sciences (Alberts, 2005).
These concerns are expressed in the first part of this chapter by Clay
Detlefsen of the International Dairy Foods Association. “Disclosure of informa-
tion that can be used to harm people needs to be limited except when necessary,”
he argues, extending the definition of “harm” to include the needless scaring of
consumers who might stop buying milk. Indeed, Detlefsen asserts, the dairy in-
dustry has been aware for years of the threats described by Wein and has been
working with the U.S. government to safeguard its operations and products from
bioterrorism. To prevent such efforts from being undermined by the release of
sensitive information to potential terrorists and other malefactors, Detlefsen sup-
ports the creation of a vetting system as a means to fairly assess and, when appro-
priate, prohibit the publication of scientific findings that could be used to develop
and launch an attack.
As workshop contributor Milton Leitenberg notes in the second contribution
to this chapter, considerably less attention has been paid to the questionable va-
141

lidity of Wein’s conclusion that milk represents “a uniquely valuable medium for
a terrorist” than to its status as a threat to national security. Leitenberg, a senior
research scholar at the University of Maryland’s Center for International Security
Studies at Maryland (CISSM), offers detailed evidence that contradicts key as-
sumptions upon which Wein based his model, most notably the ease by which
terrorists could obtain botulinum toxin and use it to launch an attack. More gener-
ally, Leitenberg notes that several existing historical reviews of agricultural ter-
rorism contain inaccuracies that serve to inflate the number of instances of actual
attacks. As a result, he concludes, U.S. policy has been influenced by “gross
exaggeration surrounding the potential for bioterrorism.”
Using the controversy over the Wein model as a jumping-off point, Dr. David
Acheson, Director of the Food and Drug Administration (FDA) Office of Food
Safety, Defense, and Outreach within the Center for Food Safety and Applied
Nutrition, outlines the FDA’s multifaceted approach to protecting the U.S. food
supply from attack in this chapter’s final paper. Acheson explains how the agency
uses risk management and vulnerability assessment tools to determine which food/
agent combinations present the greatest threats to U.S. biosecurity, and in par-
ticular how these analyses have raised concerns about the potential consequences
of the deliberate contamination of milk with botulinum toxin. He then describes
how the FDA addresses such findings through the development of guidance docu-
ments and training programs to prevent and mitigate the effects of specific
bioterrorism threats.
THE THREAT AGAINST MILK:

JUST ONE OF MANY, WITH MORE TO COME
Clay Detlefsen, M.B.A., Esq.1
International Dairy Foods Association
After September 11, 2001, leaders in this country vowed that we would never
be caught off guard again and began an extensive process by which every imagin-
able terrorist threat scenario is analyzed. The laudatory goal is to identify reason-
able mitigation strategies for any threats within the realm of possibility of being
perpetrated. More than four years later, that effort is continuing and expanding.
Today, virtually every industry is working with the government to harden itself
against a potential terrorist attack. The food industries are no exception, and the
dairy industry, in particular, has been quite active and proactive.
I have worked with the government and various industries on food-specific
scenarios involving terrorism, and I have participated in government and industry
1Vice President for Regulatory Affairs.

BIOTERRORISM AND THE FOOD SUPPLY 143
exercises to plan for chemical and biological terrorist attacks that had little to do
with the food supply. Further, I have brainstormed with government officials as
to the private-sector response to a nuclear attack on U.S. soil. Due to the sensitive
nature of the exercises and discussions, most of these activities take place with
little fanfare or public acknowledgment. In some cases, participants such as my-
self are required to sign nondisclosure agreements. The bottom line is that the
federal, state, and local government agencies and the private sector are working
closely together to enhance the public’s safety. Being discrete about it is par for
the course when dealing with a public safety or national security issue.
Secrecy or discretion is called for in these matters for fundamental reasons.
For instance, the general public can scare easily and may then needlessly avoid
the subject matter of the concern. This was exemplified by the dramatic downturn
in commercial airline travel after 9-11, which lasted, as indicated in Figure 4-1
below, until nearly January 2004.
With respect to food, the 1980s, Alar/apple scare clearly establishes how
consumers react when confronted with any implication that a food might present
a risk or contain a deleterious substance. This is so even when the risk is only
theoretical or otherwise unproven. As author Michael Fumento noted:
80
70
60
50
Millions
40
30
Deseasonalized
20
Actual
10
0
Jan-99 Jan-00 Jan-01 Jan-02 Jan-03 Jan-04 Jan-05
FIGURE 4-1 U.S. domestic airline passengers. These graphs present both actual data,
and data that have been seasonally adjusted in order to clarify the trends over time. The
data cited in the text represent actual (unadjusted) values.
SOURCE: Bureau of Transportation Statistics (2005).

Nothing makes Greens—radical environmentalists—turn an angry red faster than

invoking the word Alar to epitomize bogus environmental scares and imply that
a current one is equally phony.
Manufactured by Uniroyal Chemical Co., Alar was commonly sprayed on apples
to keep them on trees longer so that fewer would fall and rot before being har-
vested. The attack on it began in February 1989 when 60 Minutes reporter Ed
Bradley called it “the most potent cancer-causing agent in our food supply.”
Bradley’s main source was the Natural Resources Defense Council (NRDC),
which had decided to scapegoat a single substance to illustrate the horrors of all
manmade chemicals. The NRDC had retained a radical environmentalist public
relations firm, Fenton Communications, to create a front group called Mothers
and Others for Pesticide Limits and place horrifying articles in newspapers and
women’s magazines.
The result: Terrified mothers threw out their applesauce, poured out their apple
juice, and swore off apples entirely for “healthier foods” such as Twinkies. Apple
farmers across the nation suffered, and some went bankrupt. Subsequently, ar-
ticles, monographs, and books peeled the wraps off one of the slickest, most
cynical fear campaigns in recent American history (Fumento, 1999).
Although the harm in the above case is significant, it is largely one of eco-
nomics and is overshadowed by a more significant type of harm—harm that re-
sults from a deliberate attack on people and loss of human lives. Disclosure of
information that can be used to harm people needs to be limited except where
necessary. Too often, the wrong people get their bad ideas from disclosures. The
National Academies and many others in the scientific community are aware of
the “dual use” problem of attempting to advance science while at the same time
running the risk of assisting and aiding terrorists. Unfortunately, the debate seems
to end with a statement along the lines “there is nothing new here that terrorists
don’t already know, so there is no harm in publishing this article.” But, a “terror-
ist” needs to be thought of in a broader way—not just what would traditionally be
thought of as a terrorist; but potentially our own misguided or mentally ill citi-
zens, as well. Virtually every law enforcement agency in the nation is aware of,
or concerned about, copycat criminal activity. The issue has been debated and
discussed on a regular basis for decades. In recent years, a protracted period of
carjacking was theorized to have escalated because of media attention:
Carjacking has always been around, especially in large metropolitan cities, we
just rarely read about it. The crime of carjacking “took off” in the 1980s after the
media published stories of bizarre situations and the violence associated with the
crime. The media coined the phrase “carjacking,” and the crime of auto theft
took on a new identity. After a rush of publicity, other criminals “copied” the
crime of carjacking. These copycat criminals must have said, “Hey, I can steal
any vehicle I want without damaging it, I get the car keys, and I can rob the
owner too. What a concept!” (McGoey, 2006).

In more recent times, carjacking has largely disappeared and the occurrence
of a multitude of Columbine-like school shootings have been theorized to have
stemmed from the media attention given to that unfortunate event. A Google
internet search of the words copycat and Columbine yields 44,000 hits, which is a
fairly clear indication that some association exists. Further, the mimicking of
notorious events is by no means limited to our own domestic criminals. As Florida
State University professor Cecil Greek noted in his paper on censorship, the issue
is complex and may potentially link to terrorism:
Ray Surette has done extensive research on copycat crimes since the mid-1980s.
He argues that copycat crime is a persistent social phenomenon, common enough
to influence the total crime picture, but mainly by influencing crime techniques
rather than the motivation to commit a crime or the development of criminal
tendencies. A copycat criminal is likely to be a career criminal involved in prop-
erty offenses rather than a first-time violent offender. The specific relationship
between media coverage and the commission of copycat crime is currently un-
known, and the social context factors influencing copycat crimes have not been
identified. . . .
Surette also noted that copycat crimes . . . seemed to fall into at least four group-
ings with some overlap. “Mode” copiers were those who already intended to
commit a crime and who received a method from the media event. For example,
a potential car thief copies the techniques seen on a television police drama for
breaking into and hot-wiring a car. “Group” copiers were those who copied acts
in groups. In 1995, a group of Tampa, Florida, teens bragged to police they stole
cars and shot at robbery victims because earlier in the same week a 12-year-old
repeat robber had been granted probation rather than prison. The case had been
given major media attention. The other two categories were mentally ill or men-
tally deficient copiers, and terrorists. Since terrorism is partially driven by media
attention, it is not surprising that terrorists choose to repeat methods that have
produced high media ratings in the past. This has led concerned media execu-
tives to consider carefully how much attention they focus on terrorist acts
(Greek, 1997).
Last summer, the dairy industry found itself in the middle of a media flurry
over a paper that paints a terrorist scenario about botulinum toxin in milk. The
paper, by Dr. Lawrence Wein of Stanford University, described a scenario by
which terrorists could poison thousands of people through the U.S. milk supply
(Wein and Liu, 2005). Wein’s paper was initially withheld at the government’s
request over fears that it could aid attackers; later, the National Academy of Sci-
ences (NAS) published the paper, insisting that it did not put any new information
before terrorists.
Coverage of this issue was widespread, including features in the New York
Times, USA Today, the Washington Post, and on major television networks. The
story ultimately appeared around the globe in more than 500 newspapers. Today,

a Google search of the Internet using the search of the combined words Wein and
milk yields 282,000 hits.
Unbeknownst to most though, the scenario was neither novel nor new. In
fact, the industry had been working with the FDA for several years after the
FDA brought the matter to industry’s attention in 2002. Long before that, the
government had theorized about this particular scenario being perpetrated by
communists. As early as the mid 1950s government scientists studied the possi-
bility that a variety of beverages, including milk, could be contaminated with
botulinum toxin. The report’s conclusion was that the threat to the milk supply
was negligible because of the nullifying effects of pasteurization on the toxin. In
fact, the report concluded that 99 percent of any toxin would be inactivated by
pasteurization. This inactivation finding is not consistent with information ob-
tained by Wein that indicated the temperature and time required for inactivation
would be much greater. However, the research cited by Wein explored inactiva-
tion of toxin in creamed corn, tomato soup, tomato juice, string beans, and canned
corn (Woodburn et al., 1979). The research did not include research using milk.
The research of the 1950s and more recently conducted research did utilize milk,
and those studies are consistent with each other. In fairness to Wein, neither of
those studies are publicly available. Curiously, one of the researchers in the
1950s project is one of the researchers of a study cited by Wein.
In addition, what you did not see in the newspaper or on TV were the efforts
the dairy industry made behind the scenes to correct the misperceptions we feared
the Wein paper might raise, and—more broadly—the extensive work that has
already been done to address security issues.
We knew that the Wein paper was flawed in the assumptions it made about
the milk supply and about milk processing—I and others pointed those flaws out
to Wein himself, who has admitted to shortcomings in his own research. Close
scrutiny by a seasoned biosecurity expert—Milton Leitenberg—found that there
is “an extraordinary degree of uncertainty associated with Wein’s estimates,”
finding flaws with everything from his mathematical methodology to his assump-
tions on the production of the necessary toxin.
Moreover, pasteurization steps have been taken within processing plants that
substantially eliminate the threat Wein presents. Although Wein was successful
in publishing his paper, the International Dairy Foods Association (IDFA) and
others have been successful in delivering the facts to government officials—many
of whom we have built relationships with since the events of 9-11.
To be clear, the dairy industry welcomes scientific research that is aimed at
helping our nation secure its vital systems, including the food supply. But the
Wein paper does not fall into that category—and it remains a lesson on how
important it is for researchers and security experts to work together with industry
in assessing possible terrorist threats.
One area where cooperation is working well is in communication between
industry and government. An impressive amount of work has been done coopera-

tively on security since 9-11. I work closely with officials at the U.S. Department
of Homeland Security (DHS), the FDA, the U.S. Department of Agriculture
(USDA) and other federal and state government agencies on a daily basis to help
evaluate situations and further safeguard the dairy industry. Other individuals in
other sectors and industries fill similar roles.
A thorough government analysis of possible threats to the food and dairy
supply was completed fairly soon after 9-11. Based on that analysis, the dairy
industry has worked diligently, without fanfare, to implement a wide range of
measures to secure facilities and the milk supply. For example, based on guide-
lines prepared by the National Milk Producers Federation and the IDFA, dairy
farmers and processors have implemented new standards for sealing milk tank-
ers. Using these new protocols, any unauthorized opening of a tanker before its
delivery to a processing plant is immediately evident.
In addition, producers and processors have taken many proactive steps to
increase awareness among employees about security measures at the farm and in
processing facilities, including increased security of milk storage areas. Dairy
plants have secured entry systems and employee screening programs, and have
restricted access on the plant floor. And, of course, most packaging operations are
already automated, enclosed, and secure.
There is always more we can do as an industry to be vigilant—and we en-
courage dairy facilities to make every reasonable effort along these lines. But it is
also important to realize we have done quite a lot. I expect new challenges to
continually emerge between government and industry on security issues. We will
never be “done” when it comes to protecting our most valuable attribute—the
safety of our products. The good news is that we have good working relationships
and valuable new protocols in place.
Our efforts, though, should not be undermined by inappropriate publication
of sensitive material that has a potential to be used by foreign or domestic terror-
ists or criminals. Instead, the scientific community needs to work collaboratively
with industry and the government, and this may at times require self-censorship
or restraint. The downside of not being cognizant or otherwise ignoring the possi-
bility of harm being perpetrated on the U.S. citizenry can be the loss of human
lives, which is clearly unacceptable. We are aware of the scientific community’s
interest in addressing this important concern, as was recently described by Dr.
Brian Gorman in his Yale journal article:
The open science dilemma has been recognized as a top priority in the scientific
and national security communities since the terrorist attacks of 2001. It is undis-
puted that the fruits of scientific advancements may also be subject to harmful
“dual use” by enemy combatants, terrorists, and any number of other malefac-
tors with the necessary skills and resources. The dilemma over open science
arises from the incompatibility of restricting access to scientific findings in the
interests of public welfare with a notion of public welfare that is itself reliant
upon the open exchange of findings and scientific data. Therefore, great care is

needed to avoid remedies that unnecessarily impede the exchange of informa-

tion between researchers and deter important lines of inquiry. Thus, a carefully
crafted remedy is needed to cease “free ride” opportunities available to malefac-
tors interested in misusing scientific advancements without impeding much
needed advancements in science interests.
Surprisingly, the most draconian and potentially deleterious remedies to the open
science dilemma, to date, come from the scientific community. As of January
2003, over 20 scientific journals adopted a policy calling for the censorship of
articles that present unjustifiable risks (Journal Editors and Authors Group,
2003).2 However, many recognize that censorship is not a guarantee of protec-
tion. In October 2002, the former president of the American Society for Micro-
biology (ASM) warned that, “censorship of scientific communication would pro-
vide a false sense of protection” (Greenberg, 2002). Severe measures are of
concern because, if carried out, they may discourage research in areas critical to
biodefense efforts. Moreover, even if applied sparingly, censorship policies are
destined to undermine academic freedom and compromise national security
interests.
Unfortunately, there has been little discourse in the literature on specific meth-
ods to effectively remedy the problem. While the dilemma clearly calls for “an
articulated and uniform practice” to identify and assess sensitive research, ef-
forts to create formal procedures have been abandoned (Cozzarelli, 2003). For
example, the journal Proceedings of the National Academy of Sciences, which
published a sensitive article on the variola virus (Rosengard et al., 2002), aban-
doned its pursuit for uniform procedures after a self-congratulatory assessment
of its ad hoc handling of the article (Cozzarelli, 2003). Despite satisfaction with
the “natural” manner in which the article was vetted, flaws remain in the alleg-
edly successful approach. For instance, the national security community was not
consulted during a review of the article (Gorman, 2005).
Ultimately, Gorman describes a proposal to pursue a strategy for the creation
of a due process vetting system (DPVS). Gorman has clearly given considerable
thought to the problem and has proposed a complex, though fair and workable
process:
2On February 20, 2003, Nature published an editorial entitled “Statement on the consideration of
biodefense and biosecurity” Nature 421(6925):771. The editorial described a one-day workshop at
the National Academy of Sciences that was attended by representatives of editorial boards, societies
(including ASM), and a select group of investigators. The workshop culminated in adoption of four
statements pertaining to review and publication of manuscripts that might contain information that
could be harmful in the context of bioterrorism. The fourth statement is as follows: “We recognize
that on occasions an editor may conclude that the potential harm of publication outweighs the poten-
tial social benefits. Under such circumstances, the paper should be modified, or not be published.”

The DPVS is a comprehensive system that enables immediate and informed

communication between the scientific and national security communities on new
research in line for publication and public release. The rapid communication on
potentially sensitive research enables immediate cooperative vetting of flagged
articles between the scientific community and the relevant government author-
ity. The DPVS also provides temporary safe harbor for sensitive research by
consensus rather than unilateral classification imposed by the government. In
the rare occasion when the government needs to classify a research article absent
consensus, the government will have notice of the article before it reaches the
presses and the scientific community will have ample opportunity to be heard
through a fair hearing on the matter if desired. As previously stated, for the
purposes of this discussion, the administrative board charged with federal au-
thority will be deemed a new federal agency called the Biologic Regulatory
Commission (BRC). . . .
The stakes in this debate could not be higher. The potential showdown between
the scientific community and the government on open science, absent goodwill
and cooperation, would certainly yield a duel of mutual destruction.
If scientific journals can cooperate by accommodating the parameters of articles
in LRC [Least Restrictive Classification] status, and if professional stakeholders
agree on fair scaling procedures and joint vetting, the entire field of science can
move forward in a safe and efficient manner. The DPVS could provide a supe-
rior alternative to the ASM model and ad hoc approaches undertaken by the
majority of U.S. bioscience journals. But, the DPVS is just a proposal, and is by
no means seen as a comprehensive solution to the debate on open science. It is
hoped that the flaws and virtues of this proposal will help inspire a fair and
comprehensive approach to sensitive and dual use science that will accommo-
date the needs of all of the stakeholders in this debate (Gorman, 2005).
Industry and government will continue to work together and we will, as we
have in the past, involve the scientific community. It would be foolhardy to think
we could cover our security bases without the scientific community. For the sake
of the public’s safety, we will conduct our activities discretely and cautiously.
We have already achieved considerable success with our endeavors and will un-
doubtedly achieve much more. It is hoped issues involving freedom of the press
and censorship will not undermine the efforts that are so vital to the nation’s
security and the public’s safety. I encourage readers in the scientific community
not to overlook the dangers associated with our own domestic malefactors, and
to, at the very least, read Gorman’s paper and consider that as a starting point. No
one should ever be put in a position to regret their decision to publish after human
lives were lost as a result of such a publication. A robust and systematic approach
as outlined by Gorman could obviate such an occurrence.

BOTULINUM TOXIN: THE LINKAGE WITH BIOTERRORISM

Milton Leitenberg, M.S.3
University of Maryland
My task was to prepare a paper that brought three subjects together: the tradi-
tional biological weapons agent, botulinum toxin; its possible use by bioterrorists;
and its dispersion by application to food as the mechanism of such use.
The very opening lines of the guidance document for this conference read as
follows:
Secretary of the Department of Health and Human Services, Tommy Thompson
raised both concern and controversy when he remarked that he could not under-
stand why terrorists had not yet attacked our food supply “because it is so easy
to do” (Branigin et al., 2004).4
Secretary Thompson’s comment is a useful introduction to this paper. In contrast
to the expectation that it suggests, one realizes immediately that in the entire
period since 1945 there have been only two instances in which any individual or
group deliberately added a pathogen or a toxin to the U.S. food supply. The more
significant of these was the event in 1984 in The Dalles, Oregon, in which a
prepared culture of Salmonella was placed on food in a salad bar, resulting in 751
recorded cases of illness (Carus, 2000).5 Many more people were probably af-
fected, although there was no record of mortality.
In November 2000, Dr. William Fry, a plant pathologist at Cornell Uni-
versity, and an expert on potato late blight in particular (Phytophthora infestans),
the fungus that caused the historic potato famine in Ireland in 1845–1848, gave
an excellent presentation at a conference titled “Agro-Terrorism: What Is the
Threat.” His assignment for the conference was “Think Like a Terrorist,” and he
enjoined the conference attendees to do so. Yet his own detailed and thorough
presentation repeatedly emphasized the difficulties in producing an artificially
caused outbreak of potato blight, to the point of often frustrating the efforts of
3Senior Fellow, Center for International and Security Studies at Maryland.

4The original statement continued with the added words: “. . . and the fact that the United States
imports a lot of food products form the Middle East.”
5It is pertinent to note that the purpose of the Rajneesh use of the biological agent was not “terror-
ist”: It was done covertly and intended to remain covert, and its purpose was a trial run to test its
subsequent use intended to cause large-scale public absenteeism from a local election.
In his presentation to the Forum on Microbial Threats, Dr. Robert Tauxe noted that in 20 years there
had been 20,000 outbreaks of disease due to food contamination, only two of which were caused by
a deliberate act. The second event was the incident in which a laboratory worker in Texas placed
Shigella into baked goods, which she gave to her colleagues. The organism was obtained from the
laboratory in which she worked.

academic researchers when they sought to do so for purposes of their research.

He concluded that:
Devastating crop loss caused by anticrop terrorism is certainly within the realm
of possibility, but there are many obstacles to successful implementation. While
there are many examples of terrible crop destructions by plant pests, the manipu-
lation of these agents as biological warfare agents to destroy crops on a wide
scale by terrorist states or groups faces severe technical challenges. Even if an
aggressive plant pathogen can be developed or found, its potential is severely
limited by meteorological conditions. Thus, it is difficult to conceive that a bio-
logical warfare agent could be used “at will” by a terrorist group or even by a
state (Fry, 2003).6
But perhaps even more to the point was that while he urged his audience to “think
like a terrorist,” and many members of the academic and contract analytical com-
munity quickly identified ways they thought terrorists could make use of plants
or animal pathogens, no real-world terrorist organization had ever done so.
Another guide, in a similar vein to Secretary Thompson’s remark, was to be
found in the opening line of a report by the Congressional Research Service in
August 2004, stating that “The potential of terrorist attacks against agricultural
targets (agroterrorism) is increasingly recognized as a national security threat,
especially after the events of September 11, 2001” (Congressional Research Ser-
vice, 2004).7 At first thought, the statement seems logical: after 9-11, civil au-
thorities looked at every sector of the nation’s infrastructure to identify vulner-
abilities and points of access by which terrorists could wreck havoc or destruction
or injure the public. Nevertheless, the statement is a non sequitur: nothing in the
events of 9-11 suggested that any terrorist group intended to attack U.S. agricul-
tural targets or had even considered doing so. The purpose of this study, however,
is not to suggest another particular vulnerability. It is rather to attempt a classical
threat assessment: an identification and evaluation of real-world entities, their
parameters, performance, experiences, and capabilities as regards the potential
for terrorist use of botulinum toxin.
Before doing that it would be useful to examine the more general subject of
agroterrorism because it serves as an example of what quickly became evident as
a major problem in the course of this work. Two tables dealing with historical
6The last sentence in the quotation implicitly refers to plant pathogens only.
7Other reports on agroterrorism that might be of use for the reader are:
• Parker HS. 2002. Agricultural Bioterrorism: A Federal Strategy to Meet the Threat. McNair
Paper 65. Washington, D.C.: Institute for National Strategic Studies, National Defense University.
• GAO (Government Accountability Office). 2005. Homeland Security: Much Is Being Done to
Protect Agriculture from a Terrorist Attack, but Important Challenges Remain. GAO-05-214. Wash-
ington, D.C.
• GAO. 1999. Food Safety: Agencies Should Further Test Plans for Responding to Deliberate
Contamination. GAO-RCED-00-3. Washington, D.C.

aspects of agroterrorism prepared by the Center for Nonproliferation Studies of

the Monterey Institute of International Studies are posted on their Web site. Both
the center and the institute are well known, and their work would ordinarily be
considered authoritative and of the highest quality. The first table is titled “Chro-
nology of CBW Attacks Targeting Crops and Livestock 1915–2000” (CNS,
2001). It lists 18 events for the 85-year period. As the title of the table states, all
18 are characterized as “attacks.” However, an examination of the 18 entries
demonstrates the following:
• Three were false allegations;

• Three others were “threats,” and as best as is known, more accurately
described, they were bluffs;
• One was an incident in which one man killed his neighbor’s animals;
• One was unsubstantiated (Alabama);
• One was a very low-scale “economic” event (Wisconsin);
• Two, both in Israel, were low-scale economic sabotage that could perhaps
qualify as “attacks”; and
• One, the U.S. use of a herbicide in the DMZ (demilitarized zone) separat-
ing North and South Korea, was done for the purpose of impeding infiltration of
North Korean military and security personnel into South Korea. It did not target
“crops and livestock” at all.
In sum, 11 or 12 of the 18 events in the table—two-thirds of the entries—are not

what they claim to be. They are not “attacks.” At a minimum, the title for the
table should have read “Attacks, Incidents, False Allegations, and Bluffs.”
The second table is titled “Agricultural Bio-warfare: State Programs to De-
velop Offensive Capabilities” (CNS, 2000). It lists programs for 13 states. The
entries for 8 of them need corrections of varying degree:
• Egypt: The claim that Egypt has a dedicated antianimal biological weap-
ons (BW) program is based on a paper that is unreliable and unsubstantiated. The
Israeli author, Daniel Shoham, essentially listed any pathogen for which an Egyp-
tian journal publication existed. If the same criterion were applied to Israel, the
list of the pathogens would be five times longer than for Egypt. Nevertheless,
Israel does not appear in the table at all, even though it maintains an extensive
anthrax research program, for example.
• Iraq: Anthrax in the Iraqi BW program was for antihuman purposes, not
for use against animals. Studies on camel pox served as a research simulant for
smallpox. Finally, contrary to the entry in the table, there was no evidence ever
found by the UN Special Commission (UNSCOM), UN Monitoring, Verifica-
tion, and Inspection Commission (UNMOVIC), or the U.S. postwar Iraq Survey
Group to indicate that work on foot-and-mouth disease was ever part of the Iraqi
BW program.

• Rhodesia: Regarding the allegation of anthrax use in 1979 during the civil
war, the outbreak was almost certainly of natural origin, not due to government
action.
• South Africa: The anthrax produced was added to food and cigarettes to
produce intestinal or pulmonary anthrax in people; there is no evidence that it
was ever intended for or used against animals.
• USSR (Russia, Kazakhstan, Uzbekistan): The facilities and the activities
in what became those countries belonged to the Soviet-era BW program. There is
no presumption that BW-relevant work continued in them once the two new states
became independent in 1992, although the facilities continued to exist. Neither
Kazakhstan nor Uzbekistan was an independent entity at the time of the USSR, so
there is no justification for listing them.
• North Korea: If North Korea has an offensive BW program, and if that
program includes anthrax, it would in all likelihood be intended for antihuman use.
• Syria: The source given is one of the large survey studies by Cordesman;
it would have to be checked to evaluate the validity of Cordesman’s source.
• UK: The year in which the offensive BW program was terminated is
known.
Of the entries for 13 countries, 3 are totally incorrect, 5 others include vary-
ing degrees of inaccuracy, and only 5 can stand as the original entries were
written.
Literature References to the Production of

Botulinum Toxin by Terrorist Groups
References exist for the production of botulinum toxin by two terrorist
groups. The first of these was the Red Army Faction, another name of the West
German Baader-Meinhof Group.
A laboratory in a safe house of the Red Army Faction in Paris, France, was
found to have made quantities of botulinum toxin; it is believed that none was
used (Caudle, 1997).8
Allegedly, an Erlenmeyer flask containing the substance had been found in an
apartment bathtub. The source for this claim, which allegedly had taken place in
1980, was given as Brad Roberts, Weapons of the Future? (Roberts, 1993). The
German intelligence agency Bundesnachrichtendienst (BND) had always—
privately—said that the story was apocryphal, that is, it was untrue. Nevertheless,
numerous U.S. analysts and some U.S. government officials persisted in claiming
8Douglas and Livingstone, and Kupperman, citing access to classified U.S. government sources,
would frequently state the allegation as fact in various seminars in the Washington, D.C., area in the
late 1980s and early 1990s.

for two decades that this “event” had occurred. The claim was finally laid to rest
in the book edited by Jonathan Tucker in 2000 (Taylor and Trevan, 2000).
The extensive briefing materials prepared in advance of the workshop in-
cluded two published papers that referred to the production of botulinum toxin by
the Japanese Aum Shinrikyo organization or by other unidentified “terrorist”
groups. The first was by Sobel, Khan, and Swerdlow, who wrote in The Lancet in
2002, “Aum Shinrikyo . . . reportedly had produced stocks of botulinum toxin
and other biological agents” (Sobel et al., 2002). Their source for this statement
was the chapter by Kadlec, Zelicoff, and Vrtis in Joshua Lederberg’s 1999 book,
Biological Weapons, Limiting the Threat (Kadlec et al., 1999). The source for
these authors was in turn Kaplan and Marshall’s 1996 book on the Aum, which is
inaccurate in virtually all its discussion of the Aum’s work on biological agents,
except that such work was carried out and that numerous attempts were made by
the group to distribute whatever “products” they had made (Kaplan and Marshall,
1996).
The crucial point is that all the biological materials produced by the Aum
Shinrikyo group were innocuous, nonpathogenic, and nontoxic. The Aum pro-
duced no “stocks” of botulinum toxin. At first it appeared that either they had
obtained a strain that produced no toxin, or that they had not succeeded in pro-
ducing the toxin due to incompetence. It now appears certain that they never
obtained a strain of Clostridium botulinum at all. This will be discussed further
below. The Aum produced no “other biological agents,” specifically anthrax, be-
cause they only had the Sterne vaccine strain of anthrax, and in addition they did
not work with it properly. The Aum had no other biological agents of any kind.
By the end of 1999—and therefore certainly by 2002—three publications were
available that explained the above as well as additional inaccuracies that by then
had appeared in print in every reference to the Aum and BW and which continue
to appear in print to this day.9
9A detailed description of the efforts of the Aum group to produce biological agents became avail-
able in 1999 and 2000 in three publications by this author:

• Leitenberg M. 1999. Aum Shinrikyo’s efforts to produce biological weapons: A case study in the
serial propagation of misinformation. Terrorism and Political Violence (Special Issue on the Future
of Terrorism) 11(4):149–158.
• Leitenberg M. 2000. The experience of the Japanese Aum Shinrikyo group and biological agents.
In: Roberts B, Ed. Hype or Reality: The “New Terrorism” and Mass Casualty Attacks. Alexandria,
VA: Chemical and Biological Arms Control Institute.
• Leitenberg M. 2000. Aum Shinrikyo’s efforts to produce biological weapons: A case study in the
serial propagation of misinformation. In: Taylor M, Horgan J, Eds. The Future of Terrorism. London:
Frank Cass.

The second paper was by Arnon et al. in the Journal of the American Medi-
cal Association (JAMA) in 2001:
Terrorists have already attempted to use botulinum toxins as a bioweapon . . . by
the Japanese cult Aum Shinrikyo. These attacks failed, apparently because of
faulty microbiological technique, deficient aerosol generating equipment, or in-
ternal sabotage. The perpetrators obtained their C. botulinum from soil that they
collected in northern Japan. . . .
Four of the countries listed by the U.S. government as “state sponsors of terror-
ism” (Iran, Iraq, North Korea, and Syria) have developed, or are believed to be
developing, botulinum toxin as a weapon (Arnon, 2001).10
Here, there are several important points to be made. In the statement on the Aum
group, both sources used by the authors are not reliable regarding the information
that they contain about the Aum and BW. As will be explained below, it appears
that the Aum did not succeed in isolating C. botulinum from soil or obtaining it in
any other way. As regards the other countries, except for Iraq, the U.S. govern-
ment does not claim to know which specific BW agents the identified countries
produced in the past or may be developing (Leitenberg, 1996, 2004). The Russian
intelligence agency Federal’naya Sluzhba Bezopasnosti 1993 report, the only
publicly available source that could be considered authoritative, does not list botu-
linum toxin among the four BW agents that it claimed North Korea was working
with (Federal’naya Sluzhba Bezopasnosti, 1993). Finally, official U.S. govern-
ment statements consider it highly unlikely that BW or chemical weapons (CW)
would be included in state assistance to terrorist groups. It has never happened to
date despite four decades of state assistance to terrorist groups by states which do,
or may, possess both BW and CW capabilities and which have assisted terrorist
groups in every other conceivable manner (Leitenberg, 2004). That includes fund-
ing, sanctuary, training, arms, explosives, embassy support, false documents, and
other forms of assistance.
A third publication by Roger Shapiro of the Centers for Disease Control and
Prevention (CDC), also published in the JAMA in 1997, contained the following
statements (Shapiro, 1997):
• “Reports that national governments and terrorist groups have stockpiled

botulism toxin.” However, no “terrorist group” is known to have “stockpiled botu-
lism toxin” to date.
• “As many as 17 countries are suspected of either including or developing
biological agents in their offensive weapons program; botulism toxin is frequently
10The sources given in Arnon et al. for the first quotation are David Kaplan’s chapter in Toxic
Terror, which repeats all the errors in his own book, as well as a New York Times article of 1998. The
sources for the second quotation are papers by Anthony Cordesman in 1998 and Joseph Bermudez in
2001.

one of these agents.” According to official U.S. government tallies, the number
has never been alleged to exceed 13. As of mid-2005, it had been reduced by 3 or
4, again according to U.S. government statements. Only Iraq is known to have
produced and stockpiled botulinum toxin (Leitenberg 2004, 2005).
• “The Aum Shinrikyo cult in Japan also produced botulism toxin.” The
Aum group produced no toxin, and they did not have the organism.
• “Instructions for the production of botulism toxin have been broadcast on
the Internet as well.” Virtually all the “instructions . . . on the Internet” are use-
less, excluding professional journal papers that may be available online. This will
be discussed further below, and an example provided.
What then was the actual experience of the Aum Shinrikyo group and botuli-
num toxin, and why has misinformation been propagated for all these years? As
early as May 24, 1996, the major Japanese daily newspaper, Asahi Shimbun,
reporting on evidence presented by the Japanese prosecutor, wrote:
A group led by Seiichi Endo tried to culture botulinum, but failed in isolating the
germ. Then . . . Hideo Murai installed a big tank in order to make a large-scale
production of the germ. After all, the facility was not accomplished to produce
germs.
The decision of the Public Security Commission of the Public Security Investiga-
tion Agency (Japan), January 31, 1997, stated that “The Aum had failed to isolate
Clostridium botulinum.”11 In February 1998, the Chief Toxicologist of Chiba
Prefecture, adjacent to Tokyo, told this author that “The group had not been suf-
ficiently competent to succeed [in their effort] to produce biological agents,” a
statement that referred to their efforts regarding both botulinum toxin and anthrax
(personal communication, Chiba Prefecture, February 1998).12
In anticipation of this workshop, it nevertheless seemed desirable to revisit
this question once again and to try to establish as definitive an answer as possible.
I therefore sent a series of very explicit and specific questions to a Japanese aca-
demic, Masaaki Sugishima, who had examined the full Japanese prosecutorial
record in the Aum Shinrikyo court trials. I asked if the Aum group had acquired a
pathogenic strain of botulinum toxin by whatever means. All possible alterna-
tives for acquisition of the organism were explicitly enumerated, and if it had
been obtained, whether the group had been able to work with the organism to the
point of obtaining the toxin. Box 4-1, below, provides Masaaki Sugishima’s
response.
11The full report of the Public Security Commission, Production of Biological (Bacteriological)
Weapons by the Organization, is classified, but the decision is available.

12Translation provided by a Japanese colleague, Dr. Minoru Ouchi, during the conversation.

BOX 4-1
Date: 10/18/2005 8:25:54 AM EDT
Dear Milton,
As far as I know, there is NO publicly available information that the Aum

had successfully obtained a strain of Clostridium botulinum. You might
know, according to the prosecutors’ opening statement at Asahara’s trial
(Tokyo District Court, May 23, 1996).
(1) Tomomasa Nakagawa taught Asahara about the toxicity of botulinum

toxin.
(2) Asahara asked Sei-ichi Endo to isolate and cultivate Clostridium
botulinum.
(3) Endo, together with Kiyohide Hayakawa and Tomomitsu Niimi, went
to Hokkaido to collect soil for that purpose.
(4) But Endo FAILED [in] isolating Clostridium botulinum.
In this statement, prosecutors have NEVER said that the Aum had suc-
cessfully obtained (bought, stolen, etc.) a strain of Clostridium botulinum.
Best regards,
Masaaki Sugishima
School of Law, Asahi University
In a chapter of his own in a book published early in 2006 Sugishima wrote:

Endo attempted to isolate C. botulinum from soil samples collected in Hokkaido,
but there is no evidence that he was successful. Where the strain that was ulti-
mately used came from is unknown, as are its identity and toxigenicity. The fact
that multiple dissemination events led to no casualties suggests that the Aum
was using an avirulent strain or was unable to cultivate C. botulinum properly.
Nakagawa told another senior follower that the substance his team produced had
proved ineffective in mice (Wheelis and Sugishima, 2006).
The third possibility was more definitively stated above in 1997 by the Japanese
Public Security Commission, namely that the group had never isolated any C.
botulinum at all. Sugishima adds:
Finally, about a week before the Tokyo sarin incident in 1995, the Aum tried to
disseminate botulinum toxin from attaché cases with built-in spray devices.
Three such cases were found abandoned at the Kasumigaseki subway station in
Tokyo, but nothing harmful was found in them. Endo testified at Asahara’s trial

that he had been unable to produce botulinum toxin and had filled the devices
with harmless liquid (Wheelis and Sugishima, 2006).13
In contrast, the information in Kaplan and Marshall’s book on the Aum
Shinrikyo and BW derives from three reports by the Japanese National Police
Agency dating from 1995 and 1996. These would appear to be based on early
statements made to the police by members of the Aum during interrogation rather
than on forensic investigation. These were clearly not reliable. All subsequent
references in the Western international media as well as in the scientific literature
derive in one way or another from the original Kaplan and Marshall book. The
information on the Aum and BW in a lengthy report by the two legal counsels to
the U.S. Senate Committee on Governmental Affairs in October 1995 is similarly
totally incorrect for the same reason (U.S. Senate Government Affairs Permanent
Subcommittee on Investigations, 1995).
Botulinum Toxin: A Brief Description

Botulinum toxin is produced by a gram negative spore-forming anaerobe,
Clostridium botulinum. There are seven distinct serotypes, A through H, and
roughly 100 or more available isolates for each serotype.14 Many of the isolates
produce little or no toxin at all. Only serotypes A, B, E, and F are involved in
human poisoning and of these, primarily A. The toxin is a single protein with a
molecular weight of around 150,000 that acts presynaptically, blocking the re-
lease of acetyl choline, and possibly other neurotransmitters, producing a flaccid
paralysis (Middlebrook and Franz, 1997).
During the years of the U.S. offensive biological weapons program stretch-
ing from 1943 to 1969, hundreds of isolates of C. botulinum were tested for toxin
production. From these, about a dozen were selected for further research. Those
13Sugishima supplies the following Japanese-language sources for the material quoted in the text,
as well as the paragraph below.

