Early evidence of inactivated enterovirus 71 vaccine impact against hand, foot, and mouth disease in a major center of ongoing transmission in China, 2011-2018: a longitudinal surveillance study.

BACKGROUND: Enterovirus 71 (EV71) is a major causative agent of hand, foot, and mouth disease (HFMD), associated with severe manifestations of the disease. Pediatric immunization with inactivated EV71 vaccine was initiated in 2016 in the Asia-Pacific Region, including China. We analyzed time series of HFMD cases attributable to EV71, coxsackievirus A16 (CA16), and other enteroviruses in Chengdu, a major transmission center in China, to assess early impacts of immunization. METHODS: Reported HFMD cases were obtained from China's notifiable disease surveillance system. We compared observed post-vaccination incidence rates during 2017-18 with counterfactual predictions made from a negative binomial regression and a random forest model fitted to pre-vaccine years (2011-15). We fit a change point model to the full time series to evaluate whether the trend of EV71 HFMD changed following vaccination. RESULTS: Between 2011-18, 279,352 HFMD cases were reported in the study region. The average incidence rate of EV71 HFMD in 2017-2018 was 60% (95% prediction interval (PI): 41%-72%) lower than predicted in the absence of immunization, corresponding to an estimated 6,911 (95% PI: 3,246, 11,542) EV71 cases averted over two years. There were 52% (95% PI: 0.42, 0.60) fewer severe HFMD cases than predicted. However, the incidence rate of non-CA16 and non-EV71 HFMD was elevated in 2018. We identified a significant decline in the trend of EV71 HFMD four months into the post-vaccine period. CONCLUSIONS: We provide the first real-world evidence that programmatic vaccination against EV71 is effective against childhood HFMD and present an approach to detect early vaccine impact or intended consequences from surveillance data.