Vaksin Efek

September 6, 1996 / Vol. 45 / No.
RR-12
TM
Recommendations
and
Reports
Update: Vaccine Side Effects, Adverse

Reactions, Contraindications,
and Precautions
Recommendations of the Advisory Committee

on Immunization Practices (ACIP)
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service
Centers for Disease Control
and Prevention (CDC)
Atlanta, Georgia 30333
The MMWR series of publications is published by the Epidemiology Program Office,
Centers for Disease Control and Prevention (CDC), Public Health Service, U.S. Depart-
ment of Health and Human Services, Atlanta, GA 30333.
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sive page numbers].
Centers for Disease Control and Prevention .......................... David Satcher, M.D., Ph.D.
Director
The material in this report was prepared for publication by:

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Director
Epidemiology and Surveillance Division ............................ Stephen C. Hadler, M.D.

Director
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Director
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Vol. 45 / No. RR-12 MMWR i
Contents
Introduction...........................................................................................................1
Hepatitis B Vaccine ...............................................................................................7
Vaccine Side Effects and Adverse Reactions...............................................7
Poliomyelitis Prevention ......................................................................................8
Precautions and Contraindications...............................................................8
Adverse Reactions...........................................................................................9
Measles Prevention ............................................................................................10
Side Effects and Adverse Reactions ...........................................................10
Precautions and Contraindications.............................................................12
Management of Patients with Contraindications
to Measles Vaccine ...................................................................................18
Simultaneous Administration of Vaccines.................................................18
Mumps Prevention .............................................................................................19
Adverse Effects of Vaccine Use ...................................................................19
Contraindications to Vaccine Use ...............................................................20
DTP.......................................................................................................................22
Side Effects and Adverse Reactions Following
DTP Vaccination ........................................................................................22
Precautions and Contraindications.............................................................25
References...........................................................................................................31
ii MMWR September 6, 1996
Advisory Committee on Immunization Practices

June 1995
CHAIRPERSON EXECUTIVE SECRETARY
Jeffrey P. Davis, M.D. Dixie E. Snider, M.D., M.P.H.
Chief Medical Officer Associate Director for Science
Department of Health and Social Centers for Disease Control and
Services Prevention
Madison, WI Atlanta, GA
MEMBERS
Barbara A. DeBuono, M.D., M.P.H. Rudolph E. Jackson, M.D.

New York State Department of Health Morehouse School of Medicine
Albany, NY Atlanta, GA
Kathryn M. Edwards, M.D. Stephen C. Schoenbaum, M.D.
Vanderbilt University Harvard Community Health Plan
Nashville, TN of New England
Providence, RI
Marie R. Griffin, M.D., M.P.H.
Vanderbilt University Fred E. Thompson, Jr., M.D.
Nashville, TN Mississippi State Department of Health
Jackson, MS
Fernando A. Guerra, M.D.
San Antonio Metro Health District Joel I. Ward, M.D.
San Antonio, TX UCLA Center for Vaccine Research
Harbor-UCLA Medical Center
Neal A. Halsey, M.D.
Torrance, CA
Johns Hopkins University
Baltimore, MD
EX OFFICIO MEMBERS
Geoffrey Evans, M.D. John R. La Montagne, Ph.D.

Office of the Assistant Secretary National Institutes of Health
for Health Bethesda, MD
Rockville, MD
Jerry Zelinger, M.D.
M. Carolyn Hardegree, M.D. Health Care Financing Administration
Food and Drug Administration Baltimore, MD
Rockville, MD
Vol. 45 / No. RR-12 MMWR iii
Advisory Committee on Immunization Practices

June 1995 — Continued
LIAISON REPRESENTATIVES
American Academy of Family Canadian National Advisory Committee

Physicians on Immunization
Richard K. Zimmerman, M.D. David W. Scheifele, M.D.
University of Pittsburgh Vaccine Evaluation Center
Pittsburgh, PA Vancouver, British Columbia, Canada
American Academy of Pediatrics Hospital Infections Control
Georges Peter, M.D. Practices Advisory Committee
Rhode Island Hospital David W. Fleming, M.D.
Providence, RI Oregon Health Division
Portland, OR
American Academy of Pediatrics
Caroline B. Hall, M.D. Infectious Diseases Society of
University of Rochester America
Rochester, NY William P. Glezen, M.D.
Baylor College of Medicine
American College of Obstetricians
Houston, TX
and Gynecologists
Stanley A. Gall, M.D. National Vaccine Program
University of Louisville Robert F. Breiman, M.D.
Louisville, KY Centers for Disease Control
and Prevention
American College of Physicians
Atlanta, GA
Pierce Gardner, M.D.
State University of New York Pharmaceutical Research and
at Stonybrook Manufacturers of America (PhRMA)
Stonybrook, NY David J. Williams
Connaught Laboratories, Inc.
American Hospital Association
Swiftwater, PA
William Schaffner, M.D.
Vanderbilt University U.S. Department of Defense
Nashville, TN William M. Butler, M.C. U.S.N.
Office of the Assistant Secretary
American Medical Association
of Defense for Health Affairs
Edward A. Mortimer, Jr., M.D.
Washington, DC
Case Western Reserve University
Cleveland, OH U.S. Department of Veterans Affairs
Kristin L. Nichol, M.D., M.P.H.
Association of Teachers of
Veterans Administration Medical Center
Preventive Medicine
Minneapolis, MN
Richard D. Clover, M.D.
University of Louisville
Louisville, KY
iv MMWR September 6, 1996
The following CDC staff members prepared this report:
Jessica Tuttle, M.D.

Robert T. Chen, M.D., M.A.
Stephen C. Hadler, M.D.
John C. Watson, M.D., M.P.H.
Gina J. Terracciano, D.O., M.P.H.
Epidemiology and Surveillance Division
National Immunization Program
in collaboration with the
Advisory Committee on Immunization Practices (ACIP)

Vol. 45 / No. RR-12 MMWR 1
Update: Vaccine Side Effects, Adverse Reactions,

Contraindications, and Precautions
Recommendations of the Advisory Committee

on Immunization Practices (ACIP)
Summary
This report provides updated information concerning the potential adverse
events associated with vaccination for hepatitis B, poliomyelitis, measles,
mumps, diphtheria, tetanus, and pertussis. This information incorporates find-
ings from a series of recent literature reviews, conducted by an expert com-
mittee at the Institute of Medicine (IOM), of all evidence regarding the possible
adverse consequences of vaccines administered to children. This report con-
tains modifications to the previously published recommendations of the
Advisory Committee on Immunization Practices (ACIP) and is based on an ACIP
review of the IOM findings and new research on vaccine safety. In addition, this
report incorporates information contained in the “Recommendations of the Ad-
visory Committee on Immunization Practices: Use of Vaccines and Immune
Globulins in Persons with Altered Immunocompetence” (MMWR 1993;42[No.
RR-4]) and the “General Recommendations on Immunization: Recommenda-
tions of the Advisory Committee on Immunization Practices (ACIP)” (MMWR
1994;43[No. RR-1]). Major changes to the previous recommendations are
highlighted within the text, and specific information concerning the following
vaccines and the possible adverse events associated with their administra-
tion are included: hepatitis B vaccine and anaphylaxis; measles vaccine and
a) thrombocytopenia and b) possible risk for death resulting from anaphylaxis
or disseminated disease in immunocompromised persons; diphtheria and teta-
nus toxoids and pertussis vaccine (DTP) and chronic encephalopathy; and
tetanus-toxoid–containing vaccines and a) Guillain-Barré syndrome, b) brachial
neuritis, and c) possible risk for death resulting from anaphylaxis. These modifi-
cations will be incorporated into more comprehensive ACIP recommenda-
tions for each vaccine when such statements are revised. Also included in this
report are interim recommendations concerning the use of measles and mumps
vaccines in a) persons who are infected with human immunodeficiency
virus and b) persons who are allergic to eggs; ACIP is still evaluating these
recommendations.
INTRODUCTION
Immunization has enabled the global eradication of smallpox (1 ), the elimination
of poliomyelitis from the Western hemisphere (2 ), and major reductions in the inci-
dence of other vaccine-preventable diseases in the United States (Table 1). However,
although immunization has successfully reduced the incidence of vaccine-preventable
diseases, vaccination can cause both minor and, rarely, serious side effects. Public
2 MMWR September 6, 1996
TABLE 1. The maximum number of cases of specified vaccine-preventable diseases

ever reported for a calendar year compared with the number of cases of disease and
vaccine adverse events reported for 1995 — United States
Maximum
no. reported Year(s) Reported Percentage
cases during maximum no. no. cases change in
Category prevaccine era cases reported during 1995* morbidity
Disease
Congenital rubella syndrome 20,000† 1964–65 7 (–99.96)
Diphtheria 206,939 1921 0 (–99.99)
Invasive Haemophilus
influenzae 20,000† 1984 1,164 (–94.18)
Measles 894,134 1941 309 (–99.97)
Mumps 152,209 1968 840 (–99.45)
Pertussis 265,269 1934 4,315 (–98.37)
Poliomyelitis (wild) 21,269 1952 0 (–99.99)
Rubella 57,686 1969 146 (–99.75)
Tetanus 601 1948 34 (–97.82)
Vaccine adverse events§ 0 10,594
*Provisional totals.
† Estimated because national reporting did not exist in the prevaccine era.
§ Total number reported to the Vaccine Adverse Events Reporting System (VAERS).
awareness of and controversy about vaccine safety has increased, primarily because
increases in vaccine coverage resulted in an increased number of adverse events that
occurred after vaccination. Such adverse events include both true reactions to vaccine
and events coincidental to, but not caused by, vaccination. Despite concerns about
vaccine safety, vaccination is safer than accepting the risks for the diseases these vac-
cines prevent. Unless a disease has been eradicated (e.g., smallpox), failure to
vaccinate increases the risks to both the individual and society.
In response to concerns about vaccine safety, the National Childhood Vaccine
Injury Act of 1986 established a no-fault compensation process for persons possibly
injured by selected vaccines (3 ). The Act also mandated that the Institute of Medicine*
(IOM) review scientific and other evidence regarding the possible adverse conse-
quences of vaccines administered to children.
IOM constituted an expert committee to review all available information on these
vaccine adverse events; such information included epidemiologic studies, case series,
individual case reports, and testimonials. To derive their conclusions, the IOM com-
mittee members created five categories of causality to describe the relationships
between the vaccines and specific adverse events. The first IOM review examined
certain events occurring after administration of pertussis and rubella vaccines
(Table 2) (4 ). The second IOM review examined events occurring after administration
of all other vaccines usually administered during childhood (i.e., diphtheria and teta-
nus toxoids and measles, mumps, hepatitis B, Haemophilus influenzae type b [Hib],
and poliovirus vaccines) (Table 3) (5 ). Two other IOM committees have met since the
findings of the second review were published. These two committees have published
*An independent research organization chartered by the National Academy of Sciences.

