Hepatitis B and

Hepatitis B Vaccine
Epidemiology and Prevention of Vaccine-
Preventable Diseases

National Immunization Program

Centers for Disease Control and Prevention
Revised March 2002
 Hepatitis B
Epidemic jaundice described by
Hippocrates in 5th century BC

Jaundice reported among recipients of

human serum and yellow fever
vaccines in 1930s and 1940s

Australian antigen described in 1965

Serologic tests developed in 1970s

 Hepatitis B Virus
Hepadnaviridae family (DNA)

Numerous antigenic components

Humans are only known host

May retain infectivity for at least 1

month at room temperature
 Hepatitis B Virus Infection
>200 million carriers worldwide

Established cause of chronic

hepatitis and cirrhosis

Human carcinogen - cause of up to

80% of hepatocellular carcinomas
 Hepatitis B Virus
HBsAg

HBcAg

HBeAg
Hepatitis B Clinical Features
Incubation period 6 weeks to 6
months (average 120 days)

Nonspecific prodrome of fever,

malaise, headache, myalgia

Illness not specific for hepatitis B

At least 50% of infections

asymptomatic
Hepatitis B Complications
Fulminant hepatitis
Hospitalization
Cirrhosis
Hepatocellular carcinoma
Death
Chronic Hepatitis B Virus Infection

Chronic viremia

Responsible for most mortality

Overall risk 10%

Higher risk with early infection

 Risk of Chronic HBV Carriage
by Age of Infection
100
90
80
Carrier risk (%)

70
60
50
40
30
20
10
0
Birth 1-6 mo 7-12 mo 1-4 yrs 5+ yrs
Age of infection
 Hepatitis B Epidemiology
Reservoir Human. Endemic

Transmission Bloodborne
Subclinical cases
transmit

Communicability 1-2 months before

and after onset of
symptoms
Chronic carriers
Hepatitis B Perinatal Transmission*
If mother positive for HBsAg and HBeAg
70%-90% of infants infected
90% of infected infants become
chronic carriers

If positive for HBsAg only

20% of infants infected
90% of infected infants become
chronic carriers

*in the absence of postexposure prophylaxis

 Global Patterns of Chronic
HBV Infection
High (>8%): 45% of global population
lifetime risk of infection >60%
early childhood infections common

Intermediate (2%-7%): 43% of global population

lifetime risk of infection 20%-60%
infections occur in all age groups

Low (<2%): 12% of global population

lifetime risk of infection <20%
most infections occur in adult risk groups
Hepatitis B United States, 1978-2000
Decline among
homosexual men
30000 Decline among
IV drug users
25000

20000
Cases

15000

10000
Hepatitis B vaccine licensed
5000

0
1978 1982 1986 1990 1994 1998
 HBV Disease Burden in
the United States*
Total infections 80,000/yr
Current carriers >1 million
New carriers >5,000
Death
fulminant hepatitis 200
liver cancer 1,500
cirrhosis 4,000

*1999 estimates
Age of Infection of Acute and Chronic
Hepatitis B Virus Infection
Adolescent Children Perinatal Adult

6%
8% 58%
12%
84% 4%
4%

24%

Acute infection Chronic infection

CDC Sentinel Sites. 1989 data.
Risk Factors for Hepatitis B
Unknown
31%
Health care
worker Other
1% 1%

Household
contact Inj drug use
2% 15%

Homosexual
9%
Heterosexual
41%
CDC Sentinel Sites. 1992-1993 data.
 Hepatitis B Virus Infection by
Duration of High Risk Behavior
IV drug user HCWs
Homosexual men Heterosexual

100
Percent infected

80

60

40

20

0
0 3 6 9 12 15
Years at Risk
 Strategy to Eliminate Hepatitis B
Virus Transmission - United States
Prevent perinatal HBV transmission
Routine vaccination of all infants
Vaccination of children in high-risk
groups
Vaccination of adolescents
Vaccination of adults in high-risk
groups
 Hepatitis B Vaccine
1965 Discovery of Australian antigen

1973 Successful HBV infection of chimpanzees

1981 Licensure of plasma-derived vaccine

1986 Licensure of recombinant vaccine

1991 Universal infant vaccination

1996 Universal adolescent vaccination

 Hepatitis B Vaccine
Composition Recombinant HBsAg

Efficacy 95% (Range, 80%-100%)

Duration of
Immunity >15 years

Schedule 3 Doses

Booster doses not routinely recommended

Hepatitis B Vaccine Formulations
Recombivax HB (Merck)
- 5.0 mcg/0.5 ml (pediatric)
- 10 mcg/1 ml (adult)
- 40 mcg/1 ml (dialysis)

Engerix-B (GSK)
- 10 mcg/0.5 ml (pediatric)
- 20 mcg/1 ml (adult)
 Recommended Dose of
Hepatitis B Vaccine

Recombivax HB Engerix-B
Dose (mcg) Dose (mcg)
Infants and children 0.5 ml (5) 0.5 ml (10)
<11 years of age

