Abstract

Background: A significant reduction in hand-foot-mouth disease (HFMD) cases has occurred nationally since the EV71 vaccine was licensed for use in China in 2016.

Objective: To evaluate the effectiveness of EV71 vaccination against HFMD by analyzing the dynamic epidemiological and virological trends before and after its introduction in Minhang District, Shanghai.

Methods: HFMD data from 2009 to 2023 were extracted from the National Notifiable Disease and Virological Surveillance System in Minhang District, Shanghai. EV71 vaccination data were retrieved from the Shanghai Immunization Platform Information System. Epidemiological trends and virological characteristics were compared before and after EV71 vaccine introduction over a 15-year period (2009-2023). A test-negative case-control design was implemented to estimate vaccine effectiveness (VE) against HFMD across seven epidemic seasons (2017-2023).

Results: A total of 73,160 HFMD cases, 361 severe cases, and 3 deaths were reported during 2009-2023. Following EV71 vaccine introduction, significant declines occurred in the HFMD incidence rate (53.1%), case-severity rate (95.2%), and fatality rate (100.0%). The proportion of cases in the 6-10-year age group increased by 105.7%. The predominance of EV71 and CA16 serotypes was replaced by CA6 and CA10 in the post-2017 period. Full-dose immunization coverage remained above 60% during 2019-2023. The overall VE against EV71-associated HFMD was 90.0% (95% CI: 74.8 to 96.0) for the two-dose series and 66.9% (95% CI: -0.7 to 89.1) for one-dose vaccination. For two-dose vaccination, VE was 91.9% against EV71-associated outpatient visits, 87.7% against non-severe hospitalization, and 100% against severe complications. No significant association was observed between EV71 vaccination status and non-EV71-related illnesses.

Conclusion: HFMD incidence declined substantially following the introduction of EV71 vaccination in Shanghai. Two-dose EV71 vaccination provided effective protection against EV71-associated HFMD. The observed serotype replacement and predominance of non-EV71 pathogens underscores the need for multivalent vaccine development to control HFMD epidemics.