TABLE 2. Summarized conclusions of evidence regarding the possible association

between specific adverse effects and receipt of diphtheria and tetanus toxoids and
pertussis vaccine (DTP)* and RA 27/3 measles-mumps-rubella (MMR)† vaccine, by
determination of causality — Institute of Medicine, 1991§
Conclusion, by determination Adverse event reviewed
of casuality DTP vaccine RA 27/3 MMR
1. No evidence was available to Autism None
establish a causal relationship
2. Inadequate evidence to accept Aseptic meningitis Radiculoneuritis and
or reject a causal relationship Chronic neurologic damage¶ other neuropathies
Erythema multiforme or other rash Thrombocytopenic
Guillain-Barré syndrome purpura
Hemolytic anemia
Juvenile diabetes
Learning disabilities and
attention-deficit disorder
Peripheral mononeuropathy
Thrombocytopenia
3. Evidence favored rejection of a Infantile spasms None
causal relationship Hypsarrythmia
Reye syndrome
Sudden infant death syndrome
4. Evidence favored acceptance of Acute encephalopathy** Chronic arthritis
a causal relationship Shock and unusual shock-like state
5. Evidence established a causal Anaphylaxis Acute arthritis
relationship Protracted, inconsolable crying
*The evidence only differentiated between components of DTP in the event of protracted,
inconsolable crying, for which the evidence specifically implicated the pertussis vaccine
component.
† Trivalent MMR vaccine containing the RA 27/3 rubella strain.
§ This table is an adaptation of a table published previously by the Institute of Medicine (IOM)
(4 ), an independent research organization chartered by the National Academy of Sciences.
The National Childhood Vaccine Injury Act of 1986 mandated that IOM review scientific and
other evidence (e.g., epidemiologic studies, case series, individual case reports, and
testimonials) regarding the possible adverse consequences of vaccines administered to
children. IOM constituted an expert committee to review and summarize all available
information; this committee created five categories of causality to describe the relationships
between the vaccines and specific adverse events.
¶ IOM reviewed this adverse event again in 1994 (5 ).
** Defined in the controlled studies that were reviewed as encephalopathy, encephalitis, or
encephalomyelitis.
their findings concerning both the diphtheria and tetanus toxoids and pertussis vac-
cine (DTP) and chronic nervous system dysfunction (Figure 1) (6 ) and research strat-
egies for vaccine-associated adverse events (7 ).
The Advisory Committee on Immunization Practices (ACIP) recently reviewed the
findings of the IOM committees and modified the previously published ACIP recom-
mendations to ensure consistency with IOM conclusions. These recommendations,
which are included in this report, update all previously published ACIP recommen-
dations pertaining to the precautions, contraindications, side effects, and adverse re-
actions* associated with specific vaccines. ACIP accepted the IOM conclusions for
*In this publication, the terms “side effects” and “adverse reactions” are used interchangeably
to denote the undesirable secondary effects resulting from vaccination.
TABLE 3. Summarized conclusions of evidence regarding the possible association between specific adverse effects and
4
receipt of childhood vaccines, by determination of causality — Institute of Medicine, 1994* — Continued
Haemophilus influenzae
DT/Td/Tetanus toxoid† Measles vaccine§ Mumps vaccine§ OPV/IPV¶ Hepatitis B vaccine type b (Hib) vaccine
1. No evidence was available to establish a causal relationship
None None Neuropathy Transverse myelitis None None

Residual seizure (IPV )
disorder Thrombocytopenia
(IPV )
Anaphylaxis (IPV )
2. Inadequate evidence to accept or reject a causal relationship
Residual seizure Encephalopathy Encephalopathy Transverse myelitis Guillain-Barré Guillain-Barré syndrome

disorder other than Subacute sclerosing Aseptic meningitis (OPV ) syndrome Transverse myelitis
infantile spasms panencephalitis Sensorineural Guillain-Barré Demyelinating Thrombocytopenia
Demyelinating Residual seizure deafness (MMR ) syndrome (IPV ) diseases of the
Anaphylaxis
diseases of the disorder Death from SIDS†† central nervous
Insulin-dependent Death from SIDS††
central nervous system
Sensorineural diabetes mellitus
MMWR
system deafness (MMR ) Sterility Arthritis
Mononeuropathy Optic neuritis Death from SIDS††
Thrombocytopenia
Arthritis Transverse myelitis Anaphylaxis**
Erythema multiforme Guillain-Barré
syndrome
Thrombocytopenia
Insulin-dependent
diabetes mellitus
3. Evidence favored rejection of a causal relationship
Encephalopathy§§ None None None None Early onset Hib disease

Infantile spasms (conjugate vaccines)
(DT only)¶¶
Death from SIDS
September 6, 1996
(DT only)¶¶***
4. Evidence favored acceptance of a causal relationship
Guillain-Barré Anaphylaxis** None Guillain-Barré None Early-onset Hib disease

syndrome†††§§§ syndrome (OPV )§§§ in children ages
Brachial neuritis††† ≥18 mos whose first
Hib vaccination was
with unconjugated
PRP vaccine
Vol. 45 / No. RR-12
TABLE 3. Summarized conclusions of evidence regarding the possible association between specific adverse effects and
receipt of childhood vaccines, by determination of causality — Institute of Medicine, 1994* — Continued
Haemophilus influenzae
DT/Td/Tetanus toxoid† Measles vaccine§ Mumps vaccine§ OPV/IPV¶ Hepatitis B vaccine type b (Hib) vaccine
5. Evidence established a causal relationship
Anaphylaxis††† Thrombocytopenia None Poliomyelitis in Anaphylaxis None

(MMR ) recipient or contact
Anaphylaxis (MMR )** (OPV )
Death from measles- Death from polio-
vaccine–strain viral vaccine–strain viral
infection††¶¶¶ infection††¶¶¶
* This table is an adaptation of a table published previously by the Institute of Medicine (IOM) (5 ), an independent research organization chartered by
the National Academy of Sciences. The National Childhood Vaccine Injury Act of 1986 mandated that IOM review scientific and other evidence (e.g.,
epidemiologic studies, case series, individual case reports, and testimonials) regarding the possible adverse consequences of vaccines administered
to children. IOM constituted an expert committee to review and summarize all available information; this committee created five categories of causality
to describe the relationships between the vaccines and specific adverse events.
†
DT=diphtheria and tetanus toxoids for pediatric use; Td=diphtheria and tetanus toxoids for adult use.
MMWR
§
If the data derived from studies of a monovalent preparation, then the causal relationship also extended to multivalent preparations. If the data derived
exclusively from studies of the measles-mumps-rubella (MMR) vaccine, the vaccine is specified parenthetically in italics. In the absence of data concerning
¶
the monovalent preparation, the causal relationship determined for the multivalent preparations did not extend to the monovalent components.
For some adverse events, the IOM committee was charged with assessing the causal relationship between the adverse event and only oral poliovirus
vaccine (OPV) (i.e., for poliomyelitis) or only inactivated poliovirus vaccine (IPV) (i.e., for anaphylaxis and thrombocytopenia). If the conclusions for the
two vaccines differed for the other adverse events, the vaccine to which the adverse event applied is specified parenthetically in italics.
** The evidence used to establish a causal relationship for anaphylaxis applies to MMR vaccine. The evidence regarding monovalent measles vaccine
favored acceptance of a causal relationship, but this evidence was less convincing than that for MMR vaccine because of either incomplete documentation
of symptoms or the possible attenuation of symptoms by medical intervention.
††
This table lists weight-of-evidence determinations only for deaths that were classified as sudden infant death syndrome (SIDS) and deaths that were
a consequence of vaccine-strain viral infection. However, if the evidence favored the acceptance of (or established) a causal relationship between a
vaccine and a possibly fatal adverse event, then the evidence also favored the acceptance of (or established) a causal relationship between the vaccine
and death from the adverse event. Direct evidence regarding death in association with a vaccine-associated adverse event was limited to a) Td and
Guillain-Barré syndrome, b) tetanus toxoid and anaphylaxis, and c) OPV and poliomyelitis.
§§ The evidence derived from studies of DT. If the evidence favored rejection of a causal relationship between DT and encephalopathy, then the evidence
also favored rejection of a causal relationship between Td and tetanus toxoid and encephalopathy.
¶¶
Infantile spasms and SIDS occur only in an age group that is administered DT but not Td or tetanus toxoid.
*** The evidence derived primarily from studies of DTP, although the evidence also favored rejection of a causal relationship between DT and SIDS.
†††
The evidence derived from studies of tetanus toxoid. If the evidence favored acceptance of (or established) a causal relationship between tetanus toxoid
and an adverse event, then the evidence also favored acceptance of (or established) a causal relationship between DT and Td and the adverse event.
§§§
This conclusion differs from the information contained in the ACIP recommendations because of new information that became available after IOM
published this table.
¶¶¶
Deaths occurred primarily among persons known to be immunocompromised.
5
FIGURE 1. Scenarios in which acute neurologic illnesses that occur after vaccination
with diphtheria and tetanus toxoids and pertussis vaccine (DTP) might be associated
with subsequent chronic nervous system dysfunction — Institute of Medicine,* 1994
Scenario I: Scenario II: Scenario III:
DTP is administered to DTP is administered to a DTP is administered to a

a child who has no known child who has an underlying child who has an underlying
abnormality. metabolic or brain disorder. metabolic or brain disorder.
Vaccination might cause Vaccination triggers an Vaccination might cause

a serious acute neurologic already possible serious a serious acute neurologic
illness in the child. acute neurologic illness in illness in the child.
the child.
This acute illness might This acute illness might cause This acute illness is not
cause chronic dysfunction chronic dysfunction. This associated with a
consistent with a causal child might have the same subsequent chronic
relationship. acute neurologic illness and dysfunction in a child
subsequent chronic whose underlying
dysfunction in association abnormalities would have
with some trigger other than led eventually to chronic
DTP (e.g., fever or infection). dysfunction even in the
DTP does not increase the absence of an acute
overall lifetime risk for chronic neurologic illness. DTP
dysfunction in children. vaccination unmasks the
underlying disorder.
*This information is an adaptation of information published previously by the Institute of Med-

icine (IOM) (6 ), an independent research organization chartered by the National Academy of
Sciences. The National Childhood Vaccine Injury Act of 1986 mandated that IOM review
scientific and other evidence (e.g., epidemiologic studies, case series, individual case reports,
and testimonials) regarding the possible adverse consequences of vaccines administered to
children.
almost all vaccine adverse events; the few exceptions generally occurred because
new information that was available to ACIP had not been available when the IOM
committees published their recommendations. These exceptions included a) oral
poliovirus vaccine (OPV) and Guillain-Barré syndrome (GBS), b) tetanus-toxoid–
containing vaccines and GBS, and c) DTP and chronic nervous system dysfunction.
In addition, this report incorporates information contained in the “Recommenda-
tions of the Advisory Committee on Immunization Practices: Use of Vaccines and
Immune Globulins in Persons with Altered Immunocompetence” (MMWR 1993;
42[No. RR-4]) and the “General Recommendations on Immunization: Recommenda-
tions of the Advisory Committee on Immunization Practices (ACIP)” (MMWR
1994;43[No. RR-1]). To facilitate recognition of the new recommendations in this re-
port, all major changes that are being made to the previously published ACIP
statements are highlighted within the text. These changes include information on the
following vaccines and the possible adverse events associated with their administration:
• Hepatitis B vaccine and anaphylaxis;
• Measles vaccine and a) thrombocytopenia and b) possible risk for death result-
ing from anaphylaxis or disseminated disease in immunocompromised persons;
• DTP and chronic encephalopathy; and
• Tetanus-toxoid–containing vaccines and a) GBS, b) brachial neuritis, and c) pos-
sible risk for death resulting from anaphylaxis.
The modifications contained in this report, and possibly other changes as new infor-
mation becomes available, will be incorporated into more comprehensive ACIP
recommendations for each vaccine when such statements are revised.
HEPATITIS B VACCINE
The following recommendations concerning adverse events associated with hepa-
titis B vaccination update those applicable sections in “Hepatitis B Virus: A Com-
prehensive Strategy for Eliminating Transmission in the United States Through Uni-
versal Childhood Vaccination—Recommendations of the Immunization Practices
Advisory Committee (ACIP)” (MMWR 1991;40[No. RR-13]).
Vaccine Side Effects and Adverse Reactions