• Police newly identified Aum’s microbiological laboratory. 1995 (May 5). Yomiuri Shinbun.
• Aum’s two scientists were addicted to scientific experiments. 1995 (May 30). Mainichi Shinbun.
• Testimony of Endo, January 10, 2005, in Ken-ichi Furihata, Aum Hotei [Court Trials of the Aum],
vol. 12, Tokyo: Asahi Shinbun, 2005, P. 292.
The Aum Shinrikyo group did not lack for financial resources. When Japanese police finally raided
the Aum’s facility for the first time after the release of sarin by the group in the Tokyo subway, they
reportedly found “. . . a glove box, incubator, centrifuge, drier, DNA/RNA synthesizer, electron mi-
croscope, two fermenters each having about a 2,000-liter capacity, and an extensive scientific li-
brary.” Yet the group was not able to obtain or produce any pathogenic agent, demonstrating the point
that although equipment is certainly desirable, the key requirements are a culture and competence.
14These individual isolates located in various culture collections have at times been referred to as
“strains.” However, as genomic identification is not available for nearly all of them, it would be better
to refer to them as isolates.

in turn were reduced to two, one of which was finally selected for production on
the basis of its stability of toxin production, yield, and hardiness of the organism
under the condition of large-scale culture (personal communication, Dr. William
Patrick, 1988). It took many person-years of work to achieve that result. In 1997
at a NATO Advanced Research Workshop in Budapest, Hungary, Dr. Jerzy
Mierzykowski, at that time director of the Polish biodefense laboratory at Pulawy,
made an unusual appeal to the researchers present. He was about to retire after a
lifetime’s work with C. botulinum. Nevertheless, he explained, he was unable to
obtain repeatable levels of toxin production. He asked the American and the Brit-
ish scientists present to advise him on how one obtained reproducible toxin pro-
duction.15 In some months his cultures produced toxin, and in other months they
did not. The reason for this is that the structural gene for the toxin appears to vary
between chromosomal and extrachromosomal locations in the seven C. botuli-
num serotypes. Some are located in a plasmid, some in a bacteriophage, and some
apparently are chromosomally located.
Botulinum toxin—or the group of botulinal toxins—are frequently referred
to as the most toxic substances known, with an LD50 of 1 nanogram per kilo of
body weight. Although unrelated to botulinum toxin poisoning via ingestion by
food, two of the scientific publications referred to earlier, Arnon et al. (2001) and
Shapiro (1997), state that one gram of botulinum toxin if distributed as an aerosol
would result in the death of “more than one million people,” and “at least 1.5
million” people, respectively. All such estimates made on the basis of mathemati-
cal extrapolations from LD50 values assume perfect distribution. They are many
orders of magnitude from possible realization in the real world. In fact both the
United States and later the Soviet offensive BW programs discovered that botuli-
num toxin did not perform well under aerosol distribution, and both programs lost
interest in weaponizing the agent.16
Botulinum Toxin Poisoning and the U.S. Milk Supply

On May 25, 2005, the Proceedings of the National Academy of Sciences
(PNAS) announced that it would publish a paper that presented a mathematical
model of the possible consequences of deliberate botulinum toxin contamination
of the U.S. milk supply. The paper was written by Dr. Lawrence Wein of the
Stanford University Graduate School of Business, and Yifan Liu, a graduate stu-
15The author was present and contributed a chapter to the book that resulted from the conference.
See Geissler E, et al. 1998. Conversion of Former BTW Facilities. Dordrecht, The Netherlands:
Kluwer Academic Publishers.
16Among other problems, the neurotoxin protein must first cross the air-blood barrier in the lungs
and then the blood-brain barrier. Other toxins are more effective when delivered by aerosol because
they act directly on cells in the lungs.

dent. Stewart Simonson, Assistant Secretary for Public Health Emergency Pre-
paredness at the Department of Health and Human Services requested that the
paper not be published on the grounds that it served as a “road map for terrorists,”
supplied “very detailed information on vulnerability nodes in the cow-to-
consumer chain,” and that “publication is not in the interests of the United States”
(Carr, 2005a,b).17 PNAS editors agreed to a delay in publication. However, a
preprint of the paper had been released in advance to journalists, and it was pos-
sible to obtain a copy within a day or two.
On May 30, Wein (alone) published an op-ed in the New York Times titled
“Got Toxic Milk.” It presented the conclusions of the unpublished manuscript.
This short version included one crucial aspect not contained in the PNAS paper: It
stated that “a terrorist, using a 28-page manual called Preparation of Botulinum
Toxin that has been published on several jihadist Web sites and buying toxin from
an overseas black market laboratory,” could produce “a few grams of botulin”
(Wein, 2005). It took a few additional days to obtain a copy of the jihadi manual
in question, and to query appropriately informed professional colleagues in Eu-
rope as to whether any “overseas black market laboratory”—or overseas black
market—for botulinum toxin existed. With these, plus an extensive search of the
professional literature dealing with the isolation and purification of botulinum
toxin, one was able to try to make sense of the mathematical model in question.18
PNAS duly published the original paper without modification at the end of June
2005 (Wein and Liu, 2005). Comment by the general media as well as editorials
and news section reports in journals such as Nature and Science commented only
on the fact that publication of the PNAS article had been delayed. None took issue
with any aspect of the model itself (Editorial, 2005; Shane, 2005; Weiss, 2005).
Wien’s model postulated that contamination of milk with less than one gram
of botulinum toxin would cause 100,000 poisoned individuals, and that mortality
could be in the range of 400,000 or 500,000 people—“the great majority of
568,000 consumers”—if 10 grams were used. In early seminar presentations of
his model at Stanford University, Wien had even posited that the terrorists could
have 1 kilogram or more of the toxin (personal communication). His New York
Times article postulated that a single “terrorist” could achieve such levels of toxin
production. Some 15 years ago scientists at the Center for Applied Microbiologi-
cal Research in the United Kingdom had made a few grams of toxin, which served
to supply the entire European and U.S. commercial market for a decade. Produc-
ing 10 grams—down two orders of magnitude from a kilo—would be a feat for
professional scientists.
17Assistant Secretary Simonson’s letter was sent to the head of the National Academy of Sciences,
Dr. Bruce Alberts, on May 27, 2005.

18Research and part of the writing for this section of the paper were done together with Dr. George
Smith. I would also like to thank Dr. Mark Gorwitz and three other anonymous colleagues for assis-
tance in supplying references to relevant literature and other information.

To begin with, the terrorist or terrorists would have to obtain a good produc-
ing strain of C. botulinum. The jihadi manual begins by extraction from soil. The
deus ex machina that Wein invoked as an alternative, an “overseas black market
lab,” apparently does not exist to anyone’s knowledge. The 25-page jihadi manual
that Wein refers to is in fact a good one: it was composed by splicing together the
“Methods” sections of several professional scientific papers. However, applying
its directions requires a very long list of reagents and equipment, including a
walk-in cold room, a refrigerated vacuum centrifuge, a substantial number of
highly specialized reagents, a mouse colony (since the testing for various steps in
the isolation of the toxin requires repeated in vivo assays), and, not least substan-
tial, technical skill and experience. Without such knowledge, the manual is use-
less. None of these are likely to be available in any jihadi terrorist camp, and none
of them have ever been found to date in any such location. Annex 4-1 contains
excerpts from a far more typical jihadi manual concerning botulinum toxin. They
provide an indication of what the knowledge base of such a group is more likely
to be.
Alternatively, if the terrorist group obtained the services of a competent
trained scientist, or if the terrorist himself had such qualifications as well as ac-
cess to equipment and facilities (as was apparently the case for the individuals
who produced the anthrax used in the United States in October and November
2001), then there is no need to invoke a “jihadi manual.” Such an individual
would be likely to already have a culture of the organism or to know how to
obtain it from nature, know how to produce and purify the toxin, and how
to perform the in vivo mouse assays.
Fortuitously, we have the rudiments of a real-world example to measure
against. In December 2001, the United States and allied forces overran an al-
Qaeda facility in Afghanistan that contained documentary material relating to
their program to attempt to produce biological agents. This author obtained the
declassification of these materials. They demonstrated that botulinum toxin was
one of the agents in which the group was interested (Leitenberg, 2005). A Ph.D.-
level Pakistani scientist working in a Pakistani government facility had provided
the group with photocopies of papers from the journal literature that Dr. Zawahiri,
a senior al-Qaeda official, had requested. However he was not willing to do any
laboratory work himself, and as best as is publicly known, he had not provided
them with a culture of C. botulinum. In addition to journal papers on anthrax,
plague, and hepatitis A, the following were the publications that the group pos-
sessed that dealt with botulinum toxin:
• Roberts TA. 1965. Sporulation of Clostridium botulinum type E in differ-

ent culture media. Journal of Applied Bacteriology 28(1):142–146.
• Hobbs C, Roberts TA, Walker PD. 1965. Some observations on OS
variants of Clostridium botulinum type E. Journal of Applied Bacteriology
28(1):147–152.

• Roberts TA, Ingram M, Skulberg A. 1965. The resistance of Clostridium

botulinum type E to heat and radiation. Journal of Applied Bacteriology 28(1):
125–141.
• A one-page extract of a handbook of gram-positive bacteria, on
Clostridium tetani.
• A four-page extract of a medical or microbiological handbook on
Clostridium tetani and Clostridium botulinum.
There was no indication that the group had obtained a culture of C. botuli-
num from any source, and there was no indication that it had initiated any labora-
tory work.
If we return to examining Wein’s model, it appears that it was constructed
with little knowledge of the relevant literature concerning botulinum toxin. The
few sources referenced are of poor quality, inappropriate, or inaccurate. As indi-
cated, the mathematical model is built upon a thin supposition regarding what
terrorists can do. Wein starts with the assumption that terrorists can make gram
quantities of botulinum toxin. For the PNAS publication, the reasoning for this
was delivered in a little over a paragraph and based on three citations. The first is
an article published in the Journal of Bacteriology in 1971. Although it deals with
the production of botulinum toxin, it more specifically concerns the preliminary
characterization of another protein from the microbe that activates the toxin.
The second citation that Wein used to posit terrorist capability was not from
another scientific journal at all but, surprisingly, from a short news piece pub-
lished by the New York Times on April 27, 2003, written by Judith Miller, then
embedded with the U.S. Army’s Mobile Exploitation Team Alpha in Iraq. It is a
very brief interview with a scientist who worked in Iraq’s bioweapons program,
and it delivers one brief and contextually meaningless claim about the degree of
toxin concentration achieved in that country’s production of botulinum toxin. It
was a simple task to determine that neither UNSCOM, UNMOVIC, nor the Iraq
Survey Group inspectors were ever able to verify his statement or find documen-
tary verification for it in any internal Iraqi government report. Even if accurate,
the claim could not be expected to reflect an achievement level that a terrorist
group might reach. The Iraqi biological weapons program was a national pro-
gram with access to unlimited resources. Late in 1985, botulinum toxin and an-
thrax were one of the first two pathogens selected as candidate agents for the Iraqi
BW program. Initial production began in 1988, and early in 1989 full-scale pro-
duction began (United Nations Security Council, 2005). Approximately three full
years were thus taken up by Iraqi scientists and technicians in preparatory work,
and although UNSCOM inspectors never obtained any of the prepared material to
evaluate, they assumed it to have been a relatively crude preparation. Given that
this was a state program—in contrast to “a” single terrorist postulated by Wein’s
model—it perhaps offers a more realistic estimate of what might be required.
The third citation was used by Wein to bolster an argument for possible

advanced production methods in the hands of terrorists. It too is not from a scien-
tific publication, but is a reference to a “paper for discussion” attributed to Rich-
ard Danzig, a former U.S. Secretary of the Navy, which includes the single sen-
tence saying that there are such advanced methods. Of course there are advanced
methods for botulinum toxin production; the question is whether they are within
the capabilities of terrorists. Finally, the data point used in the model for toxin
survival during thermal processing was out of date, and was for canned corn
rather than for milk.
But the most critical assessment of the model results from several lines at the
very end of Wein’s PNAS paper:
In closing, it is important to stress that several elements of the model contain
enough irreducible uncertainty to preclude estimating the impact of the attack to
within several orders of magnitude. . . .
The dose-response curve, pasteurization inactivation rate, and terrorists’ release
size capabilities each contain several orders of magnitude of uncertainty. . . .
Taken together, we have reasonably accurate estimate of the number of people
who could be poisoned, but a very poor estimate of how much toxin is required
to cause a large outbreak (Wein and Liu, 2005).
As it turns out, there apparently is variability of three or more orders of magni-
tude in each of the three variables. Taken together, this could result in a possible
difference of nine orders of magnitude from the numbers presented by Wein. The
mortality result could be one billionth of Wein’s estimate. Instead of the pre-
dicted mortality of half a million people, there might not have been a single death.
By definition, Wein could not have had “a reasonably accurate estimate” if the
results could vary anywhere over a range of nine orders of magnitude. The first
and last lines in the quotation above are contradictory, and the last lines appear to
be internally contradictory. The model builder apparently knew little or nothing
of the relevant literature on botulinum toxin and nothing at all about the real-
world capabilities of would-be bioterrorists and bioterrorism. Intelligence analy-
sis and mathematical modeling share the same classic limitation: faulty assump-
tions lead to faulty conclusions. A mountain of mathematics, formulas, and curves
cannot remedy flawed basic assumptions and inputs. It is difficult to understand
how the PNAS reviewers and editors let this pass. Finally, Wein had given pre-
sentations of his model to public groups and government officials in Washington,
D.C., long before the manuscript was submitted to PNAS for publication. During
both the private and public presentations he had been informed that remedial
measures had already been taken by the U.S. milk industry to raise both the tem-
perature and duration of heating during the pasteurization process (personal com-
munication, June 2005). This sharply increased the level of toxin inactivation
reached during pasteurization—one of the three variables in question—and con-
comitantly reduced the amount of inactivated toxin that might remain. Thus one
of the two recommendations that Wein suggested at the end of his paper had
essentially already been carried out, although not mandated by law.

Although all of the public discussion surrounding the model concerned is-
sues related to the delay in its publication, the far more germane issue appears to
be that the model was wrong. At the same time, the episode served as yet another
example of the gross exaggeration surrounding the potential for bioterrorism. The
most likely outcome of such exaggeration is to prompt would-be terrorists who
might not otherwise consider or pursue the development of biological agents to
do so because a fictitious simplicity and a fictitious effectiveness was touted.
Documentation captured in Afghanistan demonstrated that precisely that occurred
in the case of al-Qaeda. On April 15, 1999, the Egyptian-born physician, Dr.
Ayman al Zawahiri, deputy to Osama bin Laden, wrote in a message to one of his
colleagues:
We only became aware of them [biological weapons] when the enemy drew our
attention to them by repeatedly expressing concerns that they can be produced
simply with easily available materials (Leitenberg, 2005).
There was a final coda to the PNAS publication, which ironically also con-
cerns publication restrictions. When PNAS published the Wein-Liu model, it
printed an accompanying lengthy commentary by Dr. Bruce Alberts, then the
president of the NAS. In it he noted:
The Wein and Liu article has been widely circulated in preprint form, generating
a great deal of discussion. For this reason, we are already aware of scientists who
plan to publish challenges to some of its conclusions. This type of give-and-take
lies at the heart of scientific progress and is precisely why scientific analyses are
made available in the open literature (Alberts, 2005).
Alberts’ reference to “scientists who plan to publish challenges” referred specifi-
cally to a very brief critique of the Wein model by this author and Dr. George
Smith. It had been submitted to PNAS asking if it could be published together
with the model. However, Dr. Nicholas Cozzarelli, the PNAS editor, had already
rejected that suggestion by June 2, a full six weeks earlier, saying “We do not
have a letters to the editor section in our journal for what you propose. You are of
course free to send in an article that will be subject to our customary peer re-
view.”19 The catch-22 however was that we did not write a scientific paper, only
a brief three-page critique very similar to the material presented here. We then
submitted the same critique to the New York Times. The editor who had published
the Wein op-ed replied, “Thank you for your submission. As a matter of policy,
we do not publish rebuttals on the op-ed page—that is the job of the letters page.
I have taken the liberty of forwarding your article to them.”20 We never heard
19Dr. Nicholas Cozzarelli, Editor, Proceedings of the National Academy of Sciences, e-mail to the
author on June 2, 2005.

20David Shipley, op-ed page editor, New York Times, e-mail to the author, June 8, 2005. Shipley’s
statement is factually incorrect, since responses that are functionally “rebuttals” appear relatively
frequently on the New York Times op-ed page.

from the letter editor. Nature had editorialized about the PNAS publication delay,
and the Washington Post had also carried an op-ed on the same aspect. The cri-
tique was submitted to both. The Washington Post declined to publish it either as
an op-ed or as a letter. There was no reply from Nature. Despite Albert’s gener-
ous anticipation, no scientific “give and take” ever appeared in print.
Alberts also claimed that when:
NAS and PNAS representatives met with government representatives to discuss
their specific concerns about the Wien and Liu article on June 7 . . . we learned
in our discussion with government representatives that a great deal has been
done to improve the pasteurization of milk since 9/11 . . . we appear to be con-
siderably safer from an attack than they [Wein and Liu] have calculated (Alberts,
2005).
Although the NAS officials and PNAS editors professed not to have previously
known what nearly everyone acquainted with the model apparently had heard
about, they suggested no revisions in the manuscript as a result of their new
knowledge, and it was printed exactly as it had been submitted with its original
projections.
A Brief Conclusion
The degree of inaccuracy in information published by members of the scien-
tific community regarding the past record and feasibility of bioterrorism by es-
sentially untrained true terrorist organizations is unbelievably bad. That is a situ-
ation that the scientific community should consider impermissible. Any scientist
that includes information concerning the record of terrorist interest and experi-
ence with biological agents in his papers is responsible to apply the same stan-
dards for accuracy to such passages as he does in reporting his own research work.
Much of that same information continues to grossly exaggerate, to misin-
form, and by suggesting the relative ease and feasibility of producing biological
weapon agents, provokes interest among potential actors, state and nonstate, to
investigate BW, which they might not otherwise have considered. As was indi-
cated, the al-Qaeda experience is a case in point: it was explicitly provoked by the
bioterrorism furor in the United States in 1996–1998. It is legitimate to explore
vulnerabilities and to improve defenses, but there is no justification for imputing
capabilities to real-world terrorists that they do not possess.
A Single Recommendation
The United States has appropriated $30 billion since FY 2002—in four
years—towards bioterrorism prevention. Fiscal year 2005 and 2006 expenditure
will amount to $12.7 billion. All further funding for “select agent” programs
should be cancelled. Future funding should be split between public health pro-
grams such as described in the presentation by Dr. Robert Tauxe to the Forum on

Microbial Threats and to preparations to anticipate an H5N1 pandemic influenza

outbreak. The former should include increased earmarked funding for state and
county public health agencies to enable them to carry out the specified programs.
The latter should include the construction of a National Influenza Vaccine Facil-
ity as well as a dedicated national pharmaceutical facility for the production of
anti-influenza pharmaceuticals. These two dedicated facilities could be rented to
commercial entities in the same way that production facilities for weapon sys-
tems were built by the federal government and rented to manufacturers during
World War II, and for a very large portion of the post-WWII period. The vaccine
facility should be prepared to produce an H5N1 vaccine. In all other years of
operation, it could produce the required U.S. quota of influenza vaccine to cover
annual needs, so that no shortfalls would continue to occur (annual flu mortality
in the United States ranges from 22,000 to more than 80,000) (GAO, 2005a,b).
Funds freed up by cancellation of existing and proposed Bioshield legislation for
“select agents,” as well as the massive spending on infrastructure targeted to work
on the same agents would more than suffice for this purpose.
ANNEX 4-1
The Microbe Clostridium

The word clostridium comes from the Greek word meaning “little spindle.”
Among its characteristics is the ease with which it can be obtained. It is widely
available in the environment, found in water and in soil, especially in areas fertile
with the dung of grass-eating animals.
These microbes can have within them organisms, microbes, or bacteria which
have potential in nonideal climatic circumstances. At this stage, they are latent
and inactive until they get into the right circumstances. At that point, the walls of
the bacteria are shed and they become active as deadly microbes. They are freed
of the glucose that creates an acidic substance. They are active in the absence of
oxygen (anaerobic).
As mentioned these kinds of poisons are of the Clostridium botulinum type.
They are considered among the most destructive poisons because they act imme-
diately on the nervous system and cause the muscles and respiratory organs to
fail. These poisons resist fever to an extent, as well as gastric acid. Their effects
are similar to food poisoning. The Clostridium microbe multiplies in fresh meat
and causes it to rot (the strength of the poison is limited in the presence of heat,
which invites the question of how it could survive the heat of an explosion. It
might be possible to position the poison somehow away from the heat of the
explosion, and transfer the poison onto, for example, legs or shoes in the case of
a suicide operation). There may also be a way to specially design something to
spit the poison out of the exhaust pipe of a car as an alternative to an aerosol.

Clostridium Bacteria
The bacteria of this microbe is killed in the presence of dry heat above 120
degrees Celsius. Its poison emerges from the cell into the environment. It might
work to capture these contents on some of the plants on which the bacteria grows.
It might be possible to obtain a lot of the poison available in the cell, after it has
been released. These poisons have a protein nature such that they lose their poi-
sonous quality if they are exposed to acid (in spite of the fact that they can stand
up to gastric acid) or to heat. This microbe is rarely transmitted on tissue, living
or dead, but it can be grown inside some cans of food, discharging its lethal
poisons. These poisons can lose their effectiveness in temperatures between 61
and 80 degrees Celsius. They causes [sic] food poisoning when food is contami-
nated with the poisons. However, in observing cases of sickness by the same
illness (botulism) occurring as a result of contamination with the microbe, it is
my opinion that its usefulness would double in suicide operations. The microbe
grows well in regular laboratory cultures under intense anaerobic conditions
(meaning its worth as a lethal biological weapon could double.) The ideal tem-
perature for growth is 25 degrees Celsius, but it can grow in temperatures be-
tween 20 and 30 degrees Celsius. The bacteria of this microbe are active in anaero-
bic conditions. The activity causes the microbe to release the poisons.
Properties of the Poisons

They are released after [exposure to] a temperature of 80 degrees Celsius for
a period of 30 minutes, or a temperature of 100 degrees Celsius for 10–15 min-
utes. They are released in acid, but the exception to that is stomach acid. The
poisons are divided into six kinds: A, B, C, D, E, F (A, B, and E cause sickness in
people, and C and D cause sickness in animals. The sickness in people is also
caused by F, which is found in water environments and produces poison symp-
toms in people and fish). In English: [it is a] “globulin of high molecular weight.”
The weight of the A part is between 6,000 and 9,000 B. These weights are benefi-
cial in the electronic separation of poisons.
How to Cultivate the Specimen

These bacteria are cultivated in normal cultures in the complete absence of
oxygen. This requirement can be met simply by lighting a candle inside the flask
containing the microbe after either a rubber stopper or a piece of cotton has closed
off the opening. This means: place the specimen contaminated with the microbe—
which is a piece of dirt—. . . .

From Where to Obtain the Specimen

From dry dirt. Place some of the dung of grass-eating animals in the dirt.
Take the specimens after some days.
The nature of the specimen, as mentioned, is simply dirt. Leave it in anaero-
bic conditions for a number of days; it will become liquid.
A Section on Poisons
Seeing as bacterial culture contain a number of substances, it is important to
use electricity on the poisons. These [processes] are known as electrophoresis
and affinity column chromatography. They separate the different materials de-
pending on the differences in their weights (references prior). Admittedly, I do
not have details on this point, nor the topics of the concentration and preservation
of poisons, may God forgive me.
THE FOOD AND DRUG ADMINISTRATION’S

APPROACH TO FOOD DEFENSE
David W. K. Acheson, M.D.21
Food and Drug Administration
A Risk-Based Approach to Food Defense

The FDA is pursuing a multipronged approach to food defense. It includes
increasing the awareness of the food industry and other stakeholders to critical
opportunities for safeguarding the U.S. food supply, developing prevention strat-
egies and building capacity to implement them, and planning for response to and
recovery from an intentional food contamination event. There are many foods
that could be intentionally contaminated, and one food that has attracted a lot of
attention of late is milk and its potential to be deliberately contaminated with
Clostridium botulinum neurotoxin. Although this scenario is discussed in more
detail below, it is important to recognize that this is only one food-agent combi-
nation amongst the many that the FDA has focused on.
Finding the Risks

The FDA has adopted a risk-based approach to determine where food de-
fense resources should be applied. Following September 11, 2001, the FDA uti-
lized an approach known as operational risk management (ORM). ORM involves
21Chief Medical Officer and Director, Office of Food Safety, Defense and Outreach, Center for
Food Safety and Applied Nutrition.

a determination of which combinations of foods and agents, and where on the

farm-to-table continuum, constitute the highest risks. The FDA began this pro-
cess with a list of potential terrorism agents that was developed by the CDC in
2000. The FDA modified the agents’ rankings according to a variety of criteria
such as the stability of the agent in a food matrix; the effect of the agent on the
odor, flavor, or color in a food matrix; the severity of public health outcomes
associated with the agent; its oral infective or toxic dose; its availability; and
perhaps most important, existing threat intelligence on the use of this agent for
foodborne bioterrorism. We then evaluated combinations of these agents with a
wide range of foods and food ingredients considered to represent possible targets
for foodborne attacks.
The ORM evaluations revealed the probability of contaminating a specific
point in the food chain with a specific agent. That information was further en-
hanced by combining it, in matrix format, with an assessment of the likely sever-
ity of outcome, as measured by estimated mortality. The construction of these
matrices involved the application of basic science, knowledge of food process-
ing, the food industry, transportation, and logic, but the availability of credible
intelligence of a food threat trumped all other factors. We recognize that any food
could potentially be contaminated by a determined person or group, thus zero-
risk foods do not exist. Higher-risk foods do, however, share several common
vulnerability factors: large batch size, which implies a large number of servings;
short shelf life, which implies rapid turnaround at retail and rapid consumption;
uniform mixing, which would maximize the number of people exposed to an
agent; and accessibility of a so-called critical node, defined as a process or activ-
ity in the farm-to-table chain during which the agent could be added, undetected,
in effective quantities.
Based on this information, the FDA developed guidance documents and train-
ing for its staff, state and local regulatory colleagues, and the food industry. This
knowledge has also contributed to shaping the agency’s considerations of pre-
ventive measures, its emergency response planning, and the setting of its research
priorities. Because the FDA does not have authority to regulate the security or
defense of the food supply, we use this information as we work cooperatively
with state and local regulatory officials, the food industry, and other stakeholders
in food defense. A For Official Use Only (FOUO) version of the FDA ORM
evaluations was prepared and distributed to both industry and states to facilitate a
better understanding of where the risks lie.
Following the ORM approach described above, which gave a broad over-
view of the relative risks, the FDA has also employed a more sophisticated vul-
nerability assessment tool called CARVER + Shock. CARVER is an acronym for
the following factors by which it assesses the vulnerability of a potential food-
agent combination as a target for terrorism:

• Criticality (public health and economic impacts)

• Accessibility (physical access to the targeted food)
• Recuperability (ability of the affected system/population to recover from
the attack)
• Vulnerability (ease of accomplishing the attack)
• Effect (losses directly attributable to attack)
• Recognizability (ease of identifying a target)
An additional measure called “shock,” which combines the physical, psy-

chological, and economic effects, was also evaluated. This framework allows a
far more detailed assessment of the farm-to-table continuum than is possible with
operational risk management. For example, we might perform a CARVER +
Shock vulnerability assessment of a specific beverage product, having already
recognized that the uniform mixing of large volumes of this beverage from differ-
ent suppliers raises the vulnerability of that commodity to terrorism. For example,
for fruit juice production a flow diagram is developed, starting with the fruit on a
tree in a growing area in the United States or abroad, and continuing with the
worker who picks that fruit, the fruit storage facilities on the farm, transport to the
dock, shipping and transport from the docks to the warehouse, every processing
step through blending and pasteurization, packaging, distribution, and retail. Ini-
tially the FDA undertook CARVER + Shock determinations within the federal
government only. The results of this process were classified documents that could
not be readily shared and thus had the distinct disadvantage of not being readily
available to the industry. To address this shortcoming the FDA worked with a
number of industries to train them in CARVER + Shock methodology so they
could perform their own assessments. With that information, food industries can
make the best use of limited resources for food defense.
The current approach for vulnerability assessments is a joint approach led by
FDA, USDA, DHS, and the Federal Bureau of Investigation (FBI), and is known
as the Strategic Partnership Program Agroterrorism (SPPA) initiative. The SPPA
was launched in July 2005 and solicits industry and state volunteers to undertake
locally based vulnerability assessments on a variety of food commodities. By
being locally based these assessments not only address a specific food commod-
ity but also facilitate local interactions between the very federal, state, and local
officials that would have to deal with a deliberate attack on the food supply.
Deliberate Contamination of Milk with Botulinum Toxin

Vulnerability assessments such as the ORM and CARVER + Shock methods
discussed above indicate certain foods of higher concern. One of these foods is
fluid milk and the specific example of botulinum toxin in milk is frequently raised,
since milk production is a significant industry, both in terms of the volume of
product consumed and its importance to the U.S. economy.

After the milking process, milk is typically stored in a tank on the farm that
may hold up to 500 gallons until it is transported to the dairy in a 5,000-gallon
tanker. At the dairy, milk received from several such tankers is held in bulk tanks
of up to 60,000 gallons before it is pasteurized and packaged. Packaged milk is
distributed first to a warehouse and then to a retail outlet. Milk has many of the
common vulnerability factors mentioned above. The same conclusion was reached
in an FOUO report prepared by the U.S. Department of Transportation’s Volpe
National Transportation Systems Center in 2004, which was intended to inform
the dairy industry about vulnerabilities in the milk supply and ways to ad-
dress them.
In response to the results of this report, and continuing discussions with the
dairy industry, changes have been made by individual milk producers and the
dairy industry as a whole that have improved the security of the U.S. milk supply.
There are multiple points along the farm-to-table continuum where food may
be vulnerable, and it is critical that the approach to this problem be multifaceted.
To this end, the FDA has produced a series of guidance documents, one of which
is targeted at the dairy industry and outlines an array of possible steps that can be
taken to minimize the chance of a deliberate attack on the food supply (CFSAN,
2003).
Fluid milk is not the only food commodity that may be subject to a deliberate
attack, and to that end the FDA produced guidance documents directed toward a
variety of other industries. These include the following:
• Retail food stores and food service establishments: www.cfsan.fda.gov/

~dms/secgui11.html
• Food producers, processors, and transporters: www.cfsan.fda.gov/~dms/
secguid6.html
• Importers and filers: www.cfsan.fda.gov/~dms/secguid7.html
• Cosmetics processors and transporters: www.cfsan.fda.gov/~dms/secgui
10.html
Each one of these documents provides general guidance as well as more focused
messages directed toward the specific industry groups.
Research Questions
During the vulnerability assessment process, whether it be ORM or CARVER
+ Shock, a number of questions typically arise that require research. FDA has
undertaken a food defense research strategy that is focused on a number of areas.
These include work on the behavior of select agents in certain food matrices, the
value of specific mitigation approaches, sensitive and specific detection methods
that are rapid, and dose-response relationships with select agents that may be
added to food.

Mitigation of Botulinum Toxin in Milk

Specific steps to mitigate the intentional contamination of milk with botuli-
num toxin are also being researched. The toxin is sensitive to the effects of heat,
and thermal destruction of the toxin occurs in foods that are heated to certain
temperatures for long enough times. Milk that is shipped in interstate commerce
has to be pasteurized using a minimum temperature of 161° Fahrenheit for 15
seconds. Consideration was therefore given to the impact of pasteurization of
milk at higher temperatures and/or for longer times. Basic research was under-
taken to address this question and the results shared with the milk industry. How-
ever, a number of other issues have to be taken into account if higher pasteuriza-
tion temperatures or longer times are considered. Such things include the
economic impact of heating, then cooling the milk, the increase in plate fouling
that occurs at higher temperatures, as well as any possible affect to milk’s taste
and color, and potential reductions in its nutritional value.
Another research question that has arisen is whether testing for botulinum
toxin in milk provides an alternative to raising pasteurization temperatures. Test-
ing could potentially be performed at various points from farm to table, and de-
pending on a variety of factors such as the sensitivity, specificity, cost, and assay
speed it could be a useful addition to other mitigation strategies. Issues such as
sensitivity are critical as approximately one million milk tanker trips occur annu-
ally in the United States, a test yielding a one percent false positive rate (e.g., an
Enzyme Immuno Assay) would falsely identify 10,000 positive tankers holding a
total of 500,000 gallons of milk each year. Dealing with such false positives in a
timely way could become complex and time consuming.
Although tests for botulinum toxin currently exist, they are not necessarily
appropriate for mass testing because of cost or time required to conduct the assay
and so on. Toward the goal of a rapid, sensitive, specific, and cost effective assay,
a DHS initiative is currently funding the first phase of a program for a rapid (less
than 20 minute turnaround), sensitive, specific (less than one per million false
positives), simple (could be performed by someone with a high school educa-
tion), and cost-effective test for botulinum toxin in food. The eventual objective
of this project is to develop a platform that could be adapted to detect multiple
agents in different food matrices.
At the end of the day, the most important message regarding mitigation strat-
egies is not to rely on a single strategy alone to produce adequate protection.
Rather put in place as many different strategies at different points on the farm-to-
table continuum that will, overall, minimize the chances of a successful attack on
the food supply.
Preparatory Measures
Being prepared for an attack on the food supply is a very important aspect of
the FDA’s work. To that end, in 2004 the FDA initiated a series of assignments

that were associated with special security events and focused on ensuring the
safety and defense of the nation’s food supply. These assignments involved ac-
tivities associated with the G8-Summit, as well as the Democratic and Republi-
can National Conventions. These special event assignments were, however, re-
gional and limited in scope. Based on heightened security during the national
election in November 2004, the FDA determined that it was appropriate to issue
a broader nationwide food defense assignment. The first assignment of this na-
ture was issued in 2003 during Operation Iraqi Freedom under Operation Liberty
Shield. In October 2004, the FDA initiated a new assignment (FDA Security
Surveillance Assignment [FSSA]) that, while similar to the Liberty Shield as-
signment, was designed to involve federal, state, local, and industry partners to a
greater extent than was done in Operation Liberty Shield and to better evaluate
our national preparedness capabilities. The primary goals of this national assign-
ment are as follows:
1. Deter intentional contamination of food through heightened and targeted

preventive activities at various points in the chain of supply; and
2. Exercise the planning and implementation of the system for responding to
a period of increased food security risk to identify and address gaps in the system.
The food items selected to be part of the assignment were based on the ORM
vulnerability assessments undertaken previously by the FDA. This process al-
lowed the FSSA to focus the limited federal, state, and local public health re-
sources on those food commodities with the highest potential for intentional con-
tamination (CFSAN, 2005). The FSSA was designed to test the FDA’s ability to
respond to a threat to the food supply, and as such FDA inspectors entered the
premises of domestic firms that produced certain foods to discuss food security
and food defense issues with their managers. They also took samples of foods in
the above categories, which were tested for a variety of chemical (e.g., cyanide)
and microbiological (e.g., botulinum toxin) agents using the Food Emergency
Response Network (FERN) laboratories. In addition, the FDA conducted an elec-
tronic vulnerability analysis of registrations for imported foods in the above cat-
egories; it identified 38 “suspicious” products that were subsequently tested us-
ing the FERN laboratories.
Response and Recovery

It is likely that a successful attack on the food supply would be detected first
at a local level, most likely due to the detection of a sick animal or a sick human,
so an effective response requires close coordination with local public health of-
ficials. Key aspects of such a response is containment of the threat and commu-
nication with the public. Achieving recovery from such an attack requires the
means to demonstrate that the food supply is safe, as well as to decontaminate

and dispose of potentially large amounts of tainted food—including food in the

homes of consumers—and processing equipment. Once again, good communi-
cation with consumers is critical to the success of a recovery program to reassure
the public of when a particular food is safe to consume.
Food Safety vs. Food Defense

Although the discussion in this chapter has been focused on food defense, it
is imperative that we do not lose sight of the importance of food safety. A delib-
erate attack on the food supply is plausible and potentially catastrophic both eco-
nomically as well as in loss of life. However, foodborne illness due to uninten-
tional events is an ongoing and real everyday event resulting in sickness and
death. As we continue to move forward in meeting our food defense goals by
increasing preparedness, developing response plans and ensuring we have the
tools to facilitate recovery, we must also integrate these approaches into our on-
going food safety work. In this context, we are talking about the same foods in the
same farms, manufacturers, warehouses, and so on, as well as the same set of
inspectors at the local, state, and federal level, and in some instances even the
same agents. The overlap is huge and obvious, and the same resources are used
for both. Food safety and food defense are here to stay, and it is critical they be
integrated to the maximum extent possible to ensure the most efficient use of
resources as well as optimizing response to an event.
REFERENCES
Alberts B. 2005. Modeling attacks on the food supply. Proceedings of the National Academy of
Sciences 102(28):9737–9738.
Arnon SS. 2001. Botulinum toxin as a biological weapon: Medical and public health management.
Journal of the American Medical Association 285(3):1059–1070.
Branigin W, Allen M, Mintz J. 2004. Tommy Thompson resigns from HHS: Bush asks Defense
Secretary Rumsfeld to stay. Washington Post. [Online]. Available: http://www.washington
post.com/wp-dyn/articles/A31377-2004Dec3.html [accessed April 13, 2006].
Bureau of Transportation Statistics. 2005 (December). Issue Brief: U.S. Airline Travel Since 9/11.
U.S. Department of Transportation, Research and Innovative Technology Administration.
[Online]. Available: http://www.bts.gov/publications/issue_briefs/number_13/pdf/entire.pdf [ac-
cessed July 18, 2006].
Carr R. 2005a (June 21). Government request stops publication of article about terror threat to milk.
New York Times Washington Wires.
Carr R. 2005b (June 26). Publication heeds U.S., pulls terror article: Professor speculates about at-
tack. Atlanta Journal-Constitution. [Online]. Available: http://www.ajc.com/print/content/
epaper/editions/sunday/news_24ebc541731e70fe0050.html [accessed April 13, 2006].
Carus SW. 2000. The Rajneeshees (1984). In: Tucker JB, Ed. Toxic Terror: Assessing Terrorist Use
of Chemical and Biological Weapons. Cambridge, MA: MIT Press. Pp. 115–137.
Caudle LC. 1997. The biological warfare threat. In: Sidell FR, Takafuji ET, Franz DR, Eds. Medical
Aspects of Chemical and Biological Warfare. Washington, D.C.: Walter Reed Army Medical
Center. P. 463.

CFSAN (Center for Food Safety and Applied Nutrition). 2003 (July 11). Dairy Farms, Bulk Milk
Transporters, Bulk Milk Transfer Stations and Fluid Milk Processors Food Security Preventive
Measures Guidance. [Online]. Available: http://www.cfsan.fda.gov/~dms/secguid8.html [ac-
cessed July 10, 2006].
CFSAN. 2005. Summary Report FDA Security Surveillance Assignment October–November 2004.
[Online]. Available: http://www.cfsan.fda.gov/~dms/fssarpt.html [accessed July 10, 2006].
CNS (Center for Nonproliferation Studies). 2000. Agricultural Biowarfare: State Programs to De-
velop Offensive Capabilities. [Online]. Available: http://cns.miis.edu/research/cbw/agprogs.htm
CNS. 2001. Agroterrorism: Chronology of CBW Attacks Targeting Crops and Livestock 1915–2000.
[Online]. Available: http://cns.miis.edu/research/cbw/agchron.htm [accessed October 1, 2005].
Cozzarelli NR. 2003. PNAS policy on publication of sensitive material in the life sciences. Proceed-
ings of the National Academy of Sciences 100(4):1463.
CRS (Congressional Research Service). 2004 (August 13). Agroterrorism: Threats and Prepared-
ness. RL 32521. Washington, D.C. P. 1.
Editorial. 2005. Risks and benefits of dual-use research. Nature 435(7044):855.
Federal’naya Sluzhba Bezopasnosti. 1993 (March 5). Proliferation Issues: A New Challenge After the
Cold War, Proliferation of Weapons of Mass Destruction. JPRS-TND-9-3-007. Russian Federa-
tion Foreign Intelligence Report [translation]. Joint Publications Research Service. JPRS-
TND93-007. P. 29.
Fry WE. 2003. Technical feasibility of anti-crop terrorism. In: Pate J, Cameron G, eds. Agro-Terror-
ism: What Is the Threat. CGSR-03-01. Livermore, CA: Lawrence Livermore National Labora-
tories. Pp. 69, 74.
Fumento M. 1999. Greens still trying to salvage their Alar-stained reputation. Outlook Magazine.
[Online]. Available: http://www.junkscience.com/jun99/salvage.htm [accessed April 12, 2006].
GAO (Government Accountability Office). 2005a. Influenza Pandemic: Applying Lessons Learned
from the 2004–05 Influenza Vaccine Shortage. GAO-06-221T. [Online]. Available: http://
www.gao.gov/docdblite/details.php?rptno=GAO-06-221T [accessed April 14, 2006].
GAO. 2005b. Influenza Vaccines: Shortages in 2005–05 Season Underscore Need for Better Prepa-
ration. GAO-05-984. [Online]. Available: http://www.gao.gov/docdblite/details.php?rptno=
GAO-05-984 [accessed April 14, 2006].
Gorman BJ. 2005. Balancing national security and open science: A proposal for due process vetting.
Yale Journal of Law and Technology. [Online.] Available: http://research.yale.edu/lawmeme/
yjolt/files/20042005Issue/3_Gorman_052005.doc [accessed April 12, 2006].
Greek C. 1997. Copy-cat crimes. In: Rasmussen RK, Ed. Ready Reference: Censorship. Pasadena,
CA: Salem Press.
Greenberg DS. 2002. Self-restraint by scientists can avert federal intrusion. Chronicles of Higher
Education 49(7):B20.
Journal Editors and Authors Group. 2003. Statement on the consideration of biodefense and bio-
security. Nature 421(6925):771.
Kadlec RP, Zelicoff AP, Vrtis AM. 1999. Biological weapons control: Prospects and implications for
the future. In: Lederberg J, Ed. Biological Weapons: Limiting the Threat. Cambridge, MA: MIT
Press. Pp. 95–111.
Kaplan DE, Marshall A. 1996. The Cult at the End of the World. New York: Crown.
Leitenberg M. 1996. Biological Weapons Arms Control: Project on Rethinking Arms Control. PRAC
Monograph 16. College Park, MD: Center for International and Security Studies. Pp. 39–51.
Leitenberg M. 2004. The Problem of Biological Weapons. Stockholm: The Swedish National Defense
College. Pp. 12–19.
Leitenberg M. 2005. Assessing the Biological Weapons and Bioterrorism Threat. Carlisle, PA: Stra-
tegic Studies Institute.

