Hepatitis B and Hepatitis

B Vaccine

Epidemiology and Prevention of Vaccine-

Preventable Diseases

National Center for Immunization and

Respiratory Diseases
Centers for Disease Control and Prevention
Revised May 2009
Note to presenters:

Images of vaccine-preventable
diseases are available from the
Immunization Action Coalition website
at http://www.vaccineinformation.org/photos/index.asp
 Hepatitis B
• Epidemic jaundice described by
Hippocrates in 5th century BCE
• Jaundice reported among recipients of
human serum and yellow fever vaccines
in 1930s and 1940s
• Australia 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 more than 7
days at room temperature
 Hepatitis B Virus Infection
• More than 350 million chronically
infected worldwide
• Established cause of chronic hepatitis
and cirrhosis
• Human carcinogen—cause of up to
80% of hepatocellular carcinomas
• More than 600,000 deaths worldwide
in 2002
 Hepatitis B Virus
HBsAg

HBcAg

HBeAg
 Hepatitis B Clinical Features
• Incubation period 60-150 days
(average 90 days)
• Nonspecific prodrome of malaise,
fever, 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 5%
• 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

• Transmission Bloodborne
Asymptomatic infections
transmit

• Communicability 1-2 months before

and after onset of
symptoms
Chronic infection
 Hepatitis B Perinatal
Transmission*
• If mother positive for HBsAg and HBeAg
– 70%-90% of infants infected
– 90% of infected infants become chronically
infected
• If positive for HBsAg only
– 5%-20% of infants infected
– 90% of infected infants become chronically
infected

*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, 1978-2007

Decline among
men who have sex with men
30000
Decline among
25000 IV drug users

20000
Cases

15000

10000 Hepatitis B vaccine licensed

5000

0
1978 1980 1985 1990 1995 2000 2005
Year
 HBV Disease Burden in the
United States
• Prevaccine era
–estimated 300,000 persons infected
annually, including 24,000 infants
and children
• 2005
–estimated 51,000 infections
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
16%
Other
5%
Hetero-
sexual,
IDU multiple
16% partners
39%

MSM
24%

MMWR 2006;55(RR-16):6-7
 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 20 years or more
• Schedule 3 Doses
• Booster doses not routinely
recommended
Hepatitis B Vaccine Formulations

• Recombivax HB (Merck)
- 5 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)
Protection* by Age Group and Dose

Dose Infants** Teens and Adults***

1 16%-40% 20%-30%
2 80%-95% 75%-80%
3 98%-100% 90%-95%

* Anti-HBs antibody titer of 10 mIU/mL or higher

** Preterm infants less than 2 kg have been shown to
respond to vaccination less often
*** Factors that may lower vaccine response rates are age
older than 40 years, male gender, smoking, obesity, and
immune deficiency
 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
Routine Infant Schedule
Minimum
Dose+ Usual Age Interval
Primary 1 Birth ---
Primary 2 1- 2 months 4 weeks
Primary 3 6-18 months* 8 weeks**

* infants who mothers are HBsAg+ or whose HBsAg status is

unknown should receive the third dose at 6 months of age
** at least 16 weeks after the first dose
+an additional dose at 4 months is acceptable if the clinician prefers to
use a combination vaccine that contains hepatitis B vaccine
 Third Dose of
Hepatitis B Vaccine
• Minimum of 8 weeks after second
dose, and
• At least 16 weeks after first dose, and
• For infants, at least 24 weeks of age
 Preterm Infants
• Birth dose and HBIG if mother HBsAg
positive (within 12 hours of birth)
• Preterm infants who weigh less than
2,000 grams have a decreased
response to vaccine administered
before 1 month of age
• Delay first dose until chronologic age
1 month if mother HBsAg negative
 COMVAX
• Hepatitis B-Hib combination
• Use when either antigen is indicated
• Cannot use at younger than 6 weeks
of age
• May be used in infants whose mother
is HBsAg positive or status is
unknown
 Pediarix
• DTaP – Hep B – IPV combination
• Approved for 3 doses at 2, 4 and 6
months
• Not approved for booster doses
• Licensed for children 6 weeks to 7
years of age
 Pediarix
• May be used interchangeably with other
pertussis-containing vaccines if
necessary
• Can be given at 2, 4, and 6 months to
infants who received a birth dose of
hepatitis B vaccine (total of 4 doses)
• May be used in infants whose mothers
are HBsAg positive or status unknown
 Combination Vaccine Rule
• The minimum intervals between
doses of a combination vaccine are
dictated by the single antigen with
the longest minimum intervals
• For Pediarix the minimum intervals
are determined by the hepatitis B
component
 Hepatitis B Vaccine
Adolescent Vaccination
• Routine vaccination recommended
through age 18 years
• 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 4 weeks
Primary 3 5 months 8 weeks*

