Duration of Hepatitis B Immunity in Low Risk Children Receiving Hepatitis B Vaccinations from Birth

Kenneth M. Petersen, MD; Lisa R. Bulkow, MS; Brian J. McMahon, MD; Carolyn Zanis, BS; Marilyn Getty, RN; Helen Peters, RN; Alan J. Parkinson, PhD

Disclosures

Pediatr Infect Dis J. 2004;23(7) 

In This Article

Materials and Methods

We conducted 2 studies in Alaska children. All the children but 1 were Alaska Natives. Since 1985, all Native children in Alaska have received hepatitis B vaccine as part of a statewide vaccination program. Hepatitis B vaccination is initiated within the first 7 days of life, with the second dose given at 4-6 weeks and the third at 6 months of age. Until 1989, a plasma-derived hepatitis B vaccine (Heptavax-B, 10 µg; Merck Sharp & Dohme, West Point, PA) was given. Since 1989, yeast recombinant hepatitis B vaccines [RecombivaxHB, 2.5 µg (Merck Sharp & Dohme), or Engerix-B, 10 µg (SmithKline Beecham, Rixensart, Belgium)] have been used. Study 1 consisted of children whose initial response to the hepatitis B vaccine series was unknown (groups 1a and 1b), and study 2 consisted of children with a documented anti-HBs titer ≥10 mIU/mL after the initial vaccine series (Groups 2a, 2b and 2c) ( Table 1 ). All booster doses in both studies used RecombivaxHB.

The institutional review boards of the Alaska Area Native Health Service, the Indian Health Service and the Centers for Disease Control and Prevention approved the protocols for both studies. Approval was also obtained from the Anchorage Native Health Board and Southcentral Foundation. Written informed consent was obtained from the parents or guardians of the children plus verbal assents from all children older than 7 years.

Study 1. Two groups of children born to HBsAg-negative mothers and vaccinated in infancy were examined. The initial antibody responses after the primary vaccination for children in this study were unknown. The first group consisted of 102 children ( Table 1 ) who had received plasma-derived vaccine in infancy (group 1a); the second consisted of 208 children who had received recombinant vaccine (group 1b). Potential participants were identified by a computer search of immunization records, and they were invited to participate.

At enrollment, sera were obtained from all children and tested for anti-HBs and antibody to hepatitis B core antigen (anti-HBc). Children who were anti-HBc-negative with anti-HBs <10 mIU/mL were randomized by a computer-generated schedule to receive either a 2.5-µg booster dose at that time or deferred for 3 years. Serum specimens were obtained 10-14 days after the booster dose and were tested for anti-HBs.

Those returning in 3 years were retested for anti-HBs and anti-HBc. Children who were anti-HBc-negative and whose anti-HBs remained <10 mIU/mL then received a 2.5-µg booster dose. After the study was under way, early results led to a desire to obtain more immediate data on the booster response of children who had originally received the plasma vaccine (group 1a). Rather than wait for 3 years, group 1a children whose booster dose had initially been deferred were recalled early, and the booster dose was given an average of 1.5 years after initial recruitment.

Study 2. These children were originally part of a long term follow-up study of children who had received hepatitis B vaccine from birth and had their sera tested for anti-HBs after completion of the initial vaccination series. Only children who responded with anti-HBs titers of ≥10 mIU/mL or ≥10 standard ratio units (used in or before 1986) were included. Group 2a consisted of 17 children of HBsAg-negative mothers who had received a plasma-derived vaccine ( Table 1 ) and were boosted with 5 µg of recombinant vaccine (Recombivax). Group 2b consisted of 36 children of HBsAg-negative mothers who had received a recombinant vaccine. Approximately one-half of the children in group 2b were randomly assigned to receive a 2.5-µg dose of recombinant vaccine, whereas the remaining children received a 5-µg dose. Group 2c included 16 children who were born of HBsAg-positive mothers and who had received a plasma-derived vaccine; they were boosted with 5 µg of recombinant vaccine.

At enrollment, sera were obtained from all children and tested for anti-HBs and anti-HBc. The children were recalled at ~2 months and 2 years after the booster dose and tested for anti-HBs. Those who did not respond initially (at the 2-month visit) to the booster dose with an anti-HBs ≥10 mIU/mL received additional doses of recombinant vaccine and were retested.

All serologic specimens were tested quantitatively by radioimmunoassay (RIA) for anti-HBc (CORAB; Abbott Laboratories, Abbott Park, IL) and qualitatively by RIA for anti-HBs (AUSAB-RIA; Abbott Laboratories). The anti-HBs titers were reported in milli-International Units (mIU) per mL using the WHO international reference standard.[13]

Anti-HBs ≥10 mIU/mL in a child was considered protected against hepatitis B infection.[6] An anamnestic response to a hepatitis B vaccine booster dose was defined as a rise of anti-HBs from <10 mIU/mL to ≥10 mIU/mL. Anti-HBs titers were log-transformed for calculating geometric mean titer (GMT), and comparisons of GMT over time were made with a paired t test with the log-transformed values. For analysis, persons with undetectable anti-HBs were assigned a value of 0.1 mIU/mL. Proportions were compared with the use of a χ2 or Fisher exact test, as appropriate. All P values were two-sided.

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