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By Philip R. Fischer, MD, DTM&H
Synopsis: New data and consensus discussions provide updated guidance about the use of hepatitis A vaccine for young children, in US residents, and in individuals who are traveling very soon after their pretravel consultations.
Sources: Mackell S. Immunization Update session, Pediatric Travel Medicine symposium. ASTMH annual meeting, Denver, November 12, 2002; DeSilvestri A, et al. Decline of maternal hepatitis A virus antibody levels in infants. Acta Paediatr. 2002;91:882-884; Kanra G, et al. Hepatitis A booster vaccine in children after infant immunization. Pediatr Infect Dis J. 2002;21:727-730; CDC. Yellow Book Update. ASTMH annual meeting, Denver, November 13, 2002.
Common us recommendations and licensing suggest that hepatitis A vaccine should not be used before 2 years of age, but European licensing includes 1 year olds, and many American travel medicine providers frequently use the vaccine in even younger children. Similarly, official recommendations call for the use of immune serum globulin (ISG) rather than vaccine to protect travelers who will be leaving within a few weeks of their pretravel consultation, but many practitioners do not follow this recommendation. New data have recently been published, and new recommendations were discussed at the recent ASTMH meeting in Denver. Awareness of this material can help travel medicine practitioners wisely choose their hepatitis A vaccine at the limits of age and for various itineraries.
Dr. Sheila Mackell capably reviewed the use of hepatitis A vaccine in children at the November 2002 ASTMH meeting. Various products are widely available and are effective both in stimulating antibody responses and in protecting against clinical hepatitis. Current US recommendations call for the use of hepatitis A vaccine in children 2 years of age and older who are traveling to or residing in a high-risk area. In fact, there are 11 western US states with relatively high risk, and hepatitis A vaccine is recommended for children residing in these states. In Europe, hepatitis A vaccine is used in younger children.
Hepatitis A infection is usually asymptomatic in young children. Some children, however, do become ill. Others can unknowingly transfer infection to peers and adult contacts for weeks after their own infection. This poses potential public health risks, especially for people in contact with returned travelers.
Currently available hepatitis A vaccines are effective in stimulating the development of protective antibody levels for 94-100% of recipients, even when children as young as 1 year of age are included in studies.1,3 What data can guide our use of hepatitis A vaccine in young children? Seronegative infants (those who did not receive antibodies transplacentally from seropositive mothers) respond well to hepatitis A vaccine.4,5 Seropositive infants tolerate the vaccine well and do have some priming response.6 However, seropositive infants usually do not achieve lasting protection from vaccine.7
When do infants clear their passively acquired anti-hepatitis A antibody? Earlier in 2002, maternal antibody levels were reported to have "decayed significantly" by 12 months of age, but 39% of tested children were still seropositive at that time.8 DeSilvestri and colleagues found a surprising 61% of 18 initially seropositive children still to be seropositive at 12 months of age; they did note, however, that some infants in their area became infected during the first year of life. Thus, it could be that some of the seropositive 12 month olds had lost maternal antibody and then acquired a new hepatitis A infection.
In the recent study noted as a source above, Kanra and colleagues followed children they had previously vaccinated as infants, many of whom were seropositive.7 At age 4 years, 77% of previously vaccinated children were seropositive. The seropositive 4 year olds who were revaccinated boosted their antibody titers, and the seronegative children converted to seropositivity.
Combining all this information, we can conclude that hepatitis A vaccine is probably effective in initially seronegative children of any age. Infants with passively acquired maternal antibody will not always receive full, lasting protection but do not have adverse outcomes related to early vaccination. Thus, potentially seropositive infants going to an area of risk can either receive early vaccine administration or undergo serologic testing to see if vaccination is warranted. If infants have been vaccinated without confirming seronegativity, they should receive subsequent immunization sometime after age 2 to confer long-lasting protection.
Travelers Soon to Depart
What should be done with travelers who present for consultation just a few days before departure? Currently, the CDC recommends ISG, rather than hepatitis A vaccine, as a means of protecting these travelers. Participants at the ASTMH meeting were told that the CDC is modifying the recommendation to suggest that vaccine be used when departure is within 2 weeks (rather than 1 month) of the pretravel consultation.
The CDC bases this modified recommendation on the knowledge that hepatitis A antibody titers rise to protective levels within 2 weeks of immunization. Others, however, point out that hepatitis A has a month-long incubation period; thus, the vaccine’s protective effect would probably overcome this slowly incubating infection if the vaccine were given right up to the time of exposure. In fact, there is some evidence that postexposure hepatitis A vaccination is protective.9,10 Nonetheless, there is 1 reported case of a healthy adult who was vaccinated 12 days prior to departure and then developed hepatitis A illness after 7 weeks in India.11
Dr. Fischer, Professor of Pediatrics, Department of Pediatric & Adolescent Medicine, Mayo Clinic, Rochester, MN, is Associate Editor of Travel Medicine Advisor.
1. WHO position paper on hepatitis A vaccines. Can Commun Dis Rep. 2000;26-05 (www.hc-sc.gc.ca/hpb/lcdc/publicat/ccdr/00vol26/dr2605ea.html)
2. Abarca K, et al. Efficacy of hepatitis A vaccination in children aged 12 to 24 months. Arch Med Res. 2001;32:468-472.
3. Lopez EL, et al. Safety and immunogenicity of a pediatric formulation of inactivated hepatitis A vaccine in Argentinean children. Pediatr Infect Dis J. 2001;20:48-52.
4. Troisi CL, et al. Immunization of seronegative infants with hepatitis A vaccine (HAVRIX:SKB): A comparative study of two dosing schedules. Vaccine. 1997; 15:1613-1617.
5. Piazza M, et al. Safety and immunogenicity of hepatitis A vaccine in infants: A candidate for inclusion in the childhood vaccination programme. Vaccine. 1999; 17:585-588.
6. Dagan R, et al. Immunization against hepatitis A in the first year of life: Priming despite the presence of maternal antibody. Pediatr Infect Dis J. 2000;19: 1045-1052.
7. Kanra G, et al. Clinical trial to evaluate immunogenicity and safety of inactivated hepatitis A vaccination starting at 2-month-old children. Turk J Pediatr. 2000;42:105-108.
8. Lieberman JM, et al. Kinetics of maternal hepatitis A antibody decay in infants: Implicatons for vaccine use. Pediatr Infect Dis J. 2002;21:347-348.
9. Sagliocca L, et al. Efficacy of hepatitis A vaccine in prevention of secondary hepatitis A infection: A randomized trial. Lancet. 1999;353:1136-1139.
10. Irwin DJ, Millership S. Control of a community hepatitis A outbreak using hepatitis A vaccine. Commun Dis Public Health. 1999;2:184-187.
11. Kurup A, et al. Acute hepatitis A in a traveler who had received preexposure inactivated hepatitis A virus vaccine. Clin Infect Dis. 1999;28:1324-1325.