*third dose must be separated from

first dose by at least 16 weeks
 Alternative Adolescent
Vaccination Schedule
• Two 1.0 mL (10 mcg) doses of
Recombivax HB separated by
4-6 months
• Approved only for adolescents 11-15
years of age
• Only applies to Merck hepatitis B
vaccine
 Adults at Risk for HBV Infection
• Sexual exposure
–sex partners of HBsAg-positive persons
–sexually active persons not in a long-
term, mutually monogamous
relationship*
–persons seeking evaluation or treatment
for a sexually transmitted disease
–men who have sex with men

*persons with more than one sex partner

during the previous 6 months
 Adults at Risk for HBV Infection
• Percutaneous or mucosal exposure to blood
– current or recent IDU
– household contacts of HBsAg-positive
persons
– residents and staff of facilities for
developmentally disabled persons
– healthcare and public safety workers with
risk for exposure to blood or blood-
contaminated body fluids
– persons with end-stage renal disease
 Adults at Risk for HBV Infection
• Others groups
–international travelers to regions with
high or intermediate levels (HBsAg
prevalence of 2% or higher) of endemic
HBV infection
–persons with HIV infection
 Twinrix
• Combination hepatitis A vaccine
(pediatric dose) and hepatitis B (adult
dose)
• Schedules
–0, 1, 6 months, or
–0, 7, 21- 30 days and a booster dose
at 12 months
• Approved for persons 18 years of age
and older
 New Twinrix Schedule
• Doses at 0, 7, 21- 30 days and a booster dose
at 12 months
• ACIP has no recommendation regarding the
new schedule
• The first 3 doses of the new schedule provide
equivalent protection to:
–the first dose in the standard single-antigen
adult hepatitis A vaccine series
–the first 2 doses in the standard adult
hepatitis B vaccine series
 New Twinrix Schedule

• Seroconversion is nearly 100% after

either 3 doses of Twinrix on the new
schedule or a single dose of single-
antigen adult hepatitis A vaccine
• No increased benefit of the new
schedule for the hepatitis B
component compared to
administration of 2 hepatitis B
vaccine doses 1 to 2 months apart
Prevaccination Serologic Testing
• Not indicated before routine vaccination of infants
or children
• Recommended for
– all persons born in Africa, Asia, the Pacific
Islands, and other regions with HBsAg
prevalence of 8% or higher
– household, sex, and needle-sharing contacts of
HBsAg-positive persons
– HIV-infected persons
• Consider for
– Groups with high risk of HBV infection (MSM,
IDU, incarcerated persons)
Postvaccination Serologic Testing
• Not routinely recommended following
vaccination of infants, children,
adolescents, or most adults
• Recommended for:
–Infants born to HBsAg+ women
–Hemodialysis patients
–Immunodeficient persons
–Sex partners of persons with chronic
HBV infection
–Certain healthcare personnel
Postvaccination Serologic Testing

Healthcare personnel who have

contact with patients or blood
should be tested for anti-HBs
(antibody to hepatitis B surface
antigen) 1 to 2 months after
completion of the 3-dose series
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 1-2 months after completing
the second series
 Persistent Nonresponse to
Hepatitis B Vaccine
• Less than 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 postexposure 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 after completion of
at least 3 doses of the HepB series at
9 through 18 months of age
(generally at the next well-child visit)
 Hepatitis B Vaccine
Adverse Reactions
Infants and
Adults Children
Pain at injection site 13%-29% 3%-9%
Mild systemic complaints
(fatigue, headache) 11%-17% 0%-20%

Temperature ≤99.9°F (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 prior dose
• Moderate or severe acute illness
CDC Vaccines and Immunization
Contact Information

• Telephone 800.CDC.INFO

• Email nipinfo@cdc.gov

• Website www.cdc.gov/vaccines