McGoey CE. 2006. Carjacking Facts, Robbery Prevention Advice. [Online]. Available: http://
www.forcedignition.com/Articles/carjacking_facts.htm [accessed April 12, 2006].
Middlebrook J, Franz DR. 1997. Botulinum toxin. In: Sidell F, Takafuji ET, Franz DR, Eds. Medical
Aspects of Chemical and Biological Warfare. Washington, D.C.: Office of the Surgeon General,
Department of the Army. Pp. 643–654.
Roberts B, ed. 1993. Biological Weapons: Weapons of the Future? Washington, D.C.: Center for
Strategic and International Studies. CSIS Significant Issues Series Vol. 15(1).
Rosengard AM, Liu Y, Nie Z, Jimenez R. 2002. Variola virus immune evasion design: Expression of
a highly efficient inhibitor of human complement. Proceedings of the National Academy of
Sciences 99(13):8808–8813.
Shane S. 2005 (June 29). Paper describes potential poisoning of milk. The New York Times.
Shapiro R. 1997. Botulism surveillance and emergency response: A public health challenge for a
global challenge. Journal of the American Medical Association 278(5):443–435.
Sobel J, Khan AS, Swerdlow DL. 2002. Threat of a biological terrorist attack on the US food supply:
Taylor T, Trevan T. 2000. The Red Army Faction (1980). In: Tucker JB, Ed. Toxic Terror. Cam-
bridge, MA: MIT Press. Pp. 107–133.
United Nations Security Council. 2005. Appendix: Biological Weapons Programme of Iraq. In:
Twenty-Second Quarterly Report on the Activities of the United Nations Monitoring, Verifica-
tion and Inspection Commission in Accordance with Paragraph 12 of Security Council Resolu-
tion 1284(1999). S/2005/545. New York: United Nations. Pp. 5–15.
U.S. Senate, Government Affairs Permanent Subcommittee on Investigations. 1995. Global Prolif-
eration of Weapons of Mass Destruction: A Case Study of the Aum Shinrikyo. Staff Statement.
Washington, D.C.: U.S. Government Printing Office. Pp. 47–102.
Wein LM. 2005 (May 30). Got toxic milk? The New York Times. [Online]. Available: http://
www.nytimes.om/2005/05/30/opinion/30wein.html?ex=1275105600&en=e5692b8396d5681e
&ei=5090&partner=rssuserland&emc=rss [accessed April 25, 2006].
Weiss R. 2005 (June 29). Report warns of threat to milk supply, release of study citing vulnerability
to bioterrorism attack was opposed by U.S. officials. The Washington Post: A 08.
Wheelis M, Sugishima M. 2006. Terrorist use of biological weapons. In: Wheelis M, Rozsa L, Dando
M, Eds. Deadly Cultures: Biological Weapons Since 1945. Cambridge, MA: Harvard Univer-
sity Press. Pp. 296–297.
Woodburn MJ, Somers E, Rodriguez J, Schantz EJ. 1979. Heat inactivation rates of botulism toxins
A, B, E and F in some foods and buffers. Journal of Food Science 44: 1658–1661.

Surveillance of the Food Supply
OVERVIEW
The search for the organisms that cause foodborne disease—both before and
after people consume them—involves a constellation of overlapping information
networks, none of which constitutes a complete surveillance system. As John
Besser of the Minnesota Department of Health notes in the first paper of this
chapter, the scores of existing food surveillance programs can be reduced to two
basic types: food monitoring (the direct detection of microbial pathogens along
the food chain) and disease surveillance (the collection of human or animal dis-
ease data, followed by analyses of case clusters and disease trends). He describes
and compares various strategies and methods of both food monitoring and
foodborne disease surveillance, noting their strengths and limitations as currently
practiced.
Although food monitoring is theoretically capable of providing primary pre-
vention against foodborne disease, Besser finds that such systems seldom meet
this standard because of the technical complexity of the task (which can only be
addressed at considerable expense). However, another workshop participant, Rob-
ert Buchanan of the Food and Drug Administration (FDA) Center for Food Safety
and Applied Nutrition (CFSAN), observed that food monitoring plays an impor-
tant role in verifying the effectiveness of food safety systems (see Summary and
Assessment, p. 15). Although Buchanan acknowledged the many technical chal-
lenges associated with the detection of disease-causing microbes in food—from
the collection of samples to the detection of tiny populations of bacteria in food
that are nevertheless capable of producing severe disease if ingested—he also
177

provided several examples of recent technological advances that have enabled

researchers to identify food contaminants in “real time” (a relative term in the
food industry, measured by the length of time the monitoring agency has to act
upon detecting contamination), as well as targeted sampling techniques that can
boost the efficiency of food safety systems.
Besser, by contrast, concludes that while microbial monitoring has its place,
particularly in high-risk situations (e.g., botulinum toxin in milk; see Chapter 4),
a better return on investment is likely to be achieved through increased funding of
foodborne disease surveillance programs. Notable among these is PulseNet, which
tracks diseases through standardized pulsed-field gel electrophoresis (PFGE) pro-
tocols (see Tauxe in Chapter 3 for descriptions of PulseNet and other foodborne
disease surveillance programs). Another source of information on foodborne dis-
ease is captured by the U.S. Department of Agriculture (USDA) Consumer
Complaint Monitoring System (CCMS), and is described in the second contribu-
tion to this chapter by Kimberly Elenberg and Artur Dubrawski. CCMS
uses an algorithm-based tool that organizes and analyzes data concerning food-
associated symptoms or foreign objects present in food in real time in order to
provide early warning of a foodborne threat. The database is used to record, evalu-
ate, and track all consumer food complaints involving meat, poultry, and egg
products. Based on its proven ability to detect low-amplitude signals amid noisy
data, CCMS appears poised to join the “network of networks” that constitute the
U.S. foodborne disease surveillance system.
SYSTEMS TO DETECT MICROBIAL CONTAMINATION

OF THE FOOD SUPPLY
John M. Besser, M.S.1
Minnesota Department of Health
Increasing concern about threats to our food supply caused by microbial con-
tamination, either intentional or accidental, has resulted in the establishment of
many local, national, and global networks to address the problem, each with its
own function and acronym (GAO, 2003, 2004), as shown in Table 5-1. Although
none of these networks by itself constitutes a complete surveillance system, each
serves some part of a broader food surveillance effort. Such surveillance efforts
fall into two main categories: (a) those involving direct detection of microbial
pathogens in food ingredients, products, or production environments (referred to
as food monitoring); and (b) those involving the collection of human or animal
foodborne disease data to identify problems in the food supply through analyses
1Clinical Laboratory Manager, Public Health Laboratory.

SURVEILLANCE OF THE FOOD SUPPLY 179
TABLE 5-1 Networks and Resources for Food Safety

Acronym Program Name
Biosense Biosense (CDC)
CAHFSE Collaboration in Animal Health and Food Safety Epidemiology (USDA;
APHIS, ARS, FSIS)
CaliciNet CaliciNet (CDC)
eFORS Electronic Foodborne Outbreak Reporting System (CDC)
eLEXNET Electronic Laboratory Exchange Network
eLRN Environmental Laboratory Response Network
Epi-X Epidemic Information Exchange
Essence Electronic Surveillance System for Early Notification of Community-based
Epidemics
FERN Food Emergency Response Network
FoodNet Foodborne Disease Active Surveillance Network
GEMS Global Environmental Monitoring System
Global Salm-Surv Global Salmonella Survey (WHO)
GOARN Global Outbreak Alert and Response Network
GPHIN Global Public Health Intelligence Network
HAN Health Alert Network
ICLN Integrated Consortium of Laboratory Networks
IDSA-EIN Infectious Disease Society of America Emerging Infections Network
INFOSAN International Food Safety Authorities Network
LRN Laboratory Response Network
NAHSS National Animal Health Surveillance System
NARMS National Antibiotic Resistance Monitoring System
NEDSS National Electronic Disease Surveillance System
NETSS National Electronic Telecommunications System for Surveillance
NPDN National Plant Diagnostic Network
NRDM National Retail Data Monitor
PulseNet PulseNet (CDC)
RASFF Rapid Alert System for Food and Feed
RODS Real-time Outbreak and Disease Surveillance
TEPHINET Training Programs in Epidemiology and Public Health Interventions
Network
UNEX Unexplained Death and Serious Illness
SOURCE: Besser (2005).
that detect clusters of cases and disease trends (referred to as disease surveil-
lance). Within each of these two broad categories, various approaches are used,
each with strengths and limitations.
The ultimate goal of all food safety programs is to prevent contaminated
products from reaching the consumer. Since the 1950s, Hazard Analysis Critical
Control Point (HACCP) programs have attempted to achieve this by identifying,
monitoring, and correcting hazards that may occur anywhere in the farm-to-table
continuum. Although HACCP programs have been useful, no prevention pro-
gram can be 100 percent effective. These efforts are challenged by the complex-

ity and ever-changing character of food production and distribution systems, by

the limitations of human behavior, and, most recently, by the potential threat of
intentional attacks on the food supply. Consequently, there is an increasing de-
mand to identify and close gaps in food safety by microbiological testing. Choos-
ing the best strategy to accomplish this, however, is difficult. Inherent limitations
of methods to detect microbial contamination make strategic choices complex
and less intuitive.
Strengths and Limitations of Food Monitoring

Direct testing of food prior to consumption is currently used primarily to
monitor the efficacy of HACCP programs. Examples of monitored processes in-
cludes oyster farming (beds monitored for fecal contamination), milk production
(monitored for somatic cell counts as a check on herd health), and ready-to-eat
meat and poultry product production. Lot-by-lot testing as a means of assuring
food safety is restricted to a few high-risk foods. Effluent from sprout farms is
monitored for Salmonella and E. coli O157:H7, and some beef trim is monitored
for E. coli O157:H7 before being made into hamburger. The use of lot-by-lot
microbial monitoring to protect food is attractive because, unlike disease surveil-
lance, food monitoring can potentially prevent initial cases. This may be the only
option for high-risk situations where initial cases are intolerable from a societal
point of view. For example, Wein et al. described a model to predict what might
happen if 10 grams of botulism toxin was introduced into a milk tanker or silo
(Wein and Liu, 2005). Even with optimum disease surveillance, hundreds of thou-
sands of people would be expected to get sick or die by the time the problem was
identified and corrected. Food monitoring may add a layer of protection as part of
a comprehensive biosecurity plan assuming the basic limitations of food monitor-
ing can be overcome.
Intrinsic limitations of food monitoring are related to sampling and testing
(see Table 5-2). Of these, sampling issues represent the greatest challenge. Be-
cause the denominator of potential food vehicles could be the total amount of
food available for consumption, that amount could be more than 350 billion
pounds per year, as estimated by the USDA in 1997 (Kantor et al., 1997). Addi-
tionally, microbial contamination of food can be introduced with or without am-
plification by bacterial growth at any step between production and consumption.
Consequently, the potential units to be analyzed include separate food plants,
individual animals, all process lots, individual servings, and everything in be-
tween. Furthermore, while grossly contaminated food may be easily detected by
discoloration, odor, or other manifestations of degradation, most types of micro-
bial contamination with infectious agents leave no visual, olfactory, or tactile
clues. Recognition of such microbial contaminates requires direct detection or
isolation by growth in culture. But the sampling of food for this purpose is highly
problematic. The distribution of microbial contaminates in a product is usually

TABLE 5-2 Comparison of Food Monitoring and Disease Surveillance

Food Monitoring Disease Surveillance
Prevention potential Prevention of initial Secondary prevention only
cases possible
Speed of detection Potentially fast Generally slower
Testing
Sampling Issues
Denominator (United States) 356 billion lbs food/year 281 million people (U.S.)b
(U.S.)a
Sample selection By risk or control point Self-selection
Agent distribution in sample Uneven Generally homogenous
Contamination introduction Many Mouth
points
Testing Issues
Pathogen load Generally low Generally high
Matrices Complex, varied Predictable
Damaged cells Common Less common (prior antibiotic use)
Inhibitory substances Common Rare
Predictive value of broad Low High
surveillance (monitoring)
Cost of broad surveillance Very high Relatively low
(monitoring)
aKantor et al. (1997)
b2000 U.S. census data.
uneven, making sampling decisions critical to success. This may be especially

true for pathogens introduced intentionally and sporadically into the food supply.
Finally, the amount of confidence in the safety of food screened by testing is
proportional to the amount of sampling done and inversely proportional to the
prevalence of the pathogen. High levels of assurance require high sampling and
expense rates, especially for rare pathogens.
In addition to the limitations imposed by sampling issues, the actual sensitiv-
ity of testing methods greatly impacts the usefulness of food monitoring. Under
some circumstances microbes may exist in food in very small quantities and still
cause significant problems when consumed by a large number of people. For
instance, in the 1994 nationwide ice cream-associated outbreak of Salmonella
enteritidis, less than six organisms per serving were found in contaminated lots,
which is far below the standard infective dose and detection limit of most tests.
Nevertheless, the wide distribution of the product caused an estimated 224,000
people to become ill (Hennesey et al., 1996). The sensitivity of laboratory tests

can be increased by increased sampling. However, the cost of testing and the cost
of food lost to testing increases proportionately. Bacterial amplification occurs in
improperly prepared or stored food, and during refrigeration of products contami-
nated with psychotrophic bacteria such as Listeria monocytogenes. In these in-
stances, bacteria or their toxins may be present in large quantities and are rela-
tively easy to detect. This is not the case with foods contaminated during
production, storage, transport, or preparation that have been otherwise handled
properly, or with foods contaminated by viruses and parasites, such as Norovirus
or Cyclospora cayetanesis, which do not amplify in food. In addition, microbial
cells tend to become damaged in food, and many food matrices (a food matrix
represents the components of food as consumed) interfere with testing proce-
dures. Damaged cells may readily revive under the perfect culture conditions of
the human body, but fare less well under the relatively harsh conditions of in vitro
culture. The problems of food testing are exemplified by the 1996 E. coli O157:H7
outbreak in Japan where, despite excellent epidemiological evidence linking 6,000
cases of disease to radish sprouts, pathogens could not be recovered from prod-
ucts after extensive screening (Michino et al., 1999). On the other side of the
equation, pathogens found in food may or may not pose a threat to public health.
For instance, not all Listeria monocytogenes found in food are likely to cause
disease in people (Jacquet et al., 2004), but discovery of nonvirulent microorgan-
isms by food monitoring may lead to unnecessary and expensive regulatory
action.
New technology has lowered the threshold for food monitoring utility.
Nucleic acid-based assays such as polymerase chain reaction (PCR) can in theory
solve in vitro viability issues of microorganisms in food and improve test sensi-
tivity and specificity. However, the technology does not change basic issues
related to sampling, low pathogen load, and test interpretation. Also, nucleic
acids typically survive microbial inactivation procedures such as pasteurization
(Hilfenhaus et al., 1997), and PCR reactions are inhibited by substances in many
food matrices, adding new interpretive challenges. Biosensor technology, while
still in its infancy, holds potential for real-time monitoring of foods (Anderson
and Taitt, 2005). Future developments may improve biosensor detection limits
and specificity, which are currently inadequate for most analytes. Although en-
couraging in terms of potential throughput and per-sample cost, biosensor tech-
nology has many of the same theoretical limitations described for nucleic acid
and conventional technology.
The sum of sampling and sensitivity issues make food monitoring impracti-
cal as a broadly applied tool for protecting the food supply. Mass food testing
would be extremely expensive and would have very low predictive values. Lot-
by-lot testing may be considered if (1) the risk cannot be reduced by process
changes or engineering controls, (2) if a test is available that can detect the con-
taminant at suitably low levels, (3) if the test turnaround time does not interfere
unduly with product requirements, and (4) if the cost to the consumer is justifiable.

Strengths and Limitations of Disease Surveillance

One hundred percent of food consumed by humans is essentially subject to a
natural bioassay in the consumers. Each case of disease represents some failure of
our food protection systems that can potentially be corrected. Disease surveil-
lance is the collection of information that can, in theory, detect problems any-
where in the food supply chain. The denominator for U.S. disease surveillance is
281 million discrete individuals (2000 census data). Unlike food products, people
can announce that they have been contaminated by presenting themselves to their
physician or by calling a foodborne disease complaint line. Microbial pathogens
tend to be evenly distributed through specimens such as feces due to extended
mixing in the digestive tract.
Pathogen load is not generally an intrinsic limiting factor in foodborne dis-
ease surveillance, as microbial amplification is part of the pathogenesis of most
foodborne infections. There are exceptions to this generalization, such as hepati-
tis A or hemolytic uremic syndrome due to E. coli O157:H7 where presenting
symptoms are secondary to primary acute infections, and occur at a point in the
disease during which pathogen numbers are declining and may limit detection.
Detection is also a problem for many enterotoxins, heavy metals, and other
foodborne toxins. Test specificity is less of a problem in disease surveillance than
food monitoring as established pathogens detected in ill humans or animals are
highly correlated with disease.
Foodborne disease surveillance also has inherent limitations. The time inter-
val between a contamination event and a surveillance signal may be considerable.
The process can involve many sequential steps. At a minimum, disease surveil-
lance requires (1) exposure, (2) incubation, and (3) presentation to a physician or
other notification. In addition, pathogen specific surveillance may also require
(4) collection of specimens, (5) diagnostic laboratory testing, (6) reporting to
public health authorities, (7) submission of samples to public health laboratories,
(8) further laboratory characterization and reporting, (9) analysis of surveillance
data, (10) interview of patients, (11) outbreak investigation, (12) case-control
study, and (13) national reporting. As a result, detection and investigation of out-
breaks can be a lengthy process. In addition, foodborne disease surveillance can-
not by definition prevent initial cases.
Although disease surveillance cannot prevent initial cases, it has been very
effective at (1) preventing ongoing transmission, (2) identifying unforeseen prob-
lems in the food and water supplies, and (3) identifying trends in foodborne dis-
ease that can guide public health policy (Besser et al., 2003). For instance, be-
tween 1997 and 2004 PulseNet and associated disease surveillance activities
played a prominent role in the recall of millions of pounds of contaminated food
withdrawn from U.S. markets. Examples of outbreak investigations that uncov-
ered unsafe practices include the 2003 outbreak due to vacuum-packed blade-
tenderized steaks allowed identification of the manufacturing process that ren-

dered the product unsafe under current cooking recommendations (Laine et al.,
2005) and the 2005 nationwide outbreak of S. typhimurium associated with the
use of uncooked potentially contaminated products in finished ice cream leading
to changed use recommendations (Center for Food Safety and Applied Nutrition,
2005). Changes in the U.S. regulatory policy occurred after Listeriosis outbreak
investigations highlighted the problems associated with hot dogs (Mead et al.,
2006) and turkey deli meat (Gottlieb et al., 2006). Finally, disease surveillance
facilitates discovery of significant trends, such as increasing fluoroquinolone re-
sistance in human infections caused by the use of agricultural antibiotics (Smith
et al., 1999) or problems associated with increasing importation of fresh produce
(Naimi et al., 2003). As much as we may want to prevent initial cases through
food monitoring, humans are the best possible culture media and bioassay for
detection of human disease agents, and disease surveillance will likely remain
our most powerful detection tool for detecting problems in the food supply for
years to come.
Types of Foodborne Disease Surveillance Programs

The three most common foodborne disease surveillance strategies, complaint
or notification systems, pathogen-specific surveillance, and syndromic surveil-
lance, differ in their application and limitations (see Table 5-3). Complaint and
notification systems use a wide variety of factors to link cases of disease. State or
local governments, industry, or institutions gather reports of diarrheal illnesses
possibly linked to foodborne exposure. The typical scenario is recognition among
attendees at a church potluck of group illness or a physician noticing a cluster of
cases with some commonality, such as a similar syndrome. Because these sys-
tems do not rely on identification of specific pathogens, they can potentially de-
tect a disease cluster caused by any disease agent, including unknown or modi-
fied agents, in a relatively short time. This makes complaint systems a valuable
adjunct to pathogen-specific surveillance. The information most often used to
TABLE 5-3 Comparison of Disease Surveillance Approaches

Pathogen-specific Notification/ Syndromic Surveillance
Surveillance Complaint (nonspecific health data)
Timeliness Relatively slow Fast Fast
Sensitivity of High Intermediate Low
cluster detection
Types of agents Standard agents under Standard or Standard or
surveillance only unconventional unconventional
Strengths Detection of widespread Detection of local Detection of large, local
outbreaks outbreaks outbreaks

link cases is personal recognition, which is a useful method for detection of local
events but by itself is less valuable for detection of low-level widespread con-
tamination events. However, outbreaks identified through complaint systems may
be linked together to detect widespread events. This can be accomplished through
disease communication systems such as Epi-X, reporting systems such as eFORS,
or through pathogen-specific systems such as PulseNet, once an agent has been
identified. All of these mechanisms were used to detect the 1998 international
outbreak of Shigella sonnei and enterotoxigenic E. coli caused by contaminated
parsley (Naimi et al., 2003).
Salmonella surveillance is one of the oldest pathogen-specific surveillance
systems. Routine collection of information about S. typhi began in 1912 and was
expanded to include all Salmonella in 1942. Serotype-specific Salmonella sur-
veillance began in 1963 (Swaminathan et al., 2006). Refinement of the case
definition due to the more specific serotype information causes outbreak cases to
stand out from background sporadic cases and strengthens the association be-
tween illness and a common source. Over the years Salmonella serotype surveil-
lance has uncovered diverse problems in the food supply that might not have
otherwise been discovered, such as persistent low-level contamination of shell
eggs (St. Louis et al., 1988), recurring contamination of pasteurized ice cream
during transport (Hennesey et al., 1996), and problems with sprout production
(CDC, 2002a). In 1997 Bender et al. showed that the benefits of increased speci-
ficity of Salmonella serotype surveillance could be extended to E. coli O157:H7
through the routine use of PFGE (Bender et al., 1997). The Centers for Disease
Control and Prevention (CDC) expanded this capability nationwide with the cre-
ation of PulseNet USA in 1998 (Swaminathan et al., 2001) and globally with
PulseNet International. The primary factors used to link cases to each other are
disease agent and time rather than personal recognition. This dramatically low-
ered the number of reported cases needed to detect widespread outbreaks. A
good example is the 2003 outbreak of vacuum-packed blade-tenderized steaks,
which was initially detected by two cases with unique PFGE subtypes and re-
sulted in the recall of 739,000 pounds of potentially contaminated product dis-
tributed in multiple states (Laine et al., 2005). Although very sensitive and spe-
cific, by definition pathogen-specific surveillance only works for those agents
under surveillance. Acts of bioterrorism or naturally occurring outbreaks caused
by agents not under surveillance would not be detected by this mechanism nor
would outbreaks due to unknown agents. Eighty-two percent of cases of food-
borne illnesses are thought to be due to unrecognized agents (Mead et al., 1999).
Although pathogen-specific surveillance samples only a small percentage of to-
tal foodborne disease cases, it nevertheless has been one of the most robust indi-
cators of problems in the food supply.
Syndromic surveillance is the third type of disease surveillance that could
potentially be applied to detection of problems in the food supply. In recent years,
this term has generally applied to broad monitoring of nonspecific health data

such as diarrheal illness or markers of illness, such as Imodium sales. This is in

contrast to complaint or notification systems described above which, while utiliz-
ing nonspecific health data such as diarrheal illness, are narrowly focused on
recognized clusters or specific complaints. Several large networks have been es-
tablished to conduct syndromic surveillance, such as BioSense, the Electronic
Surveillance System for Early Notification of Community-based Epidemics
(ESSENCE), and National Retail Data Monitor (NRDM). Potential outbreaks are
detected by spikes in the incidence of common syndromes or surrogate indicators
rather than agent or personal recognition, so in theory these systems should be
able to detect problems due to known or unknown agents. The primary problem
with syndromic surveillance is an unfavorable signal-to-noise ratio. The number
of cases needed to trip the system is inversely proportional to the specificity.
Thus, syndromic surveillance based on nonspecific health data is useful for de-
tecting very large local events but is very insensitive to small or widespread
events. One of the nation’s largest systems was established in New York City
(NYC) in 2001 (Das et al., 2005; Heffernan et al., 2004). In one year of surveil-
lance involving 2.5 million patient records, the NYC surveillance system had 18
spikes in reports of diarrhea and vomiting syndromes clustered in three outbreak
periods. One of the spikes was followed by five institutional outbreak investiga-
tions (detected by other mechanisms), but it is unclear whether the surveillance
data itself would have been of sufficient specificity to identify the outbreaks.
Surveillance for specific rare syndromes such as hemolytic uremic syndrome
or Guillain-Barre syndrome resembles pathogen-specific surveillance more than
syndromic surveillance in terms of sensitivity and specificity. Surveillance for
unexplained death or critical illnesses with possible infectious etiology is a par-
ticularly important type of surveillance. Although postmortem diagnosis of ill-
ness can be problematic, unexplained death and critical illnesses may be the only
clue that a major foodborne or other type of bioevent has occurred. Surprisingly,
only three such programs in the United States exist.
Existing Networks
A large array of acronyms are used to describe existing networks that play
serve some role in protecting the food supply (see Table 5-1). Included are
communication networks (HAN, Epi-X, INFOSAN, RASFF), surveillance data
management systems (NETSS, NEDSS), syndromic surveillance projects and
tools (Biosense, UNEX, ESSENCE, NRDM, RODS), a surveillance system de-
signed to determine the burden of foodborne disease (FoodNet), outbreak re-
sponse and reporting networks (eFORS, GOARN), animal surveillance networks
(NAHSS, CAHFSE), an enteric disease antibiotic-resistance monitoring network
(NARMS), laboratory data handling networks (eLEXNET, PulseNet, Global
Salm-Surv, CaliciNet), and laboratory response networks (LRN, FERN, NAHSS,
NPDN, eLRN, ICLN). Laboratory response networks such as LRN and FERN

have protocols for testing suspect food items but currently have no role in pri-
mary detection of problems in the food supply. Current food-monitoring pro-
grams are designed to support HACCP programs or monitor for specific patho-
gens in high-risk foods but play little role in broad monitoring for unexpected
introduction of contaminants into the food supply. Outbreak reporting systems
such as eFORS and GOARN can potentially detect national or international out-
breaks by linking local outbreaks without previously recognized connection.
PulseNet and associated foodborne disease surveillance programs are currently
the most sensitive methods for detecting unforeseen problems in the food supply.
Successes, Problems, and Promises of PulseNet

and Associated Foodborne Disease Programs
Since its inception in 1998, PulseNet has been a key tool in the detection of a
wide range of problems in the food supply, such as Listeria monocytogenes in
luncheon meat; Shigella sonnei in imported parsley; E. coli O157:H7 in meats,
unpasteurized juices, and produce; and Salmonella in almonds and custom ice
cream. Estimating cost and benefits of surveillance programs is difficult and rare,
but it is becoming clear that prevention benefits of PulseNet and associated ac-
tivities far outweigh its costs. Bell and colleagues estimated that 800 cases of
disease were prevented by the recall of 250,000 hamburgers after detection of the
1993 E. coli O157:H7 outbreak on the West Coast of the United States, which
occurred prior to development of PulseNet (Bell et al., 1994). Since that time,
PulseNet findings have directly or indirectly led to the recall of many times that
amount of contaminated products and enabled continuing contamination prob-
lems to be detected and rectified. In 1997, PulseNet enabled the Colorado Depart-
ment of Health to detect an outbreak caused by potentially contaminated beef that
led to the recall of 25,000,000 pounds of beef, and 18,600,000 pounds in 2002
(CDC, 2002b). Elbasha et al. estimated that the Colorado PulseNet system would
recover all costs if only five cases per year were prevented (Elbasha et al., 2000).
A single case of hemolytic uremic syndrome caused by E. coli O157:H7 can cost
up to $453,675 in medical costs alone (Buzby et al., 1996).
The PulseNet system is currently used to track nine diseases by use of stan-
dardized PFGE protocols, but potentially can be used to track any infectious dis-
ease confirmed by detection of a specific microorganism. It increases the inherent
sensitivity of disease surveillance by refining the case definition and provides a
platform for rapid communication and comparison of results. More specific case
definitions improve the signal-to-noise ratio, and permits small, yet significant
events to be detected. PulseNet has recently bridged the gap between food moni-
toring and disease surveillance data by incorporating data from the USDA and
FDA monitoring and investigation programs. An outbreak of Salmonella Kiambu
associated with beef jerky in 2003 was detected by linking PFGE patterns from
food monitoring to disease surveillance patterns, resulting in the recall of 22,000

pounds of contaminated product. PulseNet International has expanded the net-

work worldwide and has already had early successes at tracing an international
outbreak of shigellosis associated with airline meals (Gaynor et al., 2004) and an
outbreak associated with ground beef from a U.S. military installation (CDC,
2004). In spite of its history of successes and awards, PulseNet operates unevenly
around the country, with most activity associated with a small number of states.
Surveys by the Association of Public Health Laboratories and Council for State
and Territorial Epidemiologists found important deficits in the nation’s capacity
to detect, investigate, and respond to food safety problems (Association of Public
Health Laboratories, 2003; Council of State and Territorial Epidemiologists,
2004). Most laboratory and epidemiology programs are understaffed and
underfunded, leaving many food safety problems undetected and unresolved. As
a result of these issues, PulseNet operates at only a fraction of its potential, with
its greatest promise yet to be exploited.
Other Potential Systems

Although PulseNet is the most developed system for detection of problems
in the food supply, it is not the only useful approach. Clusters of notifiable dis-
ease can potentially be detected through analysis of data from the Public Health
Laboratory Information System, and widespread events have been detected using
the CDC’s Electronic Outbreak Reporting System (eFORS) and Epi-X postings.
Because the etiology of outbreaks reported through eFORS or Epi-X can be
known or unknown, these systems can capture complaint data not associated with
a nationally notifiable pathogen. Like PulseNet, eFORS is not being used to its
full potential. Resource limitations at the state and local level limit detection and
reporting of outbreaks. Completion of the National Electronic Disease Surveil-
lance System (NEDSS) will provide a backbone for national surveillance, but the
lack of standard forms for interviewing cases will continue to limit outbreak de-
tection in the absence of specific agent information.
Surveillance for unexplained death and serious illness caused by possible
infectious etiology has significant potential for use in detecting serious problems
in the food supply, such as intentional tampering. As much as we would like to
prevent death, it is not possible to anticipate every possible mode by which patho-
gens could be intentionally or unintentionally introduced into the food supply. It
seems that at a minimum we should be able to know that such an event is occur-
ring so that appropriate control measures can be instituted to prevent additional
cases. Investigation of unexplained death possibly caused by infectious causes is
expensive and difficult. Nevertheless, national resources dedicated for this pur-
pose is very limited and includes only small CDC-funded programs in California,
Minnesota, and Connecticut.

Conclusions
Targeted microbial monitoring of selected high-risk foods and processes
plays an important role in protecting the food supply. Expansion of monitoring
activities may be justified in situations where initial cases cannot be tolerated.
However, broadly applied food-monitoring programs are likely to be costly and
insensitive due to intrinsic sampling and testing limitations. Foodborne disease
surveillance programs cannot prevent initial cases, but are nevertheless the most
sensitive method for detecting unrecognized problems in the food supply. Cur-
rent foodborne disease surveillance programs, such as PulseNet, are operating at
only a fraction of their potential, largely because of underfunding. Disease sur-
veillance programs have a high benefit-to-cost ratio and represent a basic func-
tion of public health. Real-time foodborne disease surveillance at the state, fed-
eral, and international levels is an achievable, relatively inexpensive goal that
would have an immediate, positive impact on food safety.
THE CONSUMER COMPLAINT MONITORING SYSTEM:

ENHANCING DISCOVERY AND MITIGATION OF FOODBORNE
THREATS TO HEALTH THROUGH PATTERN SURVEILLANCE AND
MULTIPLE-ATTRIBUTE ALGORITHMS
CDR Kimberly Elenberg, M.S., R.N.2 and Artur Dubrawski, Ph.D.3
The Consumer Complaint Monitoring System (CCMS), owned by the Food

Safety and Inspection Service (FSIS) of the USDA, is a database used to record,
evaluate, and track all consumer food complaints involving meat, poultry, and
egg products. It has assisted public health professionals with evaluating approxi-
mately 4,000 consumer complaints since January 2001.
Consumer complaints are received through phone calls to the USDA field
compliance officers, and through the toll-free phone number of the Meat and
Poultry Hotline. Adverse food event reports can also be received and managed
for imported products and school lunch products distributed through USDA’s
Food and Nutrition Service. Complaints typically involve reports of illness, in-
jury, foreign objects, contamination (including chemical contamination), allergic
reactions, and improper labeling.
To further improve food safety and security, FSIS’ Office of Public Health
Science developed the Consumer Complaint Monitoring System II (CCMS II).
CCMS II complements the existing foodborne threat surveillance systems Pulse-
2Food Safety Inspection Service, United States Department of Agriculture; Office of Food Defense
and Emergency Response until June 2006, currently Commander, Director of Medical Readiness,
USPHS.
3Carnegie Mellon University; Auton Lab, The Robotics Institute.

Net and FoodNet (see Summary and Assessment and Tauxe in Chapter 3). Al-
though PulseNet and FoodNet actively track pathogen strains isolated from hu-
mans with foodborne disease, CCMS employs a form of passive surveillance to
provide the earliest possible warning of a wide variety of foodborne threats. This
system rapidly organizes and analyzes the incoming complex, multivariate data
from consumer complaints concerning such adverse events as food-associated
symptoms or foreign objects present in food.
As other contributors to this workshop have noted, the possible sources of
foodborne contamination are extremely vast. Although using adverse food re-
ports to assess possible foodborne threats presents the considerable challenge of
discerning significant trends against a background of random noise, this approach
also offers several benefits. Unlike FoodNet and PulseNet, CCMS is not limited
to assessing known pathogens, which account for a minority of foodborne illness;
unknown agents account for 81 percent of U.S. foodborne illnesses and hospital-
izations and 64 percent of deaths (Mead et al., 1999). In addition to tracking
possible emerging foodborne pathogens, including intentionally modified organ-
isms, CCMS examines chemical and foreign object contaminants in food (the
latter is the subject of 80 percent of all adverse food reports received by USDA).
Finding Patterns in Consumer Complaints

Surveillance activities involving CCMS are conducted by both the FSIS Of-
fice of Public Health Science and the FSIS Office of Food Defense and Emer-
gency Response. The analytical component of CCMS, called Emerging Patterns
in Food Complaints (EPFC), developed in collaboration with Artur Dubrawski’s
group at Carnegie Mellon University, employs computational methods, including
multiple-attribute algorithms and Bayesian probability models, to detect patterns
in complaints received by CCMS—data that are too voluminous and complex for
the human mind to grasp. Public health analysts examine the resulting patterns
and assess the likelihood that they represent material foodborne threats. CCMS
tracks several variables associated with each report, including the date, time, and
location of the event; associated symptoms and their onset times or descriptions
of foreign objects; and the type and purchase origin of the suspected product.
When two or more similar complaints are received within a reasonably close
time span (the particular range of interest varies depending on the shelf life of the
involved food), the EPFC statistically quantifies their relatedness. It compares
the group of variables that makes up each consumer complaint with a database of
approximately 4,000 past cases and also with a series of 42 causal models we
have developed based on passive surveillance records of adverse food events.
The results that public health analysts receive indicate the most similar past cases,
the likeliest causal scenarios, and the most probable case-cause combinations
matching the complaints under investigation. For example, EFPC comparisons
might find matches between the symptoms and locations associated with two

contemporary cases, but little similarity between the product sources; when these
results are in turn compared with the range of causal models, the best match is
with a community illness not related to a specific product. If CCMS continued to
receive similar complaints, we would alert the appropriate state health depart-
ment to investigate likely causes of community illness, such as water contamina-
tion. By contrast, a series of closely timed complaints with high similarity and a
common causal scenario would signify a foodborne outbreak; in that situation,
investigators would pursue this hypothesis by testing the suspected product(s)
and comparing the results with the PulseNet database. To date, the system has
recognized several outbreaks: of Salmonella, Listeria monocytogenes, and E. coli
O157:H7.
In addition to providing investigators with valuable leads for tracing the ori-
gin of suspected and confirmed contaminants, CCMS can further aid such man-
agement decisions as the identification of an emergency response that is appro-
priate to the nature, location, and extent of a threat. CCMS data can also be used
to alert food producers to more general food safety issues associated with specific
processes and/or plants. For example, a large number of apparently diverse com-
plaints associated with products from a single company might reflect on overall
condition, such as substandard sanitation. When many complaints point to a single
causal model (for example, a metal foreign object in a specific product), EPFC
analysis can pinpoint the source of the problem and lead to its solution (routinely
inspect the product with a metal detector). This process can occur rapidly. For
example, within 30 minutes of a report of students being injured with glass in
their school lunches, CCMS can identify and investigate the implicated food com-
modities and, if necessary, communicate with the affected schools to ensure that
foods containing the product are removed from cafeteria lines immediately.
Future Expansion of CCMS

Based on the demonstrated ability of the analytical component of CCMS to
detect interesting, low-amplitude signals in sparse, noisy data, further expansion
of the system is warranted. Although currently operated on a state-by-state basis,
CCMS will soon permit state public health officials to track pathogens and con-
taminants beyond their borders and to view a national “snapshot” of adverse food
events in real time. Data from earlier points in the farm-to-table continuum, which
would be especially valuable in identifying patterns associated with zoonotic dis-
ease, could be analyzed in conjunction with consumer complaints as part of an
integrated national biosurveillance system. As CCMS grows in importance and
visibility, it will be important to establish surge capacity to deal with the expected
high volume of complaints that could arise during a foodborne outbreak.
Early detection is the key to mitigating the consequences of foodborne ill-
ness. Improving the timeliness of data collection, pattern detection, and commu-
nication of information about adverse food events using CCMS and related pas-

sive surveillance technologies requires better tools as well as changes in the way
these events are reported. Finally, because tools such as CCMS are only as effec-
tive as the humans who use them, we must educate everyone who plays a role in
food safety, and encourage collaboration at all levels.
REFERENCES
Anderson GP, Taitt CR. 2005. Biosensor-based detection of foodborne pathogens. In: Fratamico PM,
Bhunia A, Smith JL, Eds. Foodborne Pathogens: Microbiology and Molecular Biology. Wy-
mondham, UK: Academic Press.
APHL (Association of Public Health Laboratories). 2003. A Recipe for Stronger Food Safety Pro-
grams. Washington, D.C.: Association of Public Health Laboratories.
Bell BP, Goldoft M, Griffin PM, Davis MA, Gordon DC, Tarr PI, Bartleson CA, Lewis JH, Barrett
TJ, Wells JG, Baron R, Kobayashi J. 1994. A multiple outbreak of Escherichia coli O157:H7-
associated bloody diarrhea and hemolytic uremic syndrome from hamburgers: The Washington
State experience. Journal of the American Medical Association 272(17):1349–1353.
Bender JB, Hedberg CW, Besser JM, Boxrud DJ, MacDonald KL, Osterholm MT. 1997. Surveillance
for Escherichia coli O157:H7 infections in Minnesota by molecular subtyping. New England
Journal of Medicine 337(6):388–394.
Besser J. 2005 (October 25). Session IV: What Are the Tools and Technologies for “Real Time”
Surveillance of the Food Supply for Conventional and Unconventional Adulterants? Presenta-
tion at the Forum on Microbial Threats Workshop Meeting, Foodborne Threats to Health: The
Policies and Practices of Surveillance, Prevention, Outbreak Investigations, and International
Coordination, Washington, D.C., Institute of Medicine, Forum on Microbial Threats.
Besser J, Beebe J, Swaminathan B. 2003. Investigation of foodborne disease outbreaks. In: Pfaller
MA, Ed. Manual of Clinical Microbiology. 8th ed. Washington, D.C.: American Society for
Microbiology Press.
Buzby JC, Roberts T, Lin JC-T, MacDonald JM. 1996. Bacterial Foodborne Disease: Medical Costs
and Productivity Losses. Agricultural Economics Report No. 741. Washington, D.C.: Depart-
ment of Agriculture.
CDC (Centers for Disease Control and Prevention). 1997. Escherichia coli O157:H7 infections asso-
ciated with eating a nationally distributed commercial brand of frozen ground beef patties and
burgers—Colorado, 1997. Morbidity and Mortality Weekly Report 46(33):777–778.
CDC. 2002a. Outbreak of Salmonella serotype kottbus infections associated with eating alfalfa
sprouts—Arizona, California, Colorado, and New Mexico, February-April 2001. Morbidity and
CDC. 2002b. Multistate outbreak of Escherichia coli O157:H7 infections associated with eating
ground beef—United States, June-July 2002. Morbidity and Mortality Weekly Report 51(29):
637–639.
CDC. 2004. Escherichia coli O157:H7 infections associated with ground beef from a U.S. military
installation—Okinawa, Japan, February 2004. Morbidity and Mortality Weekly Report 54(2):
40–42.
Center for Food Safety and Applied Nutrition. 2005 (August 19). Bulletin to the Food Service and
Retail Food Store Industry Regarding Cake Batter Ice Cream and Similar Products. [Online].
Available: http://www.cfsan.fda.gov/~ear/ret-batt.html [accessed April 10, 2006].
Council of State and Territorial Epidemiologists. 2004. National Assessment of Epidemiological Ca-
pacity: Findings and Recommendations. Washington, D.C.
Das D, Metzger K, Heffernan R, Balter S, Weiss D, Mostashari F. 2005. New York City Department
of Health and Mental Hygiene. Monitoring over-the-counter medication sales for early detection
of disease outbreaks—New York City. Morbidity and Mortality Weekly Report 54(Suppl):41–46.

