Incidence Rates of Enterovirus 71 Infections in Young Children during a Nationwide Epidemic in Taiwan, 2008–09

Objective: Enterovirus 71 (EV71) is causing life-threatening outbreaks in tropical Asia. In Taiwan and other tropical Asian countries, although nationwide EV71 epidemics occur cyclically, age-specific incidence rates of EV71 infections that are critical to estimate disease burden and design vaccine trials are not clear. A nationwide EV71 epidemic occurred in 2008–09 in Taiwan, which provided a unique opportunity to estimate age-specific incidence rates of EV71 infections. Study Design: We prospectively recruited 749 healthy neonates and conducted follow-ups from June 2006 to December 2009. Sera were obtained from participants at 0, 6, 12, 24, and 36 months of age for measuring EV71 neutralizing antibody titers. If the participants developed suspected enterovirus illnesses, throat swabs were collected for virus isolation. Results: We detected 28 EV71 infections including 20 symptomatic and 8 asymptomatic infections. Age-specific incidence rates of EV71 infection increased from 1.71 per 100 person-years at 0–6 months of age to 4.09, 5.74, and 4.97 per 100 person-years at 7–12, 13–24, and 25–36 months of age, respectively. Cumulative incidence rate was 15.15 per 100 persons by 36 months of age, respectively. Conclusions: Risk of EV71 infections in Taiwan increased after 6 months of age during EV71 epidemics. The cumulative incidence rate was 15% by 36 months of age, and 29% of EV71 infections were asymptomatic in young children. Author Summary: Enterovirus 71 (EV71) was first isolated in California, USA, in 1969. Since then, EV71 has been identified globally. Recently, EV71 caused several life-threatening outbreaks in young children in tropical Asia. Development of EV71 vaccines becomes national priority in several Asia countries including Taiwan. To design clinical trials of EV71 vaccines, age-specific incidence rates of EV71 infections are required to identify target populations, estimate disease burdens, select endpoints of clinical efficacy, and estimate sample size. In Taiwan, nationwide EV71 epidemics occurred every 3–4 years but age-specific incidences of EV71 infection are not available. In 2006, we initiated a prospective cohort study in northern Taiwan to recruit neonates and follow up them. In 2008–09, a nationwide EV71 epidemic occurred and we found that age-specific incidence rates of EV71 infection increased from 1.71 per 100 person-years at 0–6 months of age to 4.09, 5.74, and 4.97 per 100 person-years at 7–12, 13–24, and 25–36 months of age, respectively. The cumulative incidence rate was 15% by 36 months of age, and 29% of EV71 infections were asymptomatic in young children. These findings would be helpful to development of EV71 vaccines in Taiwan and other Asian tropical countries.