Hapatites

Morbidity and Mortality Weekly Report
Recommendations and Reports December 8, 2006 / Vol. 55 / No. RR-16
A Comprehensive Immunization Strategy

to Eliminate Transmission of Hepatitis B
Virus Infection in the United States
Recommendations of the Advisory
Committee on Immunization Practices (ACIP)
Part II: Immunization of Adults
INSIDE: Continuing Education Examination
depar tment of health and human ser

department vices
services
vices
Centers for Disease Control and Prevention

Prevention
MMWR
CONTENTS
The MMWR series of publications is published by the Coordinating

Center for Health Information and Service, Centers for Disease Introduction ......................................................................... 2
Control and Prevention (CDC), U.S. Department of Health and

Human Services, Atlanta, GA 30333. Methods .............................................................................. 3
Major Updates to the Recommendations ............................. 3
Suggested Citation: Centers for Disease Control and Prevention.

[Title]. MMWR 2006;55(No. RR-#):[inclusive page numbers]. Background ......................................................................... 3
Centers for Disease Control and Prevention Clinical Features and Natural History of HBV Infection ..... 3
Julie L. Gerberding, MD, MPH Interpretation of Serologic Markers of HBV Infection ......... 4
Director
Epidemiology of HBV Infection .......................................... 5
Tanja Popovic, MD, PhD
(Acting) Chief Science Officer

Prophylaxis Against HBV Infection ....................................... 8
James W. Stephens, PhD

Hepatitis B Vaccine ........................................................... 8
(Acting) Associate Director for Science
Hepatitis B Immune Globulin ............................................ 9
Steven L. Solomon, MD
Director, Coordinating Center for Health Information and Service Adult Vaccination Schedules and Results of Vaccination ..... 10
Jay M. Bernhardt, PhD, MPH Preexposure Vaccination ................................................. 10
Director, National Center for Health Marketing Postexposure Prophylaxis ................................................ 12
Judith R. Aguilar
(Acting) Director, Division of Health Information Dissemination (Proposed) Vaccine Safety ................................................................... 12
Vaccine Reactogenicity .................................................... 12
Editorial and Production Staff

Adverse Events ............................................................... 12
Frederic E. Shaw, MD, JD

(Acting) Editor, MMWR Series Contraindications and Precautions .................................. 13
Suzanne M. Hewitt, MPA Implementation Barriers and Rationale
Managing Editor, MMWR Series

for New Recommendations .............................................. 13
Teresa F. Rutledge
Lead Technical Writer-Editor Recommendations and Implementation Strategies
Jeffrey D. Sokolow, MA for Hepatitis B Vaccination of Adults ................................ 15
Project Editor
Recommendations .......................................................... 15
Beverly J. Holland
Lead Visual Information Specialist Implementation Strategies .............................................. 16
Lynda G. Cupell
Acknowledgments ............................................................. 18
Malbea A. LaPete
References ......................................................................... 18
Visual Information Specialists

Quang M. Doan, MBA
Appendices ....................................................................... 26
Erica R. Shaver
Continuing Education Activity ......................................... CE-1
Information Technology Specialists
Editorial Board
William L. Roper, MD, MPH, Chapel Hill, NC, Chairman
Virginia A. Caine, MD, Indianapolis, IN
David W. Fleming, MD, Seattle, WA
William E. Halperin, MD, DrPH, MPH, Newark, NJ
Margaret A. Hamburg, MD, Washington, DC
King K. Holmes, MD, PhD, Seattle, WA
Deborah Holtzman, PhD, Atlanta, GA
John K. Iglehart, Bethesda, MD
Dennis G. Maki, MD, Madison, WI
Sue Mallonee, MPH, Oklahoma City, OK
Stanley A. Plotkin, MD, Doylestown, PA
Patricia Quinlisk, MD, MPH, Des Moines, IA

Disclosure of Relationship
Patrick L. Remington, MD, MPH, Madison, WI
Barbara K. Rimer, DrPH, Chapel Hill, NC

CDC, our planners, and our content experts wish to disclose they
John V. Rullan, MD, MPH, San Juan, PR
have no financial interests or other relationships with the
Anne Schuchat, MD, Atlanta, GA
manufacturers of commercial products, suppliers of commercial
Dixie E. Snider, MD, MPH, Atlanta, GA
services, or commercial supporters. Presentations will not include
John W. Ward, MD, Atlanta, GA
any discussion of the unlabeled use of a product or a product under
investigational use.
Vol. 55 / RR-16 Recommendations and Reports 1
A Comprehensive Immunization Strategy
to Eliminate Transmission of Hepatitis B Virus Infection
in the United States
Recommendations of the Advisory Committee on Immunization
Practices (ACIP) Part II: Immunization of Adults
Prepared by
Eric E. Mast, MD1
Cindy M. Weinbaum, MD1
Anthony E. Fiore, MD1
Miriam J. Alter, PhD1
Beth P. Bell, MD1
Lyn Finelli, DrPH1
Lance E. Rodewald, MD2
John M. Douglas, Jr., MD3
Robert S. Janssen, MD4
John W. Ward, MD1
1
Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (proposed)
2
Immunization Services Division, National Center for Immunization and Respiratory Diseases (proposed)
3
Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (proposed)
4
Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (proposed)
Summary
Hepatitis B vaccination is the most effective measure to prevent hepatitis B virus (HBV) infection and its consequences,
including cirrhosis of the liver, liver cancer, liver failure, and death. In adults, ongoing HBV transmission occurs primarily among
unvaccinated persons with behavioral risks for HBV transmission (e.g., heterosexuals with multiple sex partners, injection-drug
users [IDUs], and men who have sex with men [MSM]) and among household contacts and sex partners of persons with chronic
HBV infection.
This report, the second of a two-part statement from the Advisory Committee on Immunization Practices (ACIP), provides
updated recommendations to increase hepatitis B vaccination of adults at risk for HBV infection. The first part of the ACIP
statement, which provided recommendations for immunization of infants, children, and adolescents, was published previously
(CDC. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States:
recommendations of the Advisory Committee on Immunization Practices [ACIP]. Part 1: immunization of infants, children,
and adolescents. MMWR 2005;54[No. RR-16]:1–33).
In settings in which a high proportion of adults have risks for HBV infection (e.g., sexually transmitted disease/human immu
nodeficiency virus testing and treatment facilities, drug-abuse treatment and prevention settings, health-care settings targeting
services to IDUs, health-care settings targeting services to MSM, and correctional facilities), ACIP recommends universal hepati
tis B vaccination for all unvaccinated adults. In other primary care and specialty medical settings in which adults at risk for HBV
infection receive care, health-care providers should inform all
patients about the health benefits of vaccination, including
The material in this report originated in the National Center for HIV/ risks for HBV infection and persons for whom vaccination is
AIDS, Viral Hepatitis, STD, and TB Prevention (proposed), Kevin
A. Fenton, MD, PhD, Director; the Division of Viral Hepatitis, John recommended, and vaccinate adults who report risks for HBV
W. Ward, MD, Director; the Division of STD Prevention, John M. infection and any adults requesting protection from HBV
Douglas, Jr., MD, Director; and the Division of HIV/AIDS infection. To promote vaccination in all settings, health-care
Prevention, Robert S. Janssen, MD, Director; the National Center
for Immunization and Respiratory Diseases, Anne Schuchat, MD,
providers should implement standing orders to identify adults
Director; and the Immunization Services Division, Lance E. Rodewald, recommended for hepatitis B vaccination and administer vac
MD, Director. cination as part of routine clinical services, not require
Corresponding preparer: Eric E. Mast, MD, Division of Viral acknowledgment of an HBV infection risk factor for adults to
Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and
TB Prevention (proposed), 1600 Clifton Road, NE, MS G-37, Atlanta, receive vaccine, and use available reimbursement mechanisms
GA 30333. Telephone: 404-718-8500; Fax: 404-718-8595; E-mail: to remove financial barriers to hepatitis B vaccination.
[email protected].
2 MMWR December 8, 2006
Introduction schedule (7). Vaccination coverage among adolescents also has

increased substantially; preliminary data from 2003 indicated
Hepatitis B is a disease caused by the hepatitis B virus (HBV),
that approximately 50%–60% of adolescents aged 13–15 years
which is transmitted through percutaneous (i.e., puncture
have records indicating vaccination (with 3 doses) against hepa
through the skin) or mucosal (i.e., direct contact with
titis B (8). During 1990–2005, incidence of acute hepatitis B
mucous membranes) exposure to infectious blood or body flu
in the United States declined 78%. The greatest decline (96%)
ids. HBV can cause chronic infection, resulting in cirrhosis of
occurred among children and adolescents, coincident with an
the liver, liver cancer, liver failure, and death. Persons with
increase in hepatitis B vaccination coverage. This success can
chronic infection also serve as the main reservoir for continued
be attributed in part to the established infrastructure for vac
HBV transmission. Although chronic infection is more likely
cine delivery to children and to federal support for perinatal
to develop in persons infected as infants or young children,
hepatitis B prevention programs.
rates of new infection and acute disease are highest among adults.
Among adults, ongoing HBV transmission occurs prima
Hepatitis B vaccination is the most effective measure to pre
rily among unvaccinated adults with risk behaviors for HBV
vent HBV infection and its consequences. Since recommen
transmission (e.g., heterosexuals with multiple sex partners,
dations for hepatitis B vaccination were first issued in 1982, a
injection-drug users [IDUs], and men who have sex with men
comprehensive strategy to eliminate HBV transmission in the
[MSM]) and among household contacts and sex partners of
United States has evolved (1–5). This strategy includes
persons with chronic HBV infection. During 2000–2004, self-
1) universal vaccination of infants beginning at birth, 2) pre
reported hepatitis B vaccination coverage among adults at risk
vention of perinatal HBV infection through routine screening
for HBV infection increased from 30% to 45% (9); this
of all pregnant women for hepatitis B surface antigen (HBsAg)
increase in vaccination coverage likely contributed to the 35%
and postexposure immunoprophylaxis of infants born to
decline in acute hepatitis B incidence that occurred during
HBsAg-positive women or to women with unknown HBsAg
this period (from 3.7 to 2.4 per 100,000 population). How
status, 3) vaccination of all children and adolescents who were
ever, incidence of acute hepatitis B remains highest among
not vaccinated previously, and 4) vaccination of previously
adults, who accounted for approximately 95% of an estimated
unvaccinated adults at risk for HBV infection (Box 1).
51,000 new HBV infections in 2005. Although acceptance of
To date, immunization strategies for infants, children, and
vaccination is high among adults offered vaccination (10),
adolescents have been implemented with considerable suc
the low adult vaccination coverage reflects the lack of hepati
cess. Recent estimates indicate that approximately 95% of
tis B vaccination services in settings in which a high propor
pregnant women are tested for HBsAg and that case manage
tion of adults have risk factors for HBV infection (e.g., sexually
ment has been effective in ensuring high levels of initiation
transmitted disease [STD]/human immunodeficiency virus
and completion of postexposure immunoprophylaxis among
[HIV] testing and treatment facilities, drug-abuse treatment
infants born to HBsAg-positive women (6). Hepatitis B vac
and prevention settings, health-care settings targeting services
cine has been integrated successfully into the childhood vac
to IDUs, health-care settings targeting services to MSM, and
cination schedule, and infant vaccination coverage levels now
correctional facilities) and missed opportunities to vaccinate
are equivalent to those of other vaccines in the childhood
adults at risk for HBV infection in primary care and specialty
medical settings. Although hepatitis B incidence among adults
BOX 1. Immunization strategy to eliminate transmission of is expected to continue to decline during the next decade as
hepatitis B virus (HBV) in the United States successive cohorts of persons vaccinated in infancy, childhood,
• Universal vaccination of infants beginning at birth and adolescence reach adulthood, new implementation strat
• Prevention of perinatal HBV infection through egies are needed to protect unvaccinated adults at risk for HBV
— routine screening of all pregnant women for infection.
hepatitis B surface antigen (HBsAg), and This report provides updated guidance from the Advisory
— immunoprophylaxis of infants born to HBsAg Committee on Immunization Practices (ACIP) to increase hepa
positive women or to women with unknown HBsAg titis B vaccination coverage among adults. It includes recom
status mendations regarding which adults should receive hepatitis B
• Routine vaccination of previously unvaccinated children vaccine and outlines implementation strategies to ensure that
and adolescents those adults are vaccinated. The first part of this statement,
• Vaccination of previously unvaccinated adults at risk which provided recommendations for immunization of infants,
for HBV infection children, and adolescents, was published previously (11).
Methods — Provide information to all adults regarding the health