Adolescents 11-19 0.5 ml (5) 0.5 ml (10)

years

Adults >20 years 1.0 ml (10) 1.0 ml (20)

 Hepatitis B Vaccine
Long-term Efficacy
Immunologic memory established
following vaccination

Exposure to HBV results in

anamnestic anti-HBs response

Chronic infection rarely documented

among vaccine responders
 Hepatitis B Vaccine

Routine booster doses

are NOT routinely
recommended for any
group
Hepatitis B Vaccine Recommendations

Year Recommendation
1981 Persons at high risk

1991 All infants

1995 Adolescents
Indications for Hepatitis B Vaccine
Infants

Adolescents 11-12 years of age

Selected adults
 Hepatitis B Vaccine
Routine Infant Schedule
Minimum
Dose Usual Age Interval
Primary 1 0-2 months* ---
Primary 2 1- 4 months 1 month
Primary 3 6-18 months 2 months

*ACIP prefers the first dose of hepatitis B vaccine be

given soon after birth and before hospital discharge.
Third Dose of Hepatitis B Vaccine

Minimum of 2 months after

second dose, and

At least 4 months after first

dose, and

For infants, at least 6 months

of age
 Very Low Birthweight Infants
Infants <2000 grams respond
poorly to vaccine

Delay first dose until chronological

age 1 month if mother HBsAg
negative

Birth dose and HBIG if mother

HBsAg positive
 COMVAX
Hepatitis B-Hib combination
Use when either antigen is
indicated
Cannot use <6 weeks of age
Not licensed for use if mother
HBsAg+
 Hepatitis B Vaccine
Adolescent Vaccination
Routine vaccination recommended
through age 18years

Integrate into routine adolescent

immunization visit

Flexible schedules
 Hepatitis B Vaccine
Adolescent and Adult Schedule
Usual Minimum
Dose Interval Interval
Primary 1 --- ---
Primary 2 1 month 1 month
Primary 3 5 months 2 months*

*third dose must be separated from

first dose by at least 4 months
 Alternative Adolescent
Vaccination Schedule
Two 10 mcg doses of Recombivax
HB separated by 4-6 months

May only be used for adolescents

11-15 years of age

Only applies to Merck hepatitis B

vaccine
Adult Hepatitis B Vaccine Candidates
Men who have sex with men
Heterosexual with multiple partners
Persons diagnosed with an STD
Prostitutes
Injection drug users
Male prison inmates
Persons receiving dialysis
Health care workers
Adult Hepatitis B Vaccine Candidates
Staff of institutions for developmentally
disabled
Alaskan Natives, Pacific Islanders
Immigrants/refugees*
Adoptees, orphans, unaccompanied minors*
Household members and sexual partners of
HBV carriers
Extended travel to areas of high endemicity
Recipients of certain blood products
*from countries of high or intermediate HBV endemnicity
Prevaccination Serologic Testing
Not indicated before routine
vaccination of infants or children

May be considered when vaccinating

adolescents in groups with high rates
of HBV infection
Alaskan Natives
Pacific Islanders
Children of immigrants from endemic
countries
Family members of HBV carriers
Postvaccination Serologic Testing
Not routinely recommended
following vaccination of infants,
children, adolescents, or most adults

Recommended for:
Infants born to HBsAg+ women
Dialysis patients
Immunodeficient persons
Certain health care workers
Postvaccination Serologic Testing

Health care workers who have

contact with patients or blood
should be tested for antibody
after vaccination.
Management of Nonresponse to
Hepatitis B Vaccine
Complete a second series of
three doses

Should be given on the usual

schedule of 0, 1 and 6 months

Retest 1 to 2 months after

completing the second series
 Persistent Nonresponse to
Hepatitis B Vaccine
<5% of vaccinees do not develop
anti-HBs after 6 valid doses

May be nonresponder or
"hyporesponder"

Check HBsAg status

If exposed, treat as nonresponder

with post exposure prophylaxis
 Prevention of Perinatal
Hepatitis B Virus Infection
Begin treatment within 12 hours of birth

Hepatitis B vaccine (first dose) and HBIG

at different sites

Complete vaccination series at 6 months

of age

Test for response at 9-15 months of age

 Twinrix
Combination hepatitis B (adult
dose) and hepatitis A vaccine
(pediatric dose)

Schedule: 0, 1, 6-12 months

Approved for persons >18 years

 Hepatitis B Vaccine
Adverse Reactions
Infants and
Adults Children
Pain at injection site 13%-29% 3%-9%

Mild systemic complaints 11%-17% 0%-20%

(fatigue, headache)

Temperature >37.7 C 1% 0.4%-6%

Severe systemic reactions rare rare

 Hepatitis B Vaccine
Contraindications and Precautions
Severe allergic reaction to a
vaccine component or following
a previous dose

Moderate or severe acute illness

National Immunization Program
Hotline 800.232.2522

Email nipinfo@cdc.gov

Website www.cdc.gov/nip