Elbasha EH, Fitzsimmons TD, Meltzer MI. 2000. Costs and benefits of a subtype-specific surveil-
lance system for identifying Escherichia coli O157:H7 outbreaks. Emerging Infectious Diseases
6(3):293–297.
FAO (Food and Agriculture Organization of the United Nations). 2004. International Cooperation on
Food Contamination and Foodborne Disease Surveillance. Second FAO/WHO global forum of
food safety regulators. [Online]. Available: http://www.fao.org/docrep/meeting/008/ae163e.htm
[accessed February 1, 2006].
GAO (General Accountability Office). 2003. Bioterrorism. A Threat to Agriculture and the Food
Supply. [Online]. Available: http://www.gao.gov/new.items/d04259t.pdf [accessed April 10,
2006].
GAO. 2004. Emerging Infectious Diseases: Review of State and Federal Disease Surveillance Ef-
forts. [Online]. Available: http://www.gao.gov/new.items/d04877.pdf [accessed April 10, 2006].
Gaynor K, Kanenaka B, Colindres R, Mintz E, Kalluri P, Kitsutani P, Nakata M, Wedel S, Boxrud D,
Jennings D, Yoshida H,Tosaka N, Park SY, Effler PV. 2004 (August). International Outbreak of
Shigella sonnei among Airline Passengers—Honolulu, Hawaii. Presentation abstract, Session
C, 54th Annual Epidemic Intelligence (EIS) Conference, April 11–15, Atlanta, GA.
Gottlieb SL, Newbern EC, Griffin PM, Graves LM, Hoekstra RM, Baker NL, Hunter SB, Holt KG,
Ramsey F, Head M, Levine P, Johnson G, Schoonmaker-Bopp D, Reddy V, Kornstein L, Gerwel
M, Nsubuga J, Edwards L, Stonecipher S, Hurd S, Austin D, Jefferson MA, Young SD, Hise K,
Chernak ED, Sobel J. 2006. Listeriosis Outbreak Working Group. Multistate outbreak of list-
eriosis linked to turkey deli meat and subsequent changes in US regulatory policy. Clinical
Infectious Diseases 42(1):29–36.
Heffernan R, Mostashari F, Das D, Besculides M, Rodriguez C, Greenko J, Steiner-Sichel L, Balter S,
Karpati A, Thomas P, Phillips M, Ackelsberg J, Lee E, Leng J, Hartman J, Metzger K, Rosselli
R, Weiss D. 2004. New York City syndromic surveillance systems. Morbidity and Mortality
Weekly Report 53(Suppl):23–27.
cine 334(20):1281–1286.
Hilfenhaus J, Groner A, Nowak T, Weimer T. 1997. Analysis of human plasma products: Polymerase
chain reaction does not discriminate between live and inactivated viruses. Transfusion 37(9):
935–940.
Jacquet C, Doumith M, Gordon JI, Martin PM, Cossart P, Lecuit M. 2004. A molecular marker for
evaluating the pathogenic potential of foodborne Listeria monocytogenes. Journal of Infectious
Diseases 189(11):2094–2100.
Kantor LS, Lipton K, Manchester A, Oliveira V. 1997. Estimating and addressing America’s food
losses. Food Review 20(1):2–12. [Online]. Available: www.ers.usda.gov/publications/
foodreview/jan1997/jan97a.pdf [accessed April 10, 2006].
Laine ES, Scheftel JM, Boxrud DJ, Vought KJ, Danila RN, Elfering KM, Smith KE. 2005. Outbreak
of Escherichia coli O157:H7 infections associated with nonintact blade-tenderized frozen steaks
sold by door-to-door vendors. Journal of Food Protection 68(6):1198–1202.
Mead PS, Dunne EF, Graves L, Wiedmann M, Patrick M, Hunter S, Salehi E, Mostashari F, Craig A,
Mshar P, Bannerman T, Sauders BD, Hayes P, Dewitt W, Sparling P, Griffin P, Morse D,
Slutsker L, Swaminathan B. 2006. Nationwide outbreak of listeriosis due to contaminated meat.
Epidemiology and Infection 134(4):744–751. Epub December 1, 2005:1–8.

Michino H, Araki K, Minami S, Takaya S, Sakai N, Miyazaki M, Ono A, Yanagawa H. 1999. Mas-
sive outbreak of Escherichia coli O157:H7 infection in schoolchildren in Sakai City, Japan,
associated with consumption of white radish sprouts. American Journal of Epidemiology
150(8):787–796.
Naimi TS, Wicklund JH, Olsen SJ, Krause G, Wells JG, Bartkus JM, Boxrud DJ, Sullivan M,
Kassenborg H, Besser JM, Mintz ED, Osterholm MT, Hedberg CW. 2003. Concurrent out-
breaks of Shigella sonnei and enterotoxigenic Escherichia coli infections associated with pars-
ley: Implications for surveillance and control of foodborne illness. Journal of Food Protection
66(4):535–541.
Smith KE, Besser JM, Hedberg CW, Leano FT, Bender JB, Wicklund JH, Johnson BP, Moore KA,
Osterholm MT. 1999. Quinolone-resistant Campylobacter jejuni infections in Minnesota, 1992–
1998. Investigation Team. New England Journal of Medicine 340(20):1525–1532.
St. Louis ME, Morse DL, Potter ME, DeMelfi TM, Guzewich JJ, Tauxe RV, Blake PA. 1988. The
emergence of grade A eggs as a major source of Salmonella enteritidis infections. New implica-
tions for the control of salmonellosis. Journal of the American Medical Association 259(14):
2103–2107.
Swaminathan B, Barrett TJ, Hunter SB, Tauxe RV. 2001. CDC PulseNet Task Force. PulseNet: The
molecular subtyping network for foodborne bacterial disease surveillance, United States. Emerg-
ing Infectious Diseases 7(3):382–389.
Swaminathan B, Barrett TJ, Fields P. 2006. Surveillance for human Salmonella infections in the
United States. Journal of AOAC International 89(2):553–559.

Reporting Foodborne Threats:

The Case of Bovine Spongiform
Encephalopathy (BSE)
OVERVIEW
The rapid reporting of foodborne threats is essential to reducing the burden
of foodborne illness, but it also carries direct and indirect costs to individuals,
communities, industries, and national economies. The balance of costs and ben-
efits associated with reporting foodborne threats is clearly illustrated by the
world’s recent and ongoing experience with bovine spongiform encephalopathy
(BSE, or mad cow disease). A series of workshop presentations by contributors to
this chapter explored the biology of BSE and its implications for food safety,
international perspectives on BSE surveillance and prevention, and public health
lessons learned from this disease and its consequences.
A member of the family of diseases known as transmissible spongiform en-
cephalopathies (TSEs; also known as prion diseases), BSE was first identified in
1986 in the United Kingdom and has since been detected in 26 countries (GAO,
2005). In the early 1980s, Stanley Prusiner, the author of this chapter’s first pa-
per, proposed that the pathogens that cause two TSEs—Creutzfeldt-Jakob disease
(CJD) and scrapie, a disease of sheep—consist entirely of an infectious form of
protein that he termed the prion; in 1997, he was awarded the Nobel Prize in
Physiology and Medicine for his work on prion biology. Researchers have since
learned that in addition to scrapie and CJD, prions cause BSE and its human
variant, vCJD, as well as chronic wasting disease in deer and elk.
Prusiner presents experimental evidence for the prion model of TSE and
describes the etiology and diagnosis of vCJD and other human prion diseases. He
emphasizes the differences between prion and viral illnesses—most notably, that
prions can arise spontaneously—and observes that the mistaken equation of the
195

two can impede the development of effective preventions against invariably fatal
prion diseases. “The only rational strategy is to test all cattle for prions and elimi-
nate those harboring prions from the food supply,” Prusiner concludes.
The second paper, by Steven Collins, codirector of the Australian National
CJD Registry, describes his country’s approach to TSE surveillance in both ani-
mals and humans. The vast majority of CJD cases in the Australian Registry are
sporadic; no cases of vCJD or endogenous cases of either BSE or scrapie have
been reported to date in the country. Collins recounts the range of measures Aus-
tralia has adopted to protect commercial livestock from BSE and scrapie, which
include bans on the importation of meat and bone meal and of live cattle from any
country reporting BSE, as well as the prohibition of ruminant-to-ruminant feed-
ing of meat and bone meal.
Maura Ricketts, who has directed prion disease surveillance and research for
Health Canada and the World Health Organization (WHO), discusses BSE and
vCJD from a public health perspective in the chapter’s third paper. After defining
and applying relevant core principles of public health, Ricketts identifies and
explores key issues that underlie the development and implementation of health
policy to address BSE and vCJD. She concludes with an overview of possible
public health actions that reflect the importance of controlling the risk of BSE
exposure.
In the chapter’s final contribution, Wil Hueston of the Center for Animal
Health and Food Safety at the University of Minnesota shares insights gained
from 16 years of involvement with BSE and the interface between animal and
human health. He distills this experience into seven lessons that lead to a series of
key actions that could be taken to address key issues raised by BSE and, more
generally, to improve the response to infectious disease.
PRIONS AND THE SAFETY OF THE FOOD SUPPLY

Stanley B. Prusiner, M.D.1
University of California San Francisco
In December 2003, mad cow disease made its U.S. debut when federal offi-
cials announced that a Holstein cow from Mabton, Washington, had been stricken
with bovine spongiform encephalopathy (BSE). Although the U.S. government
acted surprised by the finding, they should have expected such cattle based on the
biology of the prion diseases. Perhaps the novel principles of disease that have
emerged over the past two decades from investigations of prions (Prusiner, 2004b)
are still too new and different for many people to grasp easily the implications of
this discovery. Prions are unprecedented infectious pathogens that are composed
1Institute for Neurodegenerative Diseases, Departments of Neurology and of Biochemistry and
Biophysics.

REPORTING FOODBORNE THREATS 197
solely of protein; they are devoid of nucleic acid—DNA and RNA. The absence
of a nucleic genome sets prions apart from all other infectious pathogens includ-
ing viruses, viroids, bacteria, fungi, and parasites.
Because prions multiply and cause disease in the host, scientists thought for
many years that prions must be slow-acting viruses. Moreover, the identification
of varieties or strains of prions made the argument that prions must be viruses
even more appealing. Because so many attempts to detect a prion-specific nucleic
acid genome failed (Alper et al., 1967; Bellinger-Kawahara et al., 1987a,b; Safar
et al., 2005b), some scientists argued that the nucleic acid must be quite small
(Bruce and Dickinson, 1987; Chesebro, 2004; Kimberlin, 1982; Weissmann,
1991). Although the identification of micro RNAs has given new life to such
arguments in recent years, the production of synthetic prions from recombinant
prion protein (PrP) is likely to end the quest for an auxiliary molecule within the
prion (Legname et al., 2004, 2005).
Based on a wealth of data including the production of synthetic prions in
mammals and fungi, it is reasonable to define prions as infectious proteins. Prions
multiply by forcing the precursor protein to acquire a second conformation. Dif-
ferent conformations of proteins in the prion state encipher distinct strains and are
prone to aggregation. In mammals, prions accumulate to high levels in the ner-
vous system where they cause dysfunction and fatal degeneration.
Both mammalian and fungal prions have been produced in cell-free systems
(Brachmann et al., 2005; Maddelein et al., 2002; Sparrer et al., 2000; Tanaka et
al., 2004). Synthetic PrP peptides and recombinant PrP fragments have been used
to form mammalian prions, and N-terminal regions, called prion domains, that
are rich in glutamine and asparagine have been used to form fungal prions.
In mammals, prions cause a group of invariably fatal, neurodegenerative dis-
eases. No human or animal has ever recovered from a prion disease once neuro-
logic dysfunction has manifested. Prion diseases may present as genetic, infec-
tious, or sporadic disorders, all of which involve modification of normal, cellular
PrP, designated PrPC. The tertiary structure of PrP is profoundly altered as prions
are formed, and as such, prion diseases represent disorders of protein conforma-
tion. In the sporadic and genetic forms of prion disease, prions arise spontane-
ously. In contrast, infectious prion diseases result from exposure to an exogenous
source of prions. Although the incidence of sporadic prion disease in humans is
low (1–5 cases per 106 people), it is the most common form, accounting for ap-
proximately 90 percent of all cases. The genetic, or inherited, forms of prion
disease account for approximately 10 percent of all human cases and the infec-
tious forms for less than 1 percent. Whether or not the infectious forms of human
prion disease are underestimated and low levels of animal prions in the food
supply are responsible for 10–20 percent of the sporadic cases is unknown.
The prion diseases in humans include CJD, which generally presents as a
progressive dementia, as well as kuru and Gerstmann-Sträussler-Scheinker dis-
ease (GSS), both of which frequently present as ataxic maladies. Like kuru and

GSS of humans, scrapie of sheep and BSE of cattle usually manifest as ataxic
illnesses. Deer, elk, and moose with chronic wasting disease (CWD) appear ema-
ciated and ataxic.
In these diseases, mammalian PrPC is recruited and converted into the dis-
ease-causing isoform (PrPSc). PrPC has a high α-helical content and little β-sheet
structure, whereas PrPSc has less α-helical structure and a high β-sheet content.
Comparisons of secondary structures of PrPC and PrPSc were performed on pro-
teins purified from Syrian hamster (SHa) brains (Pan et al., 1993). Limited pro-
teolysis of PrPSc produces a protease-resistant core, designated PrP 27–30, which
retains prion infectivity; under these conditions, PrPC is completely hydrolyzed.
Prion Disease Paradigm

Despite some similarities between prion and viral illnesses, these disorders
are very different. Viral diseases are infectious illnesses that begin with infection
by exogenous virions. In contrast, the vast majority of prion diseases are initiated
from within the host, in which prions arise spontaneously. Often the term prion
infection is used synonymously with prion disease because once prions are formed
spontaneously they can be transferred to another host and thus, are infectious.
Unlike viral infections, no host defenses are mounted in response to prion infec-
tion: no humoral immunity, no cellular immunity, and no interferons are elicited
to the replicating prion.
Molecular genetic studies have been crucial in deciphering the novel features
of the prion disease paradigm. In the sporadic form of prion disease, the sequence
of the PrP gene is wild-type (wt); whereas, in the inherited prion diseases, the
sequence of the PrP gene harbors a nonconservative substitution or insertion.
Generally, the PrP genes of humans and animals with infectious prion disease
are wt.
Before the discovery of mutations in the PrP gene as the cause of familial
prion disease, geographic clusters of prion disease were thought to be due to
common source exposures to exogenous prions. For example, Libyan Jews with a
very high incidence of CJD were thought to have contracted the disease by eating
lightly cooked sheep brains (Alter and Kahana, 1976). Molecular genetic investi-
gations showed that every Libyan Jew developing prion disease carried a PrP
gene mutation resulting in an E→K substitution at position 200 (Goldfarb et al.,
1991; Hsiao et al., 1991). Risk analysis studies revealed that every Libyan Jew
carrying the E200K mutation would eventually develop prion disease if he or she
did not die of some other illness (Chapman et al., 1994; Spudich et al., 1995).
Synthetic Prions and Spontaneous Disease

Investigations of humans with PrP gene mutations were extended to trans-
genic (Tg) mice harboring the analogous mutation causing GSS in humans. Tg

mice expressing high levels of MoPrP(P101L) developed neurodegeneration

spontaneously (Hsiao et al., 1990; Telling et al., 1996). Extracts prepared from
the brains of these mice transmitted disease after approximately 250 days to other
Tg mice (designated Tg196) expressing low levels of MoPrP(P101L) (Hsiao,
1994). Subsequently, a synthetic PrP peptide of 55 residues carrying the P101L
mutation, designated MoPrP(89–143,P101L), was produced and inoculated into
the Tg196 mice (Kaneko et al., 2000). The Tg196 mice developed central ner-
vous system (CNS) dysfunction approximately one year after inoculation, and
brain extracts from the ill mice were found to produce disease on serial passage
(Tremblay et al., 2004). The MoPrP(89–143, P101L) peptide produced disease in
the Tg196 mice only if it was folded into a β-rich conformation (Kaneko et al.,
2000).
An approach similar to the one used in the studies with MoPrP(89–
143,P101L) peptide was employed with wt PrP. In those studies, wt MoPrP(89–
230) was produced in E. coli, purified by chromatography, and polymerized into
amyloid fibrils (Legname et al., 2004). The amyloid fibrils were injected into Tg
mice expressing MoPrP(89–231) and produced neurodegeneration after approxi-
mately 500 days. Brain extracts from the ill Tg mice contained protease-resistant
PrPSc and produced disease on subsequent passage into both wt and Tg mice
(Legname et al., 2005). These studies demonstrated that only PrP is required to
generate prion infectivity, and as such, spontaneous forms of prion disease can
occur in any mammal as PrPC seems to be ubiquitous among this class of
vertebrates.
Spontaneous prion disease contrasts with viral disorders, for which exog-
enous infection is required except in the case of latent retroviral genomes. For
example, after infection with exogenous HIV, the virus may disappear but often
its RNA genome has been reverse-transcribed into DNA, and the DNA copies
may remain dormant for years.
The dramatically different principles that govern prion biology from those
underpinning the viral diseases are frequently misunderstood. This lack of under-
standing has led to some regrettable decisions of great economic, political, and
possibly public health importance. For example, scrapie and BSE have different
names, yet they are the same disease in two different species. Scrapie and BSE
differ in only two respects: first, the PrP sequence in sheep differs from that of
cattle at seven or eight positions of 270 amino acids (Goldmann et al., 1990,
1991), which results in different PrPSc molecules. Second, most scrapie strains of
prions seem to be different from the BSE strains.
The Mad Cow Epidemic

The world awoke to the dangers of prion disease in cows after the BSE out-
break began ravaging the British beef industry in the mid-1980s. The truly novel
concepts emerging from prion science forced researchers and society to think in

unusual ways and made coping with the epidemic difficult. Investigators eventu-
ally learned that prions were being transmitted to cattle through meat-and-bone
meal (MBM), a dietary supplement prepared from the parts of sheep, cattle, pigs
and chickens that are processed, or rendered, for industrial use. High heat elimi-
nated conventional pathogens, but PrPSc survived and went on to infect cattle.
As infected cattle became food for other cattle, BSE began appearing
throughout the UK cattle population, reaching a high of 37,280 confirmed fied
cases in 1992 (Phillips, 2000). The British authorities instituted some feed bans
beginning in 1989, but it was not until 1996 that a strict ban on cannibalistic
feeding finally brought BSE under control in the United Kingdom; the country
saw 612 cases in 2004. Overall, the United Kingdom has identified approximately
180,000 mad cows, and epidemiologic models suggest that another 1.9 million
were infected but went undetected (Anderson et al., 1996).
For many people, the regulations came too late. Despite the British govern-
ment’s early assurances to the contrary, mad cow disease proved transmissible to
humans. In March 1996, Robert Will and his colleagues reported that 11 British
teenagers and young adults had died of a variant of Creutzfeldt-Jakob disease
(vCJD) (Will et al., 2004, 1996). In these young patients, the patterns of PrPSc
deposition in the brain differed markedly from that found in typical CJD patients.
Many scientists, including myself, were initially dubious of the presumed
link between BSE and vCJD. I eventually changed my mind, under the weight of
many studies. The most compelling of these studies used Tg mice genetically
engineered to resemble cattle, at least from a PrP point of view. These mice be-
came ill approximately 250 days after receiving injections of prions either from
cattle with BSE or people with vCJD, and the resulting disease looked the same
whether the prions originated from diseased cows or vCJD patients (Scott
et al., 1999).
Since the detection of mad cow disease in the United Kingdom, two dozen
other nations have uncovered cases. Canada and the United States are the latest
entrants to the list of countries affected. On May 20, 2003, Canadian officials
reported BSE in an eight-year-old cow that had spent its life in Alberta and Sas-
katchewan. (The country’s only previous mad cow had arrived as a UK import 10
years earlier.) Although the animal had been slaughtered in January 2003, slow
processing meant that officials did not test the cow remains until April. By then,
the carcass had been turned into pet food and exported to the United States.
Seven months later, on December 23, 2003, the U.S. Department of Agricul-
ture (USDA) announced the country’s first case of BSE in Washington state. The
six-year-old dairy cow had entered the United States at the age of four. The dis-
covery meant that U.S. officials could no longer labor under the misconception
that the nation is free of BSE. Like Canada, U.S. agricultural interests want the
BSE problem to disappear. Financial woes stem primarily from reduced beef
exports: 58 other countries are keeping their borders shut, and a $3 billion export

market has largely evaporated. At the time of writing, six more cases of BSE in
Canada and two additional cases in the United States have been reported.
Infectious Human Prion Diseases

Prions from different sources have infected humans. Human prions have been
transmitted to others both by ritualistic cannibalism and iatrogenic means. Kuru
in the highlands of New Guinea was transmitted by ritualistic cannibalism, as
people in the region attempted to immortalize their dead relatives by eating their
brains (Alpers, 1968; Gajdusek, 1977; Glasse, 1967). Iatrogenic transmissions
include prion-tainted human growth hormone (HGH) and gonadotropin, dura
mater grafts, and corneal transplants from people who died of CJD. In addition,
CJD cases have been recorded after neurosurgical procedures in which ineffec-
tively sterilized depth electrodes or instruments were used.
Variant Creutzfeldt–Jakob Disease (vCJD)

The first cases of vCJD in teenagers and young adults were identified in Great
Britain in 1994 (Will et al., 1996). More than 170 teenagers and young adults have
died of vCJD in Britain, France, Ireland, Italy, Japan, Portugal, and the United
States. Although the average age of vCJD patients is 26 years of age, the youngest
patient was 12 years old and the oldest was 74 years of age (Spencer et al., 2002).
The median duration of the illness is 13 months, with the range from 6 to 69 months.
In addition to the young age of these patients (Bateman et al.,1995; Britton et
al., 1995), vCJD is characterized by numerous PrP amyloid plaques surrounded by
a halo of intense spongiform degeneration in the brain (Ironside, 1997). These
unusual neuropathologic changes have not been seen in CJD cases in the United
States, Australia, or Japan (CDC, 1996; Ironside, 1997). Both macaque monkeys
and marmosets developed neurologic disease several years after inoculation with
bovine prions (Baker et al., 1993), but only the macaques exhibited numerous PrP
plaques similar to those found in vCJD (Lasmézas et al., 1996).
The majority of vCJD patients present with psychiatric symptoms, including
dysphoria, withdrawal, anxiety, insomnia, and loss of interest (Spencer et al.,
2002; Will et al., 2004). Generally, neurologic deficits do not appear until at least
four months later; these neurologic changes consist of memory loss, paresthesias,
sensory deficits, gait disturbances, and dysarthria. Most vCJD cases have been
reported from Britain, and 10 have been found in France. The one U.S. case was
a 23-year-old woman, who is thought to have been exposed to bovine prions
while living in Britain during the first 12 years of her life. From both epidemio-
logic and experimental studies, the evidence is quite compelling that vCJD is the
result of prions being transmitted from cattle with BSE to humans through con-
sumption of prion-contaminated beef products.

Transmission of vCJD Prions by Blood Transfusion

vCJD has been identified in two patients who received blood transfusions
from donors that later died of vCJD. In one case, the recipient was a 69-year-old
male who was transfused 6.5 years before the onset of neurologic dysfunction
(Llewelyn et al., 2004). Many details of the second case are not published, but the
patient is known to have died of a nonneurologic disease (Peden et al., 2004).
Although vCJD prions were found in the spleen and cervical lymph nodes of this
patient, none were found in the brain.
A glimpse of future vCJD cases caused by prion-tainted transfused blood
may come from a survey of tissues collected during appendectomies and tonsil-
lectomies. Such a survey from the United Kingdom reports that of the 12,674
appendectomy specimens examined, three were positive for PrPSc by immunohis-
tochemistry (IHC) (Hilton et al., 2004). This finding argues that as many as 3,800
people in the United Kingdom may be replicating vCJD prions in their lymphoid
tissues. Considering that immunohistochemistry (IHC) is considerably less sensi-
tive than the conformation-dependent immunoassay (CDI), the number of Brit-
ons harboring vCJD prions in their lymphoid tissues may approach 20,000 (Safar,
2005a).
Approaches to Prion Diseases

Because prion diseases have aspects that resemble illnesses caused by vi-
ruses as noted above, many people use analogies to viruses when thinking about
prions. But these analogies can sow confusion. One example is the presumed
origin of the mad cows in Canada and the United States. Although it is true that
BSE first appeared in the United Kingdom and then spread elsewhere through
exported prion-contaminated feed, approaches from a traditional bacterial or viral
epidemic are only partly helpful. In such situations, quarantines or bans can curb
the spread of disease. But prions can arise spontaneously, which is an extremely
important characteristic that distinguishes prions from viruses. In fact, any mam-
mal is capable of producing prions spontaneously.
Spontaneous prion disease is thought to have triggered the epidemic of kuru,
which decimated a group called the Fore in New Guinea in the past century.
According to one theory, sporadic (s) CJD occurred in an individual whose brain
was then consumed by his or her fellow Fore in a funerary rite involving canni-
balism. The continued practice created a kuru epidemic. Ceasing the practice of
this funerary rite also resulted in the decreased incidence of kuru.
Similarly, a feed ban that prevents cattle from eating the remains of other
animals is crucial in containing BSE. But such bans will not eliminate the pres-
ence of mad cows when pathogenic prions arise spontaneously. If every year, 1–
5 people per million spontaneously develop prion disease, why not the same inci-
dence for cows? Indeed, I suspect that the North American BSE cases are likely
to have arisen spontaneously and that afflicted animals have occasionally ap-

peared unrecognized in herds ever since humans started cattle ranching. We have
been extraordinarily lucky that a spontaneous case did not trigger an American
BSE epidemic. Or perhaps small epidemics did occur but were undetected.
Still, many prefer the idea that the mad cows in North America acquired
prions from their feed. Such reasoning allows people to equate prions with
viruses—that is, to think of prions only as infectious agents (even though most of
time, they arise spontaneously)—and to offer a seemingly plausible plan to eradi-
cate BSE by quarantining herds. But ignoring the revolutionary concepts that
govern prion biology can only hamper efforts at developing an effective program
to protect the American public from exposure to these deadly agents. We must
think beyond quarantine and bans, and test for prions even in the absence of an
epidemic.
Diagnosis of Prion Diseases

The clinical diagnosis of human prion disease is often difficult until the pa-
tient shows profound signs of neurologic dysfunction (Roos et al., 1973; Will et
al., 2004). In humans with sCJD, the most common clinical presentation is a
progressive dementia. Approximately 10 percent of sCJD patients present with a
progressive ataxia.
It is widely accepted that the clinical diagnosis must be provisional until a
tissue diagnosis either confirms or rules out the clinical assessment. Prior to the
availability of antibodies to PrP, a tissue diagnosis was generally made by histo-
logic evaluation of neuropil vacuolation. IHC using anti-glial fibrillary acidic
protein antibodies in combination with hematoxylin and eosin (H&E) staining
preceded the use of anti-PrP antibody staining.
Postmortem Tissue Detection of Prions

The role of IHC in the diagnosis of scrapie was challenged after a study of
the brains from eight clinically affected goats inoculated with the SSBP1 prion
isolate (Foster et al., 2001). Thalamic samples taken from seven of eight goats
with scrapie were positive for PrPSc by Western blotting but negative by IHC.
The eighth goat was negative by both Western blotting and IHC. Consistent with
these findings in goats are the results of a study of humans who died of sCJD or
familial (f) CJD. In this study, IHC of formalin-fixed, paraffin-embedded human
brain samples was substantially less sensitive than the conformation-dependent
immunoassay (CDI) (Safar, 2005a).
The CDI detected PrPSc in all regions of the brain that were examined in 24
sCJD and 3 fCJD(E200K) cases. Comparative analyses demonstrated that the
CDI was vastly superior to both histology and IHC. When 18 regions of 8 sCJD
and 2 fCJD(E200K) brains were compared, it was discovered that both histology
and IHC were unreliable diagnostic tools except for samples from a few brain

regions. In contrast, the CDI was a superb diagnostic procedure as it detected

PrPSc in all 18 regions in 8 of 8 sCJD and 2 of 2 fCJD(E200K) cases (Safar,
2005a).
Concerned that limited digestion with proteinase K (PK) was hydrolyzing
some or even most of the PrPSc, the CDI was developed so as not to require PK
digestion to detect PrPSc. The CDI revealed that as much as 95 percent of PrPSc is
protease sensitive (sPrPSc) and thus was being destroyed during limited proteoly-
sis used to hydrolyze PrPC. sPrPSc comprises 80–95 percent of the PrPSc found in
the frontal lobe and in the white matter of CJD patients (Safar, 2005a).
The CDI detected HuPrPSc with a sensitivity comparable to the bioassay for
prion infectivity in Tg mice expressing chimeric human-mouse PrP. The high
sensitivity achieved by the CDI is due to several factors including the use of
phosphotungstic acid (PTA) that specifically precipitates sPrPSc and rPrPSc (Lee
et al., 2005; Safar et al., 1998, 2005a). PTA has also been employed to increase
the sensitivity of Western blots, enabling the detection of rPrPSc in human muscle
and other peripheral tissues (Glatzel et al., 2003; Wadsworth et al., 2001). A
comparison between the CDI and Western blotting on brain samples from sCJD
and vCJD patients showed that the CDI is 50- to 100-fold more sensitive (Minor
et al., 2004).
The CDI has also been used to study GSS caused by the P102L mutation. In
mice expressing the GSS mutant PrP transgene, the CDI detected high levels of
sPrPSc(P101L) as well as low levels of rPrPSc(P101L) long before neurodegen-
eration and clinical symptoms occurred (Tremblay, 2004). sPrPSc(P101L) as well
as low concentrations of rPrPSc(P101L) previously escaped detection (Hsiao et al.,
1994).
BSE Testing
The transmission of kuru prions to more than 2,500 Fore people in the high-
lands of New Guinea and the transmission of BSE prions to more than 170 teen-
agers and young adults who died of vCJD argues that oral prion infection can
occur. The recognition that patients with vCJD were infected with BSE prions
from cattle (Bruce et al., 1997; Collinge et al., 1996; Scott et al., 1997, 2005)
prompted the European Union to institute testing of all cattle over 30 months of
age at the time of slaughter. Currently, both Western blotting and ELISA tests
for rPrPSc are being used on brainstems from cattle (Grassi et al., 2001; Kübler et
al., 2003). The CDI test, which measures both protease-sensitive and protease-
resistant PrPSc, has been adapted for bovine brainstems and is available for test-
ing cattle.
The recent identification of BSE-positive cattle in Canada and the United
States has prompted increased surveillance in these countries, but the number of
cattle tested remains less than 2 percent of the annual slaughter (Prusiner, 2004a).
Despite the small number of cattle being tested, new cases of BSE are being
found. These new cases are attributed to tainted feed by agriculture authorities,

who continue to think of prion diseases as being similar to infectious illnesses

caused by viruses or bacteria. These officials want to believe that BSE will disap-
pear once the consumption of ruminant-derived feed ceases. They refuse to enter-
tain the idea that most cases of prion disease are likely to be sporadic once con-
taminated feed is eliminated from the food supply. In Japan, 4 million cattle have
been tested over the last four years, and close to 20 cases of BSE have been
identified. One Japanese cow was 21 months old and another 23 months old
(Yamakawa et al., 2003), younger than the animals tested in the European Union.
It seems likely that most or all of these young animals developed sporadic BSE.
Determining how early in the incubation period BSE prions can be detected
by bioassay is now possible due to the construction of Tg mice expressing bovine
PrP, designated Tg(BoPrP)Prnp0/0 mice (Buschmann et al., 2000; Scott et al.,
1997, 1999). Prior to the production of Tg(BoPrP)Prnp0/0 mice, cattle were used
for bioassays of bovine prions. In a limited study using cattle bioassays, bovine
prions were undetectable in the obex of the bovine brainstem until 26 months
after oral inoculation (Wells, 2002). In these studies, prion infectivity was de-
tected much earlier in the lymphoid tissue of the distal ileum.
Prions in Muscle
Animal meat products consumed by humans are predominantly muscle tis-
sue. For many years, muscle tissue was thought to be devoid of prions. In studies
of the hind limb muscles of mice, prions were found at a level of 5 percent of that
in brain (Bosque et al., 2002); other muscle groups also had prions but at lower
levels. PrPSc was found in virtually all muscles after prions were fed to hamsters
(Thomzig et al., 2003). Investigations of prions in the tongue have shown high
levels of both PrPSc and prion infectivity (Bartz et al., 2003). PrPSc was identified
in the muscles of 25 percent of the sCJD patients analyzed (Glatzel et al., 2003).
In livestock, PrPSc was found in myocytes of the fore and hind limbs of sheep
with both natural and experimental scrapie (Andreoletti et al., 2004), and prion
infectivity was reported recently in extracts prepared from the muscle of BSE-
infected cattle. In the latter studies, prions were detected by transmission to Tg
mice expressing bovine PrP (Buschmann and Groschup, 2005).
The Only Rational Strategy

The only rational strategy is to test all cattle for prions and eliminate those
harboring prions from the food supply. No reasonable human would knowingly
expose himself or herself to prions as prion diseases are invariably fatal.
In Europe, a policy was instituted four years ago of prion testing for all cattle
destined for human consumption that are over 30 months of age. The 30-month
cutoff point was chosen for surveillance by the Office International des Epizooties
(OIE; also known as the World Organization for Animal Health), but it was never
intended for food safety. Some European countries have arbitrarily adopted a 24-

month cutoff. It is irrational to believe that all cattle younger than 24 months of
age are free of prions and that those older than 24 months are potentially infected.
Initially, the Japanese government proposed adopting the European Union’s test-
ing protocol, but consumer advocates forced the government to change its policy
and test every slaughtered animal.
Rapid prion tests used in Europe vary in their sensitivity and reliability. Until
now, the tests have not been sufficiently sensitive. Whether or not one or more of
the newer tests can provide the desired sensitivity is unclear. Further, confining
testing to brain tissue may be imprudent because other tissues such as muscle and
lymphoid cells can harbor substantial levels of prions.
Given that seemingly healthy animals can carry prions, I believe that testing
all slaughtered animals is the only rational policy. But this policy needs to be
accompanied by a systemic approach to reward food suppliers for identifying
livestock harboring prions. To maximize the protection from ingesting prions, we
must aim to eliminate prions from the food supply by using the most sensitive and
reliable test. The current system of using the least sensitive of the government-
approved tests to minimize the number of prion-positive livestock is an unaccept-
able, dangerous common practice that must be terminated immediately. Provid-
ing the most safe food supply is a critical responsibility of every government—it
is not an optional, incidental activity.
Acknowledgments
This work was supported by grants from the National Institutes of Health
(AG02132, AG10770, and AG021601) as well as by a gift from the G. Harold
and Leila Y. Mathers Charitable Foundation. S. B. P. has financial interests in
InPro Biotechnology, Inc.
Correspondence should be addressed to: Institute for Neurodegenerative Dis-
eases, 513 Parnassus Ave, HSE-774, University of California, San Francisco, CA
94143-0518; Tel: (415) 476-4482; Fax: (415) 476-8386. E-mail: stanley@
ind.ucsf.edu.
SURVEILLANCE AND PREVENTION OF vCJD AND BSE:

THE AUSTRALIAN PERSPECTIVE
Steven Collins, M.D.2
University of Melbourne, Parkville, Australia
As an introduction to bovine spongiform encephalopathy (BSE) and its con-

sequent zoonosis, variant Creutzfeldt-Jakob disease (vCJD), I will briefly review
the first human TSE epidemic, kuru, which contains a number of important in-
2Australian National CJD Registry and Department of Pathology.

sights and lessons. Kuru occurred endemically among the Fore linguistic group
of the eastern highlands of Papua New Guinea (PNG). The first cases of kuru
came to the attention of Western medicine in the middle to late 1950s as Austra-
lian patrols were gradually reaching the more remote areas of PNG (Gajdusek
and Zigas, 1957). Predominantly manifesting as an inexorably progressive cer-
ebellar ataxia with later onset dementia (Gajdusek, 1962), the etiology and spread
of the disease were eventually linked to cannibalistic rites of mourning for de-
ceased relatives (Gajdusek, 1977). Not long after noting neuropathologic and
other similarities between kuru and scrapie (Hadlow, 1959), kuru was proven to
be a transmissible spongiform encephalopathy (Gajdusek et al., 1966). The predi-
lection of kuru for women and children was related to their more usual consump-
tion of the highly infectious central nervous system tissues. It is believed that
ritualistic endocannibalism was successfully eradicated by the end of the 1950s.
Detailed epidemiologic studies of kuru suggested a mean incubation period
of around 12 years, but ongoing contemporary field surveillance supports the
likelihood that the most recent cases have incubation periods spanning up to 50
years (Collinge, 1999; Collinge et al., 2006). Consequently, based on these obser-
vations and those from various animal models of prion disease (Dickinson et al.,
1975; Hill et al., 2000), there may not be a finite incubation period. Once ex-
posed, the risk of developing a TSE may persist lifelong. Further, kuru indicated
that despite the very low transmissibility of TSEs compared with many conven-
tional microbes, high levels of disease can arise, including through an oral route
of inoculation, if unique circumstances prevail to support “unnatural” intraspe-
cies recycling of highly infectious tissues. At the height of the epidemic, annual
mortality from the disease approached 50 percent in some Fore villages, with
an annual incidence of approximately 10 percent in a number of Fore tribes
(Gajdusek and Zigas, 1957).
Bovine Spongiform Encephalopathy and

Variant Creutzfeldt-Jakob Disease
By the mid-1980s, United Kingdom veterinary authorities had confidently
recognized BSE as a new form of cattle disease. In retrospect, the early years of
the BSE epidemic evinced undue reassurance from the scrapie precedent. The
lack of documented evidence of scrapie transmission to humans from farmed
sheep and the generally low levels of endemic scrapie over the few hundred years
that scrapie had been recognized in sheep flocks suggested BSE would perhaps
behave similarly. In discomfiting contrast, the incidence of BSE rapidly escalated
and by 1992 at the height of the UK epidemic, some 3,500 cases per month were
confirmed; overall, an estimated 2 million contaminated cattle are believed to
have entered the human food chain (Donnelly et al., 2002). Given the dramatic
increase in BSE, in accordance with one of the recommendations of the South-
wood enquiry, national surveillance for human prion diseases was prudently re-

commenced in the United Kingdom in 1990. Particular interest was to be given to

ascertaining the occurrence of any new forms of disease that might have arisen
zoonotically from BSE. In 1996, a new or variant form of CJD (vCJD) was re-
ported by the National CJD Surveillance unit in Edinburgh, Scotland, with 10
younger adults and adolescents manifesting a phenotype hitherto not described
(Will et al., 1996). A range of subsequent research has confirmed the likely causal
link between vCJD and BSE (Hill et al., 1997).
A very recently reported case-control study of vCJD has highlighted diet as a
principal risk factor, especially the consumption of greater amounts of products
likely to contain bovine mechanically recovered meat (MRM) and bovine head
meat (sausages, burgers, and pies) (Ward et al., 2006). These bovine meats are
more prone to contamination by brain, spinal cord, and dorsal root ganglia, and
the study results are therefore consistent with the hypothesis that people develop-
ing vCJD were exposed to greater amounts of those bovine meat products more
likely to be contaminated by the highly infectious central nervous system tissue
(summarized in Figure 6-1). One caveat concerning this data is the possibility of
recall bias, suggested by the observation that the respondents for patients initially
suspected to be manifesting vCJD but eventually proven to have a different ill-
ness also reported the same dietary associations.
8
(adjusted for sex, birth cohort
7
6
& north/south)
< 1 per month

Odds Ratio
4 1 per week
3
> 1 per week
2
1
0
ef
es
M
r
ie
Be
ge
R
ag
tp
M
r
us
Bu
ea
Sa
FIGURE 6-1 Reported frequency of food consumption, odds ratio of vCJD cases versus
general population controls. Results of this case-controlled study suggest that people with
vCJD consumed foods likely to contain bovine mechanically recovered meat (MRM) and
bovine head meat (sausages, burgers, and pies) more frequently than as compared with the
general population. Such meats are more prone to contamination with central nervous
system tissue, and therefore—if the bovine source was infected with BSE—higher con-
centrations of prions. It should be noted, however, that because consumption rates were
self-reported, they may reflect recall bias (see text).
SOURCE: Adapted from Ward et al. (2006).

As of July 2006, a total of 161 cases of vCJD have been diagnosed in the
United Kingdom. Remarkable uniformity in the clinical illness has been main-
tained: it affects young people (the median age at onset is 26 years) with a median
survival of 14 months. France has the second highest number of vCJD cases (18
in total), with case numbers and the temporal profile behaving as predicted from
modeling based on transmissions through beef imported from the United King-
dom (Valleron et al., 2001). The primary United Kingdom vCJD epidemic is
thought to be in decline, and most experts expect that the total number of cases
will not exceed 200 (Valleron et al., 2001). However, the recent reports of three
cases of vCJD related to transfusion of blood products and the higher than ex-
pected potential prevalence of subclinical or preclinical vCJD suggested by the
retrospective study of archival appendix and tonsil specimens raises the sobering
possibility of a secondary wave of iatrogenic vCJD (Hilton et al., 2004; Llewelyn
et al., 2004). Based on animal transmission studies involving “species barriers”
and subsequent strain adaptation, such human-to-human transmissions may prove
far more efficient than the primary cross-species infections from cattle to humans
through oral consumption of contaminated beef. Further, not only must we be
alert to a possible secondary wave of vCJD, but given the unprecedented calami-
tous transmission of BSE to humans, we must also keep vigilant to the possibility
of other cross-species transgressions from TSEs now apparently confined to ani-
mals, such as chronic wasting disease.
Australia’s National CJD Registry

The Australian National CJD Registry (ANCJDR) is a federally funded sur-
veillance unit that commenced operation in 1993, with the initial mission to as-
certain further cases of human pituitary hormone-related CJD. At the inaugura-
tion of ANCJDR activities, five persons with pituitary hormone-related CJD were
known, and no additional cases have been detected. The scope of ANCJDR hu-
man TSE monitoring has expanded with the passage of time, and as of 1996,
following the discovery of vCJD, surveillance was broadened to include that dis-
ease (Collins et al., 2002). The ANCJDR has also participated in the European
surveillance consortium (EUROCJD) since 1997. As of 2004, the Communicable
Diseases Network Australia agreed to make human TSEs notifiable diseases in
all Australian states and territories. Primary case review of suspect notified cases
involves the ANCJDR, with evaluation outcomes a collaborative exercise be-
tween the appropriate state or territory and the registry.
Case definitions used by ANCJDR for classification purposes are those en-
dorsed by EUROCJD. A range of standard surveillance methods are employed by
the ANCJDR, including the use of semiannual surveys sent to all neurologists,
neuropathologists and pathologists within Australia. Respondents are prompted
to report any suspect, probable, or confirmed cases of CJD they have seen or been
aware of in the preceding six months. Follow-up is undertaken for positive re-

sponses, and we also receive unprompted personal communications regarding

suspect and confirmed CJD from these same medical practitioner groups. The
ANCJDR annually reviews state and territory morbidity separation codings for
citings of CJD or CJD-like illnesses, and conducts national death certificate
searches as well. Since 1997, the most important mechanism of case notification
has been through the national cerebrospinal fluid (CSF) 14-3-3 protein diagnostic
testing service that the registry offers (Collins et al., 2000). For case confirma-
tion, CSF 14-3-3 protein detection serves as a reasonably reliable and specific
marker of sporadic CJD and is now an accepted component of case definitions for
surveillance classification purposes (Zerr et al., 2000).
Neuropathologic examination of the brain remains necessary for confirma-
tion and classification as a definite case of CJD (Collins et al., 2004), and given
the problems frequently encountered with brain biopsies, postmortem examina-
tion is preferred and pursued in all patients with suspect CJD. Very occasionally
routine autopsy will detect a completely unsuspected case of TSE. Unfortunately,
however, postmortem rates in major teaching hospitals have declined dramati-
cally throughout Australia over the past 10–15 years and are now running at
around 12 percent. Further, fewer medical centers are willing to conduct autop-
sies on patients with suspected CJD. Over recent years the ANCJDR has main-
tained a postmortem rate of around 60 percent, but the aforementioned com-
bination of factors is militating against our ability to obtain neuropathologic
confirmation, which remains the gold standard for diagnosis.
Similar to all previous and ongoing human TSE surveillance, the vast major-
ity of cases in the ANCJDR are sporadic; there are several familial cases and a
small number of iatrogenic cases, but no cases of vCJD so far (see Table 6-1)
(Collinge, 1999). Measures have been undertaken to try to ensure that vCJD has
not been overlooked in Australia.
TABLE 6-1 Cases of Transmissible Spongiform Encephalopathies (TSE)

Reported to the Australian National CJD Registry (ANCJDR), January 1, 1970
Through June 30, 2005
Classification Sporadic Familial Iatrogenic Variant
CJD CJF/GSS CJD CJD Unclassified Total
Definite 265 29 5a 0 0 299
Probable 178 9 4 0 0 191
Possible 7 0 1 0 0 8
Incomplete 0 98b 98 98
Total 450 38 10 0 98 596
aIncludes one definite iatrogenic case who received pituitary hormone treatment in Australia but
disease onset and death occurred while a resident overseas. This case is not included in statistical
analysis since morbidity and mortality did not occur within Australia.
bIncludes 59 living cases.
SOURCE: Adapted from Klug et al. (2005).