benefits of hepatitis B vaccination, including risk fac
In response to continuing low rates of hepatitis B vaccina
tors for HBV infection and persons for whom vacci
tion among adults at risk for HBV infection, ACIP’s Hepati
nation is recommended.
tis Vaccines Work Group met multiple times during October
— Help all adults assess their need for vaccination by
2004–September 2005 to review previous guidelines and make
obtaining a history that emphasizes risks for sexual
recommendations for improving vaccination coverage in
transmission and percutaneous or mucosal exposure
adults. The work group examined the progress made since
to blood.
1991 in implementing the U.S. strategy to eliminate HBV
— Vaccinate all adults who report risks for HBV infection.
transmission (e.g., vaccination coverage data and hepatitis B
— Vaccinate all adults requesting protection from HBV
disease rates), surveillance data on missed opportunities for
infection, without requiring them to acknowledge a
hepatitis B vaccination among adults with acute hepatitis B,
specific risk factor.
and results of cost-effectiveness analyses. In addition, demon
stration projects conducted in settings in which a high pro
portion of clients were at risk for HBV infection identified Background
the components of successful adult hepatitis B vaccination
programs and ongoing challenges to implementing adult hepa Clinical Features and Natural History
titis B vaccination. of HBV Infection
In January 2005, the proposed recommendations were
HBV is a 42-nm DNA virus classified in the Hepadnaviridae
posted online for public comment. In May 2005, CDC con
family. The liver is the primary site of HBV replication. After
vened a meeting of external consultants, including research
a susceptible person is exposed, the virus enters the liver via
ers, physicians, state and local public health professionals,
the bloodstream; no evidence exists indicating that the virus
immunization program directors, and directors of viral hepa
replicates at mucosal surfaces. HBV infection can produce
titis, STD, and HIV/AIDS prevention programs, to obtain
either asymptomatic or symptomatic infection. The average
input into the draft recommendations and consider the feasi
incubation period is 90 days (range: 60–150 days) from
bility of the recommended strategies. In October 2005, the
exposure to onset of jaundice and 60 days (range: 40–90 days)
revised recommendations were approved by ACIP.
from exposure to onset of abnormal serum alanine aminotrans
ferase (ALT) levels (12,13).
Major Updates
The onset of acute disease typically is insidious. Infants,
children aged <5 years, and immunosuppressed adults with
to the Recommendations
newly acquired HBV infection typically are asymptomatic,
This report updates ACIP recommendations published pre whereas 30%–50% of children aged >5 years and adults have
viously for hepatitis B vaccination of adults (3). The primary initial clinical signs or symptoms (14). When present, clinical
changes from previous recommendations are as follows: symptoms and signs can include anorexia, malaise, nausea,
• In settings in which a high proportion of persons are likely vomiting, abdominal pain, and jaundice. Extrahepatic mani
to be at risk for HBV infection (e.g., STD/HIV testing festations of disease (e.g., skin rashes, arthralgias, and arthri
and treatment facilities, drug-abuse treatment and pre tis) also can occur (15). The fatality rate among persons with
vention settings, health-care settings targeting services to reported cases of acute hepatitis B is 0.5%–1.0%, with the
IDUs, health-care settings targeting services to MSM, and highest rates in adults aged >60 years; however, because a sub
correctional facilities), ACIP recommends universal hepa stantial number of infections are asymptomatic and therefore
titis B vaccination for all adults who have not completed are not reported, the overall fatality rate among all persons
the vaccine series. with HBV infection likely is lower (16).
• In primary care and specialty medical settings, ACIP rec Approximately 95% of primary infections in adults with nor
ommends implementation of standing orders to identify mal immune status are self-limited, with elimination of virus
adults recommended for hepatitis B vaccination and from blood and subsequent lasting immunity to reinfection.
administer vaccination as part of routine services. To Chronic infection occurs in <5% of infected persons aged >5
ensure vaccination of adults at risk for HBV infection years, approximately 30% of infected children aged <5 years,
who have not completed the vaccine series, ACIP recom and approximately 90% of infected infants, with continuing
mends the following implementation strategies: viral replication in the liver and persistent viremia (14,17–19).
Primary infections become chronic more frequently in immu Interpretation of Serologic Markers
nosuppressed persons (e.g., hemodialysis patients and persons of HBV Infection
with HIV infection) (19,20) and persons with diabetes (21).
Overall, approximately 25% of persons who become chroni Antigens and antibodies associated with HBV infection in
cally infected during childhood and 15% of those who become clude HBsAg and antibody to HBsAg (anti-HBs), hepatitis B
chronically infected after childhood die prematurely from cir core antigen (HBcAg) and antibody to HBcAg (anti-HBc),
rhosis or liver cancer; the majority remain asymptomatic until and hepatitis B e antigen (HBeAg) and antibody to HBeAg
onset of cirrhosis or end-stage liver disease (22). (anti-HBe). At least one serologic marker is present during
No specific treatment exists for acute hepatitis B; supportive each of the different phases of HBV infection (13,27). The
care is the mainstay of therapy. Persons who have chronic HBV serologic markers typically used to differentiate between acute,
infection require medical evaluation and regular monitoring resolving, and chronic infection are HBsAg, anti-HBc, and
(23–25). Therapeutic agents approved by the Food and Drug anti-HBs (Table 1). HBeAg and anti-HBe screening typically
Administration (FDA) for treatment of chronic hepatitis B can is used for the management of patients with chronic infec
achieve sustained suppression of HBV replication and remis tion. Serologic assays are available commercially for all mark
sion of liver disease in certain persons (24). Periodic screening ers except HBcAg because no free HBcAg circulates in blood.
with ultrasonography and alfa-fetoprotein has been demon The presence of a confirmed HBsAg-positive result in
strated to enhance early detection of hepatocellular carcinoma serum indicates active HBV infection. All HBsAg-positive per
(HCC) (25). Certain chronically infected persons with HCC sons should be considered infectious. In newly infected per
have experienced long-term survival after resection of small sons, HBsAg is the only serologic marker detected during the
hepatocellular carcinomas, and persons who were screened had first 3–5 weeks after infection. The average time from expo
HCC detected at an earlier stage and had a substantial survival sure to detection of HBsAg is 30 days (range: 6–60 days)
advantage compared with historical controls (25); however, data (12,13). Highly sensitive single-sample nucleic acid tests can
from controlled studies are lacking. Guidance for the diagnosis detect HBV DNA in the serum of an infected person 10–20
and management of hepatitis B is available (26). days before detection of HBsAg (28). Transient HBsAg posi
tivity has been reported for up to 18 days after hepatitis B
vaccination and is clinically insignificant (29,30).
TABLE 1. Typical interpretation of serologic test results for hepatitis B virus infection
Serologic marker
Total IgM§
HBsAg* anti-HBc† anti-HBc Anti-HBs¶ Interpretation
–** – – – Never infected
+††§§ – – – Early acute infection; transient (up to 18 days) after vaccination
+ + + – Acute infection
– + + + or – Acute resolving infection
– + – + Recovered from past infection and immune
+ + – – Chronic infection
– + – – False-positive (i.e., susceptible); past infection; “low-level”
chronic infection;¶¶ or passive transfer of anti-HBc to infant
born to HBsAg-positive mother
– – – + Immune if concentration is >10 mIU/mL after vaccine series
completion;*** passive transfer after hepatitis B immune
globulin administration
* Hepatitis B surface antigen.

† Antibody to hepatitis B core antigen.
§ Immunoglobulin M.
¶ Antibody to HBsAg.
** Negative test result.

†† Positive test result.
§§ To ensure that an HBsAg-positive test result is not a false-positive, samples with reactive HBsAg results should be tested with a licensed neutralizing
confirmatory test if recommended in the manufacturer’s package insert.
¶¶ Persons positive only for anti-HBc are unlikely to be infectious except under unusual circumstances in which they are the source for direct percutane
ous exposure of susceptible recipients to large quantities of virus (e.g., blood transfusion or organ transplant).
*** Milli-international units per milliliter.
Anti-HBc appears at the onset of symptoms or liver-test HBs response after a 3-dose series of hepatitis B vaccine
abnormalities in acute HBV infection and persists for life. (39,40).
Acute or recently acquired infection can be distinguished by HBeAg can be detected in the serum of persons with acute
the presence of the immunoglobulin M (IgM) class of anti- or chronic HBV infection. The presence of HBeAg correlates
HBc, which is detected at the onset of acute hepatitis B and with high levels of viral replication (i.e., HBV DNA levels
persists for up to 6 months if the disease resolves. In patients typically of 107–109 IU/mL, indicating high infectivity)
who have chronic HBV infection, IgM anti-HBc can persist (41,42). Loss of HBeAg correlates with low levels (i.e., HBV
during viral replication at low levels that typically are not DNA levels of <105 IU/mL) of replicating virus, although
detectable by assays used in the United States. However, per certain HBeAg-negative persons have HBV DNA levels up to
sons with exacerbations of chronic infection can test positive 108–109 IU/mL (43). A mutation in the precore region of
for IgM anti-HBc (31). Using IgM anti-HBc testing for diag the HBV genome has been identified in HBeAg-negative per
nosis of acute hepatitis B should be limited to persons for sons with high HBV DNA levels (44,45).
whom clinical evidence of acute hepatitis or an epidemiologic
link to a case has been identified because the positive predic Epidemiology of HBV Infection
tive value of this test is low in asymptomatic persons.
HBV is transmitted by percutaneous or mucosal exposure
In persons who recover from HBV infection, HBsAg is elimi
to infectious blood or body fluids. Although HBsAg has been
nated from the blood, and anti-HBs develops, typically within
detected in multiple body fluids, only serum, semen, and
3–4 months. The presence of anti-HBs typically indicates
saliva have been demonstrated to be infectious (46,47). HBV
immunity from HBV infection. Infection or immunization with
is concentrated most highly in serum, with lower concentra
one serotype of HBV confers immunity to all serotypes. In
tions in semen and saliva. All HBsAg-positive persons are
addition, anti-HBs can be detected for several months after hepa
infectious, but those who are also HBeAg positive are more
titis B immune globulin (HBIG) administration. Persons who
infectious because their blood contains high titers of HBV
recover from natural infection typically will be positive for both
(typically HBV DNA levels of 107–109 IU/mL) (41,42). HBV
anti-HBs and anti-HBc, whereas persons who respond to hepa
is comparatively stable in the environment and remains viable
titis B vaccine have only anti-HBs. In persons who become
for >7 days on environmental surfaces at room temperature
chronically infected, HBsAg and anti-HBc persist, typically for
(48). HBV DNA at concentrations of 102–103 IU/mL can
life. HBsAg will become undetectable in approximately 0.5%–
be present on environmental surfaces in the absence of any
2% of persons with chronic infection yearly; anti-HBs will
visible blood and still cause transmission (48,49).
occur in the majority of these persons (32–35).
For adults, the two primary sources of HBV infection are
In certain persons, the only HBV serologic marker detected
sexual contact and percutaneous exposure to blood. Person-
in serum is anti-HBc. Isolated anti-HBc can be detected after
to-person transmission of HBV also can occur in settings
HBV infection in persons who have recovered but whose anti-
involving nonsexual interpersonal contact over an extended
HBs levels have waned. Certain chronically infected persons
period (e.g., among household contacts of a person with
with anti-HBc alone have circulating HBsAg not detectable
chronic HBV infection and developmentally disabled persons
by commercial serology. HBV DNA has been detected in the
living in a long-term–care facility).
blood of <10% of persons with isolated anti-HBc (36,37).
HBV is transmitted efficiently by sexual contact among
These persons are unlikely to be infectious except under cir
heterosexuals and among MSM. Risk factors associated with
cumstances in which they are a source for direct percutaneous
sexual transmission among heterosexuals include having
exposure of susceptible recipients to substantial quantities of
unprotected sex with an infected partner, having unprotected
virus (e.g., through blood transfusion or organ transplanta
sex with more than one partner, and history of another STD.
tion) (38). An isolated anti-HBc result also can be a false-
Risk factors associated with sexual transmission among MSM
positive. Typically, the frequency of isolated anti-HBc relates
include having multiple sex partners, history of another STD,
directly to the prevalence of HBV infection in the popula
and anal intercourse.
tion. In populations with a high prevalence of HBV infec
Percutaneous transmission of HBV can occur from receipt
tion, isolated anti-HBc likely indicates previous infection, with
of blood transfusion or organ or tissue transplant from an
loss of anti-HBs. For persons in populations with a low preva
infectious donor; injection-drug use, including sharing of
lence of HBV infection, isolated anti-HBc is found in
injection-preparation equipment; and frequent exposure to
approximately 10%–20% of persons with serologic markers
blood or needles among health-care workers. In the United
of HBV infection (37) and often represents a false-positive
States, donor selection procedures and routine testing of
reaction; the majority of these persons have a primary anti-
donors have made transmission of HBV via transfusion of FIGURE 1. Reported incidence* of acute hepatitis B, by age
group and sex — United States, 2005
whole blood and blood components a rare occurrence (50,51).
Persons with hemophilia who received plasma-derived clot
<5
ting factor concentrates were previously at high risk for HBV Female
infection, but such transmission has been eliminated through 5–9
Male
viral inactivation procedures and use of recombinant clotting 10–14
factor concentrates. Among persons with bleeding disorders

15–19
treated at U.S. hemophilia treatment centers during 1998–
2002, no infections with viral hepatitis, including HBV, were 20–24
Age group (yrs)

attributable to blood products received during that time (52). 25–29
Outbreaks of HBV infection from exposure to contaminated
equipment used for therapeutic injections and other health 30–34
care–related procedures, tattooing, and acupuncture also have 35–39

