Hepatitis A and B Vaccines

1
Hepatitis A and B Vaccines

• Sheila L. Palevsky, MD MPH
• Bureau of Immunization
• New York City Department of Health and Mental
  Hygiene
• October 26, 2006

2
Hepatitis B Virus

• Epidemic jaundice described by Hippocrates in 5th
  century BCE
• Differentiated from Hepatitis A (infectious
  hepatitis) in the early 1940s
• Humans are only known host
• Resilient organism - may retain infectivity for
  at least 1 month at room temperature
• Hepadnaviridae family (DNA)

3

• HBsAg
• Antigenic determinant found on the surface of the
  virus
• Not infectious only the complete virus (Dane
  particle) is infectious
• When HBsAg is present, complete virus is also
  present
• During replication, HBV produces HBsAg in excess
  of that needed for production of the Dane
  particles
• HBcAg
• Nucleocapsid protein core of the HBV
• Not detectable in serum by conventional
  techniques
• Found in liver tissue of persons with acute or
  chronic HBV infection
• HBeAg
• A soluble protein found in the core of HBV
• Found in serum of person with high virus titers
• Anti-HBs
• Develops during convalescence to acute HBV or
  after vaccination
• Anti-HBc
• Indicates infection with HBV at an undefined time
  in the past
• Anti-HBe
• Associated with low infectivity of serum

4
Hepatitis B Clinical Features

• Incubation period 60 -150 days (average
  90 days)
• Nonspecific prodrome of fever, malaise, headache,
  myalgias
• At least 50 of infections asymptomatic
• Illness not specific for hepatitis B
• Most acute HBV infections in adults result in
  complete recovery with resultant immunity

5

• Risk of Chronic HBV Carriage by Age of Infection

CDC
6
Outcomes of Hepatitis B Infection
Acute HBV Infection
10
1-2
Recovery and Immunity
Fulminant Hepatitis
Chronic Infection carrier
63-93
25
Death
Chronic Active Hepatitis cirrhosis
hepatocellular carcinoma
CDC
7
Hepatitis B Virus Infection

• gt300 million carriers worldwide
• Established cause of chronic hepatitis and
  cirrhosis
• Human carcinogen an underlying cause of up to
  80 of hepatocellular carcinomas

8
(No Transcript)
9
Hepatitis B Epidemiology

• Reservoir Human. Endemic
• Transmission Bloodborne
• Subclinical cases transmit
• Communicability 1-2 months before and after
  onset of symptoms
• Chronic carriers

10

• Hepatitis BUnited States, 1978-2005

Infant immunization recommended (1991)
Universal birth dose (2006)
Hepatitis B vaccine licensed
Adolescent immunization recommended (1996)
Year
2005 provisional total
CDC
11
Hepatitis B Virus Infection

• In the United States
• 78,000 new infections/year
• gt5,000 new carriers/year
• gt1 million chronically infected
• 5,000 deaths/year

CDC 2001 estimates
12
(No Transcript)
13
Modes of Hepatitis B Virus Transmission

• Sexual
• Parenteral
• Perinatal

14
Body Fluid Concentrations of Hepatitis B Virus
High Moderate
Low/Not
Detectable
blood semen
urine serum
vaginal fluid feces wound
exudates saliva
sweat tears

breast milk
15
Transmission of Hepatitis B

• Percutaneous needlestick injury, IDU, body
  piercing, tattooing, inadequate sterilization
• Household transmission shared objects
  toothbrushes, razors, washcloths
• Person-to-person contact biting, oozing lesions
• Institutionalized settings biting, sexual
  contact
• Pre-chewing of food traditional practices,
  chewing gum

16
High Risk Groups For Hepatitis B

• Immigrants / refugees from endemic areas
• Children born in US to those from endemic areas
• Household contacts / sexual partners of those
  with chronic HBV
• Men who have sex with men
• Heterosexuals with multiple sexual partners
• Persons diagnosed with an STD
• Persons who trade sex for money or survival
• Injection drug users
• Inmates of long-term correctional facilities
• Persons receiving dialysis
• Healthcare workers

17

• Risk Factors for Hepatitis B

CDC
CDC Sentinel Sites. 2001 data.
18
Hepatitis B Virus Infection by Duration of
High-Risk Behavior
IV drug user
HCWs
MSM
Heterosexual
100
80
60
Percent infected
40
20
0
0
3
6
9
12
15
Years at Risk
CDC
19
Missed Opportunities for Immunization Against
Hepatitis B Virus Infection
Of persons with acute hepatitis B

• 33 have been previously treated for an STD
• 25 have been previously incarcerated
• 2 were incarcerated during the incubation
  period