Reaffirmation of Absence of vCJD in Australia

The likelihood of vCJD in a given country appears to reflect either the levels
of endemic BSE, the amounts of imported contaminated United Kingdom beef
products through 1980–1996, or—as in the experience of Canada, the United
States, and perhaps Japan—its citizens’ travel and migration patterns. Because
the travel and migration profile of Australians appears similar to that of Canadi-
ans and Americans, the ANCJDR undertook a reexamination of the clinical files
and neuropathologic reports of all cases referred to the registry who died between
January 1, 1992, and June 30, 2003, and which had been classified as either spo-
radic CJD or non-CJD. None of the 365 reexamined cases fulfilled case defini-
tions for possible, probable, or definite vCJD, and the molecular (PrP glycotyping)
profile typical of vCJD was not seen in any of the 37 cases for which frozen
tissues was available for Western blot analysis (Lewis et al., 2005).
Animal TSEs in Australia

To date, there have been no endogenous cases of either BSE or scrapie in
Australia. Scrapie was inadvertently introduced in 1952 from the United King-
dom, but was quickly recognized and the affected flock slaughtered. There have
been two cases of TSEs in felines in Australia: an imported cheetah and an Asi-
atic golden cat, both of which were believed to have contracted their disease
through contaminated feed prior to their importation to Australia.
Protective Measures
For the protection of domestic commercial livestock, Australia has adopted a
range of measures to lessen the risk of BSE and scrapie, which can be found at
www.aahc.com.au. Since 1966, there has been a ban on the importation of meat
and bone meal and any stock feed containing ruminant materials from anywhere
in the world except New Zealand; this was initially imposed to avoid the risk of
anthrax but was maintained thereafter. From 1988, live cattle from the United
Kingdom and any other country reporting BSE cannot be imported into Australia.
Owners of animals imported from countries in which BSE is subsequently dis-
covered can choose to place the imported animals under lifelong quarantine or
have them slaughtered.
A voluntary ban on ruminant-to-ruminant feeding of meat and bone meal
was established in 1996 but became compulsory through Commonwealth legisla-
tion in October 1997. This was then expanded in June 1999 and again in March
2001, whereby vertebrate materials (except for milk, gelatin, and tallow and oils
from fish and poultry) are prohibited from use in ruminant feeds (www.aahc.
com.au). To ensure compliance with the feed bans, national audits are conducted.
These include onsite visits to producers, animal feed manufacturers, and render-

ing plants, as well as PCR screening of meat and bone meal intended for feed. To
date, three such audits have been completed.
Animal TSE Surveillance

Australia’s National TSE Freedom Assurance program oversees and coordi-
nates the National TSE Surveillance Program (NTSESP), education strategies,
and enforcement of the ruminant feed ban (www.aahc.com.au). Prior to establish-
ment of the national audits, more than 3,300 brains of cattle were examined histo-
pathologically for BSE; no disease was found. In 1998, NTSESP was initiated to
satisfy OIE requirements concerning the surveillance and monitoring of BSE and
scrapie. Under this program, every animal (cow or sheep) showing signs of ner-
vous system disease must be examined by designated veterinarians, who also
take brain specimens for histopathologic examination. If disease is suspected, the
samples are subjected to Western blot analysis. Approximately 450 sheep and
400 cattle per year with neurologic illness are examined through NTSESP. The
program is designed to achieve a 99 percent confidence level, which means that it
can detect one case of BSE per one million cattle. Following a change in the OIE
terrestrial animal health code, an additional 400 sick animals (including downer
animals, those that die on the farm, and those slaughtered to contain a disease
outbreak) are now tested for BSE by Western blot of brain specimens.
Education
Education of stakeholders and the public is the final important component of
Australia’s effort to control BSE. Various media are used to introduce a broad
understanding of legislation on this issue and its rationale with dissemination
through agencies ranging from the Environmental Protection Agency, the State
Farmer’s Association, the Australian Veterinary Association, and Animal Health
Australia, as well as through various state and territory education programs.
BSE AS A CASE STUDY OF PUBLIC HEALTH

AND THE PUBLIC GOOD
Maura N. Ricketts, M.D., M.H.Sc., F.R.C.P.C.3
Health Canada
The case of BSE represents a special challenge for public health profession-
als because the initiative and the interventions necessary for the control of BSE
3Executive Director. Based upon a presentation made for the IOM’s Forum on Microbial Threats,
October 2005.

lie within the animal health sector. As a direct result of this, it is to be expected
that debate, disagreements, and occasionally dispute will populate the arena when
animal health experts and public health experts talk about BSE. Regardless, the
last 20 years of experience with BSE have refined the analysis of risk, and there is
increasingly large overlap in policy recommendations with a notable shift toward
recognition of the importance of risk perception, ethics and societal values in
shaping public policy, the implications for broader healthcare practice, and other
aspects of public health. This paper will examine BSE from the perspective of
public health in the expectation that the paradigm of public health might be seen
to be one that is particularly sensible when the protection of human health is
ultimately the goal of public policy.
What Is Public Health and What Does It Do?

The definition of public health has proven that it is, like other branches
of medicine, both an art and a science. The examination of a definition of pub-
lic health provides the foundation for understanding public health-based
recommendations:
Public health is one of the efforts organized by society to protect, promote, and
restore the people’s health. It is the combination of sciences, skills, and beliefs
that are directed to the maintenance and improvement of the health of all the
people through collective or social actions. . . . Public health activities change
with changing technology and social values, but the goals remain the same: to
reduce the amount of disease, premature death, and disease-produced discom-
fort and disability in the population. Public health is thus a social institution, a
discipline and a practice (Last, 1983).
The science and art of promoting health, preventing disease, prolonging life, and
improving the quality of life through the organized efforts of society (Last, 2001).
A key component of the definition is the reference to “the organized efforts
of society.” In Table 6-2 are the functions of public health that have been nation-
ally adopted in Canada. Even a superficial review of the functions will confirm
the extent of societal commitment that is required.
The functions of public health map themselves into core program areas (see
Table 6-3). These are the core programs that must be sustained by any functional
public health organization.
When examined in matrix format (see Table 6-4), the public health decisions
taken regarding vCJD become clearer.
What About vCJD?

How can public health principles be applied to the case of BSE? The first and
foremost function of public health is health protection. Table 6-5 lays out a well-

TABLE 6-2 The Functions of Public Health

Population Health Assessment
• Understand the health of populations and the factors that underlie good health and that create
health risks
Health Surveillance
• Early recognition of outbreaks, disease trends, health factors, and cases of illness
• Allows for earlier intervention and lessened impact
• Surveillance aids understanding of the impacts of efforts to improve health and reduce the
impact of disease
Health Promotion
• Work with individuals, agencies, and communities to understand and improve health through
healthy public policy, community-based interventions, and public participation
• Uses community development or policy advocacy and action regarding the environmental and
socioeconomic determinants of health and illness
Disease and Injury Prevention
• As much as two-thirds of premature mortality is preventable through the application of
available knowledge
• Includes investigation, contact tracing, and preventive measures targeted at reducing risks of
outbreaks of infectious disease
Health Protection and Emergency Preparedness
SOURCE: National Advisory Committee on SARS and Public Health (2003).
accepted series of steps that are followed when an outbreak of an unknown dis-
ease is found among human populations.
It is to be noted that an “outbreak” could be a single case of a disease when-
ever that disease is sufficiently unusual, as is the case with vCJD or BSE. The
reasoning for this is similar to the use of canaries in mines—as soon as the first
canary dies, it is time to act before the first person dies. In the case of vCJD, the
canary is the first case of BSE—as was so clearly illustrated in the United King-
dom (see Figure 6-2).
TABLE 6-3 Functions and Core Programs

Public Health Functions Core Program Areas
• Population health assessment • Communicable disease prevention and control
• Public health surveillance • Prevention of chronic diseases and injuries
• Disease and injury prevention • Health development through life cycle
• Health promotion • Environmental health
• Health protection • Emergency preparedness

TABLE 6-4 Activity Map for vCJD

Public Health Functions
Population Public Disease
Health Health and Injury Health Health
Core Program Areas Assessments Surveillance Prevention Promotion Protection
Communicable disease
prevention and control X X X X
Prevention of chronic
diseases and injuries
Health development
through life cycle X
Environmental health X X X X X
Emergency preparedness
SOURCE: Ricketts (2005).
TABLE 6-5 Health Protection and the Management of an Outbreak

✓ Outbreak detection
✓ Epidemic investigation
✓ Establishment of case definition
✓ Establish etiology.
✓ Confirm cases.
✓ Find cases.
✓ Define scope of problem.
✓ Descriptive epidemiology
✓ Generate and test hypothesis.
✓ Report findings to peer review.
✓ Communications
✗ Control of epidemic through public health measures
✗ Control and reduce exposure.
• Measures have been undertaken by animal health authorities, but do not result in complete
avoidance of exposure.
✗ Prevent exposure.
✗ Prevent ongoing transmission among humans.
• Infection control, transplantation, blood safety measures partly address this need, but without
screening and preclinical diagnostic testing, it is not possible to fully control exposure.
✗ Eliminate or eradicate infection source.
NOTE: Checkmarks indicate functions that are within the scope of public health; Xs indicate activi-
ties that have not or cannot be accomplished with current interventions.

Peak of First report

UK: Control BSE EC: Control
of vCJD
measures epidemic measures
implemented implemented
40,000 1,200
35,000
1,000
Continental
30,000 UK Europe 800
25,000
20,000 600
15,000
400
10,000
200
5,000
0 0
88
89
90
91
92
93
94
95
96
97
98
99
00
01
02
19
19
19
19
19
19
19
19
19
19
19
19
20
20
20
re
fo
Be
FIGURE 6-2 BSE and vCJD outbreak development in the UK; Epidemic curve of BSE in
Europe (UK n = 180,845; continental Europe n = 3,286).
SOURCE: OIE (2006).
Population Health Assessment and Decision Making in Uncertainty

Since the first case of BSE and the subsequent first case report of vCJD some
10 years later, science and public policy have come a long way. Assumptions
made early in the BSE epidemic, and even some made later, proved to be inaccu-
rate or misplaced. It might have been said in the early years that those involved in
developing policy to control BSE were, figuratively speaking, flying the plane
while building it.
In public health, as in other arenas of public policy, it is necessary to make
decisions even in the face of uncertainty. When uncertainty prevails, many other
aspects of societal influence enter into the decision making, such as economic
stability or principles such as risk avoidance or the precautionary principle. In the
case of BSE, there were enormous economic and trade implications that directly
impacted public policy.
At an entirely practical level, there are questions that will underlie the deci-
sions finally taken by society. Where there are no answers, then it is required that
assumptions are made. In an open society, the assumption should be stated. Based
upon my experience in both public health and BSE, I propose the following core
issues:

• How do people get vCJD?

• Is there any immunity? Treatment?
• Are there people at higher risk?
• Is there a test that can tell people they already are infected? Or will they
get the disease?
• Are there ways to stop people from getting BSE? Or from getting sick?
• Do people die or recover?
How Do People Get vCJD?

The principal source of route and exposure for humans is through the con-
sumption of food of bovine origin, just as for other animals. However, it can be
seen that the risk must be very low because there are very few cases despite very
large amounts of exposure. As of March 2006, 160 cases of vCJD (National CJD
Surveillance Unit UK, 2006) had been reported in the United Kingdom—this in a
country where it has been estimated that over 1 million infected cattle entered the
human food chain (Ghani et al., 2000). It is now known that most of the BSE
infectivity is found in particular parts of the infected cattle, and that the location
of the infectivity shifts somewhat with age. Collectively, the contaminated tis-
sues are referred to as specified bovine offals; those tissues that must be removed
in order to protect human populations are the specified risk materials (SRM).
Additionally, some kinds of mechanically recovered meat may become contami-
nated with neural tissue. The relative resistance of humans to BSE suggests that
the removal of SRM and the modification of methods to mechanically recover
meat would enormously reduce risks to human populations.
Human-to-human transmission is a possible secondary route of transmission
of vCJD, but in this case, the risk must be very low because very few cases of
human-to-human transmission have been recognized despite intense interest in
this problem. All cases reported thus far are from the United Kingdom, and all
involve transfusion of blood (Ward et al., 2003). In medical practice, it is anath-
ema to cause disease during the course of treatment; despite the nearly immeasur-
able risk, extensive measures have been undertaken to protect against iatrogenic
vCJD.
Is There Any Immunity? Treatment?

From the perspective of public health, the answer to both questions is no.
Despite the possible advances in clinical medicine and proposed clinical trials, it
is not possible to amend the public health risk assessment by making allowances
for immune populations or for the potential impact of treatment.

Are There People at Higher Risk?

Clearly, there are. People residing in countries with a high incidence of BSE
and where BSE control interventions have not completely removed the potential
exposure of humans to high-risk tissues are at the highest risk. Additionally, it is
recognized that people carrying the homozygous allele at codon 129 (Methion-
ine/methionine) are overrepresented among vCJD cases. The number of people in
the UK who have this gene combination and have not developed vCJD far ex-
ceeds the number of those who have. Finally, for the purposes of this paper, it
must be noted that there is a risk based upon age; the age distribution is skewed
toward younger adults. The reason for this remains obscure—could it be due to
specific exposures? Is it because of particular physiologic characteristics of the
age group? Could it be that everyone is at equal risk, but that the incubation
period varies? These questions are asked, but not answered. Resultantly, if one
was searching for a screening test that could identify high-risk populations, per-
haps to offer them special interventions, these characteristics are not useful be-
cause very, very many more people with these patterns are not ill than are.
Is There a Test?
There is, to date, no test to detect the agent in food or by testing easily avail-
able biologic tissues of living animals, including humans. Testing in humans is
completely limited to tests that are conducted after the appearance of symptoms.
In cattle, after slaughter, specific areas of cattle brains can be tested for
BSE—these tests are being used more and more extensively globally. However,
testing is comparatively expensive and requires special facilities and cannot be
conducted on site at the time of slaughter. Detailed analysis of the impact of
testing and other interventions can be found on the Canadian Food Inspection
Web site, as on other Web sites (European Union, Switzerland, United Kingdom,
France, and the United States for example).
Are There Ways to Prevent BSE Infection in Humans? Are There Ways to
Prevent People Who Are Infected from Becoming Sick?
To both questions, the answer is no. None of the most time-tested interven-
tions of public health (vaccination, prophylaxis) are useful. By implication, it is
essential that humans must avoid exposure to the source of infection (e.g., con-
taminated cattle tissue).
Do People Die? Recover?

To date, no person with diagnosed vCJD has survived. It is not yet known if
infection leads inevitably to disease, in part because there is no existing preclini-

cal diagnostic test. Once the symptom complex is diagnosed, the disease leads,
inevitably, to death. Preventing vCJD can only be accomplished, at this time, by
preventing exposure to BSE.
Unlike many other population health issues, the principal tools for protecting
the public are actually not in the control of either clinical or public health physi-
cians. Animal and food security is the first line of defence. With the lessons of the
past, it is possible to make good public policy decisions regarding vCJD and
BSE. There is not a recipe for controlling or eradicating vCJD or BSE. Table 6-6
outlines the key activities to control BSE; thorough discussion is beyond the in-
tended scope of this paper.
From the perspective of public health, a series of problems can be anticipated
even in those areas where public health has established authority. Principal among
them is the need for a highly sensitive and accurate surveillance system that can
identify all cases of human TSE and accurately distinguish vCJD. Surveillance
may be supported through legislative authorities where necessary and with the
financial commitment of government where needed. Surveillance capacity will
have to be centralized since the collection, analysis, and dissemination of infor-
mation for action requires expertise in the disease complex as well as in handling
pathogenic tissues. The very rarity of the disease and the implications of each
TABLE 6-6 Controlling BSE

Motivate reporting
Control disease spread:
• Identify at-risk animals using scientifically based criteria,
and destroy them;
• Destroy the cohort (definition of cohort is important and
ought to be based upon feed-cohorts); and
• Feed safety requires identification of all sources of cross-
contamination from slaughter to farmyard and removal of
SBOs from the animal feed chain.
Reduce risk to humans from
apparently healthy animals:
• Remove and destroy specified risk materials (SRMs are
the tissues that might contain or be contaminated by the
SBOs);
• Control animal feed security; and
• Test where necessary and where it will improve safety,
and consider that testing every animal may not lead to
improved safety if it diverts resources from prevention.
Also consider whether the test is, in fact, insufficient to
detect all contamination.
NOTE: SRM = specified risk materials; SBO = specified bovine offals.

SOURCE: Ricketts (2005).

case mean that a high, uniform standard must be set, without risk of duplication
of case reports. In order that cases are identified, there is a need for specialized
clinical knowledge. The awareness, interest, and participation of neurologists and
neuropathologists through collaborative networking is essential. Additionally,
there is a need for access to specific laboratory-based diagnostic capacity, includ-
ing EKG, CSF testing, MRI, and neuropathology, all within a context of high
autopsy rates.
The flow of accurate analysis to senior policy makers in government is re-
quired to ensure that a realistic and thorough BSE risk assessment is conducted
and uses evidence from both human and animal health perspectives. The risk
assessment model should examine modes of population exposure to the BSE agent
and must do so with consideration of the scientific evidence and the multiple
requirements of all stakeholders. There will be many interest groups and many
different messages; by fostering trust and the honest prompt disclosure of infor-
mation, nongovernmental organizations (NGOs) can support the overall public
efforts and help prevent the dissemination of inaccurate or inflammatory mes-
sages. In all countries, one must consider that a trade-based economy is resistant
to disclosure of risk and that competitive markets are affected by changes in
import and export restrictions.
Finally, one must reflect upon the role of public opinion. vCJD is a highly
dreaded disease accompanied by high levels of public outrage. People are out-
raged because they view the suffering and deaths as unnecessary; in fact, they
may suggest that justice is not served because the death of a loved one is simply
due to industry’s interest in profiting over human health concerns. In Canada,
public opinion supported the smaller and less industrialized practice of cattle
ranching seen in some Canadian provinces.
Experience in public health has demonstrated that there are a number of strat-
egies that work to prevent the spread of communicable disease. vCJD is a particu-
lar challenge because there are no opportunities to prevent vCJD short of prevent-
ing BSE infection. In no particular order, the following illustrates the range of
activities that would be pursued:
• Healthy public policy should be implemented regarding exposure to BSE-

contaminated tissues in all disciplines from occupational safety, infection control
practices, biologics development and use, transplantation and transfusion safety,
and food safety;
• Inform people about health issues so that they can make their own deci-
sions in an informed manner;
• Prevent and respond to outbreaks and emergencies, with particular em-
phasis on the need to conduct surveillance for vCJD;
• Help people develop personal skills (resilience), particularly those directly
impacted by BSE through sickness or business;

• Collaborate for intersectoral and community action, recognizing that the

entire community is affected;
• Enforce laws and regulations, notably in feed and food safety;
• Reorient and assure the quality of health services, particularly recogniz-
ing that there will be confusion between other forms of human TSEs and vCJD.
Additionally, given the experience in the United Kingdom, recognition that those
who develop the disease are young;
• Create supportive environments for all stakeholders; and
• Evaluate the impact of interventions.
Many lessons were learned as a result of the outbreak of BSE in the United
Kingdom and Europe. It is important to control the risk of BSE exposure; coun-
tries that have focused on the rate of BSE have been unable to prevent its impor-
tation and spread. As in a commonly used homily, a chain is only as strong as its
weakest link. The key link for public health practitioners is that BSE and vCJD
are the same agent. Simply put, if there were no further infections of cattle with
BSE, there would be no further cases of vCJD.
INCENTIVES AND DISINCENTIVES FOR DISEASE SURVEILLANCE

AND REPORTING: THE BSE CASE STUDY
Will Hueston, D.V.M., Ph.D.4
My contribution to this workshop comes in the form of seven lessons that I

have learned from 16 years of involvement with bovine spongiform encephalopa-
thy (BSE), followed by a brief list of recommendations derived from these les-
sons. The lessons and recommendations are drawn from my experience working
as a private practice veterinarian, a resident veterinarian for an agribusiness en-
terprise, a university faculty member, a government animal health official, and an
adviser and consultant to national and state government, national and interna-
tional organizations, and food system companies from production to retail and
food service.
Lesson 1: Detecting a New Animal Disease Is Extremely Difficult

Most individual animal diseases are treated on the farm following clinical
diagnosis by the animal owner, farm manager, or in difficult cases, a private-
practice veterinarian. If that clinical diagnosis is incorrect, and/or the animal does
not recover, the animal is usually sold (culled), eaten, or buried. Most animal
4Professor and Director, Center for Animal Health and Food Safety.

diagnostic services accessible in such situations are provided on a fee-for-service

basis. Only foreign animal disease investigations and diagnostics are provided
free of charge by government veterinarians, as they are seen as a public good.
Even then, however, the diagnostic workup is generally limited to ruling out a
specific foreign animal disease (e.g., foot-and-mouth disease or BSE); there is no
follow-up to determine the exact cause of illness if foreign animal diseases are
ruled out. Consequently, it is very difficult to detect the signals of the emergence
of a new animal disease.
Limited national monitoring and surveillance does occur, such as the Na-
tional Animal Health Monitoring system and more recently the National Animal
Health Laboratory Network. Creating inclusive national animal disease databases
has been hampered by the lack of widely accepted standardized nomenclature for
animal diseases and presenting signs. Unfortunately, most animal diagnostic labo-
ratory and veterinary hospital record-keeping systems are designed to facilitate
financial accounting and billing, not epidemiologic analysis.
By comparison with Europe, Canada, New Zealand, and Australia, the U.S.
federal animal health laboratory system is quite limited. The federal government
supports two national laboratories, one operated by the Department of Homeland
Security on Plum Island, New York, and the other is operated by the USDA
Animal and Plant Health Inspection Services Veterinary Services in Ames, Iowa.
Research and diagnostics at these facilities focus on diseases for which there is a
specific programmatic target, such as foreign animal diseases at Plum Island, and
domestic program diseases such as brucellosis, tuberculosis, and BSE at Ames.
These two laboratories provide reference services for state and private laborato-
ries (confirmation of specific program diseases). The U.S. government does not
have a national laboratory focused specifically on the detection or description of
emerging animal diseases.
Animal disease diagnostics in the United States are performed by state, uni-
versity, and private laboratories that vary greatly in terms of their quality and
capacity. About 12 of the 50 state animal diagnostic laboratories are linked in a
pilot version of a national animal health laboratory network. Limited funding has
been provided to these laboratories to allow them to cooperate with the federal
laboratories for foreign animal disease diagnostics but not for the identification
and characterization of emerging diseases.
Lesson 2: Recognizing BSE in a Low-Incidence Country Is Difficult

Even Under the Best Circumstances
BSE has no unique presenting clinical signs. Therefore, the disease can only
be detected through specialized diagnostic testing of brain samples; it cannot be
diagnosed by clinical evaluation of the live animal or by gross necropsy such as
that carried out on a dead animal on the farm.

Most countries conduct passive surveillance for BSE and other animal dis-
eases, providing diagnostic services for those animals voluntarily presented to the
laboratory rather than actively searching for cattle demonstrating clinical signs
compatible with BSE or dying of unknown causes. This focus on passive surveil-
lance leads to confusion between the absence of evidence for a disease and the
evidence of its absence. Countries with no “BSE suspects” presented for diagnos-
tic workup claim that no BSE exists, even though the clinical signs associated
with BSE (changes in mentation, sensation, and locomotion) are found in a num-
ber of commonly occurring cattle diseases that can only be differentiated from
BSE by extensive diagnostic workup. In addition, adherence to the “disease
present or absent” paradigm further reduces the effectiveness of passive surveil-
lance by establishing a bias against detecting the disease so that a country can
continue to represent themselves as “BSE-free.”
There are huge disincentives for expanding national surveillance for BSE.
BSE surveillance is expensive, with the total costs for collecting and testing each
sample usually in excess of US$20. Furthermore, it is not in the national interest
to discover BSE unless there is a plan in place for addressing it. Reporting BSE
can have devastating economic and political consequences; whereas, historically
a country’s failure to detect the disease, or its lack of an adequate surveillance
system, has been rewarded by continued trade.
Lesson 3: Most Farmers Are Honest, but Disincentives for Reporting BSE
Greatly Outweigh the Incentives
Animal production has historically been measured by the number of animals
produced, not the quantity and quality of food generated. Therefore, many pro-
ducers see themselves as raising animals rather than as part of the food system.
We are continuing to work to change that paradigm in order to foster a shared
responsibility for the food system, from producer to consumer.
For years most countries in the world have pursued a cheap food policy,
where the price of food has assumed paramount importance. Consequently, food
producers throughout the food system (from the farm to the consumer’s table)
strive to keep costs as low as possible. Although animal diseases impose costs on
farmers, they recognize that absence of disease (100 percent prevention and con-
trol) is not always the optimal economic strategy. Producers weigh the costs of
disease diagnostics, prevention, and control against the potential benefits they
may ensure. They seek diagnostic support if they believe that understanding and
preventing economically important diseases can reduce the cost of production
more than the marginal cost of the diagnostics and prevention strategies, or if
their products can be accorded a higher health status and, hence, a higher value,
as a result of negative results on diagnostic tests where the risk of positive tests
is low.

One is hard pressed to find individual producer incentives for reporting sus-
pected cases of BSE in the United States. There is no treatment for BSE, and
government-mandated controls increase production costs. Feed is the single great-
est contributor to cost of production, and government feed regulations have re-
moved a low-cost protein supplement. Removal and destruction of specified risk
materials (those tissues where BSE agent accumulates in affected cows) has in-
creased the costs of processing and reduced the value of each animal slaughtered.
Additionally, the government certifies the nation’s BSE status, but not that of
individual herds. Thus the individual producer gains no benefit from conscien-
tious submission of suspect cattle where all the test results are negative.
At the same time, there are numerous disincentives for reporting BSE. Pro-
ducers on whose farm a BSE cow is identified are ostracized by the rest of the
industry, and their products are shunned by consumers and wholesale buyers.
Their business (and personal life) is disrupted by the government, industry and
media response. Finally, disposal of affected or suspect animals is difficult and
often expensive, and government response to BSE diagnosis in a herd has all too
often involved destruction of many more animals than epidemiologically neces-
sary to control the disease.
Considering all the disincentives, a phrase uttered by the Prime Minister of
Alberta was taken out of context as a new mantra for some cattle producers:
“Shoot, shovel, and shut up” rather than report BSE suspects.
Lesson 4: Testing Can Become an End Unto Itself

Before implementing a widespread testing regime for disease surveillance or
health monitoring, the purpose of the testing must be clarified. The purpose will
change over the course of an epidemic, so it must always be clear why it is done,
in order that appropriate sample size can be determined and the test results inter-
preted appropriately.
Testing alone cannot afford safety (defined by dictionaries as the “absence of
risk”), and it is meaningless without the concurrent implementation of animal and
public health measures. Testing the wrong populations can create a false sense of
security that, while politically expedient, does not constitute a public health mea-
sure. For instance, controlled BSE challenge studies and accumulated BSE sur-
veillance results demonstrate that young animals will test negative to all of our
currently available tests even if exposed to BSE; this is because the disease takes
years to create discernible damage to the central nervous system and for the dis-
ease agent, the prion protein, to accumulate to detectable levels. Consequently,
testing only young cattle assures that all tests are negative but says nothing about
the BSE status of a country. Similarly, testing all cattle in a country with BSE
decreases the apparent prevalence of the disease because of all the young cattle
testing negative regardless of the extent of BSE in the adult population.

Lesson 5: Focus on Risk, Not the Presence or Absence of Disease

The key for human and animal health protection is effective risk manage-
ment, not the disease status of the country. Most countries have focused dispro-
portionately on the reported presence or absence of disease rather than on the
effectiveness of the risk management. Internally, the lack of positive diagnostic
tests has propelled officials to proclaim disease freedom, thereby creating a false
sense of security and reducing the imperative of prevention and control. Outside
their borders, countries have tended toward implementation of total trade bans
when a trading partner identifies BSE, a policy that ignores the fact that a variety
of risk management measures exist that allow for the safe trade of animals and
animal products from countries regardless of their disease status. Infectious dis-
eases do not respect national borders, and yet we frequently hear the statement
“we have sealed our borders,” all too often followed by the false reassurance that
the disease of concern will “never” occur here. Not only are these statements
factually inaccurate, but also they represent the ultimate risk communication
error—providing absolute guarantees. Above all else, we usually fail to consider
most zoonoses in the context of ecosystem risk management, and we develop
national public policy rather than a regional or global approach.
Lesson 6: Take Opportunity Costs into Account

Every dollar spent on BSE testing, prevention, or control is unavailable to
address a different risk or challenge. The cost of BSE testing may be dispropor-
tionate to the resulting public health benefit, as compared with addressing other
pressing issues in protecting the global food system. Similarly, taking a zero-risk
approach forecasts ever increasing costs as the precautionary principle tends to-
ward taking preemptive actions on every identified hazard, no matter how small
the risk. Developing animal health and public health priorities must be conduct-
ing from a holistic perspective in which all hazards are considered and the oppor-
tunity costs of various initiatives weighed. Similarly, surveillance priorities should
be established through broad-based considerations of risk management, not sim-
ply from a desire to impress the public or trading partners by more tests. I was
struck by the concern voiced by one of my international colleagues caught in a
massive (and expensive) government response to a few BSE cases. “What will
we tell our grandchildren,” he asked, “when we have spent all this money for a
rare cattle disease with a relatively small human health impact, while at the same
time we fail to take basic, proven public health measures for other diseases and
conditions that impact the lives of millions because ‘we have no money.’”
Lesson 7: High Health Status Is a Curse

Once high health status is attained, the impetus for maintaining an animal
health and public health infrastructure fades. We celebrate the successful eradica-

tion of a whole string of animal diseases and successful risk management of

zoonoses that plagued our grandparents such as bovine tuberculosis and undulant
fever. Having achieved this unique high health status for the entire nation, then
we turn around and ask why we are maintaining an infrastructure for something
that no longer exists. Anchoring our animal and public health infrastructure on a
limited number of “program” diseases undercuts the overall system as successes
are celebrated. As a result of the resulting budget cuts and retrenchment, we have
few resources to commit to investigating emerging disease threats and little surge
capacity when a significant infectious disease outbreak occurs. Replacing experi-
enced professionals with unseasoned new recruits saves money in the short run
but costs the nation (and world) in the long term. That is where we find ourselves
today as we struggle to manage emerging issues with limited resources. Cutting
both physical and human resources provides a rapid means for decreasing bud-
gets, but rebuilding an effective animal and public health infrastructure is a monu-
mental undertaking in terms of resources and time.
Strategies for Managing This Dilemma

• Reframe surveillance discussions to focus on the purpose and the scien-
tific basis for surveillance rather than the number of tests conducted;
• Consider the entire farm-to-table food system when designing surveil-
lance systems to support effective risk management for the end consumer and the
nation;
• Recognize that no one surveillance system fits all situations; the sampling
design, sample size, and testing protocol must be adapted to the needs of each
country in order to support optimal risk management;
• Create more incentives for reporting disease to pull in more samples,
rather than simply demanding testing through regulatory initiatives and penalties;
• Develop a national animal identification system to support rapid response
to disease outbreaks and long-term support for emerging disease detection;
• Strengthen the national animal health laboratory system and increase its
capacity, perhaps by providing federal resources to states tied to performance
requirements and reporting so that all states can meet a minimum level of profi-
ciency and quality;
• Foster increased collaboration between biologic, medical, and social sci-
ences in order to better understand the sociology and psychology of disease re-
porting and compliance. Biologic and medical sciences alone are not enough;
• Focus on risk management rather than disease eradication or “zero risk”;
• Adopt and implement science-based regulations for BSE and other emerg-
ing diseases building on international standards;
• Build public-private partnerships to address emerging diseases on a glo-
bal, rather than a national, scale;
• Recognize that all animal health issues are public health issues because of

their direct effects on human heath and their indirect effects on human well-being
through their psychologic, economic, and ecologic consequences; and
• Break down the silos that separate various professions and different stages
of the food system (agriculture, processing, distribution, retail, wholesale, and the
consumer) in order to aggressively promote transdisciplinary approaches to ani-
mal and public health.
REFERENCES
Alper T, Cramp WA, Haig DA, Clarke MC. 1967. Does the agent of scrapie replicate without nucleic
acid? Nature 214(90):764–766.
Alpers MP. 1968. Kuru: Implications of its transmissibility for the interpretation of its changing
epidemiological pattern. In: Bailey OT, Smith DE, Eds. The Central Nervous System: Some
Experimental Models of Neurological Diseases. Baltimore, MD: Williams and Wilkins Com-
pany. Pp. 234–251.
Alter M, Kahana E. 1976. Creutzfeldt-Jakob disease among Lybian Jews in Israel. Science 192
(4238):428.
Anderson RM, Donnelly CA, Ferguson NM, Woolhouse ME, Watt CJ, Udy HJ, MaWhinney S,
Dunstan SP, Southwood TR, Wilesmith JW, Ryan JB, Hoinville LJ, Hillerton JE, Austin AR,
Wells GA. 1996. Transmission dynamics and epidemiology of BSE in British cattle. Nature
382(6594):779–788.
Andreoletti O, Simon S, Lacroux C, Morel N, Tabouret G, Chabert A, Lugan S, Corbiere F, Ferre P,
Foucras G, Laude H, Eychenne F, Grassi J, Schlecher F. 2004. PrPSc accumulation in myocytes
from sheep incubating natural scrapie. Nature Medicine 10(6):591–593.
Baker HF, Ridley RM, Wells GAH. 1993. Experimental transmission of BSE and scrapie to the
common marmoset. Veterinary Record 132(16):403–406.
Bartz JC, Kincaid AE, Bessen RA. 2003. Rapid prion neuroinvasion following tongue infection.
Journal of Virology 77(1):583–591.
Bateman D, Hilton D, Love S, Zeidler M, Beck J, Collinge J. 1995. Sporadic Creutzfeldt-Jakob
disease in a 18-year-old in the UK [Letter]. Lancet 346(8983):1155–1156.
Bellinger-Kawahara C, Cleaver JE, Diener TO, Prusiner SB. 1987a. Purified scrapie prions resist
inactivation by UV irradiation. Journal of Virology 61(1):159–166.
Bellinger-Kawahara C, Diener TO, McKinley MP, Groth DF, Smith DR, Prusiner SB. 1987b. Puri-
fied scrapie prions resist inactivation by procedures that hydrolyze, modify, or shear nucleic
acids. Virology 160(1):271–274.
Bosque PJ, Ryou C, Telling G, Peretz D, Legname G, DeArmond SJ, Prusiner SB. 2002. Prions in
skeletal muscle. Proceedings of the National Academy of Sciences 99(6):3812–3817.
Brachmann A, Baxa U, Wickner RB. 2005. Prion generation in vitro: Amyloid of Ure2p is infectious.
EMBO Journal 24(17):3082–3092.
Britton TC, Al-Sarraj S, Shaw C, Campbell T, Collinge J. 1995. Sporadic Creutzfeldt-Jakob disease
in a 16-year-old in the UK [Letter]. Lancet 346(8983):1155.
Bruce ME, Dickinson AG. 1987. Biological evidence that the scrapie agent has an independent ge-
nome. Journal of General Virology 68(Pt. 1):79–89.
Bruce ME, Will RG, Ironside JW, McConnell I, Drummond D, Suttie A, McCardle L, Chree A, Hope
J, Birkett C, Cousens S, Fraser H, Bostock CJ. 1997. Transmissions to mice indicate that ‘new
variant’ CJD is caused by the BSE agent. Nature 389(6650):498–501.
Buschmann A, Groschup MH. 2005. Highly bovine spongiform encephalopathy-sensitive transgenic
mice confirm the essential restriction of infectivity to the nervous system in clinically diseased
cattle. Journal of Infectious Diseases 192(5):934–942.

Buschmann A, Pfaff E, Reifenberg K, Müller HM, Groschup MH. 2000. Detection of cattle-derived
BSE prions using transgenic mice overexpressing bovine PrP(C). Archives of Virology 16(suppl):
75–86.
CDC (Centers for Disease Control and Prevention). 1996. Surveillance for Creutzfeldt-Jakob
disease—United States. Morbidity and Mortality Weekly Report 45(31):665–668.
Chapman J, Ben-Israel J, Goldhammer Y, Korczyn AD. 1994. The risk of developing Creutzfeldt-
Jakob disease in subjects with the PRNP gene codon 200 point mutation. Neurology 44(9):1683–
1686.
Chesebro B. 2004. Biomedicine. A fresh look at BSE. Science 305(5692):1918–1921.
Collinge J. 1999. Variant Creutzfeldt-Jakob disease. Lancet 354(9175):317–323.
Collinge J, Sidle KCL, Meads J, Ironside J, Hill AF. 1996. Molecular analysis of prion strain variation
and the aetiology of “new variant” CJD. Nature 383(6602):685–690.
Collinge J, Whitfield J, McKintosh E, Beck J, Mead S, Thomas DJ, Alpers MP. 2006. Kuru in the 21st
century—an acquired human prion disease with very long incubation periods. Lancet 367(9528):
2068–2074.
Collins S, Boyd A, Fletcher A, Gonzales M, NcLean CA, Byron K, Masters CL. 2000. Creutzfeldt-
Jakob disease: Diagnostic utility of 14-3-3 protein immunodetection in cerebrospinal fluid. Jour-
nal of Clinical Neuroscience 7(3):203–208.
Collins S, Boyd A, Lee JS, Lewis V, Fletcher A, McLean CA, Law M, Kaldor J, Smith MJ, Masters
CL. 2002. Creutzfeldt-Jakob disease in Australia 1970–1999. Neurology 59(9):1365–1371.
Collins SJ, Lawson VA, Masters CL. 2004. Transmissible spongiform encephalopathies. Lancet
363(9402):51–61.
Dickinson AG, Fraser H, Outram GW. 1975. Scrapie incubation time can exceed natural lifespan.
Nature 256(5520):732–733.
Donnelly CA, Ferguson NM, Ghani AC, Anderson RM. 2002. Implications of BSE infection screen-
ing data for the scale of the British BSE epidemic and current European infection levels. Pro-
ceedings. Biological Sciences/The Royal Society 269(1506):2179–2190.
Foster J, Goldmann W, Parnham D, Chong A, Hunter N. 2001. Partial dissociation of PrPSc deposi-
tion and vacuolation in the brains of scrapie and BSE experimentally affected goats. Journal of
General Virology 82(Pt. 1):267–273.
Gajdusek DC. 1962. Kuru: An appraisal of five years of investigation. Eugenics Quarterly 9:69–74.
Gajdusek DC. 1977. Unconventional viruses and the origin and disappearance of kuru. Science
197(4307):943–960.
Gajdusek DC, Zigas V. 1957. Degenerative disease of the central nervous system in New Guinea. The
endemic occurrence of “kuru” in the native population. New England Journal of Medicine
257(20):974–978.
Gajdusek DC, Gibbs CJ Jr, Alpers M. 1966. Experimental transmission of a kuru-like syndrome to
chimpanzees. Nature 209(25):794–796.
GAO (Government Accountability Office). 2005 (February). Mad Cow Disease: FDA’s Management
of the Feed Ban Has Improved, but Oversight Weaknesses Continue to Limit Program Effective-
ness. GAO-05-101. Washington, D.C.
Ghani AC, Ferguson NM, Donnelly CA, Anderson RM. 2000. Predicted vCJD mortality in Great
Britain. Nature 406(6796):583–584.
Glasse RM. 1967. Cannibalism in the kuru region of New Guinea. Transactions of the New York
Academy of Sciences 29(6):748–754.
Glatzel M, Abela E, Maissen M, Aguzzi A. 2003. Extraneural pathologic prion protein in sporadic
Creutzfeldt-Jakob disease. New England Journal of Medicine 349(19):1812–1820.
Goldfarb LG, Brown P, Mitrova E, Cervenakova L, Goldin L, Korczyn AD, Chapman J, Galvez S,
Cartier L, Rubenstein R, et al. 1991. Creutzfeldt-Jacob disease associated with the PRNP codon
200Lys mutation: An analysis of 45 families. European Journal of Epidemiology 7(5):477–486.