been reported, although such exposures among patients with
40–44
acute hepatitis B are reported rarely (53–57). In the majority
of cases, transmission resulted from noncompliance with 45–49
aseptic techniques for administering injections and recom 50–54
mended infection-control practices designed to prevent
55–59
cross-contamination of medical equipment and devices. No
infections have been demonstrated in susceptible persons who >60
had oral mucous membrane exposure to HBsAg-positive saliva, 4.0 3.0 2.0 1.0 0 1.0 2.0 3.0 4.0
but transmission has occurred through a human bite and has
Incidence
been demonstrated in animals by subcutaneous inoculation
* Per 100,000 population.
of saliva (46,58–60).
Persons living with chronically infected persons are at risk
and transmission among MSM accounts for approximately
for HBV infection through percutaneous or mucosal expo
24% (CDC, unpublishe data, 2001–2005). Serologic evidence
sures to blood or infectious body fluids (e.g., sharing a tooth
of HBV infection (i.e., anti-HBc positive) has ranged from
brush or razor, contact with exudates from dermatologic
10% to 40% among adults seeking treatment in STD clinics
lesions, or contact with HBsAg-contaminated surfaces). Per
(62–64) and from 10% to 25% among MSM aged <30 years
sons with chronic HBV infection also can transmit HBV in
(65; CDC, unpublished data, 1999–2000). Follow-up stud
other settings (e.g., schools, child care centers, or facilities for
ies identified HBV infection in 20%–42% of susceptible het
developmentally disabled persons), especially if they behave
erosexual partners of persons with acute hepatitis B (66–68).
aggressively or have medical problems (e.g., exudative derma
Among susceptible heterosexual spouses of persons with
titis or open skin lesions) that increase the risk for exposure to
chronic HBV infection, the seroprevalence of HBV infection
blood or serous secretions.
ranged from 25% to 59% (69–71).
Adults at Risk for HBV Infection Injection-drug users. IDUs account for approximately 16%
In the United States in 2005, the highest incidence of acute of new HBV infections in the United States (CDC, unpub
hepatitis B was among adults aged 25–45 years (Figure 1). lished data, 2001–2005). Incidence of HBV infection among
Approximately 79% of newly acquired cases of hepatitis B are unvaccinated IDUs is high, ranging from 10 to 31 per 100
associated with high-risk sexual activity or injection-drug use; person-years (72–74). Risk for HBV transmission increases
other known exposures (i.e., occupational, household, travel, with the number of years of drug use and is associated with
and health-care–related) together account for 5% of new cases, frequency of injection and with sharing of drug-preparation
and 16% deny a specific risk factor for infection (61; CDC, equipment (e.g., cottons, cookers, and rinse water), indepen
unpublished data, 2001–2005). dent of syringe sharing (73,75).
Adults at risk for infection by sexual exposure. The most In a study of the seroprevalence of HBV infection among
common source of HBV infection among adults in the United IDUs admitted to drug treatment in six U.S. cities, 64%
States is sexual contact. Heterosexual transmission accounts (range: 50%–81%) had serologic evidence of HBV infection,
for approximately 39% of new HBV infections among adults, and seroprevalence increased with age (76). Studies of
street-recruited IDUs (77,78) and female IDUs (79) have iden
tified similar prevalence of HBV infection, whereas a lower Persons with chronic liver disease. Persons with chronic
prevalence (25%) was found in a study of young IDUs (aged liver disease are not at increased risk for HBV infection unless
18–30 years) (74). Chronic HBV infection has been identi they have percutaneous or mucosal exposure to infectious
fied in 3.1% of IDUs in a detention setting (77) and 7.1% of blood or body fluids. Furthermore, studies of the outcomes
IDUs with HIV coinfection (80). of acute hepatitis B among patients with chronic liver disease
Household contacts of persons with chronic HBV infec provide little evidence that acute hepatitis B increases their
tion. Seroprevalence of HBV infection among susceptible risk for an acute liver failure. However, concurrent chronic
household contacts of persons with chronic infection has var HBV infection might increase the risk for progressive chronic
ied, ranging from 14% to 60% (69,71,81–85). The risk for liver disease in HCV-infected patients (102).
infection is highest among sex partners of, and children living Travelers to HBV-endemic regions. Short-term travelers
with, a person with chronic HBV infection in a household or to regions in which HBV infection is of high or intermediate
extended family setting (83–85). endemicity (Box 2) typically are at risk for infection only
Developmentally disabled persons in long-term–care through exposure to blood in medical, health-care, or disaster-
facilities. Developmentally disabled persons in residential and relief activities; receipt of medical care that involves parenteral
nonresidential facilities historically have had high rates of HBV exposures; or sexual activity or drug use (103). Infection rates
infection (86,87), but the prevalence of infection has declined of 2%–5% per year among persons working in such regions
substantially since the implementation of routine hepatitis B for >6 months have been reported (104,105).
vaccination in these settings (88,89). Nonetheless, because HIV-positive persons. Published data on the overall preva
HBsAg-positive persons reside in such facilities, clients and lence of HBV and HIV coinfection in the United States are
staff continue to be at risk for infection.
Persons at risk for occupational exposure to HBV. BOX 2. Geographic regions* with intermediate† and high§
Before hepatitis B vaccination was widely implemented, HBV hepatitis B virus endemicity
infection was recognized as a common occupational hazard Africa: all countries
among persons who were exposed to blood while caring for East Asia: all countries
patients or working in laboratories (90,91). Since then, rou Eastern Europe and Northern Asia: all countries
tine hepatitis B vaccination of health-care workers and use of except Hungary
standard precautions to prevent exposure to bloodborne patho South Asia: all countries except Sri Lanka
gens have made HBV infection a rare event in these popula Southeast Asia: all countries
tions (92–94). Since the mid-1990s, the incidence of HBV Australia and the South Pacific: all countries and
infection among health-care workers has been lower than that territories except Australia and New Zealand
among the general population (94). Public safety workers with Middle East: all countries except Cyprus
exposures to blood also might be at risk for HBV infection Western Europe: Greece, Malta, Portugal, and Spain
(95–97); however, the prevalence of HBV infection in occu and indigenous populations of Greenland
pational groups such as police officers, firefighters, and cor North America: Alaska Natives and indigenous
rections officers generally does not differ from that in the populations of Northern Canada
general population when adjusted for race and age (97), and Central America: Belize, Guatemala, Honduras, and
infection is associated most often with nonoccupational risk Panama
factors (97,98). No increased risk for occupationally acquired South America: Argentina, Bolivia, Brazil, Ecuador, Guyana,
HBV infection has been documented in workers exposed Suriname, Venezuela, and the Amazonian areas of
infrequently to blood or body fluids (e.g., ward clerks, dietary Colombia and Peru
workers, maintenance workers, housekeeping personnel, teach Caribbean: Antigua and Barbuda, Dominica,
ers, and persons employed in day care settings) (91). Dominican Republic, Grenada, Haiti, Jamaica, Puerto
Hemodialysis patients. Since the initiation of strict infec Rico, St. Kitts and Nevis, St. Lucia, St. Vincent and
tion-control practices and hepatitis B vaccination, the rate of Grenadines, Trinidad and Tobago, and Turcs and
HBV infection among patients undergoing hemodialysis has Caicos
declined approximately 95% (99,100). Nonetheless, repeated
* A complete list of countries in each region is available at http://www.cdc.
outbreaks of HBV infection among unvaccinated patients gov/travel/destinat.htm.
† Hepatitis B surface antigen (HBsAg) prevalence of 2%–7%.
underscore the continued risk for infection in this population (101). § HBsAg prevalence of >8%.
limited. Studies of certain subgroups have identified prevalence FIGURE 3. Reported incidence* of acute hepatitis B among
persons aged >19 years, by race/ethnicity — United States,
of previous or current HBV infection of 45% in HIV-infected 1990–2005
MSM aged 22–29 years (CDC, unpublished data, 1998–2000),
24% in adolescent HIV-infected males (106), and 43% in HIV- 20
infected women, including 76% among HIV-infected female Black, non-Hispanic

Asian/Pacific Islander
IDUs (79). Chronic HBV infection has been identified in American Indian/Alaska Native
15
6%–14% of HIV-positive persons from Western Europe and Hispanic
the United States, including 9%–17% of MSM, 7%–10% of White, non-Hispanic
Incidence
IDUs, and 4%–6% of heterosexuals (107).
10
The course of HBV infection can be modified in the pres
ence of HIV, with a lower incidence of jaundice and a higher
incidence of chronic HBV infection (20,108,109). Limited 5
data also indicate that HIV-infected patients with chronic HBV
infection have an increased risk for liver-related mortality and
morbidity (110). 0
1990 1995 2000 2005
Incidence of Acute Hepatitis B Year
During 1990–2005, the overall incidence of reported acute * Per 100,000 population.
hepatitis B declined 78%, from 8.5 to 1.9 per 100,000 popu
lation (Figure 2), and the estimated number of new HBV 2002, acute hepatitis B incidence among adults decreased 35%
infections, after adjusting for underreporting and asymptom during 2002–2005, from 3.7 to 2.4 per 100,000 population
atic infections, declined from approximately 232,000 to (CDC, unpublished data, 2006). In 2005, the highest inci
approximately 51,000 infections (CDC, unpublished data, dence of acute hepatitis B occurred among persons aged
1990–2005). Among children and adolescents aged <19 years, 25–44 years.
incidence declined 96%, from 2.4 to 0.1 per 100,000 popu
lation. Among adults aged >19 years, incidence declined 76%, Prevalence of HBV Infection
from 9.9 to 2.4 per 100,000 population, and racial/ethnic During 1988–1994, the overall age-adjusted prevalence of
disparities in incidence were nearly eliminated for Asians/ HBV infection (including previous or chronic infection) in
Pacific Islanders, American Indians/Alaska Natives, and His the U.S. population was 4.9%, and the prevalence of chronic
panics (Figure 3). Incidence also declined substantially among infection was 0.4% (111). Persons who have immigrated to
blacks aged >19 years during this period, from 19.7 to 4.2 per the United States from countries in which HBV is endemic
100,000 population; however, in 2005, incidence among (Box 2, Figure 4) are affected disproportionately by chronic
blacks remained nearly three times higher than that among HBV infection; in particular, the majority of chronic HBV
other racial/ethnic populations. After leveling during 1999– infections in the United States are among Asians/Pacific
Islanders (112–114). The prevalence of chronic HBV infec
FIGURE 2. Reported incidence* of acute hepatitis B, by age tion among persons immigrating to the United States from
group — United States, 1990–2005 Central and Southeast Asia, the Middle East, and Africa var
15 ies (range: 5%–15%) and reflects the patterns of HBV infec
>20 yrs tion in the countries and regions of origin. During 1994–2003,
12–19 yrs approximately 40,000 immigrants with chronic HBV infec
10 <12 yrs
tion were admitted annually to the United States for perma
Incidence
nent residence (115; CDC, unpublished data, 2005).

5
Prophylaxis Against HBV Infection

0
Hepatitis B Vaccine
1990 1995 2000 2005
Year Hepatitis B vaccine is available as a single-antigen formula
tion and also in fixed combination with other vaccines. Two
* Per 100,000 population.
FIGURE 4. Geographic distribution of chronic hepatitis B virus (HBV) infection — worldwide, 2005*
HBsAg prevalence
>8% = high
2%–7% = intermediate
<2% = low
* For multiple countries, estimates of prevalence of hepatitis B surface antigen (HBsAg), a marker of chronic HBV infection, are based on limited data and
might not reflect current prevalence in countries that have implemented childhood hepatitis B vaccination. In addition, HBsAg prevalence might vary
within countries by subpopulation and locality.
single-antigen vaccines are available in the United States: express HBsAg in yeast, which then is purified from the cells
Recombivax HB® (Merck & Co., Inc., Whitehouse Station, by biochemical and biophysical separation techniques
New Jersey) and Engerix-B® (GlaxoSmithKline Biologicals, (118,119). Hepatitis B vaccines licensed in the United States
Rixensart, Belgium). Of the three licensed combination vac are formulated to contain 10–40 µg of HBsAg protein/mL.
cines, one (Twinrix® [GlaxoSmithKline Biologicals, Rixensart, Hepatitis B vaccines produced for distribution in the United
Belgium]) is used for vaccination of adults and two (Comvax® States do not contain thimerosal as a preservative or contain
[Merck & Co., Inc., Whitehouse Station, New Jersey] and only a trace amount (<1.0 µg mercury/mL) from the manu
Pediarix® [GlaxoSmithKline Biologicals, Rixensart, Belgium]) facturing process (120,121).
are used for vaccination of infants and young children. Twinrix
contains recombinant HBsAg and inactivated hepatitis A virus. Hepatitis B Immune Globulin
Comvax contains recombinant HBsAg and Haemophilus
HBIG provides passively acquired anti-HBs and temporary
influenzae type b (Hib) polyribosylribitol phosphate conju
protection (i.e., 3–6 months) when administered in standard
gated to Neisseria meningitidis outer membrane protein com
doses. HBIG typically is used as an adjunct to hepatitis B
plex. Pediarix contains recombinant HBsAg, diphtheria and
vaccine for postexposure immunoprophylaxis to prevent HBV
tetanus toxoids and acellular pertussis adsorbed (DTaP), and
infection. For nonresponders to hepatitis B vaccination, HBIG
inactivated poliovirus (IPV).
administered alone is the primary means of protection after
HBsAg is the antigen used for hepatitis B vaccination
an HBV exposure.
(116,117). Vaccine antigen can be purified from the plasma
HBIG is prepared from the plasma of donors with high
of persons with chronic HBV infection or produced by
concentrations of anti-HBs. The plasma is screened to elimi
recombinant DNA technology. For vaccines available in the
nate donors who are positive for HBsAg, antibodies to HIV
United States, recombinant DNA technology is used to
and hepatitis C virus (HCV), and HCV RNA. In addition, hepatitis A component in the combined vaccine is lower than
proper manufacturing techniques for HBIG inactivate viruses that in the single-antigen hepatitis A vaccine, allowing it to be
(e.g., HBV, HCV, and HIV) from the final product (122,123). administered in a 3-dose schedule instead of the 2-dose sched
No evidence exists to indicate that HBV, HCV, or HIV ever ule used for the single-antigen vaccine.
has been transmitted by HBIG commercially available in the
Nonstandard Vaccine Schedules
United States. HBIG that is commercially available in the
United States does not contain thimerosal. No apparent effect on immunogenicity has been docu
mented when minimum spacing of doses (i.e., 4 weeks
between doses 1 and 2, 8 weeks between doses 2 and 3, and
Adult Vaccination Schedules 16 weeks between doses 1 and 3) is not achieved precisely.
and Results of Vaccination Increasing the interval between the first 2 doses has little
effect on immunogenicity or final antibody concentration
Preexposure Vaccination (132–134). The third dose confers the maximum level of
seroprotection but acts primarily as a booster and appears to
Vaccination of Adults
provide optimal long-term protection (135). Longer intervals
Primary vaccination consists of >3 intramuscular doses of between the last 2 doses result in higher final antibody levels
hepatitis B vaccine (Table 2). The 3-dose vaccine series but might increase the risk for acquisition of HBV infection
administered intramuscularly at 0, 1, and 6 months produces among persons who have a delayed response to vaccination.
a protective antibody response in approximately 30%–55% No differences in immunogenicity are observed when vac
of healthy adults aged <40 years after the first dose, 75% after cines from different manufacturers are used to complete the
the second dose, and >90% after the third dose (124,125). vaccine series.
After age 40 years, the proportion of persons who have a pro
tective antibody response after a 3-dose vaccination regimen Response to Revaccination
declines below 90%, and by age 60 years, protective levels of Although serologic testing for immunity is not necessary
antibody develop in only 75% of vaccinated persons (126). after routine vaccination of adults, postvaccination testing is
In addition to age, other host factors (e.g., smoking, obesity, recommended for persons whose subsequent clinical manage
genetic factors, and immune suppression) contribute to ment depends on knowledge of their immune status, includ
decreased vaccine response (127–130). Alternative vaccina ing certain health-care and public safety workers; chronic
tion schedules (e.g., 0, 1, and 4 months or 0, 2, and 4 months) hemodialysis patients, HIV-infected persons, and other
have been demonstrated to elicit dose-specific and final rates immunocompromised persons; and sex or needle-sharing part
of seroprotection similar to those obtained on a 0-, 1-, ners of HBsAg-positive persons (Appendix A). Of persons who
6-month schedule (131). did not respond to a primary 3-dose vaccine series with anti-
The combined hepatitis A–hepatitis B vaccine (Twinrix) is HBs concentrations of >10 mIU/mL, 25%–50% responded
indicated for vaccination of persons aged >18 years with risk to an additional vaccine dose, and 44%–100% responded to
factors for both hepatitis A and hepatitis B. The dosage of the a 3-dose revaccination series (136–141). Better response to
TABLE 2. Recommended doses of currently licensed formulations of adult hepatitis B vaccine, by group and vaccine type
Single-antigen vaccine Combination vaccine
Recombivax HB®* Engerix-B®† Twinrix®†§
Dose Vol. Dose Vol. Dose Vol.
Group (µg)¶ (mL) (µg)¶ (mL) (µg)¶ (mL)
Adults (aged >20 years) 10 1.0 20 1.0 20 1.0
Hemodialysis patients and other immunocompromised

