We conducted a seroepidemiologic study to evaluate the kinetics of maternal hepatitis A antibody decay in infants. Serum samples obtained from 200 infants at 2 and 4 months of age were tested for hepatitis A antibody. Seventy-six infants (38%) were hepatitis A antibody-positive with a geometric mean antibody titer of 2634 mIU/ml. Samples collected at 4, 6 and/or 12 months of age showed seropositivity rates of 100, 95 and 39%, respectively. These data indicate that maternal antibody levels remained high through the first 6 months of life but decayed significantly by 12 months of age. The epidemiology of hepatitis A infection varies around the world. In regions with moderate to high rates of endemic infection, the majority of infections occur among young children. Even in the United States, an area of low endemicity for hepatitis A, children are commonly infected. Approximately one-third of reported hepatitis A cases in the US occur in children 14 years of age and younger. 1 However, this underestimates the incidence of hepatitis A infections in this age group, because most infants and young children have asymptomatic infection or nonspecific symptoms. 2 Furthermore young children serve as a reservoir of infection for adolescents and adults, who are much more likely to develop clinical illness. 3 Children infected with hepatitis A in day-care centers, for example, can transmit the virus to susceptible siblings, parents and child care providers. 2, 4 In the US recommendations call for routine immunization of children 2 years of age and older who reside in states and communities where the incidence of hepatitis A is at least twice the national average (≥ 20 cases per 100 000 population). 1 The two inactivated hepatitis A vaccines licensed in the US are approved for use only in persons 2 years of age and older. The ability to vaccinate children younger than 2 years of age would permit earlier incorporation of hepatitis A vaccine into the childhood vaccination schedule. This not only would offer earlier protection to young children who are at higher risk for infection but also would potentially enhance compliance with vaccination considering that children have multiple vaccination visits scheduled during the first 2 years of life. However, the serologic response of infants is adversely affected by the presence of maternal antibody. 5–7 Further knowledge about the decay of maternal antibody in infants might help determine the optimal age for hepatitis A vaccination. This study was conducted to provide such information. Methods. The Institutional Review Board of the Harbor-UCLA Research and Education Institute approved the study. Frozen sera obtained from 200 infants who had participated in past clinical trials in southern California were analyzed at Merck Research Laboratories for hepatitis A antibody with the modified HAVAB assay, which has increased sensitivity designed to detect low level vaccine responses. 8 The samples contained no personal identifiers, and all data were reported in aggregate form. Antibody titers of at least 10 mIU/ml were considered seropositive. The 2- or 4-month samples from all 200 infants were tested for hepatitis A antibody. If this initial specimen was seropositive, subsequent samples collected at 4, 6 and/or 12 months of age were then assayed to assess rates of decay. Results. Of the 200 infants 76 (38%) were hepatitis A antibody-positive in their earliest serum specimen. In these 76 infants the seropositivity rates at 2, 4, 6 and 12 months of age were 100, 100, 95 and 39%, respectively, with corresponding geometric mean titers of 2634, 563, 211 and 9 mIU/ml, respectively (Fig. 1). Of the 18 infants still seropositive at 12 months of age, 14 (78%) had antibody titers ≤33 mIU/ml, and the highest antibody titer was 130 mIU/ml.Fig. 1: Scatter plot showing the hepatitis A antibody titer for each serum specimen by the age of the child in months.Discussion. The results of this seroepidemiologic study in a cohort of young infants indicate that maternally derived antibody titers remained high through the first 6 months of life but decayed significantly by 12 months of age. In this study the geometric mean titer was >10-fold higher at Month 2 than at Month 6 and >20-fold higher at Month 6 than at Month 12. Although the seropositivity rate at 12 months of age was 39%, the antibody titers of the seropositive children were very low. In studies of infants from areas endemic for hepatitis A, seropositivity rates were low by 7 to 8 months of age, but these studies used less sensitive antibody assays. 9, 10 Maternal hepatitis A antibodies interfere with the response to inactivated hepatitis A vaccines in infancy. Clinical studies conducted with both VAQTA (Merck & Co., Inc.) and HAVRIX (GlaxoSmithKline) showed significantly diminished antibody responses in infants with detectable maternal antibody who were vaccinated beginning at 2 months of age. 5–7 Although their antibody titers are lower, these infants might be immunologically primed, as suggested by a recent study that found that the infants mounted an anamnestic response to a booster dose given at 1 year of age. 7 In determining the optimal age for vaccination against hepatitis A, policy-makers must balance the consequences of vaccinating at an older age (few scheduled visits and lack of protection in the early months or years of life) against vaccinating at a younger age (the potential for reduced vaccine effectiveness or the need for additional vaccine doses). Although the titer of passively acquired antibody that interferes with an infant’s response is not defined, the low antibody titers seen at 12 months of age suggest that vaccination beginning at 12 months is likely to be effective. Clinical studies in this age group will determine the youngest age at which hepatitis A vaccines are both sufficiently immunogenic and well-tolerated. Acknowledgment. This study was supported by a grant from Merck & Co., Inc.
No takes yet. Share an insight, caveat, or question.
Lieberman et al. (2002) studied this question.