Hepatitis B vaccines are safe to administer to adults and children. More than an
estimated 10 million adults and 2 million infants and children have been vaccinated in
the United States, and at least 12 million children have been vaccinated worldwide.
Vaccine-Associated Side Effects

Pain at the injection site (3%–29%) and a temperature greater than 37.7 C (1%–6%)
have been among the most frequently reported side effects among adults and chil-
dren receiving vaccine (8–12 ). In placebo-controlled studies, these side effects were
reported no more frequently among vaccinees than among persons receiving a pla-
cebo (11,12 ). Among children receiving both hepatitis B vaccine and DTP, these mild
side effects have been observed no more frequently than among children receiving
only DTP.
The recommendation to begin hepatitis B vaccination soon after birth has raised
the concern that a substantial number of infants will require an extensive medical
evaluation for elevated temperatures secondary to hepatitis B vaccination. Several
population-based studies to evaluate this possibility are in progress.
Adverse Events
In the United States, surveillance of adverse reactions indicated a possible associa-
tion between GBS and receipt of the first dose of plasma-derived hepatitis B vaccine
(CDC, unpublished data; 13 ). However, an estimated 2.5 million adults received one or
more doses of recombinant hepatitis B vaccine during 1986–1990, and available data
concerning these vaccinees do not indicate an association between receipt of recom-

binant vaccine and GBS (CDC, unpublished data).
Based on reports to the Vaccine Adverse Events Reporting System (VAERS), the
estimated incidence rate of anaphylaxis among vaccine recipients is low (i.e., approxi-
mately one event per 600,000 vaccine doses distributed). Two of these adverse events
occurred in children (CDC, unpublished data). In addition, only one case of anaphy-
laxis occurred among 100,763 children ages 10–11 years who had been vaccinated
with recombinant vaccine in British Columbia (D. Scheifele, unpublished data), and no
adverse events were reported among 166,757 children who had been vaccinated with
plasma-derived vaccine in New Zealand (5 ). Although none of the persons who devel-
oped anaphylaxis died, this adverse event can be fatal; in addition, hepatitis B vaccine
can—in rare instances—cause a life-threatening hypersensitivity reaction in some
persons (5 ). Therefore, subsequent vaccination with hepatitis B vaccine is contraindi-
cated for persons who have previously had an anaphylactic response to a dose of this
vaccine.
Large-scale hepatitis B immunization programs for infants in Alaska, New Zealand,
and Taiwan have not established an association between vaccination and the occur-
rence of other severe adverse events, including seizures and GBS (B. McMahon and
A. Milne, unpublished data; 14 ). However, systematic surveillance for adverse reac-
tions in these populations has been limited, and only a minimal number of children
have received recombinant vaccine. Any presumed risk for adverse events that might
be causally associated with hepatitis B vaccination must be balanced with the ex-
pected risk for hepatitis B virus (HBV)-related liver disease. Currently, an estimated
2,000–5,000 persons in each U.S. birth cohort will die as a result of HBV-related liver
disease because of the 5% lifetime risk for HBV infection.
As hepatitis B vaccine is introduced for routine vaccination of infants, surveillance
for vaccine-associated adverse events will continue to be an important part of the
program despite the current record of safety. Any adverse event suspected to be asso-
ciated with hepatitis B vaccination should be reported to VAERS. VAERS forms can be
obtained by calling (800) 822-7967.
POLIOMYELITIS PREVENTION
The following recommendations concerning adverse events associated with polio-
myelitis vaccination update those applicable sections in “Poliomyelitis Prevention:
Recommendation of the Immunization Practices Advisory Committee (ACIP)” (MMWR
1982;31:22–6,31–4) and “Poliomyelitis Prevention: Enhanced-Potency Inactivated
Poliomyelitis Vaccine—Supplementary Statement” (MMWR 1987;36:795–8).
Precautions and Contraindications

Pregnancy
Although no conclusive evidence documents the adverse effects of OPV or inacti-
vated poliovirus vaccine (IPV) in pregnant women and their developing fetuses,
vaccination of pregnant women should be avoided. However, if immediate protection
against poliomyelitis is necessary, OPV or IPV can be given.
Immunodeficiency
Persons who have congenitally acquired immune-deficiency diseases (e.g., com-
bined immunodeficiency, hypogammaglobulinemia, and agammaglobulinemia)
should not be given OPV because of their substantially increased risk for vaccine-
associated disease. Furthermore, persons who have altered immune status result-
ing from acquired conditions (e.g., human immunodeficiency virus [HIV] infection,
leukemia, lymphoma, or generalized malignancy) or who have immune systems
compromised by therapy (e.g., treatment with corticosteroids, alkylating drugs,
antimetabolites, or radiation) should not receive OPV because of the theoretical risk
for paralytic disease.
IPV—and not OPV—should be used to vaccinate immunodeficient persons and
their household contacts. Many immunosuppressed persons are already immune to
polioviruses because of previous vaccination or exposure to wild-type virus when
they were immunocompetent. Although such persons should not receive OPV, their
risk for paralytic disease may be less than that of persons who have congenitally
acquired immunodeficiency. Although a protective immune response to IPV in the im-
munodeficient patient cannot be ensured, the vaccine is safe and some protection
may result from its administration. If a household contact of an immunodeficient
person is vaccinated inadvertently with OPV, the OPV recipient should avoid close
physical contact with the immunodeficient person for approximately 4–6 weeks after
vaccination (i.e., during the period of maximum excretion of vaccine virus). If such
contact cannot be avoided, rigorous hygiene and hand washing after contact with
feces (e.g., after diaper changing) and avoidance of contact with saliva (e.g., by not
sharing eating utensils or food) should be practiced. These practices are an accept-
able, but probably less effective, alternative than refraining from contact. Because
immunodeficiency is possible in other children born to a family in which one child
is immunodeficient, OPV should not be administered to a member of such a house-
hold until the immune status of the recipient and other children in the family is
documented.
Adverse Reactions
OPV
In rare instances, administration of OPV has been associated with paralytic polio-
myelitis in healthy recipients and their contacts. Very rarely, OPV has caused fatal
paralytic poliomyelitis in immunocompromised persons (5 ). Other than efforts for
identifying persons with immune-deficiency conditions, no procedures are currently
available to identify persons likely to experience such adverse reactions. Although the
risk of vaccine-associated paralysis is extremely small for vaccinees and their suscep-
tible, close, personal contacts, they should be informed of this risk.
Available data do not indicate a measurable increased risk for GBS after receipt of
OPV. Initial reports (at the time of IOM review) of two studies conducted in Finland
suggested that OPV might cause GBS. These studies identified an apparent increased
incidence of GBS that was temporally associated with mass OPV vaccination of chil-
dren and adults who had previously received IPV (15,16 ). Since the IOM review, a
reanalysis of the data derived from the studies conducted in Finland and an analysis
of an observational study conducted in the United States have not demonstrated a

causal relationship between OPV and GBS in infants (17 ).
Because OPV contains trace amounts of streptomycin, bacitracin, and neomycin,
its use is contraindicated in persons who have previously had an anaphylactic reaction
to OPV or to these antibiotics.
IPV
No serious side effects of currently available IPV have been documented. Since
IPV contains trace amounts of streptomycin and neomycin, there is a possibility of
hypersensitivity reactions in individuals sensitive to these antibiotics.
MEASLES PREVENTION
The following recommendations concerning adverse events associated with
measles vaccination update those applicable sections in “Measles Prevention: Rec-
ommendations of the Immunization Practices Advisory Committee” (MMWR 1989;
38[No. S-9]), and they apply regardless of whether the vaccine is administered as a
single antigen or as a component of measles-rubella (MR) or measles-mumps-rubella
(MMR) vaccine. Information concerning adverse events associated with the mumps
component of MMR vaccine is reviewed later in this document (see Mumps Preven-
tion), and information concerning the rubella component is located in the previously
published ACIP statement for rubella (18 ).
Side Effects and Adverse Reactions

More than 240 million doses of measles vaccine were distributed in the United
States from 1963 through 1993. The vaccine has an excellent record of safety. From
5% to 15% of vaccinees may develop a temperature of ≥103 F (≥39.4 C) beginning
5–12 days after vaccination and usually lasting several days (19 ). Most persons with
fever are otherwise asymptomatic. Transient rashes have been reported for approxi-
mately 5% of vaccinees. Central nervous system (CNS) conditions, including en-
cephalitis and encephalopathy, have been reported with a frequency of less than one
per million doses administered. The incidence of encephalitis or encephalopathy after
measles vaccination of healthy children is lower than the observed incidence of en-
cephalitis of unknown etiology. This finding suggests that the reported severe
neurologic disorders temporally associated with measles vaccination were not caused
by the vaccine. These adverse events should be anticipated only in susceptible vac-
cinees and do not appear to be age-related. After revaccination, most reactions should
be expected to occur only among the small proportion of persons who failed to re-
spond to the first dose.
Personal and Family History of Convulsions

As with the administration of any agent that can produce fever, some children may
have a febrile seizure. Although children with a personal or family history of seizures
are at increased risk for developing idiopathic epilepsy, febrile seizures following vac-
cinations do not in themselves increase the probability of subsequent epilepsy or
other neurologic disorders. Most convulsions following measles vaccination are sim-
ple febrile seizures, and they affect children without known risk factors.
An increased risk of these convulsions may occur among children with a prior his-
tory of convulsions or those with a history of convulsions in first-degree family
members (i.e., siblings or parents) (20 ). Although the precise risk cannot be deter-
mined, it appears to be low.
In developing vaccination recommendations for these children, ACIP considered a
number of factors, including risks from measles disease, the large proportion (5%–7%)
of children with a personal or family history of convulsions, and the fact that convul-
sions following measles vaccine are uncommon. Studies conducted to date have not
established an association between MMR vaccination and the development of a resid-
ual seizure disorder (5 ). ACIP concluded that the benefits of vaccinating these children
greatly outweigh the risks. They should be vaccinated just as children without such
histories.
Because the period for developing vaccine-induced fever occurs approximately
5–12 days after vaccination, prevention of febrile seizures is difficult. Prophylaxis with
antipyretics has been suggested as one alternative, but these agents may not be effec-
tive if given after the onset of fever. To be effective, such agents would have to be
initiated before the expected onset of fever and continued for 5–7 days. However, par-
ents should be alert to the occurrence of fever after vaccination and should treat their
children appropriately.
Children who are being treated with anticonvulsants should continue to take them
after measles vaccination. Because protective levels of most currently available anti-
convulsant drugs (e.g., phenobarbital) are not achieved for some time after therapy is
initiated, prophylactic use of these drugs does not seem feasible.
The parents of children who have either a personal or family history of seizures
should be advised of the small increased risk of seizures following measles vaccina-
tion. In particular, they should be told in advance what to do in the unlikely event that
a seizure occurs. The permanent medical record should document that the small risk
of postimmunization seizures and the benefits of vaccination have been discussed.
Subacute Sclerosing Panencephalitis (SSPE)