persons aged >20 yrs 40** 1.0 40†† 2.0 NA§§ NA
* Merck & Co., Inc., Whitehouse Station, New Jersey.
† GlaxoSmithKline Biologicals, Rixensart, Belgium.
§ Combined hepatitis A and hepatitis B vaccine, recommended for persons aged >18 years who are at increased risk for both hepatitis B virus and
hepatitis A virus infections.
¶ Recombinant hepatitis B surface antigen protein dose.
** Dialysis formulation administered on a 3-dose schedule at 0, 1, and 6 months.
†† Two 1.0-mL doses administered in 1 or 2 injections on a 4-dose schedule at 0, 1, 2, and 6 months.
§§ Not applicable.
revaccination occurs in persons who have measurable but low response before exposure to HBV have a high level of protec
(<10 mIU/mL) levels of antibody after the initial series tion from infection (155,156).
(136,137). Increased vaccine doses (e.g., double the standard After primary immunization with hepatitis B vaccine, anti-
dose) were demonstrated to enhance revaccination response HBs levels decline rapidly within the first year and more slowly
rates in one study (140) but not in another (138). Intrader thereafter. Among young adults who respond to a primary
mal vaccination has been reported to be immunogenic in per vaccine series with antibody concentrations of >10 mIU/mL,
sons who did not respond to intramuscular vaccination 17%–50% have low or undetectable concentrations of anti-
(142,143); however, intradermal vaccination is not a route of HBs (reflecting anti-HBs loss) 10–15 years after vaccination
administration indicated in the manufacturers’ package label (155–157). In the absence of exposure to HBV, the persis
ing. Persons who do not have protective levels of anti-HBs tence of detectable anti-HBs after vaccination depends on the
1–2 months after revaccination either are primary concentration of postvaccination antibodies (158).
nonresponders or are infected with HBV. Genetic factors might Even when anti-HBs concentrations decline to <10 mIU/mL,
contribute to nonresponse to hepatitis B vaccination nearly all vaccinated persons remain protected against HBV
(130,137). infection. The mechanism for continued vaccine-induced pro
tection is thought to be the preservation of immune memory
Groups Requiring Different Vaccination Doses
through selective expansion and differentiation of clones of
or Schedules
antigen-specific B and T lymphocytes (159). Persistence of
Compared with immunocompetent adults, hemodialysis vaccine-induced immune memory among persons who
patients are less likely to have protective levels of antibody responded to a primary adult vaccine series 4–23 years previ
after vaccination with standard vaccine dosages; protective ously but then had anti-HBs concentrations of <10 mIU/mL
levels of antibody developed in 67%–86% (median: 64%) of has been demonstrated by an anamnestic increase in anti-HBs
adult hemodialysis patients who received 3–4 doses of either concentrations in 74%–100% of these persons 2–4 weeks
vaccine in various dosages and schedules (100). Higher after administration of an additional vaccine dose and by
seroprotection rates have been identified in patients with antigen-specific B and T cell proliferation (160). Although
chronic renal failure, particularly those with mild or moder direct measurement of immune memory is not yet possible,
ate renal failure, who were vaccinated before becoming dialy these data indicate that a high proportion of vaccinees retain
sis dependent. After vaccination with a 4-dose series, the immune memory and would have an anti-HBs response upon
seroprotection rate among adult predialysis patients with exposure to HBV.
serum creatinine levels of <4.0 mg/dL was 86%, compared Population-based studies of highly vaccinated populations
with 37% among patients with serum creatinine levels of >4.0 have demonstrated elimination of new HBV infections for up
mg/dL, 88% of whom were dialysis patients (144). to 2 decades after hepatitis B immunization programs were
Humoral response to hepatitis B vaccination also is reduced initiated (161–163). Breakthrough infections (detected by the
in other immunocompromised persons (e.g., HIV-infected presence of anti-HBc or HBV DNA) have been documented
persons, hematopoietic stem-cell transplant recipients, and in a limited percentage of vaccinated persons (159,164), but
patients undergoing chemotherapy) (145–147). Modified these infections typically are transient and asymptomatic;
dosing regimens, including doubling the standard antigen dose breakthrough infections resulting in chronic HBV infection
or administering additional doses, might increase response rates have been documented only rarely among infants born to
(148–150). However, limited data regarding response to these HBsAg-positive mothers (165) and have not been observed
alternative vaccination schedules are available. among immunocompetent adults.
Immune Memory Limited data are available on the duration of immune
memory after hepatitis B vaccination in immunocompromised
Anti-HBs is the only easily measurable correlate of vaccine- persons (e.g., HIV-infected patients, dialysis patients, patients
induced protection. Immunocompetent persons who achieve undergoing chemotherapy, or hematopoietic stem-cell trans
anti-HBs concentrations of >10 mIU/mL after preexposure plant patients). No clinically significant HBV infections have
vaccination have nearly complete protection against both acute been documented among immunocompromised persons who
disease and chronic infection, even if anti-HBs concentrations maintain protective levels of anti-HBs. In studies of long-term
decline subsequently to <10 mIU/mL (151–154). Although protection among HIV-infected persons, breakthrough infec
immunogenicity is lower among immunocompromised per tions occurring after a decline in anti-HBs concentrations to
sons, those who achieve and maintain a protective antibody <10 mIU/mL have been transient and asymptomatic (155).
However, among hemodialysis patients who responded to the However, in placebo-controlled studies, these side effects were
vaccine, clinically significant HBV infection has been docu reported no more frequently among persons receiving hepati
mented in persons who have not maintained anti-HBs con tis B vaccine than among persons receiving placebo (179).
centrations of >10 mIU/mL (166).
Adverse Events
Postexposure Prophylaxis CDC and FDA continually assess the safety of hepatitis B
Both passive-active postexposure prophylaxis (PEP) using vaccine and other vaccines through ongoing monitoring of
HBIG and hepatitis B vaccine and active PEP using hepatitis data from the Vaccine Safety Datalink (VSD) project, the
B vaccine alone are highly effective in preventing infection Vaccine Adverse Events Reporting System (VAERS), and other
after exposure to HBV (167–170). HBIG alone has also been surveillance systems. A causal association has been established
demonstrated to be effective in preventing HBV transmission between receipt of hepatitis B vaccine and anaphylaxis (178).
(68,171–173), but with the availability of hepatitis B vac On the basis of VSD data, the estimated incidence of anaphy
cine, HBIG typically is used as an adjunct to vaccination. laxis among children and adolescents who received hepatitis
Guidelines for PEP for adults with occupational (174) and B vaccine is one case per 1.1 million vaccine doses distributed
nonoccupational exposures (Appendix B) to HBV have been (95% confidence interval = 0.1–3.9) (180).
developed. Early postlicensure surveillance of adverse events suggested
The major determinant of the effectiveness of PEP is early a possible association between Guillain-Barré syndrome (GBS)
administration of the initial dose of vaccine. The effectiveness and receipt of the first dose of plasma-derived hepatitis B vac
of PEP diminishes the longer after exposure it is initiated cine among U.S. adults (181). However, in a subsequent analy
(27,175,176). Studies are limited on the maximum interval sis of GBS cases reported to CDC, FDA, and vaccine
after exposure during which PEP is effective, but the interval manufacturers, among an estimated 2.5 million adults who
is likely <7 days for needlestick (171,172,177) exposures and received >1 dose of recombinant hepatitis B vaccine during
<14 days for sexual exposures (68,154,168,170,173). 1986–1990, the rate of GBS that occurred after hepatitis B
Substantial evidence suggests that adults who respond to vaccination did not exceed the background rate among
hepatitis B vaccination are protected from chronic HBV unvaccinated persons (CDC, unpublished data, 1992). An
infection for at least 20 years even if vaccinees lack detectable Institute of Medicine review concluded that evidence was
anti-HBs at the time of an exposure (151–153). For this rea insufficient to reject or accept a causal association between
son, immunocompetent persons who have had postvaccina GBS and hepatitis B vaccination (178,182,183).
tion testing and are known to have responded to hepatitis B One retrospective case-control study (184,185) reported an
vaccination with anti-HBs concentrations of >10 mIU/mL association between hepatitis B vaccine and multiple sclerosis
do not require additional passive or active immunization after (MS) among adults. However, multiple studies (186–189) have
an HBV exposure and do not need further periodic testing to demonstrated no such association. Reviews by scientific pan
assess anti-HBs concentrations. els have favored rejection of a causal association between hepa
titis B vaccination and MS (190,191).
In rare instances, chronic illnesses have been reported after
Vaccine Safety hepatitis B vaccination, including chronic fatigue syndrome
Hepatitis B vaccines have been demonstrated to be safe when (192), neurologic disorders (e.g., leukoencephalitis, optic neu
administered to infants, children, adolescents, and adults ritis, and transverse myelitis) (193–195), rheumatoid arthri
(178). Since 1982, an estimated 70 million adolescents and tis (196,197), type 1 diabetes (198), and autoimmune disease
adults and 50 million infants and children in the United States (199). However, no evidence of a causal association between
have received >1 dose of hepatitis B vaccine (CDC, unpub these conditions or other chronic illnesses and hepatitis B vac
lished data, 2004). cine has been demonstrated (183,190,200–203).
Reported episodes of alopecia (hair loss) after rechallenge
Vaccine Reactogenicity with hepatitis B vaccine suggest that vaccination might, in
rare cases, trigger episodes of alopecia (204). However, a popu
The most frequently reported side effects in persons receiv lation-based study determined no statistically significant
ing hepatitis B vaccine are pain at the injection site (3%–29%) association between alopecia and hepatitis B vaccine (205).
and temperature of >99.9°F (>37.7°C) (1%–6%) (124,125).
Contraindications and Precautions reluctant to discuss risk behaviors (215), and providers might
not make hepatitis B vaccination a priority compared with
Hepatitis B vaccination is contraindicated for persons with
other clinical care services.
a history of hypersensitivity to yeast or any vaccine compo
One strategy demonstrated to be effective at increasing vac
nent (206–209). Despite a theoretic risk for allergic reaction
cination coverage among adults at risk for HBV infection is
to vaccination in persons with allergy to Saccharomyces cerevisiae
to offer vaccination to all adults as part of routine prevention
(baker’s yeast), no evidence exists to document adverse reac
services in settings in which a high proportion of adults have
tions after vaccination of persons with a history of yeast allergy.
HBV risk factors (10,216–223). In STD and HIV treatment
Persons with a history of serious adverse events (e.g., anaphy
facilities, health-care settings serving IDUs, and health-care
laxis) after receipt of hepatitis B vaccine should not receive
settings targeting services to MSM, nearly all patients have
additional doses. As with other vaccines, vaccination of persons
behavioral risk factors for HBV infection. Furthermore, a high
with moderate or severe acute illness, with or without fever,
proportion of persons receiving health care in HIV testing
should be deferred until illness resolves (210). Vaccination is
facilities or correctional facilities report sexual and drug-use
not contraindicated in persons with a history of MS, GBS,
risk behaviors (224,225). Therefore, providing hepatitis B
autoimmune disease (e.g., systemic lupus erythematosis or rheu
vaccination in these settings offers an efficient and effective
matoid arthritis), or other chronic diseases.
way to reach adults at highest risk. During 2001–2004, in a
Pregnancy is not a contraindication to vaccination. Limited
study of 760 adults with reported acute hepatitis B who par
data suggest that developing fetuses are not at risk for adverse
ticipated in CDC’s Sentinel Counties Study of Viral Hepati
events when hepatitis B vaccine is administered to pregnant
tis, 39% reported a history of STD treatment, 40% reported
women (211). Available vaccines contain noninfectious HBsAg
a history of incarceration, and 22% reported a history of drug
and should cause no risk of infection to the fetus.
treatment; overall, 61% would have had at least one opportu
nity to be vaccinated either during STD or drug treatment or
Implementation Barriers at a correctional facility (226).
Demonstration projects that supported the purchase of hepa
and Rationale for New titis B vaccine and its administration in settings in which a
Recommendations high proportion of adults have HBV risk factors have estab
Soon after hepatitis B vaccine was licensed in 1982, ACIP lished the feasibility of providing the vaccine as part of com
recommended vaccination for adults at increased risk for HBV prehensive STD, HIV, and hepatitis prevention services (10).
infection (212). However, the recommendations were not When clients were offered hepatitis B vaccination in such set
widely implemented, and coverage among adults at risk for tings, first-dose acceptance rates of 70%–85% were achieved
HBV infection remained low. By the early 1990s, the diffi (10,216,223,227). These demonstration projects have identi
culty in vaccinating adults at risk for HBV infection and the fied the components of successful adult hepatitis B vaccina
substantial burden of HBV-related disease resulting from tion programs (Box 3). In addition, “one-stop” delivery of
infections acquired during childhood indicated that additional integrated prevention services was preferred by the majority
hepatitis B vaccination strategies were needed (213,214). In of patients and typically resulted in enhanced delivery of all
1991, recommendations for vaccination of unvaccinated adults
at high risk for HBV infection became part of the national BOX 3. Components of a successful adult hepatitis B vac
strategy adopted by ACIP and professional medical organiza cination program
tions to eliminate HBV transmission in the United States (3). • Institutional commitment to the program
However, hepatitis B vaccine still is not offered routinely in • Trained and knowledgeable staff who promote the pro
medical settings serving adults, and a substantial number of gram
adults at risk for HBV infection remain unvaccinated. • Patients who are informed about hepatitis B and the
Multiple factors contribute to low hepatitis B vaccination health benefits of hepatitis B vaccination
coverage among adults at risk. In contrast to vaccination of • Integrated delivery of vaccination and other services
children, no national program exists to support vaccine pur • Protocols and standing orders
chase and infrastructure for vaccine delivery to uninsured and • Protected patient confidentiality
underinsured adults. Reimbursement mechanisms for vacci • Infrastructure that ensures vaccine administration is
nation of adults with health insurance also are not widely used. accessible, convenient, and flexible for patients
In addition, certain patients and health-care providers are • Funding for vaccine
prevention services (227). Return visits for second and third and drug-related behaviors, particularly when these behaviors are
doses of hepatitis B vaccine also provide opportunities for not perceived as relevant to the clinical encounter. In addition,
patients to receive other STD/HIV-related services (e.g., test despite recommendations of the U.S. Preventive Services Task
results, additional counseling, and referral). Multiple studies Force and AMA, providers might be reluctant to inquire about
have established the cost-effectiveness of providing hepatitis behavioral risk factors. For example, surveys of physicians and
B vaccination at STD/HIV counseling and testing sites, cor patients conducted during 1995–1999 indicated that fewer than
rectional institutions, drug-abuse treatment centers, and other half of patients were asked about sexual behaviors (236–238).
settings serving adults at risk for HBV infection (228–231). Health-care providers should educate all patients about the
Universal vaccination of adults in settings in which a high health benefits of hepatitis B vaccination, including risk factors
proportion of persons have HBV risk factors will reach a sub for HBV infection and the importance of vaccination for per
stantial proportion of all adults at risk for HBV infection. sons who engage in certain risk behaviors. This information
However, not all adults with risk factors for HBV infection might stimulate patients to request vaccination from their pri
visit these settings. For example, an estimated 80%–95% of mary care providers, without requiring them to acknowledge a
STDs are diagnosed in settings other than STD clinics specific risk factor.
(232,233). Therefore, primary care and clinical preventive Another possible strategy is to offer vaccination to all adults
service providers (e.g., physicians’ offices, community health in age groups with the highest incidence of infection as part
centers, family planning clinics, liver disease clinics, and travel of routine medical care (Figure 1). An age-based approach
clinics) also should provide hepatitis B vaccine whenever might simplify vaccination-related decision-making by prac
indicated or requested as part of regular preventive care. Lim titioners and remove the stigma associated with disclosure of
ited data are available regarding best practices in primary care risk behaviors. Other adult vaccines, including those for
and specialty medical settings to achieve high vaccination cov influenza and pneumococcal disease, are delivered on age-based
erage among adults at risk for HBV infection. In one project schedules. However, the effectiveness of age-based strategies
in which hepatitis B vaccine was made available free of charge in increasing hepatitis B vaccination coverage among adults
to primary care clients in community clinics, low vaccination at risk is unknown. In addition, age-based strategies for adult
coverage rates were observed, compared with rates at other vaccination would be substantially more costly than risk-
venues (10). This finding suggests that provision of free vac targeted approaches (CDC, unpublished data, 2005).
cine alone might not ensure increased use of hepatitis B vac Lack of funding for vaccine and its administration is a
cine and that other implementation strategies (e.g., education major barrier to provision of hepatitis B vaccine to adults.
and training of clinicians and standing orders) are needed to Hepatitis B vaccine often is a reimbursable charge in health-
prompt providers to offer vaccination to adults. care settings that bill insurance or Medicaid for services, and
In primary care settings, targeting vaccination to persons at surveys of public and private insurers indicate high rates of
risk is an efficient approach to preventing HBV infection. coverage for hepatitis B vaccination (239,240). In one study,
During 2001–2005, among persons with acute hepatitis B an estimated 74% of adults aged 18–49 years with risk factors
who participated in CDC’s Sentinel Counties Study of Viral for HBV infection had health insurance coverage (241). How
Hepatitis, 84% reported risk behaviors or characteristics, ever, public clinics might not have systems in place to bill for
either during the incubation period (i.e., 6 weeks–6 months) vaccination services, and reimbursement of private providers
or during their lifetimes, that placed them in a group for which might be inadequate to cover the purchase and administra
hepatitis B vaccination was recommended (CDC, unpublished tion of vaccine. Other adults either lack private insurance or
data, 2001–2005). Providers in primary care settings can are not eligible for reimbursement by Medicaid. Although the
ascertain patients’ risks for HBV infection and identify candi Vaccines for Children program provides federally funded vac
dates for hepatitis B vaccination during routine patient visits. cine and administration costs for vaccination of uninsured
Assessment of patients’ sex- and drug-related risk factors is and underinsured children and youth aged <19 years, no simi
recommended by the U.S. Preventive Services Task Force and lar program supports adult vaccination.
the American Medical Association (AMA) (234,235) and has Certain adult hepatitis B vaccination programs have been
the ancillary benefit of identifying candidates for other pre successful at identifying federal, state, or local funds to
vention interventions (e.g., screening for HIV infection and provide free or low-cost hepatitis B vaccination to uninsured
other STDs and drug-abuse treatment). or underinsured adults. For example, the Immunization Grant
However, risk-targeted approaches can miss persons in need Program, created under Section 317 of the Public Health
of prevention services. Patients might be reluctant to report sex- Service Act, provides funding to state, local, and territorial
public health agencies for vaccine purchase and vaccination- BOX 4. Adults recommended to receive hepatitis B vaccination
program operation (242). Section 317 funds can be used to Persons at risk for infection by sexual exposure
purchase childhood and adult vaccines, including adult hepa • Sex partners of hepatitis B surface antigen (HBsAg)
titis B vaccine. However, lack of adequate funding constrains positive persons
efforts to increase vaccination coverage among adults. To • Sexually active persons who are not in a long-term,
maximize available resources for hepatitis B vaccination, pub mutually monogamous relationship (e.g., persons with
lic and private health-care providers should become familiar more than one sex partner during the previous 6 months)
with insurance billing and reimbursement mechanisms that • Persons seeking evaluation or treatment for a sexually
can be used for hepatitis B vaccine. AMA billing and reim transmitted disease
bursement guidelines are available at http://www.ama-assn.org/ • Men who have sex with men
ama1/pub/upload/mm/36/ama_hep_coding_trifo.pdf. Persons at risk for infection by percutaneous or
Although HBV infections are expected to decline as a result mucosal exposure to blood
of universal childhood immunization and increased vaccina • Current or recent injection-drug users
tion of adults at risk, an estimated 1.25 million persons in the • Household contacts of HBsAg-positive persons
United States are living with chronic HBV infection and • Residents and staff of facilities for developmentally
require essential prevention services and medical management. disabled persons
In particular, Asians/Pacific Islanders in the United States have • Health-care and public safety workers with reasonably
a high prevalence of chronic HBV infection, representing a anticipated risk for exposure to blood or blood-
major health disparity. Persons with chronic HBV infection contaminated body fluids
often are unaware of their infection status or do not receive • Persons with end-stage renal disease, including
predialysis, hemodialysis, peritoneal dialysis, and home
needed care. Few programs have been implemented to iden
dialysis patients
tify HBsAg-positive persons, provide or refer these persons
Others
for appropriate medical management, and provide vaccina
• International travelers to regions with high or interme
tion to their contacts (243). During delivery of hepatitis B
diate levels (HBsAg prevalence of >2%) of endemic HBV
vaccination and provision of other preventive services, health- infection (Figure 4, Box 2)
care providers have opportunities to identify persons with • Persons with chronic liver disease
chronic HBV infection, refer them for counseling and man • Persons with HIV infection
agement, and ensure that their susceptible contacts receive • All other persons seeking protection from HBV infection
vaccination. Guidelines to identify and manage HBsAg
positive persons have been developed (Appendix C).
Implementation of the recommendations and strategies
• Providers should select the vaccine schedule they consider
outlined in this report and the companion ACIP recommen
necessary to achieve completion of the vaccine series
dations for infants, children, and adolescents (11) should lead
(Table 2, Box 5).
ultimately to the elimination of HBV transmission in the
• Public health programs and primary care providers should
United States. New information will have implications for this
adopt strategies appropriate for the practice setting to
effort, and adjustments and changes are expected to occur.
ensure that all adults at risk for HBV infection are offered
hepatitis B vaccine (Box 6).
Recommendations
and Implementation Strategies