Goldmann W, Hunter N, Manson J, Hope J. 1990. The PrP gene of the sheep, a natural host of scrapie.
Proceedings of the VIIIth International Congress of Virology. Berlin, August 26–31. P. 284.
Goldmann W, Hunter N, Martin T, Dawson M, Hope J. 1991. Different forms of the bovine PrP gene
have five or six copies of a short, G-C-rich element within the protein-coding exon. Journal of
General Virology 72(Pt. 1):201–204.
Grassi J, Comoy E, Simon S, Creminon C, Frobert Y, Trapmann S, Schimmel H, Hawkins SA,
Moynagh J, Deslys JP, Wells GA. 2001. Rapid test for the preclinical postmortem diagnosis of
BSE in central nervous system tissue. Veterinary Record 149(19):577–582.
Hadlow WJ. 1959. Scrapie and kuru [Letter]. Lancet 2:289–290.
Hill A, Desbruslais M, Joiner S, Sidle KC, Gowland I, Collinge J, Doey LJ, Lantos P. 1997. The same
prion strain causes vCJD and BSE. Nature 389(6650):448–450.
Hill AF, Joiner S, Linehan J, Desbruslais M, Lantos PL, Collinge J. 2000. Species-barrier-indepen-
dent prion replication in apparently resistant species. Proceedings of the National Academy of
Sciences 97(18):10248–10253.
Hilton DA, Ghani AC, Conyers L, Edwards P, McCardle L, Ritchie D, Penney M, Hegazy D, Ironside
JW. 2004. Prevalence of lymphoreticular prion protein accumulation in UK tissue samples.
Journal of Pathology 203(3):733–739.
Hsiao KK, Scott M, Foster D, Groth DF, DeArmond SJ, Prusiner SB. 1990. Spontaneous neuro-
degeneration in transgenic mice with mutant prion protein. Science 250(4987):1587–1590.
Hsiao K, Meiner Z, Kahana E, Cass C, Kahana I, Avrahami D, Scarlato G, Abramsky O, Prusiner SB,
Gabizon R. 1991. Mutation of the prion protein in Libyan Jews with Creutzfeldt-Jakob disease.
New England Journal of Medicine 324(16):1091–1097.
Hsiao KK, Groth D, Scott M, Yang SL, Serban H, Rapp D, Foster D, Torchia M, DeArmond SJ,
Prusiner SB. 1994. Serial transmission in rodents of neurodegeneration from transgenic mice
expressing mutant prion protein. Proceedings of the National Academy of Sciences 91(19):
9126–9130.
Ironside JW. 1997. The new variant form of Creutzfeldt-Jakob disease: A novel prion protein amyloid
disorder. Amyloid: International Journal of Clinical and Experimental Investigation 4:66–69.
Kaneko K, Ball HL, Wille H, Zhang H, Groth D, Torchia M, Tremblay P, Safar J, Prusiner SB,
DeArmond SJ, Baldwin MA, Cohem FE. 2000. A synthetic peptide initiates Gerstmann-
Sträussler-Scheinker (GSS) disease in transgenic mice. Journal of Molecular Biology 295(4):
997–1007.
Kimberlin RH. 1982. Scrapie agent: Prions or virinos? Nature 297(5862):107–108.
Klug GM, Boyd A, Lewis V, Kvasnicka M, Lee JS, Masters CL, Collins SJ. 2005. Creutzfeldt-Jakob
disease: Australian surveillance update to 31 December 2004. Communicable Diseases Intelli-
gence 29(3):269-271.
Kübler E, Oesch B, Raeber AJ. 2003. Diagnosis of prion diseases. British Medical Bulletin 66:
267–279.
Lasmézas CI, Deslys J-P, Demaimay R, Adjou KT, Lamoury F, Dormont D, Robain O, Ironside J,
Hauw JJ. 1996. BSE transmission to macaques. Nature 381(6585):743–744.
Last JM, ed. 1983. A Dictionary of Epidemiology. Oxford: Oxford University Press.
Last JM, ed. 2001. A Dictionary of Epidemiology. Oxford: Oxford University Press.
Lee IS, Long JR, Prusiner SB, Safar JG. 2005. Selective precipitation of prions by polyoxometalate
complexes. Journal of the American Chemical Society 127(40):13802–13803.
Legname G, Baskakov IV, Nguyen HO, Riesner D, Cohen FE, DeArmond SJ, Prusiner SB. 2004.
Synthetic mammalian prions. Science 305(5684):673–676.
Legname G, Nguyen HO, Baskakov IV, Cohen FE, DeArmond SJ, Prusiner SB. 2005. Strain-specified
characteristics of mouse synthetic prions. Proceedings of the National Academy of Sciences
102(6):2168–2173.
Lewis V, Hill AF, Klug GM, Boyd A, Masters CL, Collins SJ. 2005. Australian sporadic CJD analy-
sis supports endogenous determinants of molecular-clinical profiles. Neurology 65(1):113–118.

Llewelyn CA, Hewitt PE, Knight RS, Amar K, Cousens S, Mackenzie J, Will RG. 2004. Possible
transmission of variant Creutzfeldt-Jakob disease by blood transfusion. Lancet 363(9407):
417–421.
Maddelein ML, Dos Reis S, Duvezin-Caubet S, Coulary-Salin B, Saupe SJ. 2002. Amyloid aggre-
gates of the HET-s prion protein are infectious. Proceedings of the National Academy of Sci-
ences 99(11):7402–7407.
Minor P, Newham J, Jones N, Bergeron C, Gregori L, Asher D, van Engelenburg F, Stroebel T, Vey
M, Barnard G, Head M; WHO Working Group on International Reference Materials for the
Diagnosis and Study of Transmissible Spongiform Encephalopathies. 2004. Standards for the
assay of Creutzfeldt-Jakob disease specimens. Journal of General Virology 85(Pt. 6):1777–1784.
National Advisory Committee on SARS and Public Health. 2003. Learning from SARS—Renewal of
Public Health in Canada. Ottawa: Health Canada. [Online]. Available: http://www.phac-
aspc.gc.ca/publicat/sars-sras/naylor/ [accessed July 25, 2006].
National CJD Surveillance Unit UK. 2006. CJD Statistics. [Online]. Available: http://www.cjd.ed.ac.
uk/figures.htm [accessed March 17, 2006].
OIE (Office International des Epizooties). 2006. Bovine Spongiform Encephalopathy (BSE). [Online].
Available: http://www.oie.int/eng/info/en_esb.htm [accessed July 26, 2006].
Pan K, Baldwin M, Nguyen J, Gasset M, Serban A, Groth D, Mehlhorn I, Huang Z, Fletterick RJ,
Cohen FE, Prusiner SB. 1993. Conversion of a-helices into b-sheets features in the formation of
the scrapie prion proteins. Proceedings of the National Academy of Sciences 90(23):10962–
10966.
Peden AH, Head MW, Ritchie DL, Bell JE, Ironside JW. 2004. Preclinical vCJD after blood transfu-
sion in a PRNP codon 129 heterozygous patient. Lancet 364(9433):527–529.
Phillips NA, Bridgeman J, Ferguson-Smith M. 2000. The BSE Inquiry. Vol 2. London: Stationery
Office.
Prusiner SB. 2004a. Detecting mad cow disease. Scientific American 291(1):86–93.
Prusiner SB. 2004b. Prion Biology and Diseases. 2nd ed. Cold Spring Harbor, NY: Cold Spring
Harbor Laboratory Press.
Ricketts M. 2005 (October 26). Session VI: What Are the Incentives and Disincentives Associated
with Disease/Contamination Reporting? Impacts on Human Health and International Trade—
BSE as a “Case Study.” Presentation at the Forum on Microbial Threats Workshop Meeting,
Roos R, Gajdusek DC, Gibbs CJ Jr. 1973. The clinical characteristics of transmissible Creutzfeldt-
Jakob disease. Brain 96(1):1–20.
Safar J, Wille H, Itri V, Groth D, Serban H, Torchia M, Cohen FE, Prusiner SB. 1998. Eight prion
strains have PrPSc molecules with different conformations. Nature Medicine 4(10):1157–1165.
Safar JG, Geschwind MD, Deering C, Didorenko S, Sattavat M, Sanchez H, Serban A, Vey M, Baron
H, Giles K, Miller B, DeArmond SJ, Prusiner SB. 2005a. Diagnosis of human prion disease.
Proceedings of the National Academy of Sciences 102(9):3501–3506.
Safar JG, Kellings K, Serban A, Groth D, Cleaver JE, Prusiner SB, Riesner D. 2005b. Search for a
prion-specific nucleic acid. Journal of Virology 79(16):10796–10806.
Scott MR, Safar J, Telling G, Nguyen O, Groth D, Torchia M, Koehler R, Tremblay P, Walther D,
Cohen FE, DeArmond SJ, Prusiner SB. 1997. Identification of a prion protein epitope modulat-
ing transmission of bovine spongiform encephalopathy prions to transgenic mice. Proceedings
of the National Academy of Sciences 94(26):14279–14284.
Scott MR, Will R, Ironside J, Nguyen HO, Tremblay P, DeArmond SJ, Prusiner SB. 1999. Compel-
ling transgenetic evidence for transmission of bovine spongiform encephalopathy prions to hu-
mans. Proceedings of the National Academy of Sciences 96(26):15137–15142.

Scott MR, Peretz D, Nguyen HO, DeArmond SJ, Prusiner SB. 2005. Transmission barriers for bo-
vine, ovine, and human prions in transgenic mice. Journal of Virology 79(9):5259–5271.
Sparrer HE, Santoso A, Szoka FC Jr, Weissman JS. 2000. Evidence for the prion hypothesis: Induc-
tion of the yeast [PSI+] factor by in vitro-converted Sup35 protein. Science 289(5479):595–599.
Spencer MD, Knight RS, Will RG. 2002. First hundred cases of variant Creutzfeldt-Jakob disease:
Retrospective case note review of early psychiatric and neurological features. British Medical
Journal 324(7352):1479–1482.
Spudich S, Mastrianni JA, Wrensch M, Gabizon R, Meiner Z, Kahana I, Rosenmann H, Kahana E,
Prusiner SB. 1995. Complete penetrance of Creutzfeldt-Jakob disease in Libyan Jews carrying
the E200K mutation in the prion protein gene. Molcular Medicine 1(6):607–613.
Tanaka M, Chien P, Naber N, Cooke R, Weissman JS. 2004. Conformational variations in an infec-
tious protein determine prion strain differences. Nature 428(6980):323–328.
Telling GC, Haga T, Torchia M, Tremblay P, DeArmond SJ, Prusiner SB. 1996. Interactions between
wild-type and mutant prion proteins modulate neurodegeneration in transgenic mice. Genes &
Development 10(14):1736–1750.
Thomzig A, Kratzel C, Lenz G, Kruger D, Beekes M. 2003. Widespread PrPSc accumulation in
muscles of hamsters orally infected with scrapie. EMBO Reports 4(5):530–533.
Tremblay P, Ball HL, Kaneko K, Groth D, Hegde RS, Cohen FE, DeArmond SJ, Prusiner SB, Safar
JG. 2004. Mutant PrPSc conformers induced by a synthetic peptide and several prion strains.
Journal of Virology 78(4):2088–2099.
Valleron AJ, Boelle PY, Will R, Cesbron JY. 2001. Estimation of epidemic size and incubation time
based on age characteristics of vCJD in the United Kingdom. Science 294(5547):1726–1728.
Wadsworth JD, Joiner S, Hill AF, Campbell TA, Desbruslais M, Luthert PJ, Collinge J. 2001. Tissue
distribution of protease resistant prion protein in variant Creutzfeldt-Jakob disease using a highly
sensitive immunoblotting assay. Lancet 358(9277):171–180.
Ward HJT, Everington D, Sanchez-Juan P, Smith A, Cooper S, Heath C, Knight RSG, Will RG. 2003
(October 8-10). Secondary Transmission of Variant Creutzfeldt-Jakob Disease? Presentation at
the International Prion Conference, Munich.
Ward HJ, Everington D, Cousens SN, Smith-Bathgate B, Leitch M, Cooper S, Heath C, Knight RS,
Smith PG, Will RG. 2006. Risk factors for variant Creutzfeldt-Jakob disease: A case-control
study. Annals of Neurology 59(1):111–120.
Weissmann C. 1991. A “unified theory” of prion propagation. Nature 352(6337):679–683.
Wells GAH. 2002 (January 10–11). Report on TSE Infectivity Distribution in Ruminant Tissues (State
of Knowledge, December 2001). Brussels: European Commission.
Will RG, Ironside JW, Zeidler M, Cousens S, Estibeiro K, Alperovitch A, Poser S, Pocchiari M,
Hofman A, Smith PG. 1996. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet
347(9006):921–925.
Will RG, Alpers MP, Dormont D, Schonberger LB. 2004. Infectious and sporadic prion diseases. In:
Prusiner SB, Ed. Prion Biology and Diseases. 2nd ed. Cold Spring Harbor, NY: Cold Spring
Harbor Laboratory Press. Pp. 629–671.
Yamakawa Y, Hagiwara K, Nohtomi K, Nakamura Y, Nishijima M, Higuchi Y, Sato Y, Sata T;
Expert Committee for BSE Diagnosis, Ministry of Health, Labor and Welfare of Japan. 2003.
Atypical proteinase K-resistant prion protein (PrPres) observed in an apparently healthy 23-
month-old Holstein steer. Japanese Journal of Infectious Diseases 56(5-6):221–222.
Zerr I, Pocchiari M, Collins S, Brandel JP, de Pedro Cuesta J, Knight RS, Bernheimer H, Cardone F,
Delasnerie-Laupretre N, Caudrado Corrales N, Ladogana A, Bodemer M, Fletcher A, Awan T,
Ruiz Bremon A, Budka H, Laplanche JL, Will RG, Poser S. 2000. Analysis of EEG and CSF 14-
3-3 proteins as aids to the diagnosis of Creutzfeldt-Jakob disease. Neurology 55(6):811–815.

Research and Policy Opportunities
OVERVIEW
Contributors to previous chapters have addressed research and policy oppor-
tunities in food safety oversight, surveillance, and disease reporting in protecting
the food supply. Additional research and policy issues were raised in workshop
presentations that focused on animal health, food defense, and food safety science.
Dr. Lonnie King, dean of the College of Veterinary Medicine at Michigan
State University, presented key findings from the recently published report, Ani-
mal Health at the Crossroads (2005). This chapter begins with an excerpt from
this report, which explored the critical linkage between animal and human health
illustrated in case studies of key animal diseases. The study committee, assembled
by the National Research Council (NRC), evaluated existing prevention and de-
tection systems and identified opportunities and barriers to their improvement;
many of their findings directly address the reduction of foodborne illness.
The chapter concludes with a paper by Dr. Francis Busta, director of the
National Center for Food Protection and Defense (NCFPD), who describes re-
search to protect the food supply from deliberate harm and to mitigate the effects
of such an attack. Recognizing that many of the same tools and strategies could
be used to guard against any incident of food adulteration, whether accidental or
deliberate, Busta emphasizes techniques that address key questions raised by a
foodborne attack: how it was staged, which threat agent was used, what decon-
tamination and other public health measures should be taken, and how to inform
the public about the incident.
The workshop concluded with a presentation by Dr. Sanford Miller, who
noted the profound influence of such nonscientific issues on perceptions of risks
232

RESEARCH AND POLICY OPPORTUNITIES 233
to the food supply. Safety is not a biological property of food, Miller contended,
but an intellectual concept influenced as much by the political, economic, and
social factors that determine our perception of risk as by any quantifiable mea-
sure of hazard. Thus efforts to improve food safety must not only identify
foodborne threats, but also translate these discoveries into regulation, communi-
cation, and legislation that accurately reflect the risks such threats pose to society.
Meeting these challenges is the goal of the nascent field of food safety science,
which integrates nutrition, microbiology, toxicology, molecular biology, genet-
ics, functional biology, and conventional food science, and brings these disci-
plines to bear on the problem of ensuring a safe food supply through the practice
of risk assessment.
“We all feel comfortable talking about science,” Miller observed, “but the
moment comes when science has to be translated into risk, and risk has to be
translated into some kind of public policy action.” The food safety scientist he
envisions will use sophisticated, risk-based, scientifically sound models to deter-
mine how best to protect our food supply.
ANIMAL HEALTH AT THE CROSSROADS1

Committee on Assessing the Nation’s Framework
for Addressing Animal Diseases2
National Research Council
Synopsis
The national framework to safeguard animal health is of paramount impor-
tance to the U.S. economy, public health, and food supply. To strengthen the
existing framework, the nation should establish a high-level, authoritative mecha-
nism to coordinate interactions between the private sector and local, state, and
federal agencies. New tools for detection, diagnosis, and risk analysis need to be
developed now, and the capacity of the existing animal health laboratory network
should be expanded for both routine and emergency diagnostic uses. Integrative
animal health research programs, in which veterinary and medical scientists can
work as collaborators, should be established. Colleges of veterinary medicine
must lead an effort to develop a national animal health education plan to educate
and train individuals from all sectors (from animal handlers to pathologists) in
disease prevention and early detection, and to recruit veterinary students into
careers in public health, food systems, biomedical research, diagnostic laboratory
1Reprinted from NRC (2005). Animal Health at the Crossroads. Washington, D.C.: The National
Academies Press.
2Board on Agriculture and Natural Resources, Division on Earth and Life Studies.

investigation, pathology, epidemiology, ecosystem health, and food-animal prac-

tice. The United States must address the importation and health of exotic and
wild-caught animals and commit itself to shared leadership roles with other coun-
tries and international organizations that address animal disease agents. Finally, a
collective effort should be made to raise the level of public awareness about the
importance of animal health and of the national investment in the framework to
safeguard animal health.
Background
Animal health has broad implications, ranging from the health of individual
animals and the well-being of human communities to issues of global security.
Many people would be surprised by the assertion that our nation’s highest priori-
ties must include animal health, yet we must recognize and act on this reality to
ensure a safe and healthy future. Among other things, animal diseases critically
affect the adequacy of the food supply for a growing world population, and they
have huge implications for global trade and commerce. Moreover, many animal
disease agents are zoonotic—meaning that they are transmittable to humans—so
they have dramatic implications for human health and safety, and for animal dis-
ease prevention. Animal disease prevention and control is crucial to improving
public health on a global scale. Additionally, in an era of growing concern about
the threat of terrorism, the potential impact of the intentional use of animal dis-
ease agents to cause morbidity and mortality, as well as economic damage, is
enormous.
The U.S. animal health framework includes many federal, state, and local
agencies that generally have differing mandates of law, and numerous other pub-
lic and private entities and international organizations, each with its own goals
and objectives, each responsible for maintaining animal health. In the past, this
framework has been reasonably effective in responding to a range of demands
and challenges. In recent years, however, animal health has been challenged in a
manner not previously experienced.
Today animal health is at a crossroads. The risk of disease is coming from
many directions, including the globalization of commerce, the restructuring and
consolidation of global food and agriculture productions into larger commercial
units, the interactions of humans and companion animals, human incursions into
wildlife habitats, and the threat of bioterrorism. The impacts of these sources of
risk are evident in recent disease events (Box 7-1).
Given the changing nature of the risks with which the framework must cope,
it is unlikely that the current philosophy on how to protect animal health will be
adequate in the future. The risks of animal disease must be dealt with not only in
terms of protecting individual species of animals from specific pathogens, but
also in a broader context that includes anticipating the emergence and spread of
disease on local and global scales, and recognizing the relationships of animal

BOX 7-1
Impacts from Recent Disease Events
• In 2003, severe acute respiratory syndrome (SARS) sent a global
shockwave, affecting countries with even few cases, such as the United
States. Although SARS infected only 8,000 people globally, the dis-
ease spread to 30 countries and its effect on the global economy to-
taled $8 billion.
• The United Kingdom’s economy has not yet recovered from a foot-
and-mouth disease (FMD) outbreak in 2001, which also reverberated
around the world, affecting both agricultural and nonagricultural inter-
ests (such as rural businesses and tourism/recreational use of the
countryside).
• A single case of mad cow disease (bovine spongiform encephalopathy
or BSE) in Washington State on December 23, 2003, had an immedi-
ate market impact and severe, sustained economic losses due to trade
restrictions on U.S. cattle and their products. The infected animal was
discovered as part of the government’s policy to routinely test downer
cattle for BSE, which has been linked to a new variant of Creutzfeldt-
Jakob disease, a fatal neurological illness in humans. In June 2005, a
second case of BSE was confirmed in the United States.
• In 2004, a new strain of highly pathogenic avian influenza (AI) spread
through Southeast Asia, resulting in the loss of more than 100 million
birds through mortality and control measures and dozens of human
cases, highlighting the unpredictable and potentially catastrophic na-
ture of emerging zoonotic disease. This new influenza strain was trans-
mitted from birds to people, raising concern that it might be capable of
evolving into the next pandemic influenza strain.
• In 1999, West Nile virus (WNV), an arbovirus similar to St. Louis en-
cephalitis virus, emerged for the first time in the Western Hemisphere
in New York from an unknown source. Over the next five years it swept
across the continental United States, Canada, Mexico, Central Amer-
ica, and several Caribbean islands, carried by mosquito vectors infect-
ing wild birds. In the United States in 2004, the virus was detected in
approximately 2,250 humans (40 states), 1,250 horses (36 states),
nearly 7,000 wild birds, mostly corvids (45 states), and in much smaller
numbers in a few other animal species. While these numbers are sub-
stantially below those that occurred in the first wave of infection, WNV
bodes to become endemic in wild birds and an ongoing source of in-
fection transmitted to other species by mosquito vectors.

disease to human health and the environment. To address animal disease in that
context, the animal health framework will have to be more flexible and inclusive
of expertise available from research, medical, and public health communities,
and from the fields of environmental sciences and public policy, among others.
To respond comprehensively to new threats, the responsibilities of the frame-
work’s many actors will need to be clearly defined and their actions better coordi-
nated. Admittedly, the process of transformation is difficult during periods when
disease outbreaks consume all attention. However, now is the time to strengthen
the structure of the current system and to instigate a change in its culture, so that
it will be capable of responding effectively in the future.
This report explores the evolving challenges facing animal health, identifies
vulnerabilities and gaps in the animal health framework, and recommends steps
needed to fill gaps and improve the effectiveness of the framework.
Committee’s Statement of Task

Recent animal and human health events have illustrated that the national
system for protecting animal health is now facing a continuum of host-parasite
relationships involving public health, wildlife, ecosystems, and food systems,
operating in an increasingly complex global context (see Figure 7-1). Adapting
the current framework to this new reality will be both a major challenge and a
national imperative.
In recognition of the changing influences on animal health, the National
Academies developed a concept for a three-phase analysis of the U.S. system for
dealing with animal diseases and committed institutional funds to launch the first
phase of the study. This report, which embodies the first phase of the study,
presents an overview of the animal health framework and examines the frame-
work’s overall operation in the prevention, detection, and diagnosis of animal
diseases. The proposed second phase of the study (pending supplemental external
support) will focus on surveillance and monitoring capabilities, and the proposed
third phase will focus on response and recovery from an animal disease epidemic.
Although surveillance and monitoring play an important part in prevention, de-
tection, and diagnosis, the second phase of the study, as currently envisioned, will
analyze in greater depth the system’s capacity and needs for surveillance and
monitoring of animal diseases.
Relative to its respective focus, each phase of the study will: (1) review the
state and quality of the current system for dealing with animal disease; (2) iden-
tify key opportunities and barriers to successfully preventing and controlling ani-
mal diseases; and (3) identify immediate courses of action for those on the
front lines.
This first phase of the study did not attempt an in-depth review of the effec-
tiveness of each individual component of the framework or of any specific agency
involved in safeguarding animal health—a task well beyond the scope of this

Wildlife
Diseases
Human Domestic
Diseases Animal
Diseases
FIGURE 7-1 Interactions of emerging infectious diseases (EIDs) with a continuum that
includes wildlife, domestic animal, and human populations. Few diseases affect exclu-
sively one group, and the complex relations among host populations set the scene for
disease emergence. Examples of EIDs that overlap these categories include Lyme disease
(wildlife to domestic animals and humans); bovine tuberculosis (between domestic ani-
mals and wildlife); Escherichia coli O157:H7 (between domestic animals and humans);
and Nipah virus and rabies (all three categories). Companion animals are categorized in
the domestic animal section of the continuum.
effort—but did examine the effectiveness of the framework as a whole in relation

to different animal disease scenarios. In doing so, it sought to identify ways to
improve the framework.
Finally, although animals are subject to the same causes of disease as
humans—that is, diseases with chemical, physical, microbial, or genetic causes—
the study focuses primarily on infectious diseases, as directed by the Statement of
Task (see Chapter 1, Box 1-1 from the NRC report Animal Health at the Cross-
roads, for the committee’s Statement of Task). This focus arises from concern
about the growing threat posed by the spread of emerging infectious disease asso-
ciated with the increasing global interconnectedness of domestic animals, wild-
life, and humans, and by the possibility of bioterrorism.
Overview of the Animal Health Framework

The essential components of the animal health framework include the
following:

• People on the “front lines” of the animal production unit, animal habitat,
or companion animal household (including ranch and farm workers, producers,
feeders, breeders, park rangers, companion animal owners, wildlife rehabilitators,
and zoo keepers);
• Veterinarians and other sources of professional advice and care for health-
related issues (such as universities and diagnostic laboratories);
• Federal, state, and local animal health and public health agencies (con-
sisting mainly of state departments of agriculture and state diagnostics laborato-
ries within universities and elsewhere in state governments, and numerous bu-
reaus and offices within over 10 federal departments, but primarily within the
U.S. Departments of Agriculture, Homeland Security, and Health and Human
Services);
• International collaborations among agencies, organizations, and govern-
ments (such as the World Organization for Animal Health and the World Health
Organization); and
• Supporting institutions, industries, and organizations (including educa-
tors, researchers, and the public health and intelligence communities).
Because of the very large number of actors responsible in some way for
safeguarding animal health, it is not surprising that effective coordination is a
major challenge. In a retrospective analysis of numerous specific animal disease
situations, the committee examined the collective capabilities and limitations of
the framework with respect to its effectiveness in the prevention, detection, and
diagnosis of animal diseases. Several weaknesses, needs, and gaps were consis-
tently encountered in the framework’s response to a broad spectrum of disease
types including exotic Newcastle disease (END), foot-and-mouth disease (FMD),
monkeypox, bovine spongiform encephalopathy (BSE), chronic wasting disease
(CWD), West Nile virus (WNV), avian influenza (AI), and diseases caused by
coronavirus. This examination led the committee to the following conclusions:
• The framework for animal health lacks adequate systems and tools for
analyzing and managing risk, and planning for outbreaks.
• Efforts to develop and validate diagnostic assays and advanced vaccines
of a recognized pathogen need to occur more rapidly.
• The workforce on the front lines of animal care is not adequately educated
and trained to deal with animal disease issues, and there is a shortage of veterinar-
ians in the workforce for animal disease prevention, detection, and diagnosis.
• Greater collaboration between public health and animal health officials
can accelerate the detection and diagnosis of animal diseases.
• The broad capabilities that exist in universities, industry, state entities,
veterinary diagnostic laboratories, and other local animal health infrastructure are
underutilized.

• The lack of collaboration between the biomedical and veterinary commu-

nities is a lost opportunity that impedes the effectiveness of the framework.
• There is a need for state-of-the-art equipment and biocontainment facili-
ties for both research and diagnostics. Federal, state, and private entities respon-
sible for animal health have different authorities, and there are gaps in that au-
thority, particularly in relation to wildlife disease.
• The past success of international collaboration in responding to animal
disease demonstrates its importance in addressing animal diseases.
Recommendations for Strengthening the Animal Health Framework

Reflecting on the structure of the framework and based on the findings of its
analysis of past animal health events, the committee offers the following 11 rec-
ommendations as potential opportunities for strengthening the framework’s capa-
bilities in the prevention, detection, and diagnosis of animal diseases.
Coordination of Framework Components

Recommendation 1: The nation should establish a high-level, central-
ized, authoritative, and accountable coordinating mechanism or focal
point for engaging and enhancing partnerships among local, state, and
federal agencies and the private sector.
There is a need for a strategic focal point to enhance partnerships and to
integrate all stakeholders into a cohesive whole. Many federal agencies are re-
sponsible for parts of animal health policy, with significant overlaps in the pro-
grammatic functions among them and also between federal agencies and pro-
grams directed through states or animal health organizations. On the other hand,
there are also gaps in responsibility. Of particular concern is the paucity of fed-
eral oversight of the nonlivestock, animal-centered aspects of zoonotic diseases.
While there are several possible models for improved coordination in pre-
vention, detection, and diagnosis, the committee did not recommend options for a
specific system-wide mechanism, in part because it has only examined the animal
health framework from the partial perspective of prevention, detection, and
diagnosis.
Regardless of how a central coordinating mechanism or focal point is imple-
mented, it will need to promote effective communication among various stake-
holders and with the public during and outside episodes of animal disease out-
breaks. Opportunities for information-sharing between agencies using electronic
information systems should be developed. A methodic effort should be made to
identify and link key databases and establish protocols for contributing data and
generating alerts.

Technological Tools for Preventing, Detecting, and Diagnosing Animal

Diseases
Recommendation 2: Agencies and institutions—including the U.S. De-
partment of Agriculture (USDA) and the Department of Homeland Se-
curity (DHS)—responsible for protecting animal industries, wildlife, and
associated economies should encourage and support rapid development,
validation, and adoption of new technologies and scientific tools for the
detection, diagnosis, and prevention of animal diseases and zoonoses.
The current animal health framework has been slow to evaluate, validate,
and implement new scientific tools and technologies that could significantly en-
hance animal disease prevention, detection, and diagnostic capabilities for the
United States. Despite a recent surge in activity related to post-September 11
homeland security efforts and associated focused funding, the active review and
implementation of advancing technologies has been inadequate to protect and
enhance the health of the country’s animal populations and related economic sys-
tems. Technological advances—such as immune system modulators, animal-
embedded monitoring (chips embedded underneath an animal’s skin to monitor
temperature and other physiological indices), and differential vaccines as preven-
tion strategies, as well as a range of rapid, automated, sensitive, and portable
sampling and assay systems for early warning and reliable diagnosis—have not
been adequately exploited by the current animal health framework. Early
biodefense warning systems, such as DHS’ BioWatch or private industry’s gene-
based anthrax testing, are designed for rapid detection and identification of key
pathogens by sampling air in public environments. These systems have been op-
erating since early 2003 and are meant to assist public health experts in rapidly
responding to the intentional release of a biologic agent (DHS, 2004a). Early
warning technologies have not yet been adequately evaluated by the animal health
infrastructure.
Scientific Preparedness for Diagnosing Animal Diseases: Laboratory

Capacity and Capability
Recommendation 3: The animal health laboratory network should be
expanded and strengthened to ensure sufficient capability and capacity
for both routine and emergency diagnostic needs and to ensure a robust
linkage of all components (federal, state, university, and commercial
laboratories) involved in the diagnosis of animal and zoonotic diseases.
Laboratory diagnosis of animal diseases in the United States involves fed-
eral, state, university, and commercial entities. The committee focused its assess-
ment on the condition of publicly funded laboratories and the current operational
status of national laboratory networks. Funding and implementation of the pilot
National Animal Health Laboratory Network (NAHLN) in June 2002 was an

important and beneficial paradigm shift from an exclusive federal system to one
with shared state and federal responsibility for foreign animal disease diagnosis.
The pilot NAHLN involved 12 state/university diagnostic laboratories approved
for disease testing using existing and newly developed assays. The NAHLN is no
longer a pilot program and has since been redefined to include all laboratories
performing contract work for the USDA on BSE, CWD, scrapie, AI, END, and
classical swine fever (CSF). However, the current network lacks surge capacity
and is not prepared for disease agents and toxins outside the narrow list of diseases
that provided an initial focus for network development (for example, FMD or Rift
Valley fever). In addition, implementing this recommendation will require the
creation of formal linkages and operational relationships between the NAHLN,
state and university veterinary diagnostic laboratories, and the Laboratory Re-
sponse Network for Bioterrorism (LRN), established by the U.S. Centers for Dis-
ease Control and Prevention (CDC) in 1995 to improve the response capabilities
of the nation’s public health laboratory infrastructure. It will require development
of additional biosafety level 3 (BSL-3) necropsy and laboratory capacity. Popula-
tion-based diagnostic and detection systems also will need to be developed by
diagnostic laboratories in order to provide the broad diagnostic outlook necessary
for detection of new and emerging diseases.
Animal Health Research

Recommendation 4: Federal agencies involved in biomedical research
(both human and veterinary) should establish a method to jointly fund
new, competitive, comprehensive, and integrated animal health research
programs; ensure that veterinary and medical scientists can work as
collaborators; and enhance research, both domestically and internation-
ally, on the detection, diagnosis, and prevention of animal and zoonotic
disease encompassing both animal and human hosts.
This process might be modeled on the National Institutes of Health (NIH)-
administered Interagency Comparative Medicine Research Program, an inter-
agency task force model, or some comparable process that promotes this type of
cooperative research agenda.
This recommendation builds on the 2003 Institute of Medicine (IOM) report
Microbial Threats to Health: Emergence, Detection, and Response, which states:
“NIH should develop a comprehensive research agenda for infectious disease
prevention and control in collaboration with other federal research institutions
and laboratories (e.g., CDC, the U.S. Department of Defense, Department of En-
ergy, the National Science Foundation), academia, and industry” (IOM, 2003).
Currently, basic and translational research related to prevention, detection, and
diagnosis of animal and zoonotic diseases is being conducted by a complex array
of government, academic, and private institutions and there is minimal coordina-

tion, if any, in setting priorities to ensure that important research topics are not
overlooked and to ensure the most effective use of scarce resources. A forthcom-
ing National Research Council (NRC) report Critical Needs for Research in Vet-
erinary Science will contain a more in-depth assessment of national needs for
research in animal health.
Recommendation 5: To strengthen the animal health and zoonotic dis-
ease research infrastructure, the committee recommends that compet-
itive grants be made available to scientists to upgrade equipment for
animal disease research and that the nation construct and maintain gov-
ernment and university biosafety level 3 (BSL-3 and BSL-3 Ag)3 facili-
ties for livestock (including large animals), poultry, and wildlife.
Access to state-of-the-art equipment and technological tools is essential to
successfully conduct the research needed to understand, prevent, and control
emerging or exotic infectious agents. When a new infectious agent is suspected,
efforts must be made to first rapidly define and characterize the agent, under strict
biocontainment conditions. At present, few BSL-3 or BSL-3 Ag facilities are
available strategically throughout the United States or are equipped and prepared
for research on diseases of livestock, poultry, or wildlife, including zoonoses that
require BSL-3 biocontainment. Additional BSL-3 facilities are needed for re-
search and surge capacity (in case of outbreaks) for detection, diagnosis, and
prevention of many zoonotic and all exotic animal pathogens.
International Interdependence and Collaboration

Recommendation 6: The United States should commit resources and de-
velop new shared leadership roles with other countries and international
organizations in creating global systems for preventing, detecting, and
diagnosing known and emerging diseases, disease agents, and disease
threats as they relate to animal and public health.
As the United States and the rest of the world become increasingly interde-
pendent, it is essential to identify animal disease risk factors as they emerge and
to focus more attention on the sources and precursors of infections. Taken collec-
tively, the recent experience with SARS, West Nile virus, and monkeypox leads
to the inescapable conclusion that globalization, population growth, and ex-
pansion of human activity into previously unoccupied habitats has essentially
connected the United States to potential zoonotic and nonzoonotic pathogens re-
siding throughout the world. This necessitates coordinated international collabo-
3Containment facilities are classified as Biosafety Levels 1 through 4, with 4 being the most restric-
tive. Biosafety level 3 (BSL-3 or BSL-3 Ag) provides the high degree of containment that is needed
when studying a variety of organisms with a recognized potential for significant detrimental impact
on animal or human health or on natural ecosystems.

ration efforts directed at identifying potential risks worldwide, including regula-

tory mechanisms that minimize the threat of introducing emerging infectious
agents into the United States or other unaffected countries.
For potential and emerging infectious agents in other countries, assistance
from the United States is more ad hoc or piecemeal than strategic and wide-
ranging. By adopting a more comprehensive approach to helping countries
strengthen their prevention, detection, and diagnostic capabilities, the United
States will enhance its own animal health framework and security. Means to ac-
complish this include transferring technology between nations and providing
training opportunities to international students and veterinarians to ensure self-
sufficiency and sustainable surveillance. The United States can also encourage
and support the enhancement of critical competencies within the national ser-
vices, which includes active participation in the formulation of international stan-
dards and the timely reporting of zoonotic and exotic diseases. The charge to the
committee explicitly states that it will “review the U.S. system and approach for
dealing with animal diseases,” and the committee regards the international di-
mension as an extremely critical component of the U.S. animal health frame-
work. With increased globalization and movement of diseases, people, products,
pathogens, and vectors, the United States cannot continue to impose a line be-
tween domestic and international issues, but should instead adopt an animal health
system that identifies and responds to animal disease threats without regard to
national boundaries.
Importation, Sale, and Transport of Animals

Recommendation 7: Integrated and standardized regulations should be
developed and implemented nationally to address the import, sale, move-
ment, and health of exotic, nondomesticated, and wild-caught animals.
Such a policy development needs to include health professionals and laboratory-
based analysis because wild-caught and exotic animals may carry pathogens and
pose a risk of transmitting disease without demonstrating clinical signs. The
monkeypox outbreak of 2003 highlighted a number of weaknesses in the animal
health framework for addressing a newly emergent zoonotic disease. In particu-
lar, while several federal agencies (including the USDA, U.S. Department of the
Interior’s Fish and Wildlife Service, and the Department of Health and Human
Services) have roles in preventing, detecting, and diagnosing zoonotic and other
diseases transmitted by exotic animals, there is a lack of coordinated federal over-
sight of the animal-centered aspects of diseases transmitted by exotic animals.
Prior to the interim final rule banning the import, sale, or distribution of prairie
dogs and some African rodents (responsible for the monkeypox outbreak in 2003),
import and movement of exotic animals was largely uncontrolled (and most ex-
otic animal movement is still uncontrolled). Tracking of these animals in the

United States is inconsistent and ineffective, and there is a disturbing lack of

standardized testing of the health status of exotic animals at the point of origin
and in companion animal shops, trade fairs, and other venues. Considering that
the emergence of new disease agents occurs most frequently at species interfaces,
monkeypox is not likely to be the last zoonotic agent to emerge from an exotic
animal in the United States.
Addressing Future Animal Disease Risks

Recommendation 8: The USDA, DHS, Department of Health and Hu-
man Services, and state animal and public health agencies and laborato-
ries should improve, expand, and formalize the use of predictive, risk-
based tools and models to develop prevention, detection, diagnostic, and
biosecurity systems and strategies for indigenous, exotic, and emerging
animal diseases.
There has been increased recognition and use of well-structured and scien-
tifically based mathematical, epidemiological, and risk analysis models and tools
to define acceptable risks and mitigation strategies that can assist in policy and
science-based decision making. Examples include models of the spread of FMD
during the UK epidemic, and an assessment of the risk of BSE to U.S. agriculture,
developed by Harvard University’s Center for Risk Analysis for the USDA
(Cohen et al., 2003; Haydon et al., 2004). Risk analysis and modeling have been
criticized, mainly on the basis of insufficient scientific data or inappropriate as-
sumptions. Therefore, efforts to develop scientific data on disease transmission,
effectiveness of control programs, economic evaluation, and quantitative assess-
ment of all factors involved in making policies and regulations should be a prior-
ity of the animal health infrastructure, working in collaboration with academia,
industry, and global trade partners.
Threats from bioterrorism, emerging diseases, and foreign animal disease
introductions add urgency to preventing or minimizing catastrophic consequences
to the United States, other nations, and the global economy. Education and train-
ing of professionals to assess, manage, and communicate risk of animal disease
and improved information available to stakeholders, including producers and the
public, are important aspects of effective infrastructure that supports risk-based
approaches.
Education and Training

Recommendation 9: Industry, producers, the American Veterinary Med-
ical Association (AVMA), government agencies, and colleges of veteri-
nary medicine should build veterinary capacity through both recruit-
ment and preparation of additional veterinary graduates into careers in

public health, food systems, biomedical research, diagnostic laboratory

investigation, pathology, epidemiology, ecosystem health, and food ani-
mal practice.
There are insufficient graduates to meet the needs in a number of major and
distinct fields of veterinary medicine dealing with various species of food-ani-
mals, rural practice (mixed domestic animals), ecosystem health (including wild-
life disease and conservation biology), public health, the many dimensions of the
food system, and biomedical science. In addition, veterinary graduates are not
adequately prepared to deal with foreign animal diseases, public health, and eco-
system health, without further postgraduate studies. According to the Association
of American Veterinary Medical Colleges (AAVMC), the 28 veterinary colleges
in the United States graduate approximately 2,300 veterinarians per year and are
currently unable to keep up with societal needs in private or public practice.
There has been a steady decline in the number of rural practitioners and of
veterinarians employed in regulatory agencies. The USDA, underserved at
present, predicts a shortfall of 584 veterinarians on its staff by 2007. Fifty percent
of U.S. Public Health Service veterinarians are currently eligible for retirement.
Too few veterinary students are choosing to specialize in basic biomedical
science or pathology, as noted in the recently published NRC report National
Need and Priorities for Veterinarians in Biomedical Research, which suggests a
strategy for recruiting and preparing more veterinarians for careers in laboratory
animal medicine, comparative medicine, and comparative pathology (NRC,
2004). This committee endorses the recommendations of that report.
One strategy for building veterinary capacity is to design and implement
training and educational curricula to better address these underserved areas of
animal health. The Veterinary Medical Education and Workforce Development
Act of 2004, which amends the Public Health Service Act, will be a useful first
step that establishes a competitive grants program to build capacity in veterinary
medical education and expands the workforce of veterinarians engaged in public
health practice and biomedical research.
Recommendation 10: The USDA, state animal health agencies, the
AVMA, and colleges and schools of veterinary medicine and depart-
ments of animal science should develop a national animal health edu-
cation plan focusing on education and training of individuals from all
sectors involved in disease prevention and early detection through day-
to-day oversight of animals.
Responsibility for implementing the educational plan would fall on those at
the local level. Strong and well-functioning front-line detection is provided by
animal handlers and personnel working with animals on a day-to-day basis. This
backbone for effectively preventing animal disease outbreaks requires education
and training to include awareness and recognition of clinical signs, as well as an

elementary understanding of disease transmission and prevention. In addition,

those with day-to-day oversight of animals need to understand the methods and
responsibilities for reporting the signs of foreign and exotic animal diseases. Ba-
sic multilingual education and training are necessary for those with such direct
oversight of animals, whereas more in-depth education to promote a greater depth
and breadth of understanding of transmission and prevention is required for man-
agers and owners.
Improving Public Awareness of the Economic, Social, and Human Health

Effects of Animal Diseases
Recommendation 11: The government, private sector, and professional
and industry associations should collectively educate and raise the level
of awareness of the general public about the importance of public and
private investment to strengthen the animal health framework.
Increased public awareness is critical in supporting and implementing trans-
formations needed to strengthen the framework against animal disease risks. The
lack of cohesive national advocacy for public health issues generally creates a
much more difficult environment in which to increase attention and investment in
the framework for preventing, detecting, and diagnosing animal diseases.
The recent outbreaks of FMD, SARS, AI, and BSE are all reminders of the
threats such diseases pose to the U.S. food supply, global economy, public health,
and confidence in the safety of the food supply. The entire food and fiber sys-
tem—including farm inputs, processing, manufacturing, exporting, and related
services—is one of the largest sectors of the U.S. economy and accounts for
output of over $2 trillion dollars, generating $1.24 trillion in added value, and
12.3 percent of total gross domestic product in 2001 (USDA, 2003). Nearly 17
percent of all U.S. workers are employed by the food and fiber system (USDA,
2003). Producers, companion animal owners, and others on the front line have a
direct personal and private interest in detecting, diagnosing, and preventing ani-
mal diseases to avoid losses associated with reduced productivity, animal mortal-
ity, or potential effects on personal health and welfare. Although these losses can
be significant, adverse social, economic, and human health impacts associated
with animal diseases extend beyond producers or household animal owners.
Increased investment in educating the public about animal health will help to
reduce disease and transmission; enhance public and animal health; ensure a se-
cure, economical, and viable food supply; and improve trade and competitive-
ness. These educational efforts should include information about diseases of food-
animals, wildlife, and companion animals.