Measles vaccine significantly reduces the likelihood of developing SSPE, as evi-
denced by the near elimination of SSPE cases after widespread measles vaccination
began. SSPE has been reported rarely in children who do not have a history of natural
measles infection but who have received measles vaccine. The available evidence
suggests that at least some of these children may have had an unidentified measles
infection before vaccination and that the SSPE probably resulted from the natural
measles infection. The administration of live measles vaccine does not increase the
risk for SSPE, regardless of whether the vaccinee has had measles infection or has
previously received live measles vaccine (5,21 ).
Thrombocytopenia
Surveillance of adverse reactions in the United States and other countries indicates
that MMR vaccine can, in rare circumstances, cause clinically apparent thrombocy-
topenia within the 2 months after vaccination. In prospective studies, the reported
incidence of clinically apparent thrombocytopenia after MMR vaccination ranged from
one case per 30,000 vaccinated children in Finland (22 ) and Great Britain (23 ) to one
case per 40,000 in Sweden, with a temporal clustering of cases occurring 2–3 weeks
after vaccination (24 ). With passive surveillance, the reported incidence was approxi-
mately one case per 100,000 vaccine doses distributed in Canada and France (25 ), and
approximately one case per 1 million doses distributed in the United States (26 ). The
clinical course of these cases was usually transient and benign, although hemorrhage
occurred rarely (26 ). Furthermore, the risk for thrombocytopenia during rubella or
measles infection is much greater than the risk after vaccination. Of 30,000 school-
children in one Pennsylvania county who had been infected with rubella during
the 1963–64 measles epidemic, 10 children developed thrombocytopenic purpura
(incidence: one case per 3,000 children) (27 ). Based on case reports, the risk for
thrombocytopenia may be higher for persons who previously have had idiopathic
thrombocytopenic purpura, particularly for those who had thrombocytopenic purpura
after an earlier dose of MMR vaccine (5,28,29 ).
Revaccination Risks
There is no evidence of an increased risk for adverse reactions after administration
of live measles vaccine to persons who are already immune to measles as a result of
either previous vaccination or natural disease.

Pregnancy
Live measles vaccine, when given as a component of MR or MMR, should not be
given to women known to be pregnant or who are considering becoming pregnant
within the next 3 months. Women who are given monovalent measles vaccine should
not become pregnant for at least 30 days after vaccination. This precaution is based
on the theoretical risk of fetal infection, although no evidence substantiates this theo-
retical risk. Considering the importance of protecting adolescents and young adults
against measles, asking women if they are pregnant, excluding those who are, and
explaining the theoretical risks to the others before vaccination are sufficient pre-
cautions.
Febrile Illness
The decision to administer or delay vaccination because of a current or recent feb-
rile illness depends largely on the cause of the illness and the severity of symptoms.
Minor illnesses, such as a mild upper-respiratory infection with or without low-grade
fever, are not contraindications for vaccination. For persons whose compliance with
medical care cannot be assured, every opportunity should be taken to provide appro-
priate vaccinations.
Children with moderate or severe febrile illnesses can be vaccinated as soon as
they have recovered from the acute phase of the illness. This wait avoids superimpos-
ing adverse effects of vaccination on the underlying illness or mistakenly attributing a
manifestation of the underlying illness to the vaccine. Performing routine physical ex-
aminations or measuring temperatures are not prerequisites for vaccinating infants
and children who appear to be in good health. Asking the parent or guardian if the
child is ill, postponing vaccination for children with moderate or severe febrile ill-
nesses, and vaccinating those without contraindications are appropriate procedures
in childhood immunization programs.
Allergic Reactions
Hypersensitivity reactions rarely occur after the administration of MMR or any of its
component vaccines. Most of these reactions are minor and consist of a wheal and
flare or urticaria at the injection site. Immediate, anaphylactic reactions to MMR or its
component vaccines are extremely rare. Although >70 million doses of MMR vaccine
have been distributed in the United States since VAERS was implemented in 1990,
only 33 cases of anaphylactic reactions that occurred after MMR vaccination have
been reported. Furthermore, only 11 of these cases a) occurred immediately after vac-
cination and b) occurred in persons who had symptoms consistent with anaphylaxis
(CDC, unpublished data).
In the past, persons who had a history of anaphylactic reactions (i.e., hives, swel-
ling of the mouth or throat, difficulty breathing, hypotension, and shock) following
egg ingestion were considered to be at increased risk for serious reactions after re-
ceipt of measles-containing vaccines, which are produced in chick embryo fibroblasts.
Protocols requiring caution were developed for skin testing and vaccinating persons
who had had anaphylactic reactions after egg ingestion (30–34 ). However, the predic-
tive value of such skin testing and the need for special protocols when vaccinating
egg-allergic persons with measles-containing vaccines is uncertain. The results of re-
cent studies suggest that anaphylactic reactions to measles-containing vaccines are
not associated with hypersensitivity to egg antigens but with some other component
of the vaccines. The risk for serious allergic reaction to these vaccines in egg-allergic
patients is extremely low, and skin testing is not necessarily predictive of vaccine hy-
persensitivity (35–37 ). Therefore, ACIP is re-evaluating whether skin testing and the
use of special protocols are routinely necessary when administering MMR or other
measles-containing vaccines to persons who have a history of anaphylactic-like reac-
tions after egg ingestion.
MMR and its component vaccines contain hydrolyzed gelatin as a stabilizer. The
literature contains a single case report of a person with an anaphylactic sensitivity to
gelatin who had an anaphylactic reaction after receipt of the MMR vaccine licensed in
the United States (38 ). Similar cases have occurred in Japan (39 ). Therefore, ACIP is
currently considering recommendations for vaccination of persons who have had an
anaphylactic reaction to gelatin or gelatin-containing products. In the meantime, such
persons should be vaccinated with MMR and its component vaccines with extreme
caution.
MMR vaccine and its component vaccines contain trace amounts of neomycin. Al-
though the amount present is less than that usually used for a skin test to determine
hypersensitivity, persons who have experienced anaphylactic reactions to neomycin
should not be given these vaccines. Most often, neomycin allergy is manifested by
contact dermatitis rather than anaphylaxis. A history of contact dermatitis to neomy-
cin is not a contraindication to receiving measles vaccine. Live measles virus vaccine
does not contain penicillin.
Thrombocytopenia
Children who have a history of thrombocytopenic purpura or thrombocytopenia
may be at increased risk for developing clinically significant thrombocytopenia after
MMR vaccination. The decision to vaccinate should depend on the benefits of immu-
nity to measles, mumps, and rubella and the risks for recurrence or exacerbation of
thrombocytopenia after vaccination or during natural infections with measles or ru-
bella. The benefits of immunization are usually greater than the potential risks, and
administration of MMR vaccine is justified—particularly with regard to the even
greater risk for thrombocytopenia after measles or rubella disease. However, avoiding
a subsequent dose might be prudent if the previous episode of thrombocytopenia
occurred in close temporal proximity to (i.e., within 6 weeks after) the previous vacci-
nation. Serologic evidence of measles immunity in such persons may be sought in
lieu of MMR vaccination.
Recent Administration of Immune Globulins

Previous recommendations, based on data from persons who received low doses
of immune globulin preparations, stated that MMR and its individual component vac-
cines could be administered as early as 6 weeks to 3 months after administration of
immune globulins (40,41 ). However, recent evidence suggests that high doses of im-
mune globulins can inhibit the immune response to measles vaccine for more than
3 months (42,43 ). Administration of immune globulins also can inhibit the response
to rubella vaccine (42 ). The effect of immune globulin preparations on the response
to mumps vaccine is unknown, but commercial immune globulin preparations contain
antibodies to these viruses.
Blood (e.g., whole blood, packed red blood cells, and plasma) and other antibody-
containing blood products (e.g., immune globulin; specific immune globulins; and
immune globulin, intravenous [IGIV]) can diminish the immune response to MMR or
its individual component vaccines. Therefore, after an immune globulin preparation is
received, these vaccines should not be administered before the recommended
interval (Tables 4 and 5). However, the postpartum vaccination of rubella-susceptible
women with the rubella or MMR vaccine should not be delayed because anti-Rho(D)
IG (human) or any other blood product was received during the last trimester of preg-
nancy or at delivery. These women should be vaccinated immediately after delivery
and, if possible, tested at least 3 months later to ensure immunity to rubella and, if
necessary, to measles.
If administration of an immune globulin preparation becomes necessary because
of imminent exposure to disease, MMR or its component vaccines can be admin-
istered simultaneously with the immune globulin preparation, although vaccine-
induced immunity might be compromised. The vaccine should be administered at a
site remote from that chosen for the immune globulin inoculation. Unless serologic
testing indicates that specific antibodies have been produced, vaccination should be
repeated after the recommended interval (Tables 4 and 5).
If administration of an immune globulin preparation becomes necessary after
MMR or its individual component vaccines have been administered, interference can
occur. Usually, vaccine virus replication and stimulation of immunity will occur
1–2 weeks after vaccination. Thus, if the interval between administration of any of
these vaccines and subsequent administration of an immune globulin preparation is
Vol. 45 / No. RR-12
TABLE 4. Guidelines for spacing the administration of immune globulin preparations* and vaccines containing live measles,
mumps, or rubella virus
Simultaneous administration Nonsimultaneous administration
Immunobiologic administered Recommended
Immunobiologic Recommended minimum interval minimum interval
combination between doses First Second between doses
Immune globulin Should generally not be administered Immune globulin Vaccine Dose related†
and vaccine simultaneously.† If simultaneous administration
of measles-mumps-rubella [MMR], Vaccine Immune globulin 2 weeks
MMWR
measles-rubella, and monovalent measles
vaccine is unavoidable, administer at different
sites and revaccinate or test for seroconversion
after the recommended interval (Table 5).
*Blood products containing large amounts of immune globulin (such as serum immune globulin, specific immune globulins [e.g., TIG
and HBIG], intravenous immune globulin [IGIV], whole blood, packed red cells, plasma, and platelet products).
† The duration of interference of immune globulin preparations with the immune response to the measles component of the MMR,
measles-rubella, and monovalent measles vaccine is dose-related (Table 5).
15
TABLE 5. Suggested intervals between administration of immune globulin prep-

