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

Discussion

We have previously reported on long term protection in a population of Alaska Natives living in areas with a high prevalence of HBV infection.[14] In 1630 persons, anti-HBs titers were ≥10 mIU/mL in 76% at 10 years after vaccination and 82% of those age 6 months-19 years at the time of vaccination.[15] In another study from this population in which individuals were tested before and after mass vaccination (newborn and catch-up programs), none younger than 10 years of age who had received hepatitis B vaccine at birth was HBsAg-positive 10 years after vaccination, compared with 16% of persons between 10 and 30 years of age.[16] In the current report, we studied primarily groups of children vaccinated with 3 doses of a hepatitis B vaccine in infancy who were at low risk for HBV exposure and thus more typical of industrialized countries.

In low risk children who received a plasma-derived vaccine in infancy (group 1a), 59% had anti-HBs <10 mIU/mL, and 39% of these were nonresponsive to a booster dose of hepatitis B vaccine. Although some may have been primary nonresponders, it is unlikely that all were so. It is important, however, that the primary nonresponse rate has a disproportionately large effect on the estimate of proportion of vaccinees retaining memory. Therefore we examined another group (group 2a) of recipients of the plasma-derived vaccine who had a response to the primary vaccination series starting at birth, and results were similar. This implies that although most low risk infants respond to plasma-derived vaccine, for one-fourth of them long term anamnestic memory to HBV may be lost.

In children vaccinated with a recombinant vaccine from birth, anti-HBs fell faster than in those who had received plasma-derived vaccine. However, immunologic memory at 5 years of age appeared to be good because 90% of children responded to a hepatitis B booster dose, and it is possible that 5-10% may have been primary nonresponders.[3] In a group of children who had a documented initial response to recombinant vaccine, the response to a booster dose was similar. These raise concerns about the durability of immunity in later childhood when the recombinant vaccine is initiated at birth. Heijtink et al[17] have shown that there may be differences in the vaccines with regard to antigen presentation and resulting anti-HBs binding properties.

Our findings of the loss of anti-HBs over time in children vaccinated in infancy differ from those reported by some others. West et al[18] screened children at 12 years of age who had received a plasma-derived vaccine in infancy and were at low risk for hepatitis B exposure. None had anti-HBs <10 mIU/mL. Faustini et al[19] followed children at low risk who were vaccinated in infancy with a recombinant vaccine. By 5 years of age, only 7% had titers of anti-HBs <10 mIU/mL. A major difference between the children in those studies and ours is their age at initial vaccination. Those subjects were 2-3 months of age or older when they began their hepatitis B vaccine, whereas the infants in our studies began their series in the first week of life, a schedule recommended by ACIP. Indeed a study from Hawaii of low risk infants given recombinant vaccine starting at birth showed that only 19% had anti-HBs ≥10 mIU/mL at 6 years, yet all responded to a booster dose.[20] This suggests that starting the initial vaccination series later in infancy may result in better persistence of anti-HBs. However, starting at 2-3 months of age would not protect infants of HBsAg-positive mothers from perinatal transmission of HBV.

Vaccinated populations at high risk for continued exposure to hepatitis B might experience natural boosting because of exposure to HBsAg-positive household contacts, enhancing their duration of protection.[21] Several long term follow-up studies have been conducted in children of HBsAg-positive and hepatitis e antigen-positive mothers. In those studies, anti-HBs titers ≥10 mIU/mL ranged from 79 to 85% at 10-12 years of age.[10,22] Another study showed 42 instances of vaccinated children living in HBsAg-positive households exhibiting natural boosts in anti-HBs titers during a 5-year follow-up period.[23] In our study, the proportion of high risk children who had anti-HBs <10 mIU/mL on follow-up was similar to that seen for the low risk children who received the same vaccine, although the response to booster dose was slightly higher. However, the small number of high risk children followed makes it difficult to draw conclusions.

Booster doses of hepatitis B vaccine are not currently recommended.[24] In populations at high risk for continuing exposure to hepatitis B virus, hepatitis B vaccine is protective for at least 10 years, the time during which the greatest risk of chronic infection after exposure occurs.[16] However, children at low risk for exposure to hepatitis B during childhood are at greater risk of exposure for hepatitis B infection as they approach adolescence and long term protection will be important during potentially sexually active years. Our data suggest that one-fourth of children who responded to a plasma-derived hepatitis B vaccine in infancy lost protective antibody by early adolescence and did not show evidence of anamnestic response to a booster dose, although the small number of participants makes it difficult to draw precise conclusions. In addition, the lack of an anamnestic response may not mean that children are not protected against HBV disease. The long incubation period of 4-8 weeks for HBV could allow time for immunologic memory to prevent acute illness or chronic carriage while not preventing active infection. Evidence of immunologic memory did not decrease despite delayed boosting of some children.

The importance of giving hepatitis B vaccine from birth is well-established; however, it will be very important to follow children into adolescence and early adulthood for evidence of clinically significant breakthrough infections indicating a possible need for routine booster doses. Also additional long term follow-up studies at school entry and adolescence, including ones evaluating the effects of a booster dose at these times, will be necessary for low risk children initially vaccinated for hepatitis B starting at birth.

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