Epidemiology of Hand, Foot, and Mouth Disease Before and After the Introduction of Enterovirus 71 Vaccines in Chengdu, China, 2009-2018

Background: Hand, foot, and mouth disease (HFMD) has posed a serious threat to children's health. Three inactivated monovalent enterovirus 71 (EV71) vaccines are proved to be highly efficacious in phaseIIIclinical trials and are now available in China. Methods: We analyzed the citywide surveillance data on HFMD cases in Chengdu during 2009-2018, and estimated cumulative first-dose EV71 vaccination coverage among children eligible to EV71 vaccination after August 2016 in Chengdu. Time series susceptible-infected-recovered model was developed to analyze basic reproduction number and herd immunity threshold of HFMD. Overall and serotype-specific HFMD incidences and severity risks were compared before and after the EV71 vaccination. Results: Among 3 laboratory-identified serotype categories, i.e. EV71, coxsackievirus A16 (CV-A16), and other enteroviruses, the major serotype attributed to HFMD has been changing across years. The cumulative first-dose EV71 vaccination coverage rate was estimated as 60.8% during the study period in Chengdu. By contrast, herd immunity threshold for EV71-related HFMD was 94.0%. After introduction of EV71 vaccines, the overall incidence of HFMD increased 60.8%, mainly driven by 173.7% and 11.8% increased in HFMD caused by other enteroviruses and CV-A16, respectively, which offset a significant reduction in the incidence of HFMD caused by EV71. The overall case-severity risk decreased from 1.4% to 0.3%, with significantly declined presented in all serotype categories. Conclusions: The incidence and severity of EV71-related HFMD decreased following implementation of EV71 vaccination. Developing multivalent vaccines and strengthening laboratory-based surveillance could further decline burden of HFMD.