20
Prevention of Hepatocellular Carcinoma
Experience in Taiwan

• After introduction of Hepatitis B vaccine in
  1984, the rate of hepatocellular carcinoma (HCC)
  among cohorts of children declined by gt 50
• Rates of HCC in older age groups and rates of
  other childhood cancers remained stable or
  increased during this time period

Lee CL, Ko YC, Pediatrics 199799351-353
21
Liver cancer death rates among children in
Taiwan, 1975 to 1993
From Vaccine, 4th ed. Plotkin, 2004 adapted from
Lee CL, Ko YC.. Pediatrics 99351353, 1997.
22
Hepatitis B Vaccine
1965 Discovery of Australian antigen 1973 Succes
sful HBV infection of chimpanzees 1981 Licensure
of plasma-derived vaccine 1986 Licensure of
recombinant vaccine 1991 Universal infant
vaccination 1996 Universal adolescent
vaccination
23
Hepatitis B Vaccine Intervals

• 3 dose series
• dose 1
• dose 2
• at least one month after the 1st
  dose
• dose 3
• at least 4 months after the 1st dose
  and at least 2 months after the 2nd dose

For infants, the final dose not before 24 weeks
of age
24

• There is no need to ever start the hepatitis B
  vaccines series over again, no matter how long
  the interval between each dose!

25
Recommended Doses and Schedules of Hepatitis B
Vaccines
Two 1.0 ml doses given at one site in a four
dose series 0,1,2,6 months
26
Immunogenicity and Vaccine Efficacy

• Adequate antibody responses after three IM doses
  of Hep B vaccine
• gt95 of those from birth to lt19 years
• gt90 of healthy adults lt40 years
• 90 of adults 40 lt60 years
• 75 of adults gt60 years

27
Vaccine Completion Rates and Seroconversion

• Protective levels of antibodies in healthy adults
  lt40 yrs of age
• In 20-30 after one dose
• In 70-85 after two doses
• In gt90 after three doses

A full series of vaccine is recommended as there
are no data on persistence of antibody after lt3
doses of vaccine
28
Vaccine Completion Rates and Seroconversion

• Factors that may play a role in lower
  seroconversion rates
• Increased age (gt40 years)
• Male gender
• Smoking
• Obesity
• Immune dysfunction
• ?

29
Persistence of Immunity

• Immunologic memory established following
  vaccination
• Exposure to HBV results in anamnestic anti-HBs
  response
• Chronic infection rarely documented among vaccine
  responders

30
Vaccine Administration

• Vaccine must be administered IM doses given
  subcutaneously should not be counted as valid and
  should be repeated

31
Hepatitis B Vaccine

• Booster doses are
• NOT
• routinely recommended
• for any age group

32
Hepatitis B Adverse Reactions in Adults

• Pain at injection site 13-29
• Mild systemic complaints 11-17
  (fatigue, headache)
• Temperature gt37.7 C 1
• Severe systemic reactions rare

33
Hepatitis B Vaccine

• Contraindications
• Severe allergic reaction to a vaccine component
  (hypersensitivity to Bakers yeast)
• Severe allergic reaction following a previous
  dose
• Precaution
• Moderate or severe acute illness

34
Childhood/Adolescent Hepatitis B Vaccine
Recommendations

• All newborns prior to hospital or birthing center
  discharge
• All children
• All adolescents
• NYS PHL2164 requires a complete series of
  hepatitis B vaccines for attendance in daycare /
  preK / K-12

35
Adult Hepatitis B Vaccine Candidates

• Men who have sex with men
• Heterosexuals with multiple partners
• Persons diagnosed with an STD
• Persons who trade sex for money or survival
• Injection drug users
• Inmates of long-term correctional facilities
• Persons receiving dialysis
• Persons with chronic liver disease (not HBV)
• Healthcare workers

36
Adult Hepatitis B Vaccine Candidates(contd)

• 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
37
Prevaccination Serologic Testing

• Not indicated before routine vaccination of
  infants or children
• May be considered in persons where there is a
  high rate of HBV infection
• Injection drug users
• MSM
• Sexual contacts of persons with HBV infection
• Family members of HBV carriers
• Immigrants/refugees from endemic areas
• Adoptees from HBV endemic countries
• Pacific Islanders, Alaskan Natives

38
Postvaccination Serologic Testing

• Not routinely recommended following vaccination
  of infants, children, adolescents, or most adults
• Recommended for
• Infants born to HBsAg women
• Sexual partners of HBsAg persons
• Hemodialysis patients
• Immunodeficient persons
• Certain healthcare workers

39
Management of Non-response 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 2 months after completing the second
  series