BOX 5. Hepatitis B vaccine schedules for adults (aged >20
years)*
for Hepatitis B Vaccination of Adults
0, 1, and 6 months
Recommendations 0, 1, and 4 months
• Hepatitis B vaccination is recommended for all unvacci 0, 2, and 4 months
nated adults at risk for HBV infection and for all adults 0, 1, 2, and 12 months†
requesting protection from HBV infection (Box 4). * All schedules are applicable to single-antigen hepatitis B vaccines;
Acknowledgment of a specific risk factor should not be a Twinrix® (combined hepatitis A and hepatitis B vaccine) may be
administered at 0, 1, and 6 months.
requirement for vaccination. † A 4-dose schedule of Engerix-B® is licensed for all age groups.
BOX 6. Implementation strategies for adult hepatitis B BOX 7. Settings in which hepatitis B vaccination is recom
vaccination mended for all adults
Settings in which a high proportion of persons have • Sexually transmitted disease treatment facilities
risk factors for hepatitis B virus (HBV) infection • Human immunodeficiency virus testing and treatment
• Implement standing orders to administer hepatitis B vac facilities
cine as part of routine services to all adults who have • Facilities providing drug-abuse treatment and preven
not completed vaccination.* tion services
Primary care and specialty medical settings • Health-care settings targeting services to injection-drug users
• Implement standing orders to identify adults recom • Correctional facilities
mended for hepatitis B vaccination and administer vac • Health-care settings targeting services to men who have
cination as part of routine services. sex with men
— Provide information to all adults regarding the • Chronic-hemodialysis facilities and end-stage renal
health benefits of hepatitis B vaccination, includ disease programs
ing risk factors for HBV infection and persons for • Institutions and nonresidential day care facilities for
whom vaccination is recommended. developmentally disabled persons
— Help adults assess their need for vaccination by ob
taining a history that emphasizes risks for sexual
transmission and percutaneous or mucosal expo — when feasible, hepatitis B vaccination should be
sure to blood. offered in outreach and other settings in which ser
— Administer hepatitis B vaccine to all adults who re vices are provided to persons at risk for HBV infection
port risks for HBV infection.* (e.g., needle-exchange programs, HIV testing sites,
— Provide hepatitis B vaccine to all adults seeking pro HIV prevention programs, and homeless shelters).
tection from HBV infection. Acknowledgment of • In primary care and specialty medical settings (e.g.,
a specific risk factor for HBV infection is not a re physician’s offices, family planning clinics, community
quirement for vaccination. health centers, liver disease clinics, and travel clinics), pro
Occupational health programs viders should implement standing orders to identify adults
• Identify staff whose work-related activities involve expo recommended for hepatitis B vaccination and administer
sure to blood or other potentially infectious body fluids. vaccination as part of routine services. To ensure vaccina
• Provide education to encourage vaccination. tion of persons at risk for HBV infection, health-care
• Implement active follow-up, with reminders to track providers should
vaccine-series completion among persons receiving vac
— provide information to all adults regarding the health
cination.
benefits of hepatitis B vaccination, including the risk
• Provide appropriate postvaccination testing 1–2 months
factors for HBV infection and persons for whom
after vaccine-series completion.
vaccination is recommended;
* In populations that have expected high rates of previous HBV infection,
prevaccination testing might reduce costs by avoiding vaccination of — help all adults assess their need for vaccination by
persons who are already immune (see Appendix A, Prevaccination obtaining a history that emphasizes risks for sexual
Serologic Testing for Susceptibility).
transmission and percutaneous or mucosal exposure
to blood;
Implementation Strategies — administer hepatitis B vaccine to adults who report
• In settings in which a high proportion of persons have risk factors for HBV infection; and
risk factors for HBV infection (Box 7) — provide hepatitis B vaccine to all adults requesting pro
— all adults should be assumed to be at risk for HBV tection from HBV infection without requiring
infection and should be offered hepatitis B vaccina acknowledgment of a specific risk factor.
tion if they have not completed a licensed hepatitis B • Occupational health programs should
vaccine series; — identify all staff whose work-related activities involve
— health-care providers should implement standing exposure to blood or other potentially infectious body
orders (244) to administer hepatitis B vaccine as part fluids in a health-care, laboratory, public safety, or
of routine services to adults who have not completed institutional setting (including employees, students,
the vaccine series and make hepatitis B vaccination a contractors, attending clinicians, emergency medical
standard component of evaluation and treatment for technicians, paramedics, and volunteers);
STDs and HIV/AIDS (Table 3); and — provide education to staff to encourage vaccination;
TABLE 3. Recommended HIV/AIDS, sexually transmitted disease (STD), and viral hepatitis prevention services, by risk population
Risk population* Recommended services
High-risk heterosexuals
Persons seeking STD evaluation or treatment Hepatitis B vaccination
Testing for human immunodeficiency virus (HIV) infection†
Testing for syphilis, gonorrhea, and chlamydia, as clinically indicated§
Sexually active men not in a long-term, Hepatitis B vaccination

mutually monogamous relationship Annual testing for HIV infection†¶
Sexually active women not in a long-term, Hepatitis B vaccination**

mutually monogamous relationship Annual testing for HIV infection†¶
Annual testing for chlamydia (Note: also recommended for all sexually active females aged <25 yrs)§
Men who have sex with men (MSM)

All MSM Hepatitis A vaccination
Hepatitis B vaccination**
Sexually active MSM not in a long-term, Hepatitis A vaccination

mutually monogamous relationship Hepatitis B vaccination**
Annual testing for HIV infection†
Annual testing for syphilis, gonorrhea, and chlamydia§
Injection-drug users Hepatitis A vaccination††

Hepatitis B vaccination
Testing for hepatitis C virus infection§§
Annual testing for HIV infection†
Substance-abuse treatment¶¶
* Testing for HIV infection, chlamydia, gonorrhea, syphilis, and hepatitis B surface antigen also is recommended for pregnant women (CDC. Revised
recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR 2006;55[No. RR-14]; CDC. Sexually
transmitted diseases treatment guidelines. MMWR 2006;55[No. RR-11]; CDC. A comprehensive immunization strategy to eliminate transmission of
hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices [ACIP]. Part 1: immunization of
infants, children, and adolescents. MMWR 2005;54[No. RR-16]).
† CDC. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR 2006;55(No. RR-14).
§ CDC. Sexually transmitted diseases treatment guidelines 2006. MMWR 2006;55(No. RR-11).
¶ HIV screening is recommended for all persons aged 13–64 years. Repeat screening is recommended at least annually for persons likely to be at high
risk for HIV infection, including MSM or heterosexuals who themselves or whose sex partners have had more than one partner since their most recent
HIV test.
** Hepatitis B vaccination is recommended for persons with more than one sex partner during the previous 6 months.
†† CDC. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices
(ACIP). MMWR 2006;55(No. RR-7).
§§ CDC. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR 1998;47(No. RR-19).
Recommended frequency of testing for hepatitis C virus infection has not been determined.
¶¶ CDC. Substance abuse treatment for injection drug users: a strategy with many benefits. Atlanta, GA: US Department of Health and Human Services,
CDC; 2002. Available at http://www.cdc.gov/idu/facts/treatment.htm.
— implement active follow-up, with reminders to track appropriate referrals for counseling and medical man
completion of the vaccine series among persons agement (Appendix C);
receiving vaccination; and — provide culturally appropriate materials to educate
— provide appropriate postvaccination testing adults about hepatitis B and the importance of vacci
(Appendix A). nation (available at http://www.cdc.gov/ncidod/
• Providers in all settings in which hepatitis B vaccine is diseases/hepatitis/b/index.htm#materials);
provided should — offer vaccination in a way that is accessible, conve
— assess patients’ needs for other vaccines recommended nient, and flexible for patients;
for adults (schedule available at http://www.cdc.gov/ — be familiar with ACIP’s general recommendations on
nip/recs/adult-schedule.htm) and administer these immunization (210), which provide technical guid
vaccines at the same office visit at which hepatitis B ance regarding common immunization concerns of
vaccine is administered; health-care providers;
— identify and vaccinate all susceptible household, sex, — give persons who are eligible for vaccination a copy
and needle-sharing contacts of HBsAg-positive per of the most current vaccine information statement
sons, and provide HBsAg-positive persons with for hepatitis B vaccine, as required by federal law
(see Appendix A, Hepatitis B Vaccine Dose and Acknowledgments

