Rationale:

• Children play an important role in the transmission of HAV.
• Despite widespread use of postexposure prophylaxis with immunoglobulin, community-wide outbreaks of hepatitis A are difficult to control.
• Outbreaks of hepatitis A continue to occur in the U.S.
• Hepatitis A rates have decreased dramatically in response to vaccination of children.
• Hepatitis A mortality rates have declined during the past decade when hepatitis A vaccine has been available.

Evidence:

• U.S. surveillance data from 1983 through 1995 indicate that children, who are often asymptomatic, may be an important source of HAV transmission in communities (1; 2).
• Analysis of risk factor data for hepatitis A during two community-wide outbreaks suggests that asymptomatic children may be an important source of viral transmission within and between households and communities (3; 4).
• Analysis of the effectiveness of hepatitis A vaccine use among children in four high-rate communities indicated interruption of ongoing HAV transmission, reduced disease incidence, and prevention of anticipated outbreaks (5; 6; 7; 8).
• Outbreaks of hepatitis A continue to occur in the U.S. (9).
• U.S. surveillance data suggest that in communities where routine hepatitis A vaccination was recommended, and where vaccine purchase was greatest, there were large decreases in hepatitis A rates (10).
• A retrospective study of hepatitis A hospitalizations from 1996 to 2004 included in the Medstat MarketScan databases indicate that from the pre-vaccine era to 2004, hospitalizations due to hepatitis A declined by 68.5% and ambulatory vists with a hepatitis A diagnosis code declined by 41.5% (11).
• Research is ongoing to determine the persistence of vaccine-induced antibody among persons who received hepatitis A vaccine. Evidence from animal modeling and epidemiologic studies show that hepatitis A vaccine is protective for at least 10 years after immunization. There is currently no recommendation for booster doses of vaccine (12; 13; 14; 15; 16).
• Research suggests that hepatitis A vaccine is immunogenic following a delay in dose 2 of the vaccine for up to at least 5 years in adults and 25 years in children (17).
• Passively acquired maternal anti-HAV results in significantly lower final antibody response in infants. However, the clinical implications of lower anti-HAV are unclear (18; 19; 20).
• Hepatitis A vaccine has been found to be safe and immunogenic when administered with other routine childhood vaccines (20; 21; 22).
• U.S. death certificates from 1990 to 2004 listing hepatitis A as the underlying cause of death were analyzed to compare the average annual age-adjusted mortality rates during the pre- and post-hepatitis A vaccine era. The hepatitis A mortality rate declined during the past decade; however, chronic liver disease remains a preventable contributing cause of death due to hepatitis A (23).
• To compare morbidity and mortality before and after widespread implementation of national vaccine recommendations for 13 vaccine-preventable diseases, including hepatitis A, for which recommendations were in place prior to 2005, pre-vaccine baselines were assessed based on representative historical data from primary sources and were compared to the most recent morbidity (2006) and mortality (2004) data. Declines were 80% or greater for cases and deaths from most vaccine-preventable diseases targeted since 1980, including hepatitis A (24).

Comments:

• The ACIP recommends universal childhood immunization with hepatitis A vaccine (25; 26).
• The FDA has licensed available hepatitis A vaccines, VAQTA® and HAVRIX®, to include their use in children aged 1 year and older (27).
• Current vaccine schedules are available from the National Immunization Program or the Immunization Action Coalition.
• Vaccines for children are available from the Vaccines for Children program.
• HIV-positive individuals respond less well to the two-dose series of hepatitis A vaccine compared with immunocompetent individuals. Available studies suggest that 50% of HIV-infected individuals have an immune response that is considered protective. However, factors associated with protection vary among studies.
• A study of 214 HIV-infected individuals found that the response to hepatitis A vaccine was directly related to the CD4 count at vaccination. Higher CD4 counts were associated with higher vaccine response rates, independent of the nadir CD4 count and the viral load level (28).
• A retrospective study of 138 HIV-infected persons who completed the two-dose hepatitis A vaccine series and had post-vaccine titers evaluated determined that 48% of study participants responded to vaccine. Multivariate analyses determined that female sex and higher CD4 counts were independent predictors of response (29).
• A serologic study of 238 HIV-infected individuals determined that 50% developed immunity after the two-dose series. Factors associated with a protective response were HIV plasma RNA level <1000 copies/mL and male gender (30).
• Approximately 150 HAV-seronegative, HIV-infected individuals with 200 to 500 CD4+ T cells/mm³ and HIV-1 RNA titers <50,000 copies/mL were randomly assigned to a two-dose or three-dose hepatitis A vaccine study group. Seroconversion rates and geometric mean anti-HAV titers were higher in the three-dose group compared with the two-dose group. No serious adverse events were associated with the vaccine. Absence of tobacco smoking was an independent predictor of response to vaccine (31).
• Manufacturers of hepatitis A vaccine (GlaxoSmithKline [HAVRIX®] and Merck & Co. [VAQTA®]) recommend that primary immunization be completed at least 2 weeks prior to expected exposure.
• In persons aged 18 years or older who need vaccination against both hepatitis A and B, combined hepatitis A and B vaccine (GlaxoSmithKline [TWINRIX®]) can be used.
• A Medline review shows no evidence of an increase in autoimmune manifestations after hepatitis A vaccine (32).
• A study of 34 pediatric patients with chronic liver disease and 55 pediatric control subjects found the hepatitis A vaccine to be safe and immunogenic (33).
• Cohorts of children aged 1 to 6 years and 6 to 15 years were followed-up for 7.5 and 10 years, respectively, for persistence of anti-HAV and anti-HBV after a three-dose series of combined hepatitis A and B vaccine (TWINRIX®). All children and adolescents had anti-HAV, and 86.5% of children aged 1 to 6 years (32 of 37) and 95.5% of children aged 6 to 15 years (21 of 22) had anti-HBs titers 10 mIU/mL, suggesting good long-term protection from the combined vaccine (34).
• A study of children aged 3 to 7 years and adults followed-up for 10 years after hepatitis A vaccination showed that 100% of children and 96% of adults had persistence of anti-HAV (35).