Objective: Hand, foot, and mouth disease (HFMD) is an important public health issue in China. Although efficacy has been demonstrated by randomized controlled trials, the evidence for effectiveness of the monovalent Enterovirus 71 (EV71) vaccine against HFMD remains unknown. This study aimed to assess the vaccine effectiveness for HFMD in Guangzhou, China. Methods: Routinely collected vaccination and HFMD surveillance data were captured from the China Information System for Disease Control and Prevention. We estimated the EV71 vaccine effectiveness using spatial ecologic and time-series analysis approaches. Results: A total of 174,002 HFMD cases under 5 years of age were reported to the Guangzhou, China surveillance system from January 2016 to December 2018. A total of 408,664 children completed a two-dose EV71 vaccination series. In an ecologic analysis, a two-dose EV71 vaccination rate above the median conferred lower HFMD risk relative to a vaccination rate below the median (ratio ratio = 0.955, 95% confidence interval (CI): 0.949, 0.962; P < .001). In the time-series approach, 0.9% fewer HFMD cases were associated with a 1% increase in the two-dose EV71 vaccination rate, but without statistical significance (P = .094). However, we detected statistically significant protective associations for HFMD among children 3 years of age (0.9% fewer HFMD cases with a 1% increased vaccination rate; P = .046), and for EV71 (1.4%; P = .012) and "other viruses" (1.3%; P = .002), although not for Coxsackievirus A16 (CVA16). Conclusion: Our findings, based on real-world data, provide evidence of EV71 vaccine effectiveness for preventing EV71 and "other" viruses associated with HFMD. An expanded program of EV71 vaccination is urgently needed.
Keywords: Hand; enterovirus 71 vaccine; foot; mouth disease; vaccine effectiveness.