arations for various indications and vaccines containing live measles virus*
Time interval
(mos) before
measles
Indication Dose (including mg IgG/kg) vaccination
Tetanus (TIG) prophylaxis 250 units (10 mg IgG/kg) IM 3
Hepatitis A (IG) prophylaxis
Contact prophylaxis 0.02 mL/kg (3.3 mg IgG/kg) IM 3
International travel 0.06 mL/kg (10 mg IgG/kg) IM 3
Hepatitis B prophylaxis (HBIG) 0.06 mL/kg (10 mg IgG/kg) IM 3
Rabies immune globulin (HRIG) 20 IU/kg (22 mg IgG/kg) IM 4
Varicella prophylaxis (VZIG) 125 units/10 kg 5
(20–40 mg IgG/kg) IM
(maximum 625 units)
Measles prophylaxis (IG)
Standard (i.e.,
nonimmunocompromised contact) 0.25 mL/kg (40 mg IgG/kg) IM 5
Immunocompromised contact 0.50 mL/kg (80 mg IgG/kg) IM 6
Blood transfusion:
Red blood cells (RBCs), washed 10 mL/kg (negligible IgG/kg) IV 0
RBCs, adenine-saline added 10 mL/kg (10 mg IgG/kg) IV 3
Packed RBCs (Hct 65%)† 10 mL/kg (60 mg IgG/kg) IV 6
Whole blood cells (Hct 35%–50%)† 10 mL/kg (80–100 mg IgG/kg) IV 6
Plasma/platelet products 10 mL/kg (160 mg IgG/kg) IV 7
Replacement therapy for immune
deficiencies 300–400 mg/kg IV§ (as IGIV) 8
Treatment of:
Immune thrombocytopenic purpura¶ 400 mg/kg IV (as IGIV) 8
Immune thrombocytopenic purpura¶ 1,000 mg/kg IV (as IGIV) 10
Kawasaki disease 2 g/kg IV (as IGIV) 11
*This table is not intended for determining the correct indications and dosage for the use of
immune globulin preparations. Unvaccinated persons may not be fully protected against
measles during the entire suggested time interval, and additional doses of immune globulin
and/or measles vaccine may be indicated after measles exposure. The concentration of measles
antibody in a particular immune globulin preparation can vary by lot. The rate of antibody
clearance after receipt of an immune globulin preparation also can vary. The recommended
time intervals are extrapolated from an estimated half-life of 30 days for passively acquired
antibody and an observed interference with the immune response to measles vaccine for
5 months after a dose of 80 mg IgG/kg (42 ).
† Assumes a serum IgG concentration of 16 mg/mL.
§ Measles vaccination is recommended for most HIV-infected children who do not have evidence
of severe immunosuppression, but it is contraindicated for patients who have congenital dis-
orders of the immune system.
¶ Formerly referred to as idiopathic thrombocytopenic purpura.
<14 days, vaccination should be repeated after the recommended interval (Tables 4
and 5), unless serologic testing indicates that antibodies were produced.
Altered Immunocompetence
Non-HIV–Infected Persons. Replication of vaccine viruses can be enhanced in per-
sons with immune-deficiency diseases and in persons with immunosuppression, as
occurs with leukemia, lymphoma, generalized malignancy, or therapy with alkylating
agents, antimetabolites, radiation, or large doses of corticosteroids. Evidence based
on case reports has linked measles vaccine and measles infection to subsequent
death in some severely immunocompromised children. Of the >200 million doses of
measles vaccine administered in the United States, fewer than five such deaths have
been reported (5 ). Patients who have such conditions or are undergoing such thera-
pies (excluding most HIV-infected patients) should not be given live measles virus
vaccine.
Patients with leukemia in remission who have not received chemotherapy for at
least 3 months may receive live-virus vaccines. The exact amount of systemically ab-
sorbed corticosteroids and the duration of administration needed to suppress the
immune system of an otherwise healthy child are not well defined. Most experts agree
that steroid therapy usually does not contraindicate administration of live virus
vaccine when it is short term (i.e., <2 weeks); low to moderate dose; long-term, alter-
nate-day treatment with short-acting preparations; maintenance physiologic doses
(replacement therapy); or administered topically (skin or eyes), by aerosol, or by intra-
articular, bursal, or tendon injection (44 ). Although of recent theoretical concern, no
evidence of increased severe reactions to live vaccines has been reported among per-
sons receiving steroid therapy by aerosol, and such therapy is not in itself a reason to
delay vaccination. The immunosuppressive effects of steroid treatment vary, but
many clinicians consider a dose equivalent to either 2 mg/kg of body weight or a total
of 20 mg per day of prednisone as sufficiently immunosuppressive to raise concern
about the safety of vaccination with live virus vaccines (44 ). Corticosteroids used in
greater than physiologic doses also can reduce the immune response to vaccines.
Physicians should wait at least 3 months after discontinuation of therapy before ad-
ministering a live-virus vaccine to patients who have received high systemically
absorbed doses of corticosteroids for ≥2 weeks.
HIV-Infected Persons. Because of the increased risk for severe complications asso-
ciated with measles infection and the absence of serious adverse events after measles
vaccination among HIV-infected persons (41,45 ), ACIP has recommended that MMR
vaccine be administered to all asymptomatic HIV-infected persons and that MMR vac-
cine be considered for administration to all symptomatic HIV-infected persons who
would otherwise be eligible for measles vaccine—even though the immune response
may be attenuated in such persons (41,44,45 ). There is a theoretical risk for an in-
crease (probably transient) in HIV viral load following MMR vaccination because such
effects have been observed with other vaccines (46,47 ).
Because of the recently reported case of pneumonitis in a measles vaccinee
who had an advanced case of acquired immunodeficiency syndrome (AIDS) (48 ) and
because of other evidence indicating a diminished antibody response to measles vac-
cination among severely immunocompromised persons (49 ), ACIP is re-evaluating
the recommendations for vaccination of severely immunocompromised HIV-infected

persons. In the interim, it may be prudent to withhold MMR or other measles-
containing vaccines from HIV-infected persons with evidence of severe immunosup-
pression, defined as either a) CD4+ T-lymphocyte counts <750 for children ages
<12 months, <500 for children ages 1–5 years, or <200 for persons ages ≥6 years; or
b) CD4+ T-lymphocytes constituting <15% of total lymphocytes for children ages
<13 years or <14% for persons ages ≥13 years (50,51 ).
ACIP continues to recommend MMR for HIV-infected persons without evidence of
measles immunity (47 ) who are not severely immunocompromised (50,51 ). Severely
immunocompromised and other symptomatic HIV-infected patients who are exposed
to measles should receive immune globulin (IG), regardless of prior vaccination status
(44 ). In addition, health-care providers should weigh the risks and benefits of measles
vaccination or IG prophylaxis for severely immunocompromised HIV-infected patients
who are at risk for measles exposure because of outbreaks or international travel.
Because the immunologic response to both live and killed antigen vaccines may
decrease as HIV disease progresses (44,52 ), vaccination early in the course of HIV
infection may be more likely to induce an immune response. Therefore, HIV-infected
infants without severe immunosuppression should routinely receive MMR as soon as
possible upon reaching their first birthday. Evaluation and testing of asymptomatic
persons to identify HIV infection are not necessary before deciding to administer MMR
or other measles-containing vaccine (44 ).
Management of Patients with Contraindications

to Measles Vaccine
If immediate protection against measles is required for persons with contraindica-
tions to measles vaccination, passive immunization with IG, 0.25 mL/kg (0.11 mL/lb) of
body weight (maximum dose=15 mL), should be given as soon as possible after
known exposure. Exposed symptomatic HIV-infected and other immunocompromised
persons should receive IG regardless of their previous vaccination status; however, IG
in usual doses may not be effective in such patients. For immunocompromised per-
sons, the recommended dose is 0.5 mL/kg of body weight if IG is administered
intramuscularly (maximum dose=15 mL). This corresponds to a dose of protein of ap-
proximately 82.5 mg/kg (maximum dose=2,475 mg). Intramuscular IG may not be
needed if a patient with HIV infection is receiving 100–400 mg/kg IGIV at regular inter-
vals and the last dose was given within 3 weeks of exposure to measles. Because the
amounts of protein administered are similar, high-dose IGIV may be as effective as IG
given intramuscularly. However, no data are available concerning the effectiveness of
IGIV in preventing measles.
Simultaneous Administration of Vaccines

In general, simultaneous administration of the most widely used live and inacti-
vated vaccines does not impair antibody responses or increase rates of adverse
reactions (53 ). The administration of MMR vaccine yields results similar to the ad-
ministration of individual measles, mumps, and rubella vaccines at different sites or at
different times.
Vaccines recommended for administration at 12–15 months of age can be adminis-

tered at either one or two visits. There are equivalent antibody responses and no
clinically significant increases in the frequency of adverse events when DTP, MMR,
and OPV (or IPV) vaccines and H. influenzae type b conjugate vaccine (HbCV) are ad-
ministered either simultaneously at different sites or at separate times. If a child might
not be brought back for future vaccinations, all vaccines (including DTP [or DTaP], OPV
[or IPV], MMR, varicella, HbCV, and hepatitis B vaccines) may be administered simul-
taneously, as appropriate to the child’s age and previous vaccination status.
MUMPS PREVENTION
mumps vaccination update those applicable sections in “Mumps Prevention”
(MMWR 1989;38:388–92,397–400), and they apply regardless of whether the vaccine is
administered as a single antigen or as a component of MR or MMR vaccine. Informa-
tion concerning adverse events associated with the measles component of MMR
vaccine is reviewed earlier in this document (see Measles Prevention), and informa-
tion concerning the rubella component is located in the previously published ACIP
statement for rubella (18 ).
Adverse Effects of Vaccine Use

In field trials before licensure, illnesses did not occur more often in vaccinees than
in unvaccinated controls (54 ). Reports of illnesses following mumps vaccination have
mainly been episodes of parotitis and low-grade fever. Allergic reactions including
rash, pruritus, and purpura have been temporally associated with mumps vaccination
but are uncommon and usually mild and of brief duration. The reported occurrence of
encephalitis within 30 days of receipt of a mumps-containing vaccine (0.4 per million
doses) is not greater than the observed background incidence rate of CNS dysfunction
in the normal population. Aseptic meningitis has been epidemiologically associated
with receipt of the vaccine containing the Urabe strain of mumps virus, but not with
the vaccine containing the Jeryl Lynn strain, the latter of which is used in vaccine
distributed in the United States (5 ). During 1988–1992, 15 sentinel surveillance labora-
tories in the United Kingdom identified 13 aseptic meningitis cases that had occurred
within 15–35 days after vaccination with the Urabe strain (i.e., 91 cases per 1 million
doses distributed) (55 ). No vaccine-associated aseptic meningitis cases have been re-
ported since 1992, when only the Jeryl Lynn strain has been used (23 ). Febrile
seizures also have been infrequently reported. However, no evidence suggests that
mumps vaccine causes residual seizure disorder (5 ). Although sensorineural deaf-
ness following mumps vaccination has been reported rarely, the data are inadequate
to distinguish vaccine from nonvaccine causation. No association has been estab-
lished between mumps vaccination and pancreatic damage or subsequent develop-
ment of diabetes mellitus (5 ).
Contraindications to Vaccine Use

Pregnancy
Although mumps vaccine virus has been shown to infect the placenta and fetus
(56 ), there is no evidence that it causes congenital malformations in humans. How-
ever, because of the theoretical risk of fetal damage, it is prudent to avoid giving live
virus vaccine to pregnant women. Live mumps vaccine, when combined with rubella
vaccine, should not be administered to women known to be pregnant or who are con-
sidering becoming pregnant within the next 3 months. Women vaccinated with
monovalent mumps vaccine should avoid becoming pregnant for 30 days after the
vaccination. Routine precautions for vaccinating postpubertal women include asking
if they are or may be pregnant, excluding those who say they are, and explaining the
theoretical risk to those who plan to receive the vaccine. Vaccination during pregnancy
should not be considered an indication for termination of pregnancy. However, the
final decision about interruption of pregnancy must rest with the individual patient
and her physician.
Severe Febrile Illness

