Comparison of Nonpolio Enteroviruses in Children With Herpangina and Hand, Foot and Mouth Disease in Taiwan

Background: Nonpolio enterovirus (NPEV) infections are often present with herpangina (HA) and hand, foot and mouth disease (HFMD). Most countries sample NPEVs in HFMD cases, targeting enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) that are associated with outbreaks and severe complications. HA is also monitored in Taiwan and several other countries, but its viral characteristics are underreported. Methods: Through Taiwan's National Virologic Surveillance, information regarding similar to 100,000 child respiratory samples (2002-2015) was linked to concurrent (0-6 days before the sampling date) outpatient records from the National Health Insurance databases, including similar to 15,000 HA-related and similar to 7000 HFMD-related samples. We assessed sample representation and NPEV positive rates, and estimated total numbers of EV-A71 and CV-A16. Results: There were more HA events (4.0 millions) than HFMD events (1.2 millions) in Taiwan. In every 1000 events with HFMD and HA, 6.0 and 4.1, respectively, respiratory samples were collected. The NPEV positive rate in HFMD-related samples was 48%, consistent across most sampling seasons, and predominantly EV-A71 or CV-A16 (74%). By comparison, the HA-related samples had a lower positive rate overall (43%), occasionally EV-A71 or CV-A16 (13%), and the positive rate depended strongly on HA incidence (P < 10(-12)). Compared with sampling HFMD alone, inclusion of HA-related information predicted an earlier onset of EV-A71 outbreak in 2011, and predicted 30% more EV-A71 cases. Conclusions: This is the first representative report on viral characteristics of HA. Our findings confirm that HFMD monitoring is a reliable strategy, but there is a measurable additional benefit when HA is also monitored.