40
Persistent Non-response to Hepatitis B Vaccine

• lt5 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

41
Hepatitis A

• Enteric viral infection oral fecal spread
• Acute disease and asymptomatic infection no
  chronic infection
• Incubation period 15-50 days
• Non-specific illness usually self-limited
• Age-related clinical illness
• Young children generally asymptomatic
• Teens and adults symptomatic
• Fulminant hepatitis A results in 100 deaths/yr

42
GEOGRAPHIC DISTRIBUTION OF HEPATITIS A VIRUS
INFECTION
CDC
43
(No Transcript)
44
Risk Factors Among Persons with Hepatitis A,
Reported Cases, United States, 1990-2000
Household and sexual contact
Other
Common source outbreak 4
14
8
Child care contact
6
45
Unknown
Child care 2
10
6
MSM
Illicit drug users
International travel 5
CDC sentinel counties
45
Hepatitis A, United States

• Most disease occurs in the context of
  community-wide outbreaks
• Infection transmitted from person to person in
  households and extended family settings
• Some groups at increased risk
• No risk factor identified in 50 of cases
• Asymptomatic pediatric travelers play a role in
  silent transmission
• Between 25-50 of adults with no clear risk
  factor have contact with asymptomatic child
• Consider travel to endemic region as a risk factor

46
Hepatitis A Vaccine Recommendations

• Universal vaccination at 12 - 23 months of age
• In NYC vaccination of all children 12 59
  months of age in certain communities
• Men who have sex with men
• Drug users
• Persons with chronic liver disease, including
  hepatitis C
• International travelers
• Recipients of clotting factors
• Persons with occupational risk

47
Hepatitis A Vaccine Recommendations

• Health care workers
• not routinely recommended
• Day care centers
• not routinely recommended
• Plumbers and sewer workers
• not routinely recommended
• Food handlers
• may be considered based on local circumstances

48
Hepatitis A Vaccine

• Two brands of vaccines
• HAVRIX (GlaxoSmithKline)
• VAQTA (Merck)
• Pediatric (12 months -18 years) and adult (gt19
  years) formulations
• Vaccine licensed for use in persons aged 12
  months and older
• Vaccines are equivalent and interchangeable
• 2 dose series for all ages
• A minimum of 6 months between doses

49
Duration of Protection

• Persistence of antibody
• At least 10 years for 95-100 of adult vaccinees
• At least 6 years for 99 of vaccinated children
• Mathematical models of antibody decline suggest
  protective antibody levels persist for minimum of
  15-25 years

50
Efficacy of Hepatitis A Vaccine After Exposure to
Hepatitis A Virus

• Indirect evidence
• Animal models
• Efficacy studies
• No cases in vaccinees gt 16 days after vaccination
• No cases in vaccinated children at 9 years of
  follow-up
• Randomized trial comparing vaccine to no
  intervention
• Hospitalized cases
• Household contacts vaccinated within 8 days
• 79 efficacy 95 CI 7-95
• Randomized trial comparing vaccine to IG just
  completed

51
Hepatitis A Serologic Testing

• Pre-vaccination
• Not routinely indicated for children
• Cost-effective for
• Persons born or lived in high endemic areas
• Adults in high prevalence groups
• Adults gt40 years
• Post-vaccination
• Not routinely indicated or recommended
• Not all commercially available assays are
  sensitive enough to detect lower (protective)
  levels of vaccine-induced antibody

52
Safety of Hepatitis A Vaccine

• Most common side effects related to injection
  site
• Reported by 20-50 of recipients
• No severe adverse reactions attributed to vaccine
• Safety in pregnancy not determined risk likely
  low

53
Contraindications and Precautions

• Contraindications
• Severe adverse reaction to previous dose
• Severe allergy to a vaccine component
• Precaution
• Moderate to severe illness

54
Twinrix (GSK)

• Combination hepatitis B (adult dose) and
  hepatitis A vaccine (pediatric dose)
• Schedule 0, 1, 6-12 months
• Approved for persons gt18 years

55
Mixed Schedules Twinrix and Hep A

• Adult formulation single antigen HepA vaccine may
  be used to complete a schedule begun with Twinrix
  and vice versa
• Acceptable schedules
• 2 Twinrix and 1 hepatitis A (adult formulation
• 1 Twinrix and 2 hepatitis A (adult formulation)
• Maintain spacing recommended for Twinrix

56
The Citywide Immunization Registry (CIR)

• The NYC DOHMHs centralized, computerized
  database of immunization records
• Citywide implementation January 1, 1997 and
  extended August 18, 2005
• Mandated reporting for NYC children lt19 years
• Voluntary reporting for NYC adults gt19 years
  (consent in their medical record)
• Access to the CIR for authorized health care
  providers, parents, legal guardians and
  custodians, and patients

212-676-2323 www.nyc.gov/health/cir
NYC Health Code sections 11.04 and (d)11.07