Vaccine administration should not be postponed because of minor or intercurrent
febrile illnesses, such as mild upper respiratory infections. However, vaccination of
persons with severe febrile illnesses should generally be deferred until they have re-
covered from the acute phase of the illness.
Allergic Reactions
Hypersensitivity reactions rarely occur after the administration of MMR or any of its
component vaccines. Most of these reactions are minor and consist of a wheal and
flare or urticaria at the injection site. Immediate, anaphylactic reactions to MMR or its
component vaccines are extremely rare. Although >70 million doses of MMR vaccine
have been distributed in the United States since VAERS was implemented in 1990,
only 33 cases of anaphylactic reactions that occurred after MMR vaccination have
been reported. Furthermore, only 11 of these cases a) occurred immediately after vac-
cination and b) occurred in persons who had symptoms consistent with anaphylaxis
(CDC, unpublished data).
In the past, persons who had a history of anaphylactic reactions (i.e., hives, swel-
ling of the mouth or throat, difficulty breathing, hypotension, and shock) following
egg ingestion were considered to be at increased risk for serious reactions after re-
ceipt of mumps-containing vaccines, which are produced in chick embryo fibroblasts.
Protocols requiring caution were developed for skin testing and vaccinating persons
who had had anaphylactic reactions after egg ingestion (30–34 ). However, the predic-
tive value of such skin testing and the need for special protocols when vaccinating
egg-allergic persons with mumps-containing vaccines is uncertain. The results of re-
cent studies suggest that anaphylactic reactions to mumps-containing vaccines are
not associated with hypersensitivity to egg antigens but with some other component
of the vaccines. The risk for serious allergic reaction to these vaccines in egg-allergic
patients is extremely low, and skin testing is not necessarily predictive of vaccine hy-
persensitivity (35–37 ). Therefore, ACIP is re-evaluating whether skin testing and the
use of special protocols are routinely necessary when administering mumps-contain-

ing vaccines to persons who have a history of anaphylactic-like reactions after egg
ingestion.
MMR and its component vaccines contain hydrolyzed gelatin as a stabilizer. The
literature contains a single case report of a person with an anaphylactic sensitivity to
gelatin who had an anaphylactic reaction after receipt of the MMR vaccine licensed in
the United States (38 ). Similar cases have occurred in Japan (39 ). Therefore, ACIP is
currently considering recommendations for vaccination of persons who have had an
anaphylactic reaction to gelatin or gelatin-containing products. In the meantime, such
persons should be vaccinated with MMR or other mumps vaccines with extreme
caution.
Since mumps vaccine contains trace amounts of neomycin (25 µg), persons who
have experienced anaphylactic reactions to topically or systemically administered
neomycin should not receive mumps vaccine. Most often, neomycin allergy is mani-
fested as a contact dermatitis, which is a delayed-type (cell-mediated) immune
response, rather than anaphylaxis. In such persons, the adverse reaction, if any, to
25 µg of neomycin in the vaccine would be an erythematous, pruritic nodule or papule
at the site of injection after 48–96 hours. A history of contact dermatitis to neomycin is
not a contraindication to receiving mumps vaccine. Live mumps virus vaccine does
not contain penicillin.
Recent Injection of Immune Globulin

The effect of immune globulin preparations on the response to mumps vaccine is
unknown, but commercial immune globulin preparations contain mumps antibodies.
Therefore, monovalent mumps or rubella-mumps vaccine should be given at least
2 weeks before the administration of an immune globulin preparation or deferred until
approximately 3 months after the administration of an immune globulin preparation.
For suggested time intervals between administration of immune globulin prepara-
tions and vaccines containing live measles virus, refer to Table 5.
Altered Immunocompetence
In theory, replication of the mumps vaccine virus may be potentiated in patients
with immune deficiency diseases and by the suppressed immune responses that
occur with leukemia, lymphoma, or generalized malignancy or with therapy with cor-
ticosteroids, alkylating drugs, antimetabolites, or radiation. In general, patients with
such conditions should not be given live mumps virus vaccine. Because vaccinated
persons do not transmit mumps vaccine virus, the risk of mumps exposure for those
patients may be reduced by vaccinating their close susceptible contacts.
An exception to these general recommendations is in persons infected with HIV;
asymptomatic HIV-infected children should receive MMR as soon as possible upon
reaching their first birthday (44 ), and MMR vaccine should be considered for all symp-
tomatic HIV-infected children who do not have evidence of severe immuno-
suppression (see Measles Prevention, Altered Immunocompetence).
Patients with leukemia in remission whose chemotherapy has been terminated for
at least 3 months may also receive live mumps virus vaccine. Most experts agree that
steroid therapy usually does not contraindicate administration of live virus vaccine
when it is short term (i.e., <2 weeks); low to moderate dose; long-term, alternate-day
treatment with short-acting preparations; maintenance physiologic doses (replace-

ment therapy); or administered topically (skin or eyes), by aerosol, or by intra-
articular, bursal, or tendon injection (44 ). However, mumps vaccine should be avoided
if systemic immunosuppressive levels are reached by prolonged, extensive, topical
application.
DTP
DTP vaccination update those applicable sections in “Diphtheria, Tetanus, and
Pertussis: Recommendations for Vaccine Use and Other Preventive Measures—
Recommendations of the Immunization Practices Advisory Committee (ACIP)”
(MMWR 1991;40[No. RR-10]).
Side Effects and Adverse Reactions Following DTP Vaccination

Local reactions (generally erythema and induration with or without tenderness) are
common after the administration of vaccines containing diphtheria, tetanus, or pertus-
sis antigens. Occasionally, a nodule may be palpable at the injection site of adsorbed
products for several weeks. Sterile abscesses at the injection site have been reported
rarely (6–10 events per million doses of DTP). Mild systemic reactions such as fever,
drowsiness, fretfulness, and anorexia occur frequently. These reactions are substan-
tially more common following the administration of DTP than of DT, but they are
self-limited and can be safely managed with symptomatic treatment.
Acetaminophen is frequently given by physicians to lessen fever and irritability as-
sociated with DTP vaccination, and it may be useful in preventing seizures among
febrile-convulsion–prone children. However, fever that does not begin until ≥24 hours
after vaccination or persists for more than 24 hours after vaccination should not be
assumed to be due to DTP vaccination. These new or persistent fevers should be
evaluated for other causes so that treatment is not delayed for serious conditions such
as otitis media or meningitis. Moderate-to-severe systemic events include high fever
(i.e., temperature of ≥40.5 C [≥105 F]); persistent, inconsolable crying lasting ≥3 hours;
collapse (hypotonic-hyporesponsive episode); or short-lived convulsions (usually
febrile). These events occur infrequently. These events appear to be without sequelae
(57–59 ). Other more severe neurologic events, such as a prolonged convulsion or
encephalopathy, although rare, have been reported in temporal association with DTP
administration.
Approximate rates for the occurrence of adverse events following receipt of DTP
(regardless of dose number in the series or age of the child) are shown in Table 6
(60,61 ). The frequencies of local reactions and fever are substantially higher with in-
creasing numbers of doses of DTP, while other mild-to-moderate systemic reactions
(e.g., fretfulness, vomiting) are substantially less frequent (59–61 ).
Concern about the possible role of pertussis vaccine in causing neurologic reac-
tions has been present since the earliest days of vaccine use. Rare but serious acute
neurologic illnesses, including encephalitis/encephalopathy and prolonged con-
vulsions, have been anecdotally reported following receipt of whole-cell pertussis vac-
cine given as DTP (62,63 ). Whether pertussis vaccine causes or is only coincidentally
related to such illnesses or reveals an inevitable event has been difficult to determine
conclusively for the following reasons: a) serious acute neurologic illnesses often oc-
cur or become manifest among children during the first year of life irrespective of
vaccination; b) there is no specific clinical sign, pathologic finding, or laboratory test
which can determine whether the illness is caused by the DTP; c) it may be difficult to
determine with certainty whether infants <6 months of age are neurologically normal,
which complicates assessment of whether vaccinees were already neurologically im-
paired before receiving DTP; and d) because these events are exceedingly rare,
appropriately designed large studies are needed to address the question.
Despite these methodologic difficulties, the National Childhood Encephalopathy
Study (NCES) and other controlled epidemiologic studies have provided evidence that
DTP can cause acute encephalopathy (64–68 ). This adverse event occurs rarely, with
an estimated risk of zero to 10.5 episodes per million DTP vaccinations (68 ). A detailed
follow-up of the NCES indicated that children who had had a serious acute neurologic
illness after DTP administration were significantly more likely than children in the con-
trol group to have chronic nervous system dysfunction 10 years later. These children
with chronic nervous system dysfunction were more likely than children in the control
group to have received DTP within 7 days of onset of the original serious acute
neurologic illness (i.e., 12 [3.3%] of 367 children vs. six [0.8%] of 723 children) (69 ).
After reviewing the follow-up data, IOM concluded that the NCES provided evi-
dence of an association between DTP and chronic nervous system dysfunction in
children who had had a serious acute neurologic illness after vaccination with DTP.
The committee proposed three possible explanations for this association. First, the
acute neurologic illness and subsequent chronic nervous system dysfunction might
have been caused by DTP. Second, DTP might trigger an acute neurologic illness and
subsequent chronic nervous system dysfunction in children who have underlying
brain or metabolic abnormalities. Such children might experience similar chronic dys-
function in the absence of DTP vaccination if other stimuli (e.g., fever or infection) are
present. Third, DTP might cause an acute neurologic illness in children who have un-
derlying brain or metabolic abnormalities that would inevitably have led to chronic
TABLE 6. Adverse events* occurring within 48 hours after vaccination with diphtheria
and tetanus toxoids and pertussis vaccine (DTP)
Event Frequency of event†
Local reaction
• Pain 1 per 2 doses
• Swelling 2 per 5 doses
• Redness 1 per 3 doses
Systemic reaction
• Fever ≥100.4 F (≥38 C) 1 per 2 doses
• Fretfulness 1 per 2 doses
• Drowsiness 1 per 3 doses
• Anorexia 1 per 5 doses
• Vomiting 1 per 15 doses
• Persistent, inconsolable crying (i.e., for ≥3 hrs) 1 per 100 doses
• Fever ≥105 F (≥40.5 C) 1 per 330 doses
• Collapse (hypotonic-hyporesponsive episode) 1 per 1,750 doses
• Convulsions (with or without fever) 1 per 1,750 doses
*Adapted from Cody CL, Baraff LJ, Cherry JD, et al., 1981 (60 ).
† Rate per total number of doses, regardless of dose number in DTP series.
nervous system dysfunction even if the acute neurologic illness had not developed
(6 ) . IOM concluded that the NCES data do not support one explanation over another.
According to IOM, the balance of evidence was consistent with a causal relation-
ship between DTP and some forms of chronic nervous system disorders in children
who had developed an acute neurologic disorder after receiving DTP. However, IOM
also concluded that the results were insufficient to determine whether DTP increases
the overall risk for chronic nervous system dysfunction in children.
A subcommittee of the National Vaccine Advisory Committee (NVAC) also re-
viewed the study and concluded that the results were insufficient to determine
whether DTP administration before the acute neurologic event influenced the poten-
tial for neurologic dysfunction 10 years later (Ad hoc Subcommittee of the NVAC,
unpublished data, 1994). ACIP concurs with this evaluation.
Although the NCES examined and reported risk for the 7 days after DTP vaccina-
tion, the increased risk for serious acute neurologic illness occurred primarily during
the first 3 days after DTP administration (64 ). Thus, if an association between DTP and
chronic encephalopathy exists, the risk is primarily in the first 3 days after DTP
vaccination.
Among a subset of children who were participating in the NCES and who had infan-
tile spasms, both DTP and DT vaccination appeared either to precipitate early
manifestations of the condition or to lead to its identification by parents (70 ). IOM
reviewed this and other studies and concluded that neither vaccine causes the illness
(71,72 ).
Sudden infant death syndrome (SIDS) is listed on death certificates as the cause of
death for 5,000–6,000 infants (ages 0–364 days) each year in the United States. Be-
cause the peak incidence of SIDS for infants occurs at 2–4 months of age, many
instances of a close temporal relation between SIDS and receipt of DTP are to be ex-
pected by simple chance. Only one methodologically rigorous study has suggested
that DTP vaccination might cause SIDS (73 ). A total of four deaths were reported
within 3 days of DTP vaccination, compared with 1.36 expected deaths. However,
these deaths were unusual in that three of the four occurred within a 13-month inter-
val during the 12-year study. These four children also tended to be vaccinated at older
ages than their controls, suggesting that they might have had other unrecognized risk
factors for SIDS independent of vaccination. In contrast, DTP vaccination was not as-
sociated with SIDS in several larger studies performed in the past decade (62,74–76 ).
In addition, none of three studies that examined unexpected deaths among infants not
classified as SIDS found an association with DTP vaccination (73,75,76 ). IOM re-
viewed these studies and concluded that the available information does not establish
a causal relationship between DTP and SIDS (4 ).
IOM concluded recently that no available evidence indicates that DTP might cause
transverse myelitis, other more subtle neurologic disorders (e.g., hyperactivity, learn-
ing disorders, and infantile autism), and progressive degenerative conditions of the
CNS (4 ). Furthermore, one study indicated that children who received pertussis vac-
cine exhibited fewer school problems than those who did not, even after adjustment
for socioeconomic status (77 ).
Recent data suggest that infants and young children who have ever had convul-
sions (febrile or afebrile) or who have immediate family members with such histories
are more likely to have seizures following DTP vaccination than those without such
histories (78,79 ). For those with a family history of seizures, the increased risks of
seizures occurring within 3 days of receipt of DTP or 4–28 days following receipt of
DTP are identical, suggesting that these histories are nonspecific risk factors and are
unrelated to DTP vaccination (79 ).
Rarely, immediate anaphylactic reactions (i.e., swelling of the mouth, breathing dif-
ficulty, hypotension, or shock) have been reported after receipt of preparations
containing diphtheria, tetanus, and/or pertussis antigens. However, no deaths caused
by anaphylaxis following DTP vaccination have been reported to CDC since the incep-
tion of vaccine-adverse-events reporting in 1978, a period during which more than
80 million doses of publicly purchased DTP vaccine were administered. While sub-
stantial underreporting exists in this passive surveillance system, the severity of
anaphylaxis and its immediacy following vaccination suggest that such events are
likely to be reported. Although no causal relation to any specific component of DTP
has been established, the occurrence of true anaphylaxis usually contraindicates fur-
ther doses of any one of these components. Rashes that are macular, papular,
petechial, or urticarial and appear hours or days after a dose of DTP are frequently
antigen-antibody reactions of little consequence or are due to other causes, such as
viral illnesses, and are unlikely to recur following subsequent injections (80,81 ). In
addition, there is no evidence for a causal relation between DTP vaccination and
hemolytic anemia or thrombocytopenic purpura.