Administration); The following persons contributed to the development of this
— institute methods to identify persons with a history of report: Guthrie S. Birkhead, MD, AIDS Institute, New York State
vaccination (see Appendix A, Unknown or Uncertain Department of Health, Albany, New York; Anna S. F. Lok, MD,
Division of Gastroenterology, University of Michigan, Ann Arbor,
Vaccination Status);
Michigan; Molli C. Conti, Hepatitis B Foundation, Doylestown,
— provide vaccinated persons with a personal record Pennsylvania; Josiah D. Rich, MD, Brown University, Providence,
card documenting receipt of vaccination (available Rhode Island; Robert A. Gunn, MD, San Diego County Health
at http://www.immunize.org/guide/aov21_appb_ and Human Services Agency, San Diego, California; Harold S.
record.pdf ); Margolis, MD, Joanna Buffington, MD, Alison Greenspan, MPH,
— develop tracking and reminder systems to ensure Stephanie M. Neitzel, Kevin P. O’Connor, MA, Annemarie Wasley,
completion of the vaccine series (descriptions of such PhD, Brigette F. Ulin, MPH, Ian T. Williams, PhD, Division of
systems are available at http://www.cdc.gov/nip/ Viral Hepatitis, Matthew T. McKenna, MD, Division of HIV/AIDS
publications/adultstrat.htm); Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD,
— report adverse events to VAERS using report forms and TB Prevention (proposed); William L. Atkinson, MD, Edward
and assistance available from CDC at telephone W. Brink, MD, Immunization Services Division, Susan A. Maloney,
1-800-822-7967 or from VAERS at http://www.vaers. MD, Division of Global Migration and Quarantine, National
Center for Immunization and Respiratory Diseases (proposed),
hhs.gov; and
CDC.
— be familiar with billing and reimbursement guidelines
for hepatitis B vaccination (available at http://www. References
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tion strategies. JAMA 1990;263:1218–22. reported cases of sexually transmitted disease by sex and reporting
214. Armstrong GL, Mast EE, Wojczynski M, Margolis HS. Childhood source: United States, 2004. Atlanta, GA: US Department of Health
hepatitis B virus infections in the United States before hepatitis and Human Services, CDC; 2005. Available at http://www.cdc.gov/
B immunization. Pediatrics 2001;108:1123–8. std/stats/tables/tablea2.htm.
215. Liddicoat RV, Horton NJ, Urban R, Maier E, Christiansen D, Samet 234. US Preventive Services Task Force. Counseling to prevent HIV infec
JH. Assessing missed opportunities for HIV testing in medical set tion and other sexually transmitted diseases. Guide to clinical pre
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2005;82:151–61. Chicago, IL: American Medical Association; 2004.
217. Charuvastra A, Stein J, Schwartzapfel B, et al. Hepatitis B vaccina 236. Maheux B, Haley N, Rivard M, Gervais A. STD risk assessment and
tion practices in state and federal prisons. Public Health Rep 2001; risk-reduction counseling by recently trained family physicians. Acad
116:203–9. Med 1995;70:726–8.
237. Bull SS, Rietmeijer C, Fortenberry JD, et al. Practice patterns for the 241. Jain N, Yusuf H, Wortley PM, Euler GL, Walton S, Stokley S. Fac
elicitation of sexual history, education, and counseling among tors associated with receiving hepatitis B vaccination among high-
providers of STD services: results from the gonorrhea community risk adults in the United States: an analysis of the National Health
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238. Maheux B, Haley N, Rivard M, Gervais A. Do physicians assess 242. CDC. Programs in brief: immunizations. Immunization Grant Pro
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Presented at the 38th National Immunization Conference, Nashville, infection. Am J Prev Med 2001;20:272–6.
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240. Rosenbaum S, Stewart A, Cox M, Lee A. The epidemiology of U.S. tion Practices. MMWR 2000;49(No. RR-1):15–26.
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Appendix A
Immunization Management Issues
Hepatitis B Vaccine Dose ately after infusion of coagulation factor. Subcutaneous

and Administration administration of vaccine can be considered for these
persons but might result in lower response and increased
• Recommended vaccine doses vary by product, age of local reaction.
recipient, and needs of special populations (see Table 2). • Hepatitis B vaccine should be stored at 35°F–46°F
Although the antigen contents of vaccines differ, vaccines (2°C–8oC) and should not be frozen.
made by different manufacturers are interchangeable for • A vaccine information statement (VIS) must be provided
all adult schedules. to recipients of hepatitis B vaccine. The National Childhood
• Hepatitis B vaccine should be administered by intramus Vaccine Injury Act of 1986 (42 U.S.C. § 300aa-26)
cular injection. The deltoid muscle is the recommended requires vaccine providers to give a copy of the most cur
site of administration for adults. Injection into the but rent vaccine-specific VIS to all recipients of vaccines that
tock is associated with decreased immunogenicity (1–4). are included on the National Vaccine Injury Compensa
Intradermal administration can result in a lower sero tion Program table maintained by the Health Resources
conversion rate and final concentration of antibody to and Services Administration (available at http://www.hrsa.
hepatitis B surface antigen (anti-HBsAg) compared gov). Hepatitis B vaccine is included on this table. The
with intramuscular administration; limited data are avail most current VIS for hepatitis B vaccine is available at
able to assess long-term protection from this route of http://www.cdc.gov/nip/publications/vis. Statements in
administration (5,6). languages other than English are available from the
• For intramuscular injection, the needle should be long Immunization Action Coalition at http://www.immunize.org.
enough to reach the muscle mass and prevent vaccine from • Adverse events should be reported to the Vaccine Adverse
seeping into subcutaneous tissue, but not so long as to Events Reporting System; report forms and assistance are
involve underlying nerves and blood vessels or bone (7). available from CDC at telephone 1-800-822-7967 or at
The appropriate needle length for adults is 1”–1½” http://www.vaers.hhs.gov.
(25–38 mm), depending on the recipient’s weight
(1” [25 mm] for males and females weighing <60 kg
[<130 lbs]; 1”–1½” [25–38 mm] for females weighing Hepatitis B Immune Globulin (HBIG)
60–90 kg [130–200 lbs] and males weighing 60–118 kg Dose and Administration
[130–260 lbs]; and 1½” [38 mm] for females weighing • The standard dose of HBIG is 0.06 mL/kg for all
>90 kg [>200 lbs] and males weighing >118 kg applications in adults.
[>260 lbs]). A 22- to 25-gauge needle should be used.* • HBIG may be administered simultaneously with
• Hepatitis B vaccine administered by any route or site other hepatitis B vaccine but in a different injection site.
than intramuscularly in the deltoid muscle should not be • HBIG is administered by intramuscular injection. An
counted as valid and should be repeated unless serologic appropriate muscle mass (i.e., deltoid or gluteal) should
testing indicates that an adequate response has been be chosen in which to deliver the large volumes of HBIG
achieved (see Postvaccination Testing for Serologic required by using a needle length appropriate for the
Response). person’s age and size (7).
• Hepatitis B vaccine and other vaccines administered during • HBIG should be stored at 35°F–46°F (2°C–8°C) and
the same visit should be given in different injection sites. should not be frozen.
• For persons at risk for hemorrhage (e.g., persons with
hemophilia), the risk for bleeding after intramuscular Unknown or Uncertain Vaccination
injection can be minimized by using a 23-gauge (or
Status
smaller) needle, applying direct pressure to the injection
site for 1–2 minutes, and administering vaccine immedi • A reliable vaccination history is defined as a written, dated
record (e.g., personal, school, physician, or immuniza
tion registry) of each dose of a complete series.
* Certain experts recommend a 5/8” (16 mm) needle for males and females
weighing <60 kg (<130 lbs) (7).
• In the majority of clinical practice settings, providers Minimum Dosing Intervals

should accept only written and dated records as evidence and Management of Persons
of vaccination. Although vaccinations should not be post Who Were Vaccinated Incorrectly
poned if records cannot be located, providers should try
to locate missing records by contacting previous health- • The third dose of vaccine must be administered at least
care providers and asking patients to search for personally 8 weeks after the second dose and should follow the first
held records. Persons whose records cannot be located dose by at least 16 weeks; the minimum interval between
should be considered susceptible and started or continued the first and second doses is 4 weeks.
on the age-appropriate vaccine schedule. • Inadequate doses of hepatitis B vaccine (see Table 2) or
• In settings in which written vaccination records are not doses received after a shorter-than-recommended dosing
accessible (e.g., sexually transmitted disease [STD] treat interval should be readministered, using the correct
ment facilities, human immunodeficiency virus [HIV] dosage or schedule.
testing facilities, or correctional facilities), an oral history
of completing a hepatitis B vaccine series can be used to Accelerated Vaccine Schedules
defer hepatitis B vaccination. Persons in these settings who • The Food and Drug Administration has not approved
are uncertain about their vaccination status should be accelerated schedules in which hepatitis B vaccine is
vaccinated. Other methods for assessing vaccination his administered more than once in 1 month. If an accelerated
tory (e.g., assuming a person received hepatitis B vaccine schedule (e.g., doses at 0, 7, and 14 days) is used, the patient
to comply with preschool or middle school entry require also should receive a booster dose at least 6 months after the
ments or participation in the U.S. military) might be con start of the series to promote long-term immunity.
sidered, but such methods require further research before
they can be recommended as reliable alternatives.
Hemodialysis Patients and Other
• Determining immunity from previous infection through
serologic testing is an alternative to vaccination. How Immunocompromised Persons
ever, using serologic testing to assess immunity from vac • Hepatitis B vaccination is recommended for pre–end-stage
cination in persons with unknown or uncertain renal disease patients before they become dialysis depen
vaccination status can be problematic (see Prevaccination dent and for peritoneal and home dialysis patients
Serologic Testing for Susceptibility). because they might require in-center hemodialysis.
• Persons who reside in the United States but were vacci • Higher hepatitis B vaccine doses are recommended for
nated in other countries should be considered fully vacci adult dialysis patients and other immunocompromised
nated if they have written documentation of >3 doses of persons (see Table 2).
vaccine administered at recommended minimum • Serologic testing of hemodialysis patients and other
intervals, including the final dose at age >24 weeks. If immunocompromised persons is recommended 1–2
they were not vaccinated according to recommended mini months after administration of the final dose of the pri
mum intervals, they should be revaccinated (see Mini mary vaccine series to determine the need for revaccina
mum Dosing Intervals and Management of Persons Who tion (see Postvaccination Testing for Serologic Response).
Were Vaccinated Incorrectly). Persons without written In addition, booster doses of vaccine might be needed
documentation of full vaccination should receive doses (see Booster Doses).
to complete the age-appropriate vaccine series.
Prevaccination Serologic Testing
Interrupted Vaccine Schedules for Susceptibility
• When the hepatitis B vaccine schedule is interrupted, the • Vaccination of persons who are immune to hepatitis B
vaccine series does not need to be restarted. virus (HBV) infection because of current or previous
• If the series is interrupted after the first dose, the second infection or vaccination does not increase the risk for
dose should be administered as soon as possible, and the adverse events. However, in adult populations that have
second and third doses should be separated by an interval expected high rates of previous HBV infection,
of at least 8 weeks. prevaccination testing might reduce costs by avoiding
• If only the third dose has been delayed, it should be ad vaccination of persons who are already immune (Box).
ministered as soon as possible. Prevaccination testing is recommended for all foreign-born
BOX. Method to determine cost-effectiveness of prevac nated previously or whose vaccination status is unknown,
cination screening for hepatitis B virus infection when the
first vaccine dose is administered at the time of blood draw
interpretation of anti-HBs results can be problematic.
Postvaccination anti-HBs concentrations decline over
Prevaccination testing is cost effective when the cost time, and vaccine responders remain protected even when
of serologic testing is less than or equal to the cost of anti-HBs concentrations are no longer detectable; there
vaccinating persons who are already immune, as ex fore, a negative anti-HBs result does not necessarily indi
pressed by the formula cate lack of immunity in vaccinated persons. In addition,
T <P1 x [P2 + P2(P3)] x v an anti-HBs-positive result can occur even for persons
where who received >1 dose of vaccine but did not complete the
T = cost of serologic testing (including cost of blood series. However, long-term protection has been
draw); demonstrated only for persons who have completed a
P1 = prevalence of previous infection; licensed vaccination series and have ever had an anti-HBs
P2 = percentage of recipients of first dose who actually concentration of >10 mIU/mL; persons with an anti-HBs
receive a second dose; positive result but who did complete a vaccine schedule
P3 = percentage of recipients of doses 1 and 2 who receive might not have long-term protection from HBV infection.
dose 3; • Serologic testing should not be a barrier to vaccination of
[P2 + P2 (P3)] = average number of doses for a person susceptible persons, especially in populations that are dif
starting the series; and ficult to access. The first vaccine dose typically should be
v = cost per dose of vaccine, including administrative administered immediately after collection of the blood
costs. sample for serologic testing.
Postvaccination Testing for Serologic

