A LONGITUDINAL COHORT STUDY OF ENTEROVIRUS A71 INFECTIONS IN YOUNG CHILDREN IN TAIWAN

Abstract

Intro: Enterovirus A71 (EV-A71), the major pathogen causing hand, foot, and mouth disease, affects young children in the Asia-Pacific region with cyclical epidemics. Numerous studies estimated seroprevalence of EV-A71 neutralizing antibodies. However, evidence of incidence rates from longitudinal studies is scarce. This study aims to examine age-specific incidence rates of EV-A71 infection, and to investigate dynamics of serum neutralizing antibody response to infection by following a birth cohort. Methods: We recruited 759 neonates in northern Taiwan from June 2006 to December 2009 and followed these children for 7 years. Study participants’ sera were collected at birth, 6, 12, 24, 36, 48, 60, 72 and 84 months of age (m) for conducting neutralization test on EV-A71 to measure age-specific incidence rates and to observe reinfections at different ages. Findings: A total of 576 children returning for follow-up were analyzed from 2006 to 2013. The incidence rates increased gradually from 0.68 per 100 personyears at 6m to 19.33 at 60m, and reduced to 9.57 at 72m. The cumulative incidence rate of primary and secondary infections by 84m reached 37.97% and 6.96%, respectively. Of the 123 children with a primary infection, 43% were asymptomatic. The cumulative negative conversion rate of serum neutralizing antibody was 12%, 16.84%, and 23.51% in the first, second, and third year post primary infection, respectively. The decay rate of neutralizing antibody titer was estimated as 4.37% per month, and the half-life of infection-induced neutralizing antibody was estimated as 15.9 months. Discussion: Our findings suggest that cumulative incidence of primary and secondary infections by 7 years of age was about 38% and 7% after experiencing 2 epidemics. We also characterized the dynamics of neutralizing antibody titers after EV-A71 infections. Conclusion: These findings provide critical information for designing efficacy trials of EV-A71 vaccines and formulating vaccination policy.