General Considerations
The decision to administer or delay DTP vaccination because of a current or recent
febrile illness depends largely on the severity of the symptoms and their etiology.
Although a moderate or severe febrile illness is sufficient reason to postpone vaccina-
tion, minor illnesses such as mild upper-respiratory infections with or without
low-grade fever are not contraindications. If ongoing medical care cannot be assured,
taking every opportunity to provide appropriate vaccinations is particularly important.
Children with moderate or severe illnesses with or without fever can receive DTP as
soon as they have recovered. Waiting a short period before administering DTP avoids
superimposing the adverse effects of the vaccination on the underlying illness or mis-
takenly attributing a manifestation of the underlying illness to vaccination.
Routine physical examinations or temperature measurements are not prerequisites
for vaccinating infants and children who appear to be in good health. Appropriate
immunization practice includes asking the parent or guardian if the child is ill, post-
poning DTP vaccination for those with moderate or severe acute illnesses, and
vaccinating those without contraindications or precautionary circumstances.
When an infant or child returns for the next dose of DTP, the parent should always
be questioned about any adverse events that might have occurred following the pre-
vious dose.
A history of prematurity generally is not a reason to defer vaccination (82–84 ). Pre-
term infants should be vaccinated according to their chronological age from birth.
Immunosuppressive therapies—including irradiation, antimetabolites, alkylating
agents, cytotoxic drugs, and corticosteroids (used in greater than physiologic doses)
—may reduce the immune response to vaccines. Short-term (<2-week) corticosteroid
therapy or intra-articular, bursal, or tendon injections with corticosteroids should not

be immunosuppressive. Although no specific studies with pertussis vaccine are avail-
able, if immunosuppressive therapy will be discontinued shortly, it is reasonable to
defer vaccination until the patient has been off therapy for 1 month; otherwise, the
patient should be vaccinated while still on therapy (85 ).
Special Considerations for Preparations Containing Pertussis Vaccine

Precautions and contraindications guidelines that were previously published re-
garding the use of pertussis vaccine were based on three assumptions about the risks
for adverse events associated with pertussis vaccination: a) that the vaccine on rare
occasions caused acute encephalopathy resulting in permanent brain damage; b) that
pertussis vaccine aggravated preexisting CNS disease; and c) that certain non-
encephalitic reactions are predictive of more severe reactions with subsequent doses
(86 ). In addition, children from whom pertussis vaccine was withheld were thought to
be well protected by herd immunity, a belief that is no longer valid. The current re-
vised ACIP recommendations reflect better understanding of the risks associated not
only with pertussis vaccine but also with pertussis disease.
Contraindications
If any of the following events occur in temporal relationship to the administration
of DTP, further vaccination with DTP is contraindicated (Table 7):
1. An immediate anaphylactic reaction. The rarity of such reactions to DTP is
such that they have not been adequately studied. Because of uncertainty as
to which component of the vaccine might be responsible, no further vaccina-
tion with any of the three antigens in DTP should be carried out. Alternatively,
because of the importance of tetanus vaccination, such individuals may be
referred for evaluation by an allergist and desensitized to tetanus toxoid if a
specific allergy can be demonstrated (87,88 ).
2. Encephalopathy (not due to another identifiable cause). This is defined as an
acute, severe CNS disorder occurring within 7 days following vaccination and
generally consisting of major alterations in consciousness, unresponsive-
ness, generalized or focal seizures that persist more than a few hours, with
failure to recover within 24 hours. Even though causation by DTP cannot be
established, no subsequent doses of pertussis vaccine should be given. It
TABLE 7. Contraindications and precautions to subsequent vaccination with

diphtheria and tetanus toxoids and pertussis vaccine (DTP)
Classification/Response to DTP vaccination
Contraindications
• An immediate anaphylactic reaction.
• Encephalopathy occurring within 7 days after vaccination.
Precautions
• Fever ≥105 F (≥40.5 C) that is not attributed to another identifiable cause occurring
within 48 hours after vaccination.
• Collapse or shock-like state (i.e., a hypotonic-hyporesponsive episdode) occurring within
48 hours after vaccination.
• Persistent, inconsolable crying lasting ≥3 hours and occurring within 48 hours after
vaccination.
• Convulsions with or without fever occurring within 3 days after vaccination.
may be desirable to delay for months before administering the balance of the
doses of DT necessary to complete the primary schedule. Such a delay allows
time for clarification of the child’s neurologic status.
Precautions
If any of the following events occur in temporal relation to receipt of DTP, the deci-
sion to give subsequent doses of vaccine containing the pertussis component should
be carefully considered (Table 7). Although these events were considered absolute
contraindications in previous ACIP recommendations, there may be circumstances,
such as a high incidence of pertussis, in which the potential benefits outweigh possi-
ble risks, particularly because these events are not associated with permanent
sequelae (86 ). The following events were previously considered contraindications
and are now considered precautions:
1. Temperature of ≥40.5 C (≥105 F) within 48 hours not due to another identifi-
able cause. Such a temperature is considered a precaution because of the
likelihood that fever following a subsequent dose of DTP also will be high.
Because such febrile reactions are usually attributed to the pertussis compo-
nent, vaccination with DT should not be discontinued.
2. Collapse or shock-like state (hypotonic-hyporesponsive episode) within
48 hours. Although these uncommon events have not been recognized to
cause death nor to induce permanent neurological sequelae, it is prudent to
continue vaccination with DT, omitting the pertussis component (58,89 ).
3. Persistent, inconsolable crying lasting ≥3 hours, occurring within 48 hours.
Follow-up of infants who have cried inconsolably following DTP vaccination
has indicated that this reaction, though unpleasant, is without long-term se-
quelae and not associated with other reactions of greater significance (59 ).
Inconsolable crying occurs most frequently following the first dose and is less
frequently reported following subsequent doses of DTP (60 ). However, crying
for >30 minutes following DTP vaccination can be a predictor of increased
likelihood of recurrence of persistent crying following subsequent doses
(59 ) . Children with persistent crying have had a higher rate of substantial
local reactions than children who had other DTP-associated reactions (includ-
ing high fever, seizures, and hypotonic-hyporesponsive episodes), sug-
gesting that prolonged crying was really a pain reaction (89 ).
4. Convulsions with or without fever occurring within 3 days. Short-lived con-
vulsions, with or without fever, have not been shown to cause permanent
sequelae (57,90 ). Furthermore, the occurrence of prolonged febrile seizures
(i.e., status epilepticus*), irrespective of their cause, involving an otherwise
normal child does not substantially increase the risk for subsequent febrile
(brief or prolonged) or afebrile seizures. The risk is significantly increased
(p=0.018) only among those children who are neurologically abnormal before
their episode of status epilepticus (91 ). Accordingly, although a convulsion
following DTP vaccination has previously been considered a contraindication
to further doses, under certain circumstances subsequent doses may be indi-
cated, particularly if the risk of pertussis in the community is high. If a child
*Any seizure lasting >30 minutes or recurrent seizures lasting a total of 30 minutes without the
child regaining full consciousness.
has a seizure following the first or second dose of DTP, it is desirable to delay
subsequent doses until the child’s neurologic status is better defined. By the
end of the first year of life, the presence of an underlying neurologic disorder
has usually been determined and appropriate treatment instituted. DT vac-
cine should not be administered before a decision has been made about
whether to restart the DTP series. Regardless of which vaccine is given, it is
prudent also to administer acetaminophen, 15 mg/kg of body weight, at the
time of vaccination and every 4 hours subsequently for 24 hours (92,93 ).
Vaccination of infants and young children who have