PRIORITIES FOR RESEARCH IN FOOD DEFENSE

Francis F. Busta, Ph.D.,4 Shaun Kennedy, B.S.E.,5 and Julie Ostrowsky, M.Sc.6
University of Minnesota–Twin Cities Campus
Food defense, dealing with the threat of intentional acts of contamination at

any point in the food system, is distinct from food safety, even though the two
areas are closely linked. Food safety efforts target unintentional problems, such
as “natural” or accidental contamination with microbial (e.g., E. coli or Salmo-
nella) or chemical agents, with some degree of predictability regarding agents,
processes, and products of concern. Food defense, by contrast, responds to the
threat of sporadic manmade (terrorist) activity, involving high concentrations of
contaminants that would not occur naturally or accidentally in the food supply
(e.g., B. anthracis, biologically engineered organisms, or chemical toxins). Fur-
ther, food defense involves dealing with hoaxes or threats sufficient to cause
widespread disruption, fear, and panic, and, ultimately, the potential for large-
scale, coordinated attacks with catastrophic results. Food defense, unlike food
safety, is thereby integral to homeland security, particularly regarding efforts to
strengthen critical infrastructure protection, threat assessment, and emergency
preparedness and response.
The vulnerability of the nation’s food system to terrorist attack (described
in the Summary and Assessment and by several workshop contributors, e.g.,
Osterholm and Henry in Chapter 1; Acheson in Chapter 4) stems from several
major factors. The farm-to-table food system encompasses a wide range of inter-
dependent elements, from farm inputs, such as seeds and fertilizers, to produc-
tion, manufacturing and processing, wholesale, distribution, through to the con-
sumer via retail sales and food service. Both domestic and imported ingredients
and products move throughout the system. This complexity offers a vast array of
potential sites—accessible targets—for intentional contamination to occur. In
addition, the degree to which foodborne illness occurs annually (due to “natural”
or accidental contamination), despite extensive systems in place to protect the
safety of the food supply, underscores the limitations of available food safety
efforts. Although necessary to minimize the burden of foodborne illness, those
efforts also provide the very information that could be misused deliberately as a
roadmap for targeting an attack on the food system. Another major factor is the
potentially high impact of a food-related terrorism incident or even an announced
threat without an actual attack, given the likelihood of widespread fear and panic
in the population and economic devastation to the private sector.
4Director,National Center for Food Protection and Defense.

5Deputy Director, National Center for Food Protection and Defense.
6Senior Program Analyst, National Center for Food Protection and Defense.

The federal government coordinates food defense activities under the um-
brella of the DHS, with sector-specific responsibilities residing jointly with the
DHHS and the USDA. Homeland Security Presidential Directive 7 (HSPD-7)
issued in 2003 first identified the agriculture and food sector among the nation’s
critical infrastructures/key resources singled out for special protection under
homeland security initiatives (White House, 2003). In 2004, the Homeland Secu-
rity Presidential Directive 9 (HSPD-9) established a national policy to protect the
food and agriculture system from terrorist attack (White House, 2004). DHS’s
National Infrastructure Protection Plan, currently under development, incorpo-
rates food and agriculture sector protection among its initiatives to protect the
nation’s critical infrastructures and key assets (DHS, 2005a,b; SEMP, 2005).
Addressing these critical issues surrounding the potential for food to be ex-
ploited as a vehicle for catastrophic attack requires a broad-based, comprehensive
approach. Food defense, as a recently defined concept, creates new links among
previously unrelated fields. This leads to a diverse, multidisciplinary agenda for
food defense research, education, and training. On an operational level, collabo-
rative initiatives across academia, industry, and government are necessary to de-
velop and maintain new channels of communication, leverage resources, and co-
ordinate responsibilities. The effectiveness of food defense efforts will depend on
the quality of research outcomes as well as on the successful integration of newly
developed technologies, programs, tools, and expertise into public- and private-
sector stakeholder communities.
This discussion focuses on identifying high-priority areas for research that
address two central issues in food defense: preventing major attacks on the food
system and responding effectively if such an attack (or credible threats of an
attack) were to occur. This research effort is central to the mission of the National
Center for Food Protection and Defense (NCFPD), whose program is aimed at
reducing the potential for contamination at any point along the food supply chain
and mitigating potentially catastrophic public health and economic effects.7
NCFPD Programs
NCFPD (2006), led by the University of Minnesota, is one of six academic
Centers of Excellence funded through grants from the DHS with the specific
7Investing in food defense research may well carry significant collateral benefits, beyond its pri-
mary value to homeland security, in terms of health and economic effects. Much of what we are
learning about preventing and responding to potentially catastrophic attacks on the food system can
be applied to ongoing efforts to reduce the burden of foodborne illness caused by more common
sources of contamination (natural and accidental). Such advances can also be applied to enhancing
routine security operations, such as reduction in the incidence of theft of food products, which com-
monly occurs all along the supply chain.

mandate for a food protection and defense center coming from HSPD-9 (DHS,
2004a). Other Homeland Security Centers of Excellence include: Center for Risk
and Economic Analysis of Terrorism Events, led by the University of Southern
California; National Center for Foreign Animal and Zoonotic Disease Defense,
led by Texas A&M University; National Center for the Study of Terrorism and
Responses to Terrorism, led by the University of Maryland; Center for the Study
of Preparedness and Catastrophic Event Response, led by Johns Hopkins Univer-
sity; and Center for Advancing Microbial Risk Assessment, led by Michigan State
University, in collaboration with the U.S. Environmental Protection Agency
(EPA) (DHS, 2006).
Developed as a multidisciplinary and mission-focused research consortium,
NCFPD addresses the vulnerability of the nation’s food system to attack through
intentional contamination with biological, chemical or radiological agents.
NCFPD takes a comprehensive, farm-to-table view of the food system, encom-
passing all aspects from primary production through transportation and food pro-
cessing to retail and food service. In delivering on its mission to defend the safety
and security of the food system through research and education, NCFPD places a
high priority on threats to the food system that could lead to catastrophic damage
to public health or the economy.
Academic collaborators in NCFPD’s research consortium include the
University of Minnesota, Michigan State University, University of Wisconsin–
Madison, North Dakota State University, Georgia Institute of Technology, Uni-
versity of Tennessee–Knoxville, and individual investigators from 21 other uni-
versities. Additional research partners are drawn from private-sector research
organizations, professional organizations, and food and agriculture agencies. Over
30 industry experts serve as unpaid advisors, providing technical advice, critical
end-user feedback, and strategic oversight. To leverage expertise and resources
programmatically, close collaboration is maintained with federal and state regu-
latory agencies, other Homeland Security Centers of Excellence, the national labo-
ratories, and private-sector stakeholders.
NCFPD’s program incorporates cutting-edge research aimed at food defense
from a variety of disciplines, including supply chain management, logistics, epi-
demiology, public health, risk assessment, economics, molecular biology, food
microbiology, biomedical engineering, toxicology, and risk communication. More
than 140 experts in these areas were selected to participate in NCFPD’s research
consortium, based on approval of peer-reviewed research proposals submitted by
teams of investigators. Thirty-four collaborative research and education projects
are currently in progress. A summary of NCFPD initiatives appears in Table 7-1.
NCFPD’s program provides a comprehensive framework for identifying pri-
orities and unmet needs in food defense research. Based on the fundamental is-
sues outlined in DHS’s Broad Agency Announcement (DHS, 2004b) calling for
proposals for a university Center of Excellence in food protection and defense,
NCFPD’s program is organized thematically into three primary areas: systems,

TABLE 7-1 National Center for Food Protection and Defense Research
Initiatives
• Strategies for hardening the supply chain
• Improved outbreak surveillance/investigation approaches for rapid event identification and
traceback
• Realistic models to guide investments and intervention strategy selection for cost-effective
preparedness, response, and recovery
• Detection technologies to rapidly identify contamination to accelerate containment, recall,
response, and recovery
• Inactivation approaches to enable facility recovery now, with preferred options for the future
• Food handling and processing approaches to reduce the probability of harm
• Risk communication tools, standards and training to maximize appropriate actions while
minimizing fear
• Educational programs to train the next generation of food system professionals
• Integrative, transdisciplinary effort spanning the food chain from field to fork
• Strategic partnerships with all key food system stakeholder groups:
– Significantly leveraging opportunities
– Connected to the users to ensure relevance
– Technology transfer options and multiuse opportunities identified up front
• Focused on realistic vulnerabilities and real-world solutions; new technologies, tools and
approaches
SOURCE: Busta (2005).
agents, and training. Priorities for research in each of these areas are outlined
below.
Research Needs: Systems

Supply chain security encompasses policies and practices within industry
and its regulators to reduce vulnerabilities, minimize disruptions caused by threats
or contamination incidents, and maximize the system’s resiliency through effec-
tive response plans. Major research needs include the following:
• Characterizing and benchmarking supply chain security practices, such as

basic security processes (e.g., protecting employees), incident management, lo-
gistics and transportation security, and companies’ supply chain relationships.
• Assessing those practices that have the greatest impact on efforts to en-
hance supply chain security.
• Developing a common standard for security guidelines within the food
industry.
• Providing strategies for secure communication and information manage-
ment among federal, state, and industry officials during a potential attack on the
food system.

An effective public health response to incidents of contamination can directly

limit the scope of an incident, reduce the risk of foodborne illness, mitigate eco-
nomic damage, and possibly help deter future attempts. Priorities for research
include the following:
• Develop predictive models and tools to assess the nature, scope, and im-
pact of intentional contamination incidents and responses to those incidents.
• Improve strategies for coordinating preparedness and response act-
ivities across local, state, and federal public health, laboratory, and regulatory
jurisdictions.
Given the nature of the food system and its interdependency with other sectors of
the economy, a deliberate attack on the food system could have broad impacts on
the national economy. Estimates of the potential national cost of such attacks are
relevant to policy decisions involving the allocation of scarce resources. Research
needs include the following:
• Assess the potential economic impact of a major food system attack on

the national economy and on the private sector.
• Analyze the cost-effectiveness of public, nongovernmental, and industry
investment in strategies to enhance supply chain security (e.g., use of “smart
seals” or radio frequency identification (RFID) tags to track products through
shipment).
• Evaluate the public’s willingness to support greater public investment in
measures to protect the food system from deliberate contamination.
• Assess the probability of future attacks on the food system.
Research Needs: Agents

To better recognize foodborne attacks and identify the contaminating agent
involved, technologies are needed to sample and detect contaminants in food and
to trace contaminated food products (or their ingredients) through the supply
chain. Detection of food contaminants is complicated by the food matrix—the
chemical and molecular nature of individual foods and the effects of food viscos-
ity, homogeneity, conductivity, and pH on a given agent. Chemical agents present
an especially daunting problem because they are difficult to detect and many of
them resist food processing designed to safeguard against biological contamina-
tion. Existing toxicological tests for chemical agents are limited. Current research
aims to take advantage of such properties as chemical class, molecular weight,
and solubility as a means to detection. Overall needs for detection include the
following:

• Develop rapid, accurate, and reliable methods to detect select agents and
chemical toxins in the food supply.
• Enable efficient monitoring and testing in a range of food production,
processing, distribution, and retail settings.
• Enhance preanalytical effective preparation of samples for rapid analysis
by separation, concentration, and/or purification of select agents from food matri-
ces, recognizing that the complex environments of foods place a premium on
preanalytical processes to enable effective detection.
• Facilitate the rapid translation and integration of newly developed diag-
nostic research methods into the national laboratory infrastructure, for example
by assuring that new methodologies are appropriately validated and by coordinat-
ing surge capacity among laboratories during a food contamination incident.
Protecting public health in the event of a foodborne attack will involve the decon-
tamination of affected products, people, and physical environments, as well as
the safe disposal of contaminated foods. Such processes are managed at the fed-
eral level by the EPA and regulated by EPA restrictions on disinfectant use (state
level variations are also important). Priorities for research in this area include the
following:
• Develop effective large-scale means of disposing of contaminated food

and decontaminating individuals, facilities, or sites.
• Develop safe and practical methods for neutralizing selected biological
agents in food processing facilities and in consumer households.
• Develop effective protocols for managing disposal, containment, remedi-
ation, and recovery processes following a contamination incident.
• Develop methods to isolate or inactivate potential contaminants, includ-
ing spores, toxins, and chemical agents, to facilitate detection in the food matrix
and to provide a routine level of protection against contamination.
Research Needs: Training

Preparedness for dealing effectively with a food system attack goes beyond
appropriate technical preparation of the first responder groups to include capa-
bilities for rapidly mobilizing and delivering appropriate and credible risk com-
munication messages to the public, as well as prior training of key spokespersons
in the public and private sectors. Research needs include the following:
• Education and training strategies from undergraduate programs through

to specialized graduate and professional training to prepare all relevant food sys-
tem stakeholders with the knowledge and skills to prevent, minimize the conse-
quences of, and recover from a food system attack.

• Develop guidelines and best practices for active engagement of multiple

audiences in effective risk communications prior to, during, and after an inten-
tional food contamination event or hoax.
• Develop methods to enhance the training of key spokespersons and sub-
ject matter experts to improve their risk communication expertise.
Effective engagement in food defense efforts at all levels depends critically on

the development of a cadre of professionals equipped to deal with this wide array
of issues. High-quality education and training programs are needed to expand the
pool of available personnel with expertise in food defense. This includes devel-
oping just-in-time training materials, advanced course content, virtual training
programs, and interdisciplinary degree options for undergraduates, graduates, and
professionals.
Conclusion
Many researchers, including NCFPD collaborators, have broken ground on
issues essential to protecting the U.S. food supply and defending it from deliber-
ate contamination. Preventing intentional contamination of the food system re-
quires a shift in mindset: traditional food safety efforts must move from minimiz-
ing the possibility of contamination events that can normally happen to preventing
those that cannot be permitted to occur. Not only must these efforts be continued
and expanded, but to be most effective, their results also need to be shared. Sev-
eral workshop participants have advocated the creation of a multidimensional
database of accumulated knowledge regarding foodborne attack agents, food tar-
gets, and detection and decontamination under various conditions. Such a re-
source could reduce the considerable duplication of research on food defense that
occurs in the absence of scientific exchange, and it may also provide a spring-
board for innovation in the field.
REFERENCES
Busta F. 2005 (October 26). Session VII: Threat Reduction Research and Policy Opportunities. Pre-
sentation at the Forum on Microbial Threats Workshop Meeting, Foodborne Threats to Health:
The Policies and Practices of Surveillance, Prevention, Outbreak Investigations, and Interna-
tional Coordination, Washington, D.C., Institute of Medicine, Forum on Microbial Threats.
Cohen, JT, Duggar K, Gray GM, Kreindel S, Abdelrahman H, HabteMariam T, Oryang D, and Tameru
B. 2003. Revised Risk Assessment: Evaluation of the Potential for Bovine Spongiform Encepha-
lopathy in the United States. Harvard Center for Risk Analysis, Harvard School of Public Health.
Prepared for the U.S. Department of Agriculture. November 26, 2001, revised October 2003.
[Online]. Available: http://www.hcra.harvard.edu/pdf/madcow.pdf [accessed June 27, 2006].
DHS (U.S. Department of Homeland Security). 2004a (January 29). President’s Budget Includes
$254 Million to Further Improve Nation’s Bio-Surveillance Capabilities. [Online]. Available:
http://www.dhs.gov/dhspublic/display?content=3092 [accessed June 27, 2006].

DHS. 2004b. Homeland Security Presidential Directive/HSPD-9, Defense of U.S. Agriculture and
Food. [Online]. Available: http://www.whitehouse.gov/news/releases/2004/02/20040203-2.html
DHS. 2004c. Broad Agency Announcement. [Online]. Available: http://www.dhs.gov/interweb/
assetlibrary/BAA_Agro.doc [accessed April 17, 2006].
DHS. 2005a. Draft National Infrastructure Protection Plan. [Online]. Available: http://www.fas.org/
irp/agency/dhs/nipp110205.pdf [accessed April 17, 2006].
DHS. 2005b. Interim National Infrastructure Protection Plan. [Online]. Available: http://www.
newsecurityconcepts.com/DataFiles/interim-nipp.pdf [accessed April 17, 2006].
DHS. 2006. Homeland Security Centers of Excellence. [Online]. Available: http://www.dhs.gov/
dhspublic/interapp/editorial/ editorial_0498.xml [accessed April 17, 2006].
Haydon DT, Kao RR, and Kitching PK. 2004. The UK foot and mouth disease outbreak—the after-
math. Nature Reviews 2(8):675–681.
IOM (Institute of Medicine). 2003. Microbial Threats to Health: Emergence, Detection, and Re-
sponse. Washington, D.C.: The National Academies Press.
NCFPD (National Center for Food Protection and Defense). 2006. NCFPD Homepage. [Online].
Available: http://www.ncfpd.umn.edu/ [accessed April 17, 2006].
NRC (National Research Council). 2004. National Need and Priorities for Veterinarians in Biomedi-
cal Research. Washington, D.C.: The National Academies Press.
NRC. 2005. Animal Health at the Crossroads. Washington, D.C.: The National Academies Press.
SEMP (Suburban Emergency Management Project). 2005. What Is the Interim National Infrastruc-
ture Protection Plan? [Online]. Available: http://www.semp.us/biots/biot_200.html [accessed
April 17, 2006].
USDA (U.S. Department of Agriculture). 2003 (October 16). Food Market Structures: The U.S. Food
and Fiber System. [Online]. Available: http://ers.usda.gov/briefing/foodmarketstructures
/foodandfiber.htm [accessed June 27, 2006].
White House. 2003. Homeland Security Presidential Directive HSPD-7. [Online]. Available: http://
www.whitehouse.gov/news/releases/2003/12/20031217-5.html [accessed April 17, 2006].
White House. 2004. Homeland Security Presidential Directive HSPD-9. [Online]. Available: http://
www.whitehouse.gov/news/releases/2004/02/print/20040203-2.html [accessed April 17, 2006].

APPENDIX
A
Board on Global Health

Institute of Medicine
The National Academies
Foodborne Threats to Health: The Practice and Policies of Surveillance,

Prevention, Outbreak Investigations, and International Coordination
October 25 and 26, 2005
KECK 100
National Academies
500 Fifth Street, N.W.
Washington, D.C. 20001
AGENDA
Tuesday, October 25, 2005

8:30–9:00: Continental Breakfast
9:00: Welcome and Opening Remarks
Stanley Lemon, The University of Texas Medical Branch,
Galveston
Chair, Forum on Microbial Threats
Margaret A. (Peggy) Hamburg, Nuclear Threat Initiative
255

Vice-chair, Forum on Microbial Threats
Session I: The Current U.S. Food Supply—Ruth Berkelman, Moderator

9:20: Globalization of the food supply—Discussion to address the
“inputs” to the U.S. food supply—locally, regionally, and
globally—and how the percentage of those inputs has changed
over time.
• Craig Henry, Vice president, FPA
9:50: Discussion
10:15: Break
Session II: The Food Supply “Threat Spectrum”—Michael Osterholm,

Moderator
9:00: Welcome and Opening Remarks
10:30: Overview of the threat spectrum—Unintentional vs.
intentional
• Michael Osterholm, University of Minnesota
11:00: Discussion
11:15: Burden of illness associated with foodborne threats to health
• Rob Tauxe, CDC, Atlanta, GA
11:45: Discussion
12:00–12:45: Lunch
Session III: The Food Supply “Threat Spectrum”: Case Studies—David

Acheson, Moderator
12:45: Cyclosporiasis in imported fresh basil
• Barbara Herwaldt, CDC, Atlanta, GA
• Dean Bodager, Florida Department of Public Health
1:15: Hepatitis A from imported green onions
• Beth Bell, CDC, Atlanta, GA
1:45–2:15: Discussion
2:15–2:30: Break

APPENDIX A 257
2:30–3:30: Botulinum toxin—David Acheson, presenter

Discussants:
• Milton Leitenberg, University of Maryland
• Clay Detlefsen, Vice president for Regulatory Affairs,
International Dairy Foods Association
Session IV: What are the Tools and Technologies for Real-Time
Surveillance of the Food Supply for Conventional and Unconventional
Adulterants? Local/Regional/National/Global—Dr. Pat Fitch, Moderator
3:50–5:00:
• John Besser, Minnesota Department of Health
• Bob (Robert L.) Buchanan, Director, Office of Science,
CFSAN
• Kimberly Elenberg, USDA, FSIS, Office of Food Safety
and Emergency Preparedness
5:00–5:45: Open Discussion of Day 1/Adjournment of the first day
6:00: Reception
7:15: Dinner Meeting of the Forum on Microbial Threats
[location: The Atrium, 3rd Floor; KECK Center]
Wednesday, October 26, 2005

8:00–8:30: Continental Breakfast
8:30: Opening Remarks/Summary of Day 1
P. Frederick Sparling, UNC, Vice-chair, Forum on
Microbial Threats
Session V: Who Is Responsible for Ensuring the Wholesomeness of the

Food Supply? Domestic and International Perspectives—Dr. Jim Hughes,
Moderator
8:45: The U.S. Food Safety System
• John Bailar, III, University of Chicago (Chair, NRC
Report: Ensuring Safe Food: From Production to
Consumption)

9:15: The International Food Safety System—WHO perspective

• Jørgen Schlundt, Director of the Food Safety Program
(WHO)
9:45: Discussion
10:15–10:30: Break
Session VI: What Are the Incentives and Disincentives Associated with
Disease/Contamination Reporting? Impacts on Human Health and
International Trade—BSE as a “Case Study”—Dr. Lonnie King,
Moderator
10:30–12:00: Case study of BSE—Human illness associated with BSE-tainted
meat and meat products; surveillance tools and technologies;
impacts on international trade associated with reporting a
“positive”
Overview: Stanley Prusiner, UC San Francisco
• Steven Collins, Department of Pathology, University of
Melbourne, Parkville, Australia
• Maura Ricketts, Executive Director, Health Canada
• Wil Hueston, University of Minnesota
12:15–12:45: Discussion of Morning Sessions
12:45–1:30: Lunch
Session VII: Threat Reduction Research and Policy Opportunities—Dr.

George Korch, Moderator
1:30–2:45: Panelists
• Lonnie King, Chair, NRC Report: Animal Health at the
Crossroads
• Sanford Miller, Food Policy Institute
• Frank Busta, University of Minnesota
3:15–4:00: Next Steps
4:15: Adjourn

APPENDIX
B
Acronyms1
AAVMC Association of American Veterinary Medical Colleges

AEI American Enterprise Institute
AI avian influenza
AMS Agricultural Marketing Service
ANCJDR Australian National CJD Registry
APHIS Animal and Plant Health Inspection Service
APHL Association of Public Health Laboratories
ARS Agriculture Research Service
ASM American Society for Microbiology
AVMA American Veterinary Medical Association
BIDS Border Infectious Disease Surveillance

BRC Biologic Regulatory Commission
BSE bovine spongiform encephalopathy
BSL biosafety level
BW biological weapons
CAMR Center for Applied Microbiological Research

CBW chemical and biological weapons
CCMS Consumer Complaint Monitoring System
CDC Centers for Disease Control and Prevention
CDI Conformation Dependent Immunoassay
1Also, see P. 179 in Chapter 5, Table 5-1: Networks and Resources in Food Safety.
259

CFSAN Center for Food Safety and Applied Nutrition

CISSM Center for International Security Studies at Maryland
CRS Congressional Research Service
CSF classic swine fever
CSPI Center for Science in the Public Interest
CSREES Cooperative State Research, Education, and Extension Service
CSTE Council for State and Territorial Epidemiologists
CVM Center for Veterinary Medicine
CW chemical weapons
CWD chronic wasting disease
DHS Department of Homeland Security

DPVS due process vetting system
EID emerging infectious disease

END exotic Newcastle disease
EPA Environmental Protection Agency
EPFC Emerging Patterns in Food Complaints
ERS Economic Research Service
EUROCJD European and Allied Countries CJD Group
FAO Food and Agriculture Organization of the United Nations

FBI Federal Bureau of Investigation
fCJD familial Creutzfeldt-Jakob disease
FDA Food and Drug Administration
FEMA Federal Emergency Management Agency
FMD foot-and-mouth disease
FMI Food Marketing Institute
FOUO For Official Use Only
FSIS Food Safety and Inspection Service
FSSA FDA Security Surveillance Assignment
GAO Government Accountability Office

GFAP glial fibrillary acidic protein
GIPSA Grain Inspection, Packers and Stockyards Administration
HACCP Hazard Analysis and Critical Control Point

HAV hepatitis A virus
HGH human growth hormone
HHS Department of Health and Human Services
HSPD Homeland Security Presidential Directive
IDFA International Dairy Foods Association

APPENDIX B 261
IHC immunohistochemistry
IHR international health regulations
IOM Institute of Medicine
LRC Least Restrictive Classification

LRN Laboratory Response Network
MBM meat-and-bone meal

MRM mechanically recovered meat
NAHLN National Animal Health Laboratory Network

NASS National Agricultural Statistics Service
NATO North Atlantic Treaty Organization
NCFPD National Center for Food Protection and Defense
NCTR National Center for Toxicological Research
NGO nongovernmental organization
NIH National Institutes of Health
NMFS National Marine Fisheries Service
NOAA National Oceanic and Atmospheric Administration
NRC National Research Council
NRDC Nature Resources Defense Council
OECA Office of Enforcement and Compliance Assurance

OIE Office International des Epizooties
OPPTS Office of Prevention, Pesticides and Toxic Substances
ORA Office of Regulatory Affairs
ORACBA Office of Risk Assessment and Cost-Benefit Analysis
ORM operational risk management
OTA Organic Trade Association
PFGE pulsed-field gel electrophoresis

PH public health
PHL public health laboratories
PNG Papua New Guinea
RFID radio frequency identification

RT-PCR reverse transcriptase polymerase chain reaction
SARS severe acute respiratory syndrome

SBO specified bovine offal
sCJD sporadic Creutzfeldt-Jakob disease
SPPA Strategic Partnership Program Agroterrorism
SRM specified risk materials

TSE transmissible spongiform encephalopathy
UNMOVIC United Nations Monitoring, Verification, and Inspection

Commission
UNSCOM United Nations Special Commission
USAMRIID United States Army Medical Research Institute for Infectious
Diseases
USDA U.S. Department of Agriculture
vCJD variant Creutzfeldt-Jakob disease
WHO World Health Organization

WNV West Nile virus

APPENDIX
C
Forum Member Biographies
Stanley M. Lemon, M.D. (Chair), is the John Sealy Distinguished University

Chair and director of the Institute for Human Infections and Immunity at the
University of Texas Medical Branch (UTMB) at Galveston. He received his un-
dergraduate A.B. degree in biochemical sciences from Princeton University
summa cum laude, and his M.D. with honors from the University of Rochester.
He completed postgraduate training in internal medicine and infectious diseases
at the University of North Carolina at Chapel Hill, and is board certified in both.
From 1977 to 1983, he served with the U.S. Army Medical Research and Devel-
opment Command, followed by a 14-year period on the faculty of the University
of North Carolina School of Medicine. He moved to UTMB in 1997, serving first
as chair of the Department of Microbiology and Immunology, then as dean of the
School of Medicine from 1999 to 2004. Dr. Lemon’s research interests relate to
the molecular virology and pathogenesis of the positive-stranded RNA viruses
responsible for hepatitis. He has had a long-standing interest in antiviral and vac-
cine development, and has served previously as chair of the Anti-Infective Drugs
Advisory Committee of the U.S. Food and Drug Administration (FDA). He is the
past chair of the Steering Committee on Hepatitis and Poliomyelitis of the World
Health Organization (WHO) Programme on Vaccine Development. He presently
serves as a member of the U.S. Delegation of the U.S.–Japan Cooperative Medi-
cal Sciences Program, and chairs the Board of Scientific Councilors of the Na-
tional Center for Infectious Diseases (NCID) of the Centers for Disease Control
and Prevention (CDC). He was co-chair of the Committee on Advances in Tech-
nology and the Prevention of their Application to Next Generation Biowarfare
Threats for the National Academy of Sciences (NAS) and recently chaired an
Institute of Medicine (IOM) study committee related to vaccines for the protec-
tion of the military against naturally occurring infectious disease threats.
263

P. Frederick Sparling, M.D. (Vice-chair), is the J. Herbert Bate Professor

Emeritus of Medicine, Microbiology, and Immunology at the University of North
Carolina (UNC) at Chapel Hill and is director of the North Carolina Sexually
Transmitted Infections Research Center. Previously, he served as chair of the
Department of Medicine and chair of the Department of Microbiology and Im-
munology at UNC. He was president of the Infectious Disease Society of America
from 1996–1997. He was also a member of the IOM’s Committee on Microbial
Threats to Health (1991–1992). Dr. Sparling’s laboratory research is in the mo-
lecular biology of bacterial outer membrane proteins involved in pathogenesis,
with a major emphasis on gonococci and meningococci. His current studies focus
on the biochemistry and genetics of iron-scavenging mechanisms used by gono-
cocci and meningococci and the structure and function of the gonococcal porin
proteins. He is pursuing the goal of a vaccine for gonorrhea.
Margaret A. Hamburg, M.D. (Vice-chair), is vice president for Biological Pro-

grams at the Nuclear Threat Initiative, a charitable organization working to re-
duce the global threat from nuclear, biological, and chemical weapons. She is in
charge of the biological program area. She completed her internship and resi-
dency in internal medicine at the New York Hospital/Cornell University Medical
Center and is certified by the American Board of Internal Medicine. Dr. Hamburg
is a graduate of Harvard College and Harvard Medical School. Before taking on
her current position, she was the Assistant Secretary for Planning and Evaluation,
U.S. Department of Health and Human Services (DHHS), serving as a principal
policy advisor to the Secretary of Health and Human Services with responsibili-
ties including policy formulation and analysis, the development and review of
regulations and/or legislation, budget analysis, strategic planning, and the con-
duct and coordination of policy research and program evaluation. Prior to this,
she served for almost six years as the Commissioner of Health for the City of
New York. As chief health officer in the nation’s largest city, her many accom-
plishments included the design and implementation of an internationally recog-
nized tuberculosis control program that produced dramatic declines in tuberculo-
sis cases, the development of initiatives that raised childhood immunization rates
to record levels, and the creation of the first public health bioterrorism prepared-
ness program in the nation. She currently serves on the Harvard University Board
of Overseers. She has been elected to membership in the IOM, the New York
Academy of Medicine, and the Council on Foreign Relations, and is a fellow of
the American Association for the Advancement of Science and the American
College of Physicians.
David W. K. Acheson, M.D., is chief medical officer at the FDA’s Center for
Food Safety and Applied Nutrition. He received his medical degree at the Univer-
sity of London. After completing internships in general surgery and medicine, he
continued his postdoctoral training in Manchester, England, as a Wellcome Trust

APPENDIX C 265
research fellow. He subsequently was a Wellcome Trust training fellow in Infec-

tious Diseases at the New England Medical Center and at the Wellcome Research
Unit in Vellore, India. He was associate professor of medicine, Division of Geo-
graphic Medicine and Infectious Diseases, New England Medical Center, until
2001. He then joined the faculties of the Department of Epidemiology and Pre-
ventive Medicine and Department of Microbiology and Immunology at the Uni-
versity of Maryland Medical School. Currently at the FDA, his research concen-
tration is on foodborne pathogens and encompasses a mixture of molecular
pathogenesis, cell biology, and epidemiology. Specifically, his research focuses
on Shiga toxin-producing E. coli and understanding toxin interaction with intesti-
nal epithelial cells using tissue culture models. His laboratory has also under-
taken a study to examine Shiga toxin-producing E. coli in food animals in relation
to virulence factors and antimicrobial resistance patterns. More recently, Dr.
Acheson initiated a project to understand the molecular pathogenesis of Campylo-
bacter jejuni. Other studies have undertaken surveillance of diarrheal disease in
the community to determine causes, outcomes, and risk factors of unexplained
diarrhea. Dr. Acheson has authored or coauthored more than 72 journal articles,
and 42 book chapters and reviews, and is coauthor of the book Safe Eating (Dell
Health, 1998). He is reviewer of more than 10 journals and is on the editorial
board of Infection and Immunity and Clinical Infectious Diseases. He is a fellow
of the Royal College of Physicians, and the Infectious Disease Society of
America, and holds several patents.
Ruth L. Berkelman, M.D., is the Rollins Professor and director of the Center for
Public Health Preparedness and Research at the Rollins School of Public Health,
Emory University in Atlanta. She received her A.B. from Princeton University
and her M.D. from Harvard Medical School. Board certified in pediatrics and
internal medicine, she began her career at the CDC in 1980, and later became
deputy director of the NCID. She also served as a senior advisor to the director,
CDC, and Assistant Surgeon General in the U.S. Public Health Service. In 2001,
she came to her current position at Emory University, directing a center focused
on emerging infectious disease and other urgent threats to health, including ter-
rorism. She has also consulted with the biologic program of the Nuclear Threat
Initiative and is most recognized for her work in infectious diseases and disease
surveillance. She was elected to the IOM in 2004. Currently a member of the
IOM’s Forum on Microbial Threats and the Board on Life Sciences of the Na-
tional Academy of Science, she also chairs the Board of Public and Scientific
Affairs at the American Society of Microbiology.
Enriqueta C. Bond, Ph.D., is president of the Burroughs Wellcome Fund. She

received her undergraduate degree from Wellesley College, her M.A. from the
University of Virginia, and her Ph.D. in molecular biology and biochemical ge-
netics from Georgetown University. She is a member of the Institute of Medi-

cine, the American Association for the Advancement of Science, the American
Society for Microbiology, and the American Public Health Association. Dr. Bond
serves on the council of the IOM as its vice-chair; she chairs the Board of Scien-
tific Counselors for the NCID at the CDC, and she chairs the IOM’s Clinical
Research Roundtable. She serves on the board and executive committee of
the Research Triangle Park Foundation and on the board of the Medicines for
Malaria Venture. Prior to being named president of the Burroughs Wellcome
Fund in 1994, she served on the staff of the IOM since 1979, becoming the
IOM’s executive officer in 1989.
Roger G. Breeze, Ph.D., received his veterinary degree (1968) and Ph.D. degree
in veterinary pathology (1973) at the University of Glasgow, Scotland. He was
engaged in teaching, diagnostic pathology, and research on respiratory and car-
diovascular diseases at the University of Glasgow Veterinary School from 1968
to 1977 and at Washington State University College of Veterinary Medicine,
where he was professor and chair of the Department of Microbiology and Pathol-
ogy from 1977 to 1987. From 1984 to 1987 he was deputy director of the Wash-
ington Technology Center, the state’s high-technology sciences initiative, based
in the College of Engineering at the University of Washington. In 1987, he was
appointed director of the USDA’s Plum Island Animal Disease Center, a biosafety
level 3 facility for research and diagnosis of the world’s most dangerous livestock
diseases. In that role, he initiated research into the genomic and functional ge-
nomic basis of disease pathogenesis, diagnosis, and control of livestock RNA and
DNA virus infections. This work became the basis of U.S. defense against natural
and deliberate infection with these agents and led to his involvement in the early
1990s in biological weapons defense and proliferation prevention. From 1995 to
1998 he directed research programs in 20 laboratories in the southeast for the
USDA Agricultural Research Service before going to Washington, D.C., to es-
tablish biological weapons defense research programs for the USDA. He received
the Distinguished Executive Award from President Clinton in 1998 for his work
at Plum Island and in biodefense. Since 2004, he has been CEO of Centaur Sci-
ence Group, which provides consulting services in biodefense. His main commit-
ment is to the Defense Threat Reduction Agency’s Biological Weapons Prolifera-
tion Prevention program in Europe, the Caucasus, and Central Asia.
Steven J. Brickner, Ph.D., is research advisor, antibacterials chemistry, at Pfizer

Global Research and Development. He received his Ph.D. in organic chemistry
from Cornell University and was a National Institutes of Health (NIH)
postdoctoral research fellow at the University of Wisconsin–Madison. He is a
medicinal chemist with nearly 20 years of research experience in the pharmaceu-
tical industry, all focused on the discovery and development of novel antibacte-
rial agents. He is an inventor or coinventor on 21 U.S. patents and has published

APPENDIX C 267
numerous scientific papers, primarily within the area of the oxazolidinones. Prior
to joining Pfizer in 1996, he led a team at Pharmacia and Upjohn that discovered
and developed linezolid, the first member of a new class of antibiotics to be
approved in the last 35 years.
Nancy Carter-Foster, M.S.T.M., is senior advisor for health affairs for the U.S.
Department of State, Assistant Secretary for Science and Health, and the Sec-
retary’s Representative on HIV/AIDS. She is responsible for identifying emerg-
ing health issues and making policy recommendations for the United States
foreign policy concerns regarding international health, and coordinates the depart-
ment’s interactions with the nongovernmental community. She is a member of
the IOM’s Forum on Microbial Threats, the Infectious Diseases Society of
America (IDSA), and the American Association of the Advancement of Science
(AAAS). She has helped bring focus to global health issues in U.S. foreign policy
and brought a national security focus to global health. In prior positions as direc-
tor for congressional and legislative affairs for the Economic and Business Af-
fairs Bureau of the U.S. Department of State, Foreign Policy Advisory to the
majority whip U.S. House of Representatives, trade specialist advisor to the House
of Representatives Ways and Means Trade Subcommittee, and consultant to the
World Bank, Asia Technical Environment Division, Ms. Carter-Foster has worked
on a wide variety of health, trade, and environmental issues, amassing in-depth
knowledge and experience in policy development and program implementation.
Gail H. Cassell, Ph.D., is vice president of Scientific Affairs, Distinguished Lilly

