Hepatitis A Prevention, Immunization : Vaccine, Part 2

by CDC

(Page 8 of 13)

Efficacy After Exposure. Studies of chimpanzees indicate that hepatitis A vaccine can prevent HAV infection if administered shortly after exposure. Because the incubation period of hepatitis A can be 50 days, the fact that during a clinical efficacy trial, no cases of hepatitis A occurred in vaccine recipients beginning 17 days after vaccination also suggests a possible postexposure effect. In a limited randomized trial, investigators determined that hepatitis A vaccine was 79% efficacious in preventing IgM anti-HAV positivity after household exposure to hepatitis A compared with no treatment. However, the CI was extremely wide (7% - 95%), and investigators did not assess the efficacy of the vaccine compared with IG. Results of an appropriately designed clinical trial comparing the postexposure efficacy of vaccine with that of IG are needed to determine if hepatitis A vaccine without IG can be recommended to prevent hepatitis A after exposure.

Effectiveness in Populations. The effectiveness of hepatitis A vaccine in populations has been studied in demonstration projects and by analysis of surveillance and vaccine coverage data. The earliest such studies focused on communities with the historically highest hepatitis A rates, such as Alaska Native and American Indian communities. Demonstration projects conducted soon after hepatitis A vaccines became available indicated that routine vaccination of children living in these communities was feasible and that when relatively high vaccination coverage was achieved and sustained, ongoing epidemics were interrupted and a reduction in disease incidence was sustained. For example, a 1992 - 1993 communitywide epidemic among Alaska Natives in one rural area ended within 4 - 8 weeks of vaccinating approximately 80% of children and young adults. After publication in 1996 of ACIP recommendations for routine vaccination of children in these areas, surveys indicated that vaccine coverage among preschool- and school-aged American Indian and Alaska Native children was 50% - 80%, suggesting that recommendations were being implemented. By 2000, hepatitis A incidence among American Indians and Alaska Natives had declined 97% compared with the beginning of the decade and was lower than the overall U.S. rate. These low rates have been sustained in subsequent years; the 2004 rate of 0.1 case per 100,000 population among American Indian and Alaska Natives was the lowest of any racial/ethnic population.

Results of a demonstration project in Butte County, California, provided evidence that considerable reductions in overall incidence also could be achieved in populations with consistently elevated hepatitis A rates with a program of ongoing routine vaccination of children that achieved fairly modest coverage. During the 6-year project, 66% of the approximately 45,000 eligible children aged > 2 years received >1 dose of hepatitis A vaccine. The number of reported cases declined 94%, and the four cases reported in 2000 during the last year of the project was the lowest number ever reported in the county since hepatitis surveillance began in 1966.

The most comprehensive indication of the performance of hepatitis A vaccines in populations is derived from analysis of trends in hepatitis A incidence after publication of ACIP's 1999 recommendations for routine vaccination of children living in 17 states with consistently elevated hepatitis A rates. The 2003 rate (2.5 cases per 100,000 population) in these states represented a decline of approximately 88% compared with the average rate (21.1 cases per 100,000 population) during the baseline prevaccine period on which the recommendations were based of. Rates among regions with and without statewide recommendations for routine vaccination of children are now approximately equal. Compared with 1990 - 1997, rates declined most dramatically among children aged 2 - 18 years, and the proportion of cases among children declined from 35% to 19%. Because hepatitis A incidence has been cyclic in the United States, the precise contribution of vaccination of children to the observed decline in rates has been difficult to quantify. Modeling studies suggested that during 1995 - 2001, an estimated 97,800 hepatitis A cases were averted because of the direct effects of immunization and herd immunity, including 39% of potential cases in 2001.

Available information concerning vaccine use indicates that the observed declines in rates among children appear to have been achieved with modest levels of vaccine coverage, suggesting a strong herd immunity effect. Declines in rates among adults also suggest that vaccination of children might have reduced transmission in other age groups through herd immunity. Similar findings have been reported from other countries (e.g., Israel and parts of Spain) in which routine hepatitis A vaccination of infants or children has been implemented. Results of modeling the relationship between hepatitis A incidence and vaccine coverage have also indicated a strong herd immunity effect, accounting for more than one third of the estimated number of cases prevented by vaccination.

Interest has been expressed regarding use of hepatitis A vaccine to interrupt ongoing communitywide epidemics by vaccinating children in these populations, but the strategy has proved difficult to implement. Typically, first-dose coverage was low (20% - 45%), and the impact of vaccination always was limited to vaccinated age groups that did not represent the majority of cases. Efforts are probably better directed towards sustained routine vaccination of children to maintain high levels of immunity and prevent future epidemics.

Long-Term Protection. All 31 adults who received 3 doses of HAVRIX (720 EL.U. per dose at 0-, 1-, and 6-month intervals) had anti-HAV levels >15 mIU/mL 12 years after the initial dose. Ten years after vaccination, all 307 adults administered 2 doses of 1,440 EL.U. of HAVRIX had anti-HAV levels >20 mIU/mL. Protective levels of anti-HAV were still observed in 544 (99%) of 549 children evaluated 5 - 6 years after receiving VAQTA. A recent review concluded that estimates of antibody persistence derived from kinetic models of antibody decline indicate that protective levels of anti-HAV could be present for >25 years in adults and >14 - 20 years in children. Whether other mechanisms (e.g., cellular memory) also contribute to long-term protection is unknown. Surveillance data and population-based studies are being used to monitor the long-term protective efficacy of hepatitis A vaccine and to determine the possible need for a booster dose. In the longest such follow-up study reported to date, no cases of hepatitis A have been detected among children studied for 9 years after vaccination.

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