underlying neurologic disorders
Infants and children with recognized, possible, or potential underlying neurologic
conditions present a unique problem. They seem to be at increased risk for the ap-
pearance of manifestations of the underlying neurologic disorder within 2–3 days
after vaccination. However, more prolonged manifestations or increased progression
of the disorder or exacerbation of the disorder as a result of DTP vaccination have not
been recognized (94 ). In addition, most neurologic conditions in infancy and young
childhood are associated with evolving, changing neurological findings. Functional
abnormalities are often unmasked by progressive neurologic development. Thus,
confusion over the interpretation of progressive neurologic signs may arise when DTP
vaccination or any other therapeutic or preventive measure is carried out.
Protection against diphtheria, tetanus, and pertussis is as important for children
with neurologic disabilities as for other children. Such protection may be even more
important for neurologically disabled children. They often receive custodial care or
attend special schools where the risk of pertussis is greater because DTP vaccination
is avoided for fear of adverse reactions. Also, if pertussis affects a neurologically
disabled child who has difficulty in handling secretions and in cooperating with symp-
tomatic care, it may aggravate preexisting neurologic problems because of anoxia,
intracerebral hemorrhages, and other manifestations of the disease. Whether and
when to administer DTP to children with proven or suspected underlying neurologic
disorders must be decided on an individual basis. Important considerations include
the current local incidence of pertussis, the near absence of diphtheria in the United
States, and the low risk of infection with Clostridium tetani. On the basis of these con-
siderations and the nature of the child’s disorder, the following approaches are
recommended:
1. Infants and children with previous convulsions. Infants and young children
who have had prior seizures, whether febrile or afebrile, appear to be at in-
creased risk for seizures following DTP vaccination than children and infants
without these histories (79 ). A convulsion within 3 days of DTP vaccination in
a child with a history of convulsions may be initiated by fever caused by the
vaccine in a child prone to febrile seizures, may be induced by the pertussis
component, or may be unrelated to the vaccination. As noted earlier, current
evidence indicates that seizures following DTP vaccination do not cause per-
manent brain damage. Among infants and children with a history of previous
seizures, it is prudent to delay DTP vaccination until the child’s status has
been fully assessed, a treatment regimen established, and the condition
stabilized. It should be noted, however, that delaying DTP vaccination until

the second 6 months of life will increase the risk of febrile seizures among
persons who are predisposed. When DTP or DT is given, acetaminophen,
15 mg/kg, should also be given at the time of the vaccination and every
4 hours for the ensuing 24 hours (92,93 ).
2. Infants as yet unvaccinated who are suspected of having underlying
neurologic disease. It is prudent to delay initiation of vaccination with DTP or
DT (but not other vaccines) until further observation and study have clarified
the child’s neurologic status and the effect of treatment. The decision as to
whether to begin vaccination with DTP or DT should be made no later than
the child’s first birthday.
3. Children who have not received a complete series of vaccine and who have a
neurologic event occurring between doses. Infants and children who have
received one or more doses of DTP and who experience a neurologic disorder
(e.g., a seizure) not temporally associated with vaccination, but before the
next scheduled dose, present a special management challenge. If the seizure
or other disorder occurs before the first birthday and before completion of the
first three doses of the primary series of DTP, further doses of DTP or DT
(but not other vaccines) should be deferred until the infant’s status has been
clarified. The decision whether to use DTP or DT to complete the series
should be made no later than the child’s first birthday and should take into
consideration the nature of the child’s problem and the benefits and possible
risks of the vaccine. If the seizure or other disorder occurs after the first birth-
day, the child’s neurologic status should be evaluated to ensure that the
disorder is stable before a subsequent dose of DTP is given.
4. Infants and children with stable neurologic conditions. Infants and children
with stable neurologic conditions, including well-controlled seizures, may be
vaccinated. The occurrence of single seizures (temporally unassociated with
DTP) do not contraindicate DTP vaccination, particularly if the seizures can be
satisfactorily explained. Parents of infants and children with histories of con-
vulsions should be informed of the increased risk of postvaccination seizures.
Acetaminophen, 15 mg/kg, every 4 hours for 24 hours, should be given to
children with such histories to reduce the possibility of postvaccination fever
(92,93 ).
5. Children with resolved or corrected neurologic disorders. DTP vaccination is
recommended for infants with certain neurologic problems, such as neonatal
hypocalcemic tetany or hydrocephalus (following placement of a shunt and
without seizures), that have been corrected or have clearly subsided without
residua.
Vaccination of infants and young children who have a family history

of convulsion or other CNS disorder
A family history of convulsions or other CNS disorder is not a contraindication to
pertussis vaccination (95 ). Acetaminophen should be given at the time of DTP vacci-
nation and every 4 hours for 24 hours to reduce the possibility of postvaccination
fever (92,93 ).
Preparations Containing Diphtheria Toxoid and Tetanus Toxoid

The only contraindication to tetanus and diphtheria toxoids is a history of a
neurologic or severe hypersensitivity reaction following a previous dose. Vaccination
with tetanus and diphtheria toxoids is not known to be associated with an increased
risk of convulsions. Local side effects alone do not preclude continued use. If an ana-
phylactic reaction to a previous dose of tetanus toxoid is suspected, intradermal skin
testing with appropriately diluted tetanus toxoid may be useful before a decision is
made to discontinue tetanus toxoid vaccination (86 ). In one study, 94 of 95 persons
with histories of anaphylactic symptoms following a previous dose of tetanus toxoid
were nonreactive following intradermal testing and tolerated further tetanus toxoid
challenge without incident (86 ). One person had erythema and induration immedi-
ately following skin testing, but tolerated a full IM dose without adverse effects. Mild,
nonspecific skin-test reactivity to tetanus toxoid, particularly if used undiluted, ap-
pears to be fairly common. Most vaccinees develop inconsequential cutaneous
delayed hypersensitivity to the toxoid. Although very rare, severe hypersensitivity re-
actions may occur after receipt of tetanus-toxoid–containing vaccines; these reactions
can be life-threatening (5 ).
Persons who experienced Arthus-type hypersensitivity reactions or a temperature
of >103 F (>39.4 C) following a prior dose of tetanus toxoid usually have high serum
tetanus antitoxin levels and should not be given even emergency doses of Td more
frequently than every 10 years, even if they have a wound that is neither clean nor
minor.
If a contraindication to using tetanus-toxoid–containing preparations exists for a
person who has not completed a primary series of tetanus toxoid immunization and
that person has a wound that is neither clean nor minor, only passive immunization
should be given using tetanus IG (TIG).
On the basis of a) a report of a 42-year-old man who had GBS on three separate
occasions after receipt of tetanus toxoid and b) evidence that a vaccine-induced im-
munologic response can cause GBS, IOM concluded that tetanus-toxoid–containing
vaccines can trigger the onset of GBS in adults. GBS can be a life-threatening disease.
Persons who have a history of GBS associated with a particular vaccine may be at
increased risk for recurrent GBS after subsequent doses of that vaccine (5 ). However,
in a study in which an estimated 1.2 million doses of tetanus-containing toxoid were
administered to persons >18 years of age, two cases of GBS were expected by chance
alone during the 6 weeks after vaccination, and only one case was reported (CDC,
unpublished data). This finding suggests that the risk for GBS after administration of
tetanus toxoid is extremely low.
No increased risk for GBS has been observed with the use of DTP in children. In a
study of 0.7 million children of preschool-ages who were vaccinated with DTP during
a 7-year period, three cases of GBS were expected by chance alone during the 6 weeks
after vaccination, and only two cases were reported (17 ).
Because tetanus vaccination has been associated rarely with recurrence of GBS,
the decision to administer additional doses of tetanus-toxoid–containing vaccine to
persons who have had GBS within 6 weeks after receiving tetanus toxoid should be
based on the benefits of subsequent vaccination and the risk for recurrence of GBS.
For example, vaccination is usually justified for children whose primary immuniza-
tion schedules are incomplete (i.e., fewer than three doses have been received); but
routine booster vaccination probably is not indicated for adults who have received
three or more doses.
Vaccination with tetanus-toxoid–containing vaccines has been associated with bra-
chial neuritis in adult vaccinees, with a relative risk of 5–10 in comparison with the
population-based background incidence and a 1-month attributable incidence of ap-
proximately one-half to one case per 100,000 recipients of tetanus toxoid (5 ).
Although no evidence exists that tetanus and diphtheria toxoids are teratogenic,
waiting until the second trimester of pregnancy to administer Td is a reasonable pre-
caution for minimizing any concern about the theoretical possibility of such reactions.
Misconceptions Concerning Contraindications to DTP

Some health-care providers inappropriately consider certain conditions or circum-
stances as contraindications to DTP vaccination. These include the following:
1. Soreness, redness, or swelling at the DTP vaccination site or temperature of
<40.5 C (<105 F).
2. Mild, acute illness with low-grade fever or mild diarrheal illness affecting an
otherwise healthy child.
3. Current antimicrobial therapy or the convalescent phase of an acute illness.
4. Recent exposure to an infectious disease.
5. Prematurity. The appropriate age for initiating vaccination among the prema-
turely born infant is the usual chronological age from birth (82–84 ). Full
doses (0.5 mL) of vaccine should be used.
6. History of allergies or relatives with allergies.
7. Family history of convulsions.
8. Family history of SIDS.
9. Family history of an adverse event following DTP vaccination.
References
1. World Health Organization. The global eradication of smallpox: final report of the Global Com-
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September 6, 1996 / Vol. 45 / No.

Update: Vaccine Side Effects, Adverse

Recommendations of the Advisory Committee

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

The material in this report was prepared for publication by:

Epidemiology and Surveillance Division ............................ Stephen C. Hadler, M.D.

Recommendations and Reports ...................................... Suzanne M. Hewitt, M.P.A.

Copies can be purchased from Superintendent of Documents, U.S. Government

Advisory Committee on Immunization Practices

Barbara A. DeBuono, M.D., M.P.H. Rudolph E. Jackson, M.D.

Geoffrey Evans, M.D. John R. La Montagne, Ph.D.

Advisory Committee on Immunization Practices

American Academy of Family Canadian National Advisory Committee

The following CDC staff members prepared this report:

Jessica Tuttle, M.D.

in collaboration with the

Advisory Committee on Immunization Practices (ACIP)

Update: Vaccine Side Effects, Adverse Reactions,

Recommendations of the Advisory Committee

TABLE 1. The maximum number of cases of specified vaccine-preventable diseases

*An independent research organization chartered by the National Academy of Sciences.

TABLE 2. Summarized conclusions of evidence regarding the possible association

1. No evidence was available to establish a causal relationship

None None Neuropathy Transverse myelitis None None

2. Inadequate evidence to accept or reject a causal relationship

Residual seizure Encephalopathy Encephalopathy Transverse myelitis Guillain-Barré Guillain-Barré syndrome

3. Evidence favored rejection of a causal relationship

Encephalopathy§§ None None None None Early onset Hib disease

4. Evidence favored acceptance of a causal relationship

Guillain-Barré Anaphylaxis** None Guillain-Barré None Early-onset Hib disease

5. Evidence established a causal relationship

Anaphylaxis††† Thrombocytopenia None Poliomyelitis in Anaphylaxis None

Scenario I: Scenario II: Scenario III:

DTP is administered to DTP is administered to a DTP is administered to a

Vaccination might cause Vaccination triggers an Vaccination might cause

*This information is an adaptation of information published previously by the Institute of Med-

Vaccine Side Effects and Adverse Reactions

Vaccine-Associated Side Effects

concerning these vaccinees do not indicate an association between receipt of recom-

Precautions and Contraindications

of an observational study conducted in the United States have not demonstrated a

Side Effects and Adverse Reactions

Personal and Family History of Convulsions

Subacute Sclerosing Panencephalitis (SSPE)

Precautions and Contraindications

Recent Administration of Immune Globulins

TABLE 5. Suggested intervals between administration of immune globulin prep-

the recommendations for vaccination of severely immunocompromised HIV-infected

Management of Patients with Contraindications

Simultaneous Administration of Vaccines

Vaccines recommended for administration at 12–15 months of age can be adminis-

Adverse Effects of Vaccine Use

Contraindications to Vaccine Use

Severe Febrile Illness

use of special protocols are routinely necessary when administering mumps-contain-

Recent Injection of Immune Globulin

treatment with short-acting preparations; maintenance physiologic doses (replace-

Side Effects and Adverse Reactions Following DTP Vaccination