persons (including immigrants, refugees, asylum seekers, Response
and internationally adopted children) born in Africa, Asia,
the Pacific Islands, and other regions with high endemic • Serologic testing for immunity is not necessary after
ity of HBV infection (HBsAg prevalence of >8%) (see routine vaccination of adults.
Figure 4 and Box, Appendix C); for household, sex, and • Testing after vaccination is recommended only for the
needle-sharing contacts of HBsAg-positive persons; and following persons whose subsequent clinical management
for HIV-infected persons (8). In addition, testing might depends on knowledge of their immune status:
be cost effective in adult populations with a prevalence of — Health-care workers and public safety workers at high
HBV infection of >20% (e.g., injection-drug users, risk for continued percutaneous or mucosal exposure
incarcerated persons, men who have sex with men; and to blood or body fluids (e.g., acupuncturists, dentists,
persons born in countries with intermediate levels of dental hygienists, emergency medical technicians, first
endemic HBV infection [HBsAg prevalence of 2%–7%] responders, laboratory technologists/technicians,
[see Figure 4 and Box 2]). In a study conducted in correc nurses, nurse practitioners, phlebotomists, physicians,
tional facilities, the cost of prevaccination testing was physician assistants, and students entering these pro
equivalent to vaccination without testing at a threshold fessions), to determine the need for revaccination and
prevalence of HBV infection of 25% (9). to guide postexposure prophylaxis. Testing persons at
• Prevaccination testing can be done with a single test (anti- low risk for continued mucosal or percutaneous
HBc) or with a panel of tests (e.g., HBsAg and anti-HBs). exposure to blood or body fluids (e.g., public safety
The typical interpretation of HBV serologic markers has workers and health-care workers without direct patient
been described (see Table 1). contact) is not likely to be cost effective. Health-care
• When a single test is used, testing for anti-HBc is pre and public safety workers who have written documen
ferred because it identifies all persons with previous HBV tation of a complete vaccine series but who have never
infection, including persons with chronic HBV infection. had postvaccination testing do not need serologic test
• If prevaccination testing for anti-HBs is used to identify ing for anti-HBs unless they have a percutaneous or
immunity after previous HBV infection, HBsAg testing mucosal exposure to blood or body fluids (10).
also must be performed to identify persons with chronic — Chronic hemodialysis patients, HIV-infected persons,
HBV infection. However, for persons who were vacci and other immunocompromised persons (e.g.,
hematopoietic stem-cell transplant recipients or per
sons receiving chemotherapy), to determine the need age group, except in certain circumstances (see Postvacci
for revaccination and the type of follow-up testing. nation Testing for Serologic Response).
— Sex partners of HBsAg-positive persons, to determine • For hemodialysis patients, the need for booster doses
the need for revaccination and for other methods of should be assessed by annual anti-HBs testing. A booster
protection against HBV infection. dose should be administered when anti-HBs levels
• Testing should be performed 1–2 months after adminis decline to <10 mIU/mL.
tration of the last dose of the vaccine series using a method • For other immunocompromised persons (e.g., HIV-
that allows determination of a protective concentration infected persons, hematopoietic stem-cell transplant
of anti-HBs (>10 mIU/mL). recipients, and persons receiving chemotherapy), the need
• Persons found to have anti-HBs concentrations of >10 for booster doses has not been determined. When anti-
mIU/mL after the primary vaccine series are considered HBs levels decline to <10 mIU/mL, annual anti-HBs test
to be immune. ing and booster doses should be considered for persons
— Immunocompetent persons have long-term protection with an ongoing risk for exposure.
and do not need further periodic testing to assess anti-
References
HBs levels. 1. Shaw FE Jr, Guess HA, Roets JM, et al. Effect of anatomic injection
— Immunocompromised persons might need annual test site, age and smoking on the immune response to hepatitis B vaccina
ing to assess anti-HBs concentrations (see Booster tion. Vaccine 1989;7:425–30.
Doses). 2. Weber DJ, Rutala WA, Samsa GP, Santimaw JE, Lemon SM. Obesity
• Persons found to have anti-HBs concentrations of <10 as a predictor of poor antibody response to hepatitis B plasma vaccine.
JAMA 1985;254:3187–9.
mIU/mL after the primary vaccine series should be 3. CDC. Suboptimal response to hepatitis B vaccine given by injection
revaccinated. Administration of 3 doses on an appropri into the buttock. MMWR 1985;34:105–8, 113.
ate schedule (see Box 5), followed by anti-HBs testing 4. Ukena T, Esber H, Bessette R, Parks T, Crocker B, Shaw FE Jr. Site of
1–2 months after the third dose, usually is more practical injection and response to hepatitis B vaccine. N Engl J Med 1985;
than serologic testing after 1 or more doses of vaccine. 313:579–80.
5. Bryan JP, Sjogren MH, MacArthy P, Cox E, Legters LJ, Perine PL.
• Persons who do not have a protective concentration of
Persistence of antibody to hepatitis B surface antigen after low-dose,
anti-HBs after revaccination should be tested for HBsAg. intradermal hepatitis B immunization and response to a booster dose.
— If the HBsAg test result is positive, the person should Vaccine 1992;10:33–8.
receive appropriate management, and any household, 6. Coberly JS, Townsend T, Repke J, Fields H, Margolis H, Halsey NA.
sex, or needle-sharing contacts should be identified and Suboptimal response following intradermal hepatitis B vaccine in
vaccinated (see Appendix C). infants. Vaccine 1994;12:984–7.
7. CDC. General recommendations on immunization 2006: recommen
— Persons who test negative for HBsAg should be con dations of the Advisory Committee on Immunization Practices (ACIP).
sidered susceptible to HBV infection and should be MMWR. In press.
counseled about precautions to prevent HBV infec 8. CDC. Treating opportunistic infections among HIV-infected adults
tion and the need to obtain HBIG postexposure pro and adolescents: recommendations from CDC, the National Institutes
phylaxis for any known or likely parenteral exposure of Health, and the HIV Medicine Association/Infectious Diseases
Society of America. MMWR 2004;53(No. RR-15).
to HBsAg-positive blood (10).
9. CDC. Hepatitis B vaccination of inmates in correctional facilities—
Texas, 2000–2002. MMWR 2004;53:681–3.
Booster Doses 10. CDC. Updated U.S. Public Health Service guidelines for the
management of occupational exposures to HBV, HCV, and HIV
• Booster doses are not recommended for persons with and recommendations for postexposure prophylaxis. MMWR 2001;
normal immune status who were vaccinated as infants, 50(No. RR-11).
children, adolescents, or adults. Serologic testing is not
recommended to assess antibody concentrations in any
Appendix B
Postexposure Prophylaxis to Prevent Hepatitis B Virus Infection
This appendix provides guidelines for management of the appropriate dose of hepatitis B immune globulin
persons with nonoccupational exposure to hepatitis B virus (HBIG) and should complete the vaccine series.
(HBV) through a discrete, identifiable exposure to blood or • Unvaccinated persons should receive both HBIG and
body fluids (Table). Guidelines for postexposure prophylaxis hepatitis B vaccine as soon as possible after exposure (pref
of occupational exposures have been published separately (1) erably within 24 hours). Hepatitis B vaccine may be
and are intended for use in settings in which postvaccination administered simultaneously with HBIG in a separate
testing is recommended for certain employees (see Appendix injection site. The hepatitis B vaccine series should be
A, Postvaccination Testing for Serologic Response) and in completed in accordance with the age-appropriate vac
which programs are available to implement testing and fol cine dose and schedule (see Table 2 and Box 5).
low-up algorithms. Recommendations for management of
infants born to hepatitis B surface antigen (HBsAg)–positive Exposure Source with Unknown HBsAg
mothers also have been published separately (2). Status
• Persons with written documentation of a complete
HBsAg-Positive Exposure Source hepatitis B vaccine series require no further treatment.
• Persons who have written documentation of a complete • Persons who are not fully vaccinated should complete the
hepatitis B vaccine series and who did not receive postvac vaccine series.
cination testing should receive a single vaccine booster dose. • Unvaccinated persons should receive the hepatitis B vac
• Persons who are in the process of being vaccinated but cine series with the first dose administered as soon as pos
who have not completed the vaccine series should receive sible after exposure, preferably within 24 hours. The
TABLE. Guidelines for postexposure prophylaxis* of persons with nonoccupational exposures† to blood or body fluids that
contain blood, by exposure type and vaccination status
Treatment
Exposure Unvaccinated person§ Previously vaccinated person¶
HBsAg**-positive source
Percutaneous (e.g., bite or needlestick) or mucosal Administer hepatitis B vaccine series and Administer hepatitis B vaccine
exposure to HBsAg-positive blood or body fluids hepatitis B immune globulin (HBIG) booster dose
Sex or needle-sharing contact of an HBsAg-positive person Administer hepatitis B vaccine series and Administer hepatitis B vaccine
HBIG booster dose
Victim of sexual assault/abuse by a perpetrator who is Administer hepatitis B vaccine series and Administer hepatitis B vaccine
HBsAg positive HBIG booster dose
Source with unknown HBsAg status
Victim of sexual assault/abuse by a perpetrator with Administer hepatitis B vaccine series No treatment
unknown HBsAg status
Percutaneous (e.g., bite or needlestick) or mucosal Administer hepatitis B vaccine series No treatment
exposure to potentially infectious blood or body fluids
from a source with unknown HBsAg status
Sex or needle-sharing contact of person with unknown Administer hepatitis B vaccine series No treatment
HBsAg status
* When indicated, immunoprophylaxis should be initiated as soon as possible, preferably within 24 hours. Studies are limited on the maximum interval
after exposure during which postexposure prophylaxis is effective, but the interval is unlikely to exceed 7 days for percutaneous exposures or 14 days
for sexual exposures. The hepatitis B vaccine series should be completed.
† These guidelines apply to nonoccupational exposures. Guidelines for management of occupational exposures have been published separately (1) and
also can be used for management of nonoccupational exposures, if feasible.
§ A person who is in the process of being vaccinated but who has not completed the vaccine series should complete the series and receive treatment as
indicated.
¶ A person who has written documentation of a complete hepatitis B vaccine series and who did not receive postvaccination testing.
** Hepatitis B surface antigen.
vaccine series should be completed in accordance with 2. CDC. A comprehensive immunization strategy to eliminate transmis
the age-appropriate dose and schedule (see Table 2 and sion of hepatitis B virus infection in the United States: recommenda
tions of the Advisory Committee on Immunization Practices (ACIP).
Box 5).
Part 1: immunization of infants, children, and adolescents. MMWR
References 2005;54(No. RR-16).
1. CDC. Updated U.S. Public Health Service guidelines for the
management of occupational exposures to HBV, HCV, and HIV
and recommendations for postexposure prophylaxis. MMWR 2001;
50(No. RR-11).
Appendix C
Identification and Management of Hepatitis B
Surface Antigen (HBsAg)–Positive Persons
Persons with chronic hepatitis B virus (HBV) infection are BOX. Geographic regions* with high † hepatitis B virus
at high risk for chronic liver disease and are a major reservoir endemicity
of HBV infection. Foreign-born populations from Africa, Asia,
Africa: all countries except Algeria, Djibouti, Egypt,
and the Pacific Islands have high rates of chronic HBV infec
Libya, Morocco, and Tunisia
tion (i.e., HBsAg prevalence of >8%). During delivery of rec
Southeast Asia: all countries except Malaysia
ommended hepatitis B vaccination services (e.g., HBsAg
East Asia: China, Hong Kong, Mongolia, North Korea,
screening of pregnant women and serologic testing to assess
South Korea, and Taiwan
susceptibility), vaccination providers will identify persons who
Australia and South Pacific: all countries except
are HBsAg positive. These persons require counseling and
Australia, Guam, and New Zealand
medical management for chronic HBV infection to reduce
Middle East: Jordan and Saudi Arabia
their risk for chronic liver disease. Their susceptible house
Eastern Europe and Northern Asia: Albania, Armenia,
hold, sex, and needle-sharing contacts also should be vacci
Azerbaijan, Bulgaria, Croatia, Georgia, Kazakhstan,
nated against hepatitis B.
Kyrgyzstan, Moldova, Tajikistan, Turkmenistan, and
Extending screening, referral, and contact vaccination ser
Uzbekistan
vices to persons identified as HBsAg positive can help prevent
Western Europe: Malta and indigenous populations in
serious sequelae in persons with chronic infection and enhance
Greenland
vaccination strategies to eliminate HBV transmission. This
North America: Alaska Natives and indigenous
appendix provides guidance for vaccination providers concern
populations in Northern Canada
ing identification and management of persons with chronic
South America: Amazonian areas of Bolivia, Brazil,
HBV infection. These guidelines are not intended to repre
Columbia, Peru, and Venezuela
sent a comprehensive prevention program for persons with
Caribbean: Turks and Caicos
chronic infection.
* A complete list of countries in each region is available at http://www.cdc.
gov/travel/destinat.htm.
† Hepatitis B surface antigen prevalence of >8%.
Identification of Persons Who Are
Potentially HBsAg Positive
• All foreign-born persons (including immigrants, refugees, tion is highly endemic and provide HBsAg testing and
asylum seekers, and internationally adopted children) from follow-up. Retesting of persons who were tested for
Africa, Asia, the Pacific Islands, and other regions with HBsAg in other countries should be considered.
high endemicity of HBV infection (Box) should be tested • Other persons who should be tested for HBsAg as part of
for HBsAg, regardless of vaccination status. vaccination services include
— For all persons born in countries in which HBV is — all pregnant women (1);
highly endemic who are applying for permanent U.S. — persons who receive prevaccination testing for suscep
residence, HBsAg screening and appropriate follow- tibility and who test positive for anti-HBc (see
up on the basis of HBsAg test results should be Appendix A, Prevaccination Serologic Testing for
included as part of the required overseas premigration Susceptibility);
and domestic adjustment-of-visa status medical exami — hemodialysis patients; and
nation process; information about this process is avail — nonresponders to vaccination (see Appendix A, Post
able at http://www.cdc.gov/ncidod/dq/health.htm. vaccination Testing for Serologic Response).
HBsAg-positive persons should be considered eligible
for migration and adjustment-of-visa status and coun Management of Persons Identified
seled and recommended for follow-up medical evalua
tion and management in U.S. resettlement communities.
as HBsAg Positive
— In all settings that provide health care, providers should • All HBsAg-positive laboratory results should be reported
identify persons born in countries in which HBV infec- to the state or local health department, in accordance with
state requirements for reporting of chronic HBV infec their immunity documented (persons should be made
tion; information about state requirements is available at aware that use of condoms and other prevention meth
http://www.cste.org/NNDSSSurvey/2004NNDSS/ ods might reduce their risks for HIV and other STDs);
nndssstatechrreporcond2005.asp. — cover cuts and skin lesions to prevent spread through
• HBsAg-positive persons should be referred for evaluation to infectious secretions or blood;
a physician experienced in the management of chronic liver — refrain from donating blood, plasma, tissue, or semen
disease; a directory of liver specialists is available at (organs may be donated to HBV-immune or chroni
http://www.hepb.org/resources/other_links_physician.htm. cally infected persons needing a transplant; decisions
Certain patients with chronic HBV infection will benefit about organ donation should be made on an individual
from early intervention with antiviral treatment, manage basis); and
ment of factors that can contribute to disease progres — refrain from sharing household articles (e.g., tooth
sion, or screening to detect hepatocellular carcinoma at an brushes, razors, or personal injection equipment) that
early stage. could become contaminated with blood.
• Household, sex, and needle-sharing contacts of HBsAg • To protect the liver from further harm, HBsAg-positive
positive persons should be identified. Unvaccinated sex persons should be advised to
partners and household and needle-sharing contacts — avoid or limit alcohol consumption because of the
should be tested for susceptibility to HBV infection (see effects of alcohol on the liver;
Appendix A, Prevaccination Serologic Testing for Suscep — refrain from taking any new medicines, including over
tibility) and should receive the first dose of hepatitis B the-counter and herbal medicines, without consulting
vaccine immediately after collection of blood for sero with their health-care provider; and
logic testing. Susceptible persons should complete the — obtain vaccination against hepatitis A if chronic liver
vaccine series using an age-appropriate vaccine dose and disease is present (2).
schedule (see Table 2 and Box 5). Persons who are not • When seeking medical or dental care, HBsAg-positive
fully vaccinated should complete the vaccine series. persons should be advised to inform those responsible for
• Sex partners of HBsAg-positive persons should be coun their care of their HBsAg status so that they can be evalu
seled to use methods (e.g., condoms) to protect them ated and their care managed appropriately.
selves from sexual exposure to infectious body fluids (e.g., • Other counseling messages include the following:
semen or vaginal secretions) unless they have been dem — HBV is not spread by breastfeeding, kissing, hugging,
onstrated to be immune after vaccination (i.e., antibody coughing, ingesting food or water, sharing eating uten
to HBsAg concentrations of >10 mIU/mL) or previously sils or drinking glasses, or casual contact.
infected (anti-HBc positive). Partners should be made — Persons should not be excluded from work, school,
aware that use of condoms and other prevention meth play, child care, or other settings on the basis of their
ods might reduce their risks for human immunodeficiency HBsAg status, unless they are prone to biting (3).
virus (HIV) and other sexually transmitted diseases — Involvement with a support group might help patients cope
(STDs). with chronic HBV infection. Information about support
• To prevent or reduce the risk for transmission to others, groups is available at http://www.hepprograms.org/support/
HBsAg-positive persons should be advised concerning the hepb.asp and http://www.hepb.org/patients/support_
risks for groups.htm.
— perinatal transmission to infants born to HBsAg
References
positive women and the need for such infants to 1. CDC. A comprehensive immunization strategy to eliminate transmis
receive hepatitis B vaccine beginning at birth (1) and sion of hepatitis B virus infection in the United States: recommenda
— transmission to household, sex, and needle-sharing tions of the Advisory Committee on Immunization Practices (ACIP).
contacts and the need for such contacts to receive hepa Part 1: immunization of infants, children, and adolescents. MMWR
titis B vaccine. 2005;54(No. RR-16).
2. CDC. Prevention of hepatitis A through active or passive immuniza
• HBsAg-positive persons should also be advised to tion: recommendations of the Advisory Committee on Immunization
— notify their sex partners about their status; Practices (ACIP). MMWR 2006;55(No. RR-7).
— use methods (e.g., condoms) to protect nonimmune 3. Shapiro CN, McCaig LF, Gensheimer KF, et al. Hepatitis B virus trans
sex partners from acquiring HBV infection from sexual mission between children in day care. Pediatr Infect Dis J 1989;8:870–5.
activity until the sex partners can be vaccinated and
Morbidity and Mortality Weekly Report
Recommendations and Reports December 8, 2006 / Vol. 55 / No. RR-16