Research Scholar for Infectious Diseases, Eli Lilly & Company. Previously, she
was the Charles H. McCauley Professor and (since 1987) chair of the Department
of Microbiology, University of Alabama Schools of Medicine and Dentistry at
Birmingham, a department which, under her leadership, has ranked first in re-
search funding from the NIH since 1989. She is a member of the Director’s Advi-
sory Committee of the CDC. Dr. Cassell is past president of the American Soci-
ety for Microbiology (ASM) and is serving her third three-year term as chair of
the Public and Scientific Affairs Board of the ASM. She is a former member of
the NIH Director’s Advisory Committee and a former member of the Advisory
Council of the National Institute of Allergy and Infectious Diseases (NIAID).
She has also served as an advisor on infectious diseases and indirect costs of
research to the White House Office on Science and Technology and was previ-
ously chair of the Board of Scientific Counselors of the NCID at the CDC. She
served eight years on the Bacteriology-Mycology-II Study Section and served as
its chair for three years. She serves on the editorial boards of several prestigious
scientific journals and has authored over 275 articles and book chapters. She has
been intimately involved in the establishment of science policy and legislation
related to biomedical research and public health. Dr. Cassell has received several

national and international awards and an honorary degree for her research on
infectious diseases.
COL Ralph (Loren) Erickson, M.D., Dr.P.H., M.P.H., is the Director of the
Department of Defense Global Emerging Infections Surveillance and Response
System (DoD-GEIS) headquartered in Silver Spring, Maryland. He holds degrees
in Chemistry (B.S., University of Washington), Medicine (M.D., Uniformed Ser-
vices University of the Health Sciences), and Public Health (M.P.H., Harvard;
Dr.P.H., Johns Hopkins). Residency trained and board certified in Preventive
Medicine, Dr. Erickson has held a number of leadership positions within the Army
Medical Department to include: Director of the General Preventive Medicine
Residency Program, Walter Reed Army Institute of Research; Director of Epide-
miology and Disease Surveillance, U.S. Army Center for Health Promotion and
Preventive Medicine; Commander of the U.S. Army Center for Health Promotion
and Preventive Medicine (Europe); and Specialty Leader for all U.S. Army Pre-
ventive Medicine physicians.
Mark B. Feinberg, M.D., Ph.D., is vice president for Policy, Public Health, and
Medical Affairs in the Merck Vaccine Division of Merck & Co., Inc. He received
his bachelor’s degree magna cum laude from the University of Pennsylvania in
1978, and his M.D. and Ph.D. degrees from Stanford University School of Medi-
cine in 1987. From 1985–1986, Dr. Feinberg served as a project officer for the
Committee on a National Strategy for AIDS of the IOM and the National Acad-
emy of Sciences (NAS). Following receipt of his M.D. and Ph.D. degrees, he
pursued postgraduate residency training in internal medicine at the Brigham and
Women’s Hospital of Harvard Medical School and postdoctoral fellowship re-
search in the laboratory of Dr. David Baltimore at the Whitehead Institute for
Biomedical Research. From 1991 to 1995, Dr. Feinberg was an assistant profes-
sor of medicine and microbiology and immunology at the University of Califor-
nia, San Francisco (UCSF), where he also served as an attending physician in the
AIDS/Oncology Division and as director of the Virology Research Laboratory at
San Francisco General Hospital. From 1995 to 1997, he was a medical officer in
the Office of AIDS Research in the office of the director of the NIH, and chair of
the NIH Coordinating Committee on AIDS Etiology and Pathogenesis Research.
During this period, he also served as executive secretary of the NIH Panel to
Define Principles of Therapy of HIV Infection. Prior to joining Merck in 2004,
Dr. Feinberg served as professor of medicine and microbiology and immunology
at the Emory University School of Medicine and as an investigator at the Emory
Vaccine Center. He also founded and served as the medical director of the Hope
Clinic—a clinical research facility devoted to the clinical evaluation of novel
vaccines and to translational research studies of human immune system biology.
At UCSF and Emory, Dr. Feinberg and colleagues were engaged in the preclini-
cal development and evaluation of novel vaccines for HIV and other infectious

APPENDIX C 269
diseases and in basic research studies focused on revealing fundamental aspects

of host-virus relationships that underlie the pathogenesis of HIV and simian im-
munodeficiency virus (SIV) infections. In addition to his other professional roles,
he has also served as a consultant to, and member of, several committees of the
IOM and the NAS.
J. Patrick Fitch, Ph.D., joined Battelle in 2006 as vice president for Biodefense
Programs, after more than 20 years of experience leading multidisciplinary ap-
plied science teams as large as 250 staff members (including biologists, veteri-
narians, physicians, engineers, physicists, chemists, and computer scientists) as
well as a $75 million per year program at the Lawrence Livermore National Labo-
ratory (LLNL). From 2001 to 2006, he led LLNL’s Chemical and Biological
National Security Program (CBNP), which ranges from basic pathogen biology
and material science to deployed systems and has had many accomplishments
including performing more than one million assays on national security samples,
stand-up and operation of 24/7 reachback capabilities, stand-up of a nationwide
bio-alert system, three R&D 100 awards, and design of signatures for validated
assays in the CDC Laboratory Response Network. Under Dr. Fitch’s leadership,
BASIS was designed, demonstrated, and deployed, leading to the nationwide sys-
tem, BioWatch. He has authored several books and book chapters including An
Engineering Introduction to Biotechnology. He has chaired and served on several
panels of the National Academies. His advisory board activities have included
the U.S. Animal Health Association, the Texas A&M University DHS Center of
Excellence, Central Florida University (College Engineering), Colorado State
University (College of Engineering), the California State Breast Cancer Research
Program, and Biomolecular Engineering. Dr. Fitch was a fellow of the American
Society for Laser Medicine and Surgery and an associate editor of Circuits, Sys-
tems and Signal Processing. He has received two national awards for medical
devices, a technical writing award for an article in Science, and an international
best paper award from the IEEE. He also co-invented the technology, developed
the initial business plan, and successfully raised venture investments for a spin-
out high tech medical device start-up company. Dr. Fitch received his Ph.D. from
Purdue University and B.S. degrees from Loyola College.
Capt. Darrell R. Galloway, MSC, Ph.D., is chief of Medical S&T Division for
the Chemical & Biological Defense Directorate at the Defense Threat Reduction
Agency. He received his baccalaureate degree in microbiology from the Califor-
nia State University in Los Angeles in 1973. After completing military service in
the U.S. Army as a medical corpsman from 1969–1972, Captain Galloway en-
tered graduate school and completed a doctoral degree in biochemistry in 1978
from the University of California, followed by two years of postgraduate training
in immunochemistry as a Fellow of the National Cancer Institute at the Scripps
Clinic and Research Foundation in La Jolla, CA. Captain Galloway began his

Navy career at the Naval Medical Research Institute in Bethesda, MD, where he
served as a research scientist from 1980–1984 working on vaccine development.
In late 1984 Captain Galloway left active service to pursue an academic appoint-
ment at The Ohio State University where he is a tenured faculty member in the
Department of Microbiology. He also holds appointments at the University of
Maryland Biotechnology Institute and the Uniformed Services University
of Health Sciences. He has an international reputation in the area of bacterial
toxin research and has published more than 50 research papers on various studies
of bacterial toxins. In recent years Captain Galloway’s research has concentrated
on anthrax and the development of DNA-based vaccine technology. His labora-
tory has contributed substantially to the development of a new DNA-based vac-
cine against anthrax which has completed the first phase of clinical trials. Captain
Galloway is a member of the American Society for Microbiology and has served
as past president of the Ohio Branch of that organization. He received an NIH
Research Career Development Award. In 2005 Captain Galloway was awarded
the Joel M. Dalrymple Award for significant contributions to biodefense vaccine
development.
S. Elizabeth George, Ph.D., is deputy director, Biological Countermeasures Port-

folio Science and Technology Directorate, Department of Homeland Security
(DHS). Until merging into the new department in 2003, she was the program
manager of the Chemical and Biological National Security Program in the De-
partment of Energy’s National Nuclear Security Administration’s Office of Non-
proliferation Research & Engineering. Significant accomplishments include the
design and deployment of BioWatch, the nation’s first civilian biological threat
agent-monitoring system and PROTECT, the first civilian operational chemical
detection and response capability deployed in the Washington subway system.
Previously, she spent 16 years at the U.S. Environmental Protection Agency
(EPA), Office of Research and Development, National Health and Ecological
Effects Research Laboratory, Environmental Carcinogenesis Division, where she
was branch chief of the Molecular and Cellular Toxicology Branch. She received
her B.S. in biology (1977) from Virginia Polytechnic Institute and State Univer-
sity and M.S. and Ph.D. in microbiology (1979 and 1984) from North Carolina
State University. She was an NRC fellow (1984–1986) in the laboratory of Dr.
Larry Claxton at the U.S. EPA. Dr. George is the 2005 chair of the Chemical and
Biological Terrorism Defense Gordon Research Conference. She has served as
councilor for the Environmental Mutagen Society and president and secretary of
the Genotoxicity and Environmental Mutagen Society. She holds memberships in
the American Society for Microbiology and the American Association for the
Advancement of Science and is an adjunct faculty member in the School of Rural
Public Health, Texas A&M University. She is a recipient of the EPA Bronze
Medal and Scientific and Technological Achievement Awards and DHS Under

APPENDIX C 271
Secretary’s Award for Science and Technology. She is author of numerous jour-
nal articles and has presented her research at national and international meetings.
Jesse L. Goodman, M.D., M.P.H., was professor of medicine and chief of in-
fectious diseases at the University of Minnesota, and is now serving as deputy
director for the FDA’s Center for Biologics Evaluation and Research, where he
is active in a broad range of scientific, public health, and policy issues. After
joining the FDA commissioner’s office, he has worked closely with several cen-
ters and helped coordinate the FDA’s response to the antimicrobial resistance
problem. He was cochair of a recently formed federal interagency task force that
developed the national Public Health Action Plan on antimicrobial resistance.
He graduated from Harvard College and attended the Albert Einstein College of
Medicine followed by internal medicine, hematology, oncology, and infectious
diseases training at the University of Pennsylvania and University of California–
Los Angeles, where he was also chief medical resident. He received his master’s
of public health from the University of Minnesota. He has been active in com-
munity public health activities, including creating an environmental health part-
nership in St. Paul, Minnesota. In recent years, his laboratory’s research has
focused on the molecular pathogenesis of tick-borne diseases. His laboratory
isolated the etiological intracellular agent of the emerging tick-borne infection,
human granulocytic ehrlichiosis, and identified its leukocyte receptor. He has
also been an active clinician and teacher and has directed or participated in ma-
jor multicenter clinical studies. He is a fellow of the Infectious Diseases Society
of America and, among several honors, has been elected to the American Soci-
ety for Clinical Investigation.
Eduardo Gotuzzo, M.D., is principal professor and director at the Instituto de

Medicina Tropical “Alexander von Humbolt,” Universidad Peruana Cayetan
Heredia (UPCH), in Lima, Peru, as well as chief of the Department of Infectious
and Tropical Diseases at the Cayetano Heredia Hospital. He is also an adjunct
professor of medicine at the University of Alabama–Birmingham School of Medi-
cine. Dr. Gotuzzo is an active member in numerous international societies, and
has been president of the Latin America Society of Tropical Disease (2000–2003),
the Scientific Program of Infectious Diseases Society of America (2000–2003),
the International Organizing Committee of the International Congress of Infec-
tious Diseases (1994–present), president elect of the International Society for
Infectious Diseases (1996–1998), and president of the Peruvian Society of Inter-
nal Medicine (1991–1992). He has published over 230 articles and chapters as
well as 6 manuals and 1 book. Recent honors and awards include being named an
honorary member of American Society of Tropical Medicine and Hygiene (since
2002), associate member of the National Academy of Medicine (since 2002),
honorary member of the Society of Internal Medicine (since 2000), distinguished

visitor at the Faculty of Medical Sciences, University of Cordoba, Argentina

(since 1999), and received the Golden Medal for Outstanding Contribution in the
Field of Infectious Diseases awarded by the Trnava University, Slovakia (1998),
among many others.
Jo Handelsman, Ph.D., received her Ph.D. in molecular biology from the Uni-
versity of Wisconsin (UW)–Madison in 1984 and joined the faculty of the UW–
Madison Department of Plant Pathology in 1985 where she is currently a Howard
Hughes Medical Institute (HHMI) Professor. Her research focuses on the genetic
and functional diversity of microorganisms in soil and insect gut communities.
The Handelsman lab has concentrated on discovery and biological activity of
novel antibiotics from cultured and uncultured bacteria and has contributed to the
pioneering of a new technique, called metagenomics, that facilitates the genomic
analysis of assemblages of uncultured microorganisms. Handelsman is studying
the midgut of the gypsy moth to understand the basis for resistance and suscepti-
bility of microbial communities to invasion, developing it as a model for the
microbial community in the human gut. In addition to her passion for understand-
ing the secret lives of bacteria, Dr. Handelsman is dedicated to improving science
education and the advancement of women in research universities. She is director
of the Howard Hughes Medical Institute New Generation Program for Scientific
Teaching, which is dedicated to teaching graduate students and postdoctoral stu-
dents the principles and practices of teaching and mentoring. She is codirector of
the National Academies Summer Institute for Undergraduate Education in Biol-
ogy, which is a collaborative venture between HHMI and the National Acad-
emies that aims to train a nationwide network of faculty who are outstanding
teachers and mentors. Dr. Handelsman is codirector of the Women in Science and
Engineering Leadership Institute, at the University of Wisconsin–Madison, whose
mission is to understand the impediments to the successful recruitment and ad-
vancement of women faculty in the sciences and to develop and study interven-
tions intended to reduce the barriers.
Carole A. Heilman, Ph.D., is director of the Division of Microbiology and In-

fectious Diseases (DMID) of the NIAID. She received her bachelor’s degree in
biology from Boston University in 1972, and earned her master’s degree and
doctorate in microbiology from Rutgers University in 1976 and 1979, respec-
tively. Dr. Heilman began her career at the NIH as a postdoctoral research associ-
ate with the National Cancer Institute where she carried out research on the regu-
lation of gene expression during cancer development. In 1986, she came to NIAID
as the influenza and viral respiratory diseases program officer in DMID and, in
1988, she was appointed chief of the respiratory diseases branch where she coor-
dinated the development of acellular pertussis vaccines. She joined the Division
of AIDS as deputy director in 1997 and was responsible for developing the Inno-
vation Grant Program for Approaches in HIV Vaccine Research. She is the re-

APPENDIX C 273
cipient of several notable awards for outstanding achievement. Throughout her

extramural career, Dr. Heilman has contributed articles on vaccine design and
development to many scientific journals and has served as a consultant to the
World Bank and WHO in this area. She is also a member of several professional
societies, including the Infectious Diseases Society of America, the American
Society for Microbiology, and the American Society of Virology.
David L. Heymann, M.D., is currently the executive director of the WHO Com-
municable Diseases Cluster. From October 1995 to July 1998 he was director of
the WHO Programme on Emerging and Other Communicable Diseases Surveil-
lance and Control. Prior to becoming director of this program, he was the chief of
research activities in the Global Programme on AIDS. From 1976 to 1989, prior
to joining WHO, Dr. Heymann spent 13 years working as a medical epidemiolo-
gist in sub-Saharan Africa (Cameroon, Ivory Coast, the former Zaire, and Malawi)
on assignment from the CDC in CDC-supported activities aimed at strengthening
capacity in surveillance of infectious diseases and their control, with special em-
phasis on the childhood immunizable diseases, African hemorrhagic fevers, pox
viruses, and malaria. While based in Africa, he participated in the investigation of
the first outbreak of Ebola in Yambuku (former Zaire) in 1976, then again inves-
tigated the second outbreak of Ebola in 1977 in Tandala, and in 1995 directed the
international response to the Ebola outbreak in Kikwit. Prior to 1976, Dr.
Heymann spent two years in India as a medical officer in the WHO Smallpox
Eradication Programme. He holds a B.A. from the Pennsylvania State University,
an M.D. from Wake Forest University, and a Diploma in Tropical Medicine and
Hygiene from the London School of Hygiene and Tropical Medicine. He has also
completed practical epidemiology training in the Epidemic Intelligence Service
(EIS) training program of the CDC. He has published 131 scientific articles on
infectious diseases in peer-reviewed medical and scientific journals.
Phil Hosbach, Ph.D., is vice president of New Products and Immunization Policy
at Sanofi Pasteur. The departments under his supervision are new product mar-
keting, state and federal government policy, business intelligence, bids and con-
tracts, medical communications, public health sales, and public health marketing.
His current responsibilities include oversight of immunization policy develop-
ment. He acts as Sanofi Pasteur’s principle liaison with the CDC. Mr. Hosbach
graduated from Lafayette College in 1984 with a degree in biology. He has 20
years of pharmaceutical industry experience, including the last 17 years focused
solely on vaccines. He began his career at American Home Products in Clinical
Research in 1984. He joined Aventis Pasteur (then Connaught Labs) in 1987 as
clinical research coordinator and has held research and development positions of
increasing responsibility, including clinical research manager and director of clini-
cal operations. Mr. Hosbach also served as project manager for the development
and licensure of Tripedia, the first diphtheria, tetanus, and acellular pertussis

(DTaP) vaccine approved by the FDA for use in U.S. infants. During his clinical
research career at Aventis Pasteur, he contributed to the development and licen-
sure of seven vaccines and has authored or coauthored several clinical research
articles. From 2000 through 2002, Mr. Hosbach served on the board of directors
for Pocono Medical Center, in East Stroudsburg, Pennsylvania. Since 2003 he
has actively served on the board of directors of Pocono Health Systems, which
includes Pocono Medical Center.
James M. Hughes, M.D., received his B.A. in 1966 and M.D. in 1971 from
Stanford University. He completed a residency in internal medicine at the Uni-
versity of Washington and a fellowship in infectious diseases at the University of
Virginia. He is board certified in internal medicine, infectious diseases, and pre-
ventive medicine. He first joined the CDC as an epidemic intelligence service
officer in 1973. During his CDC career, he has worked primarily in the areas of
foodborne disease and infection control in healthcare settings. He became direc-
tor of the NCID in 1992. The center is currently working to address domestic and
global challenges posed by emerging infectious diseases and the threat of
bioterrorism. He is a member of the IOM and a fellow of the American College of
Physicians, the Infectious Diseases Society of America, and the American Asso-
ciation for the Advancement of Science. He is an Assistant Surgeon General in
the Public Health Service.
Stephen A. Johnston, Ph.D., is a professor and director at the University of

Texas Southwestern Medical Center. A major focus of his lab has been technol-
ogy development. His interest of late has been especially in the area of vaccine
development. He was coinventor with Dr. John Sanford of the hand-held, helium
gene gun, and he and Dr. Sanford used the gene gun to first demonstrate gene
(DNA) immunization. Genetic vaccines have revolutionized approaches to deliv-
ering and developing vaccines. In this regard, Johnston’s group first published on
a method, expression library immunization, that offers a systematic approach to
searching genomic information for new vaccines. His group has also developed
techniques for discovering peptides that target specific cells and is employing this
to create more effective, targeted vaccines. Through the Center for Biomedical
Inventions, his group with collaborators in immunology, instrumentation, genom-
ics, and chemistry is attempting to forge a fully integrated approach to developing
the best methods for delivery and discovering vaccines.
Gerald T. Keusch, M.D., is provost and dean for Global Health at Boston Uni-
versity and Boston University School of Public Health. He is a graduate of Co-
lumbia College (1958) and Harvard Medical School (1963). After completing a
residency in internal medicine, fellowship training in infectious diseases, and two
years as an NIH research associate at the SEATO Medical Research Laboratory
in Bangkok, Thailand, Dr. Keusch joined the faculty of Mt. Sinai School of Medi-

APPENDIX C 275
cine in 1970, where he established a laboratory to study the pathogenesis of bacil-

lary dysentery and the biology and biochemistry of Shiga toxin. In 1979, he moved
to Tufts Medical School and New England Medical Center in Boston to found the
Division of Geographic Medicine, which focused on the molecular and cellular
biology of tropical infectious disease. In 1986, he integrated the clinical infec-
tious diseases program into the Division of Geographic Medicine and Infectious
Diseases, continuing as division chief until 1998. He has worked in the laboratory
and in the field in Latin America, Africa, and Asia on basic and clinical infectious
diseases and HIV/AIDS research. From 1998 to 2003, he was associate director
for international research and director of the Fogarty International Center at the
NIH. Dr. Keusch is a member of the American Society for Clinical Investigation,
the Association of American Physicians, the American Society for Microbiology,
and the Infectious Diseases Society of America. He is the recipient of the Squibb
(1981), Finland (1997), and Bristol (2002) Awards of the Infectious Diseases
Society of America. In 2002, he was elected to the IOM.
Rima F. Khabbaz, M.D., is director of the NCID at the CDC. She received her
B.S. in 1975 and her M.D. in 1979 from the American University of Beirut in
Beirut, Lebanon. She trained in internal medicine and completed a fellowship in
infectious diseases at the University of Maryland in Baltimore. She is board cer-
tified in internal medicine. She first joined the CDC as an epidemic intelligence
service officer in 1980. During her CDC career, she worked primarily in the areas
of healthcare-associated infections and viral diseases. She is a fellow of the Infec-
tious Diseases Society of America and an elected member of the American Epi-
demiologic Society. She served on the Blood Product Advisory Committee of the
FDA, on the FDA’s Transmissible Spongiform Encephalopathy Advisory Com-
mittee, and on the Infectious Diseases Society of America’s Annual Meeting Sci-
entific Program Committee. She played a leading role in developing the CDC’s
programs related to blood safety and food safety and in the CDC’s responses to
outbreaks of new and reemerging diseases.
Lonnie J. King, D.V.M., is dean of the College of Veterinary Medicine, Michi-

gan State University. His previous positions include both associate administrator
and administrator of the USDA Animal and Plant Health Inspection Service
(APHIS) and deputy administrator for USDA/APHIS/Veterinary Services. Be-
fore his government career, Dr. King was in private practice. He also has experi-
ence as a field veterinary medical officer, station epidemiologist, and staff assign-
ments involving emergency programs and animal health information. He has also
directed the American Veterinary Medical Association’s Office of Governmental
Relations and is certified in the American College of Veterinary Preventive Medi-
cine. He has served as president of the Association of American Veterinary Medi-
cine Colleges and currently serves as cochair of the National Commission on
Veterinary Economic Issues, is the lead dean at Michigan State University for

food safety with responsibility for the National Food Safety and Toxicology Cen-
ter, and also serves at the Institute for Environmental Toxicology and the Center
for Emerging Infectious Diseases. He is codeveloper and course leader for sci-
ence, politics, and animal health policy. He received his B.S. and D.V.M degrees
from Ohio State University and his M.S. degree in epidemiology from the Uni-
versity of Minnesota. He has also completed the Senior Executive Program at
Harvard University, and received an M.P.A. from American University. Dr. King
previously served on the Committee for Opportunities in Agriculture, the Steer-
ing Committee for a Workshop on the Control and Prevention of Animal Dis-
eases, and the Committee to Ensure Safe Food from Production to Consumption.
COL George W. Korch, Ph.D., is commander, United States Army Medical

Research Institute for Infectious Diseases, Ft. Detrick, Maryland. Dr. Korch at-
tended Boston University and earned a B.S. in biology in 1974, followed by post-
graduate study in mammalian ecology at the University of Kansas from 1975 to
1978. He earned his Ph.D. from the Johns Hopkins School of Hygiene and Public
Health in immunology and infectious diseases in 1985, followed by postdoctoral
experience at Johns Hopkins from 1985 to 1986. His area of training and spe-
cialty is the study of the epidemiology of zoonotic viral pathogens and in medical
entomology. For the past 15 years, he has also engaged in research and program
management for medical defense against biological pathogens used in terrorism
or warfare.
Joshua Lederberg, Ph.D., is professor emeritus of molecular genetics and

informatics and Sackler Foundation Scholar at the Rockefeller University in New
York City. His lifelong research, for which he received the Nobel Prize in 1958,
has been in genetic structure and function in microorganisms. He has a keen
interest in international health and was cochair of a previous IOM Committee on
Emerging Microbial Threats to Health (1990–1992) and currently is cochair of
the Committee on Emerging Microbial Threats to Health in the 21st Century. He
has been a member of the NAS since 1957 and is a charter member of the IOM.
Lynn G. Marks, M.D., is board certified in internal medicine and infectious

diseases. He was on faculty at the University of South Alabama College of Medi-
cine in the Infectious Diseases Department focusing on patient care, teaching,
and research. His academic research interest was on the molecular genetics of
bacterial pathogenicity. He subsequently joined SmithKline Beecham’s (now
GlaxoSmithKline) anti-infectives clinical group and later progressed to global
head of the Consumer Healthcare Division Medical and Regulatory Group. He
then returned to pharmaceutical research and development as global head of the
Infectious Diseases Therapeutic Area Strategy Team for GlaxoSmithKline.

APPENDIX C 277
Mary McBride, Ph.D., is the Deputy Program Leader for Science and Technol-
ogy within the Chemical and Biological National Security Program (CBNP) at
Lawrence Livermore National Laboratory. The Program’s primary mission is to
develop and field advanced strategies that dramatically improve the nation’s ca-
pabilities to prevent, prepare for, detect and respond to chemical or biological
terrorism. Dr. McBride directs and manages the research efforts of more than 65
multidisciplinary professional and technical staff in a program of integrated re-
search that leverages investments across all sectors (academic to industrial). She
plans, coordinates, evaluates, and manages the transition from basic research, to
proof of principle, to demonstration and pilots, to operational systems with hand-
off to end-users and commercialization for numerous projects. She conceived and
developed a research program to develop diagnostic assays and instrumentation
for infectious diseases intended for use at point-of-care. Recently, Dr. McBride
also initiated a research program to rapidly prototype a chip-based system for
detection and identification of microbial antibiotic resistance and virulence fac-
tors with intended hand-off to industry for commercialization within 18 months.
Dr. McBride is also especially interested and active in a variety of interagency
activities. She is the technical lead for a project designed to establish assay equiva-
lency and interoperability between DoD, USPS, and HHS biomonitoring sys-
tems, and she is developing an integrated plan intended to enable private sector,
academia, and USG performers to establish detection/identification assays as
“public health actionable”. She recently completed four month assignment at De-
partment of Homeland Security serving as an advisor to S&T Biological Counter-
measures. Dr. McBride earned a Ph.D. from the University of California, Davis
in analytical chemistry in 1998. She joined LLNL as a postdoctoral research asso-
ciate in 1999. She has published over 30 peer-reviewed publications, holds five
patents related to biodetection instrumentation/assays, and has received an R&D
100 award and LLNL’s highest scientific achievement award, the Laboratory
S&T award.
Edward McSweegan, Ph.D., is a program officer at NIAID. He graduated from

Boston College in 1978 (B.S.) and has degrees in microbiology from the Univer-
sity of New Hampshire (M.S.) and the University of Rhode Island (Ph.D.). He
was an NRC Associate from 1984 to 1986 and did postdoctoral research at the
Naval Medical Research Institute in Bethesda, Maryland. Dr. McSweegan served
as an American Association for the Advancement of Science Diplomacy fellow
in the U.S. State Department from 1986 to 1988 and negotiated science and tech-
nology agreements with Poland, Hungary, and the former Soviet Union. After
moving to the NIH, he continued to work on international health and science
projects in Egypt, Israel, India, and Russia. Currently, he manages NIAID’s bilat-
eral program with India, the Indo–U.S. Vaccine Action Program, and represents
NIAID in the DHHS Biotechnology Engagement Program (BTEP) with Russia

and related countries. He is a member of the American Association for the Ad-
vancement of Science, the American Society for Microbiology, and the D.C. Sci-
ence Writers Association. He is the author of numerous journal articles and
science articles.
Stephen S. Morse, Ph.D., is director of the Center for Public Health Prepared-
ness at the Mailman School of Public Health of Columbia University and is a
faculty member in the epidemiology department. He recently returned to Colum-
bia from four years in government service as program manager at the Defense
Advanced Research Projects Agency (DARPA), where he codirected the Patho-
gen Countermeasures Program and subsequently directed the Advanced Diag-
nostics Program. Before coming to Columbia, he was assistant professor of virol-
ogy at the Rockefeller University in New York, where he remains an adjunct
faculty member. He is the editor of two books, Emerging Viruses (Oxford Uni-
versity Press, 1993; paperback, 1996) (selected by American Scientist for its list
of 100 Top Science Books of the 20th Century), and The Evolutionary Biology of
Viruses (Raven Press, 1994). He currently serves as a section editor of the CDC
journal, Emerging Infectious Diseases, and was formerly an editor-in-chief of the
Pasteur Institute’s journal, Research in Virology. Dr. Morse was chair and princi-
pal organizer of the 1989 NIAID/NIH Conference on Emerging Viruses (for
which he originated the term and concept of emerging viruses/infections); served
as a member of the IOM-NAS Committee on Emerging Microbial Threats to
Health (and chaired its Task Force on Viruses), and was a contributor to its re-
port, Emerging Infections (1992); was a member of the IOM’s Committee on
Xenograft Transplantation; currently serves on the Steering Committee of the
IOM’s Forum on Emerging Infections, and has served as an adviser to WHO, the
Pan-American Health Organization, the FDA, the Defense Threat Reduction
Agency, and other agencies. He is a fellow of the New York Academy of Sci-
ences and a past chair of its microbiology section. He was the founding chair of
ProMED (the nonprofit international Program to Monitor Emerging Diseases)
and was one of the originators of ProMED-mail, an international network inaugu-
rated by ProMED in 1994 for outbreak reporting and disease monitoring using
the Internet. Dr. Morse received his Ph.D. from the University of Wisconsin–
Madison.
Michael T. Osterholm, Ph.D., M.P.H., is director of the Center for Infectious

Disease Research and Policy at the University of Minnesota where he is also
professor at the School of Public Health. Previously, Dr. Osterholm was the
state epidemiologist and chief of the acute disease epidemiology section for the
Minnesota Department of Health. He has received numerous research awards
from the NIAID and the CDC. He served as principal investigator for the CDC-
sponsored Emerging Infections Program in Minnesota. He has published more
than 240 articles and abstracts on various emerging infectious disease problems

APPENDIX C 279
and is the author of the best selling book, Living Terrors: What America Needs
to Know to Survive the Coming Bioterrorist Catastrophe. He is past president of
the Council of State and Territorial Epidemiologists. He currently serves on the
NAS-IOM Forum on Emerging Infections. He has also served on the IOM Com-
mittee to Ensure Safe Food from Production to Consumption, the IOM Commit-
tee on the Department of Defense Persian Gulf Syndrome Comprehensive Clini-
cal Evaluation Program, and as a reviewer for the IOM report on chemical and
biological terrorism.
George Poste, Ph.D., D.V.M., is director of the Arizona Biodesign Institute and
Dell E. Webb Distinguished Professor of Biology at Arizona State University.
From 1992 to 1999, he was chief science and technology officer and president,
Research and Development of SmithKline Beecham (SB). During his tenure at
SB, he was associated with the successful registration of 29 drug, vaccine, and
diagnostic products. He is chairman of diaDexus and Structural GenomiX in Cali-
fornia and Orchid Biosciences in Princeton. He serves on the board of directors of
AdvancePCS and Monsanto. He is an advisor on biotechnology to several ven-
ture capital funds and investment banks. In May 2003, he was appointed as direc-
tor of the Arizona Biodesign Institute at Arizona State University. This is a major
new initiative combining research groups in biotechnology, nanotechnology,
materials science, advanced computing, and neuromorphic engineering. He is a
fellow of Pembroke College at Cambridge and distinguished fellow at the Hoover
Institution and Stanford University. He is a member of the Defense Science Board
of the U.S. Department of Defense, and in this capacity he chairs the Task Force
on Bioterrorism. He is also a member of the NAS Working Group on Defense
Against Bioweapons. Dr. Poste is a board-certified pathologist, a fellow of the
Royal Society, and a fellow of the Academy of Medical Sciences. He was awarded
the rank of Commander of the British Empire by Queen Elizabeth II in 1999 for
services to medicine and for the advancement of biotechnology. He has published
over 350 scientific papers; coedited 15 books on cancer, biotechnology, and in-
fectious diseases; and serves on the editorial board of multiple technical journals.
He is invited routinely to be the keynote speaker at a wide variety of academic,
corporate, investment, and government meetings to discuss the impact of bio-
technology and genetics on healthcare and the challenges posed by bioterrorism.
David A. Relman, M.D., Ph.D., is an associate professor of medicine (infec-

tious diseases and geographic medicine) and of microbiology and immunology
at Stanford University School of Medicine, Stanford, CA, and chief of the infec-
tious disease section at the Veterans Affairs (VA) Palo Alto Health Care System,
Palo Alto, CA. Dr. Relman received his B.S. in biology from Massachusetts
Institute of Technology, Cambridge, Massachusetts, and his M.D. from Harvard
Medical School. He completed his residency in internal medicine and a clinical
fellowship in infectious diseases at Massachusetts General Hospital, Boston, af-

ter which he moved to Stanford in 1994. His major focus is laboratory research
directed toward characterizing the human endogenous microbial flora, host-
microbe interactions, and identifying previously unrecognized microbial patho-
gens using molecular and genomic approaches. He has described a number of
new human microbial pathogens. Dr. Relman’s lab (http://relman.stanford.edu)
is currently exploring human oral and intestinal microbial ecology, sources of
variation in host genomewide expression responses to infection and during states
of health, and how Bordetella species (including the agent of whooping cough)
cause disease. He has published over 150 peer-reviewed articles, reviews, edito-
rials, and book chapters on pathogen discovery and bacterial pathogenesis. He
has served on scientific program committees for the American Society of Micro-
biology; the Infectious Diseases Society of America (IDSA); advisory panels for
the NIH, CDC, the Departments of Energy and Defense, and the National Aero-
nautics and Space Administration. He was cochair of the Committee on Ad-
vances in Technology and the Prevention of their Application to Next Genera-
tion Biowarefare Threats for the NAS. He is a member of the board of directors
of the IDSA and the Board of Scientific Counselors at the National Institute of
Dental and Craniofacial Research at the NIH. He received the Squibb Award
from the IDSA in 2001, the Senior Scholar Award in Global Infectious Diseases
from the Ellison Medical Foundation in 2002, and is a fellow of the American
Academy of Microbiology.
Gary A. Roselle, M.D., received his M.D. from Ohio State University School of
Medicine in 1973. He served his residency at Northwestern University School
of Medicine and his infectious diseases fellowship at the University of Cincinnati
School of Medicine. He is the program director for infectious diseases for the VA
Central Office in Washington, D.C., as well as the chief of the medical service at
the Cincinnati VA Medical Center. He is a professor of medicine in the Depart-
ment of Internal Medicine, Division of Infectious Diseases at the University of
Cincinnati College of Medicine. Dr. Roselle serves on several national advisory
committees. In addition, he is currently heading the Emerging Pathogens Initia-
tive for the Department of Veterans Affairs. He has received commendations
from the Cincinnati Medical Center Director, the Under Secretary for Health for
the Department of Veterans Affairs, and the Secretary of Veterans Affairs for his
work in the infectious diseases program for the Department of Veterans Affairs.
He has been an invited speaker at several national and international meetings and
has published over 80 papers and several book chapters.
Janet Shoemaker is director of the American Society for Microbiology’s Public

Affairs Office, a position she has held since 1989. She is responsible for manag-
ing the legislative and regulatory affairs of this 42,000-member organization, the
largest single biological science society in the world. She has served as principal
investigator for a project funded by the National Science Foundation (NSF) to

APPENDIX C 281
collect and disseminate data on the job market for recent doctorates in microbiol-
ogy and has played a key role in American Society for Microbiology (ASM)
projects, including the production of the ASM Employment Outlook in the Micro-
biological Sciences and The Impact of Managed Care and Health System Change
on Clinical Microbiology. Previously, she held positions as assistant director of
public affairs for the ASM, as ASM coordinator of the U.S./U.S.S.R. Exchange
Program in Microbiology, a program sponsored and coordinated by the NSF and
the U.S. Department of State, and as a freelance editor and writer. She received
her baccalaureate, cum laude, from the University of Massachusetts, and is a
graduate of the George Washington University programs in public policy and in
editing and publications. She has served as commissioner to the Commission on
Professionals in Science and Technology, and as the ASM representative to the
ad hoc Group for Medical Research Funding, and is a member of Women in
Government Relations, the American Society of Association Executives, and the
American Association for the Advancement of Science. She has coauthored pub-
lished articles on research funding, biotechnology, biological weapons control,
and public policy issues related to microbiology.
Brian J. Staskawicz, Ph.D., is professor and chair, Department of Plant and

Microbial Biology, University of California, Berkeley. Dr. Staskawicz received
his B.A. in biology from Bates College in 1974 and his Ph.D. from the University
of California, Berkeley in 1980. Dr. Staskawicz’s work has greatly contributed to
understanding the molecular interactions between plants and their pathogens. He
was elected to the NAS in 1998 for elucidating the mechanisms of disease resis-
tance, as his lab was the first to clone a bacterial effector gene from a pathogen
and among the first to clone and characterize plant disease resistance genes. Dr.
Staskawicz’s research focuses on the interaction of the bacteria, Pseudomonas
and Xanthomonas, with Arabidopsis, tomato and pepper. He has published exten-
sively in this area and is a one of the leading scientists in the world working on
elucidating the molecular basis of plant innate immunity.
Terence Taylor is president and director of the International Council for the Life
Sciences (ICLS). He is responsible for the overall direction of the ICLS and its
programs, which have the goal of enhancing global biosafety and biosecurity.
Previously he was assistant director of the International Institute for Strategic
Studies (IISS) (1995 to 2005), a leading independent international institute and
president and executive director of its U.S. office (2001 to 2005). He studies
international security policy, risk analysis, scientific and technological develop-
ments and their impact on political and economic stability worldwide. At IISS he
was one of the Institute’s leading experts on issues associated with nuclear, bio-
logical, and chemical weapons and their means of delivery. In his previous ap-
pointments he has had particular responsibilities for issues affecting public safety
and security in relation to biological risks and advances in the life sciences. He

was one of the commissioners to the UN Special Commission on Iraq for which
he also conducted missions as a chief inspector. He was a research fellow on the
Science Program at the Center for International Security and Co-operation at
Stanford University where he carried out, among other subjects, studies of the
implications for government and industry of the weapons of mass destruction
treaties and agreements. He has also carried out consultancy work for the Interna-
tional Committee of the Red Cross on the implementation and development of
the laws of armed conflict. He has served as chairman of the World Federation of
Scientists’ Permanent Monitoring Panel on Risk Analysis. He served as a career
officer in the British Army on operations in many parts of the world including
counterterrorist operations and UN peacekeeping. His publications include mono-
graphs, book chapters and articles for, among others, Stanford University, the
World Economic Forum, the Stockholm International Peace Research Institute
(SIPRI), the Crimes of War Project, the International Herald Tribune, the Wall
Street Journal, the International Defence Review, the Independent (London),
Tiempo (Madrid), the International and Comparative Law Quarterly, The Wash-
ington Quarterly, and other scholarly journals including unsigned contributions
to IISS publications.

Addressing Foodborne Threats To Health

Uploaded by

Copyright:

Available Formats

Addressing Foodborne Threats To Health

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Addressing Foodborne Threats To Health

Uploaded by

Copyright:

Available Formats

Addressing Foodborne Threats to Health: Policies,

Practices, and Global Coordination, Workshop

Copyright © National Academy of Sciences. Permission is granted for this material to be

Forum on Microbial Threats

Copyright © National Academy of Sciences. All rights reserved.

International Standard Book Number-10 0-309-10043-7 (Book)

Copyright 2006 by the National Academy of Sciences. All rights reserved.

Printed in the United States of America.

Copyright © National Academy of Sciences. All rights reserved.

“Knowing is not enough; we must apply.

Advising the Nation. Improving Health.

Copyright © National Academy of Sciences. All rights reserved.

The National Academy of Sciences is a private, nonprofit, self-perpetuating society of

Copyright © National Academy of Sciences. All rights reserved.

FORUM ON MICROBIAL THREATS

Copyright © National Academy of Sciences. All rights reserved.

RIMA F. KHABBAZ, National Center for Preparedness, Detection and

Copyright © National Academy of Sciences. All rights reserved.

BOARD ON GLOBAL HEALTH

Copyright © National Academy of Sciences. All rights reserved.

Copyright © National Academy of Sciences. All rights reserved.

Copyright © National Academy of Sciences. All rights reserved.

Copyright © National Academy of Sciences. All rights reserved.

The Forum on Emerging Infections was created in 1996 in response to a

ABOUT THE WORKSHOP

Copyright © National Academy of Sciences. All rights reserved.

http://www.healthfinder.gov/news/newsstory.asp?docID=522737 [accessed June 27, 2006].

foodborneinfections_g.htm#foodbornedisease [accessed June 27, 2006].

D.C.: The Library of Congress.

Bioterrorism Defense. New York: Wiley-Liss, Inc. Pp. 215–220.

Copyright © National Academy of Sciences. All rights reserved.

Stanley M. Lemon, Chair

Copyright © National Academy of Sciences. All rights reserved.

Copyright © National Academy of Sciences. All rights reserved.

SUMMARY AND ASSESSMENT 1

1 THE U.S. FOOD SYSTEM 31

Copyright © National Academy of Sciences. All rights reserved.

2 FOOD SAFETY OVERSIGHT 53

3 INVESTIGATING FOODBORNE THREATS 70

5 SURVEILLANCE OF THE FOOD SUPPLY 177

Copyright © National Academy of Sciences. All rights reserved.

6 REPORTING FOODBORNE THREATS: THE CASE OF

7 RESEARCH AND POLICY OPPORTUNITIES 232

Copyright © National Academy of Sciences. All rights reserved.

Copyright © National Academy of Sciences. All rights reserved.

Tables and Figures

2-1 Overlap in Federal Food Safety Oversight, 56

Copyright © National Academy of Sciences. All rights reserved.

xx TABLES AND FIGURES

3-1 Foodborne Pathogens in the United States, 73

5-1 Networks and Resources for Food Safety, 179

6-1 Cases of Transmissible Spongiform Encephalopathies (TSE)

7-1 National Center for Food Protection and Defense Research

Copyright © National Academy of Sciences. All rights reserved.

TABLES AND FIGURES xxi

1-4 Food expenditures as a share of disposable personal income, United

2-1 The WHO International Food Safety Authorities Network (INFOSAN):

3-1 Reported outbreaks of foodborne diseases, 1990–2004, United

4-1 U.S. domestic airline passengers, 143