Dynamic epidemiological changes of hand, foot, and mouth disease and real-world effectiveness of EV-A71 vaccination: A case study in Shanghai (2009–2023)

A significant reduction in hand-foot-mouth disease (HFMD) cases has occurred across the country, since EV-A71 vaccine was licensed for use in China in 2016. We compared the epidemiology and virological characteristics before and after the implementation of EV-A71 vaccination over a 15-y period in Minhang district, Shanghai, and conducted a test-negative design to estimate the vaccine effectiveness (VE) of EV-A71 vaccine against HFMD. A total of 73,160 HFMD cases, 361 severe cases, and 3 fatalities were reported in the Minhang district, Shanghai during 2009-2023. After the implementation of EV-A71 vaccine program, the incidence rate, case-severity rate, and fatality rate of HFMD showed a significant decline by 56.7%, 95.2%, and 100.0%, respectively. The proportion of age group 6-10 y increased by 105.7%. The predominance of EV-A71 and CV-A16 was replaced by CV-A6 and CV-A10 in the post-2017 period. Full-dose immunization coverage rate maintained 50% during 2019-2023. The overall VE against EV-A71-associated HFMD and herpangina was 89.9% (95% CI: 74.5-96.0) for two-dose series and 67.9% (95% CI: 2.6-89.6) for one-dose vaccination. The VE for two-dose vaccination was 92.2%, 88.1%, and 100% against EV-A71-associated outpatient visit, non-severe hospitalization, and severe complications, respectively. There was no cross-protective effect of EV-A71 vaccination against non-EV-A71 serotype infection. EV-A71 vaccination program substantially reduced HFMD burden in Shanghai, with two-dose series providing robust protection against EV-A71-associated HFMD and herpangina. The shift of non-EV-A71 serotypes warrants an effort to develop multivalent vaccines to control HFMD epidemics.