Continuing Education Activity Sponsored by CDC
A Comprehensive Immunization Strategy to Eliminate Transmission of Hepatitis B Virus Infection
in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP)
Part II: Immunization of Adults
EXPIRATION — December 8, 2009
You must complete and return the response form electronically or by mail by 3.0 contact hours Continuing Nursing Education (CNE) credit. If you return the
December 8, 2009, to receive continuing education credit. If you answer all form electronically, you will receive educational credit immediately. If you mail
of the questions, you will receive an award letter for 3.0 hours Continuing the form, you will receive educational credit in approximately 30 days. No fees are
Medical Education (CME) credit; 0.25 Continuing Education Units (CEUs); or charged for participating in this continuing education activity.
INSTRUCTIONS
By Internet By Mail or Fax
1. Read this MMWR (Vol. 55, RR-16), which contains the correct answers to 1. Read this MMWR (Vol. 55, RR-16), which contains the correct answers to
the questions beginning on the next page. the questions beginning on the next page.
2. Go to the MMWR Continuing Education Internet site at http://www.cdc. 2. Complete all registration information on the response form, including your
gov/mmwr/cme/conted.html. name, mailing address, phone number, and e-mail address, if available.
3. Select which exam you want to take and select whether you want to register 3. Indicate whether you are registering for CME, CEU, or CNE credit.
for CME, CEU, or CNE credit. 4. Select your answers to the questions, and mark the corresponding letters on
4. Fill out and submit the registration form. the response form. To receive continuing education credit, you must
5. Select exam questions. To receive continuing education credit, you must answer all of the questions. Questions with more than one correct answer
answer all of the questions. Questions with more than one correct answer will instruct you to “Indicate all that apply.”
will instruct you to “Indicate all that apply.” 5. Sign and date the response form or a photocopy of the form and send no
6. Submit your answers no later than December 8, 2009. later than December 8, 2009, to
7. Immediately print your Certificate of Completion for your records. Fax: 404-498-2388
Mail: MMWR CE Credit
Coordinating Center for Health Information and Service, MS E-90
1600 Clifton Rd, N.E.
Atlanta, GA 30333
6. Your Certificate of Completion will be mailed to you within 30 days.
ACCREDITATION
Continuing Medical Education (CME). CDC is accredited by the Accreditation Council for Continuing Medical Education to provide continuing
medical education for physicians. CDC designates this educational activity for a maximum of 3.0 hours in category 1 credit toward the AMA Physician’s
Recognition Award. Each physician should claim only those hours of credit that he/she actually spent in the educational activity.
Continuing Education Unit (CEU). CDC has been approved as an authorized provider of continuing education and training programs by the International
Association for Continuing Education and Training. CDC will award 0.25 continuing education units to participants who successfully complete this activity.
Continuing Nursing Education (CNE). This activity for 3.0 contact hours is provided by CDC, which is accredited as a provider of continuing education
in nursing by the American Nurses Credentialing Center’s Commission on Accreditation.
depar tment of health and human ser

department vices
services
vices

Prevention
CE-2 MMWR December 8, 2006
Goal and Objectives

This report updates the immunization strategy to eliminate hepatitis B virus (HBV) transmission in the United States. The report includes new recommendations
regarding which adults should receive hepatitis B vaccine and provides implementation strategies to ensure that those adults are vaccinated. The goal of the report
is to provide strategies for health-care professionals to increase hepatitis B vaccination coverage among adults at risk for HBV infection. Strategies are directed toward
settings in which a high proportion of persons have risks for HBV infection and primary care and specialty medical settings in which persons at risk for HBV infection
receive care. Upon completion of this educational activity, the reader should be able to 1) identify adults who are recommended to receive hepatitis B vaccination,
2) identify settings in which a high proportion of persons are likely to be at risk for HBV infection, 3) identify components of a successful adult hepatitis B vaccination
program, 4) identify strategies to increase vaccination coverage among adults at risk for HBV infection, 5) describe practices that should be implemented in settings
in which adults receive hepatitis B vaccine, and 6) describe adult vaccination schedules.
To receive continuing education credit, please answer all of the following questions.
1. In which settings is universal hepatitis B vaccination recommended 6. Which of the following statements regarding hepatitis B vaccination
because of the high proportion of adults with behavioral risk factors are true? (Indicate all that apply.)
for HBV infection? A. Hepatitis B vaccine is available as a single-antigen formulation only.
A. Sexually transmitted disease and human immunodeficiency virus B. Primary vaccination against hepatitis B consists of 3 doses
(STD/HIV) testing and treatment facilities. administered at 0, 1, and 6 months.
B. Drug-abuse treatment and prevention settings. C. Increasing the interval between the first 2 doses has little effect on
C. Health-care settings targeting services to men who have sex with men immunogenicity or final antibody concentration.
(MSM). D. Differences in immunogenicity have been observed when hepatitis B
D. Correctional facilities. vaccines produced by different manufacturers are used to complete the
E. Hospitals. vaccine series.
E. Routine vaccination of adults should be followed by postvaccination
2. The Advisory Committee on Immunization Practices (ACIP) testing to determine serologic response.
recommends standing orders to identify adults recommended for
hepatitis B vaccination and administer vaccination as part of routine 7. Which of the following statements regarding immune memory for
services in primary care and specialty medical settings. hepatitis B are true? (Indicate all that apply.)
A. True. A. Antibody to HBsAg (anti-HBs) is the only easily measurable correlate
B. False. of vaccine-induced protection.
B. After primary vaccination with hepatitis B vaccine, anti-HBs
3. Which of the following practices should be implemented in primary concentrations decline rapidly within the first year.
care and specialty medical settings to ensure vaccination of adults at C. When anti-HBs concentrations decline to <10 mIU/mL, all
risk for HBV infection? (Indicate all that apply.) vaccinated persons should receive a booster dose of hepatitis B vaccine.
A. Provide information to all adults regarding the benefits of hepatitis B D. A booster dose of hepatitis B vaccine is recommended 10 years after the
vaccination, including the risk factors for HBV infection and persons 3rd dose of vaccine was received.
for whom vaccination is recommended.
B. Help adults assess their need for vaccination by obtaining a history that 8. Which of the following statements regarding hepatitis B immune
emphasizes risks for sexual transmission and percutaneous or mucosal globulin (HBIG) are true? (Indicate all that apply.)
exposure to blood. A. HBIG provides temporary protection when administered in standard
C. Provide hepatitis B vaccine to persons who report risk factors for HBV doses.
infection. B. HBIG typically is used instead of hepatitis B vaccine for postexposure
D. Request that adults acknowledge a specific factor for HBV infection immunoprophylaxis to prevent HBV infection.
before offering hepatitis B vaccine. C. No evidence exists that HBV, hepatitis C virus, or HIV have ever been
transmitted by HBIG in the United States.
4. Which of the following are components of a successful adult hepatitis D. HBIG administered alone is the primary means of protection after an
B vaccination program? (Indicate all that apply.) HBV exposure for nonresponders to hepatitis B vaccination.
A. Protocols and standing orders.
B. Protected patient confidentiality. 9. Postvaccination testing is recommended for which of the following
C. Trained and knowledgeable staff. populations? (Indicate all that apply.)
D. Funding for vaccine. A. Certain health-care and public safety workers.
E. Billing and reimbursement mechanisms. B. Chronic hemodialysis patients.
C. HIV-infected persons.
5. Which of the following persons are recommended to receive hepatitis D. HCV-infected persons.
B vaccine because they have a risk factor for HBV infection? (Indicate E. Sex partners of HBsAg-positive persons.
all that apply.)
A. Sexually active persons who are not in a long-term, mutually 10. Which best describes your professional activities?
monogamous relationship. A. Physician.
B. Injection-drug users. B. Nurse.
C. MSM. C. Health educator.
D. Persons who live in a household with a person who is hepatitis B surface D. Office staff.
antigen (HBsAg)–positive. E. Other.
E. Persons seeking treatment for an STD. 11. I plan to use these recommendations as the basis for… (Indicate all
F. Pregnant women. that apply.)
A. health education materials.
B. insurance reimbursement policies.
C. local practice guidelines.
D. public policy.
E. other.
Vol. 55 / No. RR-16 Recommendations and Reports CE-3
12. Overall, the length of the journal report was… 16. After reading this report, I am confident I can identify strategies to
A. much too long. increase vaccination coverage among adults at risk for HBV infection.
B. a little too long. A. Strongly agree.
C. just right. B. Agree.
D. a little too short. C. Undecided.
E. much too short. D. Disagree.
13. After reading this report, I am confident I can identify adults who are E. Strongly disagree.
recommended to receive hepatitis B vaccination. 17. After reading this report, I am confident I can describe practices that
A. Strongly agree. should be implemented in settings in which adults receive hepatitis B
B. Agree. vaccine.
C. Undecided. A. Strongly agree.
D. Disagree. B. Agree.
E. Strongly disagree. C. Undecided.
14. After reading this report, I am confident I can identify settings in D. Disagree.
which a high proportion of persons are likely to be at risk for HBV E. Strongly disagree.
infection. 18. After reading this report, I am confident I can describe adult
A. Strongly agree. vaccination schedules.
B. Agree. A. Strongly agree.
C. Undecided. B. Agree.
D. Disagree. C. Undecided.
E. Strongly disagree. D. Disagree.
15. After reading this report, I am confident I can identify components of E. Strongly disagree.
a successful adult hepatitis B vaccination program. 19. The learning outcomes (objectives) were relevant to the goals of this
A. Strongly agree. report.
B. Agree. A. Strongly agree.
E. Strongly disagree.
(Continued on pg CE-4)
Detach or photocopy.
A Comprehensive Immunization Strategy to Eliminate Transmission of Hepatitis B
nonphysicians
Virus Infection in the United States: Recommendations of the Advisory Committee
Date I Completed Exam

[ ]C [ ]D [ ]E [ ]F
MMWR Response Form for Continuing Education Credit
CME Credit
CEU Credit
CNE Credit
Failure to complete these items can result in a delay or rejection of your application
Check One
CME for
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2. indicate your choice of CME, CME for nonphysicians, CEU, or CNE credit;
Fill in the appropriate blocks to indicate your answers. Remember, you must answer all
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To receive continuing education credit, you must
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of the questions to receive continuing education credit!
Fax Number
First Name
4. sign and date this form or a photocopy;
State
[ ]E [ ]F
3. answer all of the test questions;
or
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for continuing education credit.
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Signature
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CE-4 MMWR December 8, 2006
20. The instructional strategies used in this report (text, tables, figures, 25. The availability of continuing education credit influenced my
boxes, and appendices) helped me learn the material. decision to read this report.
A. Strongly agree. A. Strongly agree.
B. Agree. B. Agree.
C. Undecided. C. Undecided.
D. Disagree. D. Disagree.
E. Strongly disagree. E. Strongly disagree.
21. The content was appropriate given the stated objectives of the report. 26. The MMWR format was conducive to learning this content.
A. Strongly agree.
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A. Strongly agree. 27. Do you feel this course was commercially biased? (Indicate yes or no;
B. Agree. if yes, please explain in the space provided.)
C. Undecided. A. Yes.
D. Disagree. B. No.
E. Strongly disagree. 28. How did you learn about the continuing education activity?
23. Overall, the quality of the journal report was excellent. A. Internet.
A. Strongly agree. B. Advertisement (e.g., fact sheet, MMWR cover, newsletter, or journal).
B. Agree. C. Coworker/supervisor.
C. Undecided. D. Conference presentation.
D. Disagree. E. MMWR subscription.
E. Strongly disagree. F. Other.
24. These recommendations will improve the quality of my practice.
A. Strongly agree.
B. Agree. and E. 6. B and C. 7. A and B. 8. A, C, and D. 9. A, B, C, and E.
C. Undecided. 1. A, B, C, and D. 2. A. 3. A, B, and C. 4. A, B, C, D, and E. 5. A, B, C, D,
D. Disagree. Correct answers for questions 1–9.
MMWR
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Morbidity and Mortality Weekly Report

Recommendations and Reports December 8, 2006 / Vol. 55 / No. RR-16

A Comprehensive Immunization Strategy

Recommendations of the Advisory

Committee on Immunization Practices (ACIP)

Part II: Immunization of Adults

INSIDE: Continuing Education Examination

depar tment of health and human ser

Centers for Disease Control and Prevention

The MMWR series of publications is published by the Coordinating

Control and Prevention (CDC), U.S. Department of Health and

Major Updates to the Recommendations ............................. 3

Suggested Citation: Centers for Disease Control and Prevention.

Tanja Popovic, MD, PhD

(Acting) Chief Science Officer

James W. Stephens, PhD

(Acting) Associate Director for Science

Hepatitis B Immune Globulin ............................................ 9

Jay M. Bernhardt, PhD, MPH Preexposure Vaccination ................................................. 10

Director, National Center for Health Marketing Postexposure Prophylaxis ................................................ 12

Vaccine Reactogenicity .................................................... 12

Editorial and Production Staff

Frederic E. Shaw, MD, JD

Suzanne M. Hewitt, MPA Implementation Barriers and Rationale

Managing Editor, MMWR Series

Jeffrey D. Sokolow, MA for Hepatitis B Vaccination of Adults ................................ 15

Visual Information Specialists

Information Technology Specialists

Virginia A. Caine, MD, Indianapolis, IN

David W. Fleming, MD, Seattle, WA

William E. Halperin, MD, DrPH, MPH, Newark, NJ

Margaret A. Hamburg, MD, Washington, DC

King K. Holmes, MD, PhD, Seattle, WA

Deborah Holtzman, PhD, Atlanta, GA

John K. Iglehart, Bethesda, MD

Dennis G. Maki, MD, Madison, WI

Sue Mallonee, MPH, Oklahoma City, OK

Stanley A. Plotkin, MD, Doylestown, PA

Patricia Quinlisk, MD, MPH, Des Moines, IA

Barbara K. Rimer, DrPH, Chapel Hill, NC

A Comprehensive Immunization Strategy

to Eliminate Transmission of Hepatitis B Virus Infection

in the United States

Recommendations of the Advisory Committee on Immunization

Practices (ACIP) Part II: Immunization of Adults

Eric E. Mast, MD1

Cindy M. Weinbaum, MD1

Anthony E. Fiore, MD1

Miriam J. Alter, PhD1

Beth P. Bell, MD1

Lyn Finelli, DrPH1

Lance E. Rodewald, MD2

John M. Douglas, Jr., MD3

Robert S. Janssen, MD4

John W. Ward, MD1

Introduction schedule (7). Vaccination coverage among adolescents also has

Methods — Provide information to all adults regarding the health

HBsAg* anti-HBc† anti-HBc Anti-HBs¶ Interpretation

–** – – – Never infected

88. Chaudhary RK, Perry E, Cleary TE. Prevalence of hepatitis B infec