A longitudinal cohort study of enterovirus A71 infections in young children in Taiwan

Abstract

Background: Enterovirus A71 (EV-A71) is causing cyclical epidemics of fatal hand-foot-mouth disease (HFMD) in Taiwan and other Asian countries. Evidence of its incidence rates and risk factors based on longitudinal cohort studies is scarce. This study aims to investigate age-specific and cumulative incidence rates and risk factors of EV71 infections from 2006 to 2012 in northern Taiwan. Methods and materials: A total of 759 neonates born between 2006 and 2009 were recruited. Participants’ sera were collected at their 6, 12, 24, 36, 48, 60, and 72 months of age to conduct serum neutralization test. In addition, throat swabs of the participants who presented symptoms of HFMD or herpangina were collected for virus isolation and molecular tests to detect EV71 infections. Asymptomatic primary infections and reinfections were identified based on >= 4-fold rise of serum neutralizing antibody titers in consecutive sera. We calculated age-specific and cumulative incidence rates, and fitted a Cox proportional hazards model to identify risk factors of EV71 infections. Results: Among the 576 participants being followed, 127 persons (22.0%) were confirmed as with EV71 infections (70 symptomatic, 57 asymptomatic cases). Of the 127 cases, 22 (17.3%) occurred their second (n = 20) or third (n = 2) reinfections (all asymptomatic) after the primary infection. Phylogenetic analysis revealed that two distinguishable genotype B5 viruses were introduced from southern Asia to cause large-scale epidemics in Taiwan in 2008 and 2012, respectively. Age-specific incidence increased from 2.03 per 100 person-years during 0–6 months of age to 19.33 during 49–60 months of age, and reduced to 9.57 during 61–72 months of age. The cumulative incidence till 72 months of age was 31.78%. A higher number of co-residing children under 5 years old was associated with higher risk of EV71 infections (hazard ratio = 1.28, 95% CI: 1.03–1.59). Conclusion: Our results indicated incidence rates increased with age and peaked at 5 years-old, cumulative incidence rate was nearly 32% by 6 years of age, and higher number of co-residing young children was associated with higher risk of EV71 infections. This longitudinal cohort study contributes to precisely estimate incidence rates of EV71 infections via a long-term follow-up, and provides insights into clinical trial designs of EV71 vaccines.