Correspondence
Six Years' Follow-up after Hepatitis A Vaccination
N Engl J Med 1998; 338:1160April 16, 1998
- Article
To the Editor:
Epidemics of hepatitis A occurred in four of the six years preceding the Monroe efficacy trial 1 of an inactivated hepatitis A vaccine (VAQTA).2 Post-trial surveillance included semiannual household telephone surveys, county disease-report surveys, and physical examinations, and γ-glutamyltransferase and IgM antibody tests in suspected cases. In six post-trial years, despite sporadic cases in people who were not vaccinated, Monroe has had no hepatitis A outbreaks or cases among vaccinated people, whereas in three similar, unvaccinated neighboring communities the combined annual cases for 1993 through 1997 totaled 31, 38, 106, 53, and 6. Our data suggest the degree of vaccine coverage needed for outbreak control, a mechanism for long-term protection, and the time interval between vaccination and protection.
Extrapolating from pretrial serologic screening,2 we estimated that by March 1996 approximately 35 percent of Monroe's 4150 2-to-16-year-olds, plus most of those >17 years old, had natural immunity to hepatitis A. The anti–hepatitis A seropositivity rate was approximately 76 percent in the participants less than 17 years old. The people who were seropositive included 1017 trial participants (placebo recipients were vaccinated at the end of the trial), approximately 700 others vaccinated since then, and approximately 1450 people who were naturally immune. Conservatively, the people who were previously not immune had approximately 63 percent vaccination coverage (41 percent of the 4150 total).
Vaccine-induced immune memory, like postinfection immunity,3 raises antibody titers rapidly after viral-antigen reexposure, providing protection regardless of the detectability of pre-reexposure antibodies. Even vaccine recipients who serorevert respond anamnestically after a booster.4 Disease developed in none of the seven vaccine recipients with prebooster exposure to hepatitis A (6 to 74 days after vaccination). Three of these recipients (who were seronegative before vaccination), who each received one 25-unit dose of vaccine before case contact, had markedly elevated anti–hepatitis A titers after contact (ranging from 2050 to 29,931 mIU per milliliter), suggesting a booster effect of contact with the wild virus.
On the basis of the number of cases manifested >50 or >30 days after vaccination (per protocol), one dose induced 100 percent observed preexposure protection.2 Adult travelers vaccinated 14 days before departure who are exposed on arrival (day 15) will face >15 incubation days, after which (>30 days after vaccination) >95 percent will have detectable protective vaccine-induced antibodies.4 Among 52 vaccinated household case contacts in Monroe, there was only one secondary case of hepatitis, in a subject exposed 2 weeks before vaccination who became ill 14 days after vaccination. The last vaccine recipient with hepatitis A in the study, also probably infected before vaccination, became ill on day 16 after vaccination (mistakenly reported earlier as day 18 1). Subtracting 28 days (the average incubation period among case contacts in Monroe) from day 16 suggests that the vaccination may have conferred some postexposure protection. Hence, in this study this hepatitis A vaccine was shown to be highly effective after one dose and, after one booster, to confer persistent protection and long-term outbreak control. During six years of follow-up, no vaccine recipient has had hepatitis A despite community exposure.
4 ReferencesAlan Werzberger, M.D.
Kiryal Joel Medical Research Institute, Monroe, NY 10950Barbara Kuter, Ph.D., M.P.H.
Merck Research LaboratoriesDavid Nalin, M.D.
Merck Vaccine Division, West Point, PA 19486-00041
Smith PF ,Grabau JC ,Werzberger A , et al. The role of young children in a community-wide outbreak of hepatitis A. J Epidemiol Infect 1997;118:243-252
CrossRef | Web of Science | Medline2
Werzberger A ,Mensch B ,Kuter B , et al. A controlled trial of a formalin-inactivated hepatitis A vaccine in healthy children. N Engl J Med 1992;327:453-457
Full Text | Web of Science | Medline3
Villarejos VM ,Serra J ,Anderson-Visona K ,Mosley JW . Hepatitis A virus infection in households. Am J Epidemiol 1982;115:577-586
Web of Science | Medline4
Nalin DR . VAQTA hepatitis A vaccine, purified inactivated. Drugs Future 1995;20:24-29
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T–HBs) combination vaccine. Vaccine 25:43, 7549-7558
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Mara Dinits-Pensy, Graeme N. Forrest, Alan S. Cross, Michael K. Hise. (2005) The Use of Vaccines in Adult Patients With Renal Disease. American Journal of Kidney Diseases 46:6, 997-1011
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Craig, Allen S., Schaffner, William, . (2004) Prevention of Hepatitis A with the Hepatitis A Vaccine. New England Journal of Medicine 350:5, 476-481
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J. Tessier, R. Miller, W. Emmons, E. Holmboe, R. Hawkins. (1999) Zoonotic Infection with Group G Sterptococcus. Clinical Infectious Diseases 28:6, 1322-1323
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