Hand, Foot, and Mouth Disease Surveillance in Anhui, After Introduction of the Enterovirus 71 Vaccine and During the COVID-19 Pandemic: Ecological Interrupted Time Series Study.

backgroundRoutine surveillance is important for understanding hand, foot, and mouth disease (HFMD) after monovalent enterovirus 71 (EV71) vaccine introduction, but interpretation is difficult when etiologic typing is sparse and the COVID-19 pandemic overlaps with the postvaccine era.

objectiveThis study described surveillance-derived changes in HFMD burden and typed serotype composition in Anhui Province, China, after EV71 vaccine introduction and during the COVID-19 pandemic.

methodsWe conducted a retrospective ecological surveillance study using HFMD records from January 2008 to December 2023. The primary analysis used negative-binomial interrupted time series (ITS) counterfactual models for all reported HFMD cases and typed EV71 monthly counts. Vaccine-era models were trained using data from January 2013 through May 2016; the previous specification covering January 2010 through May 2016 was retained as a sensitivity analysis. COVID-19-period models were trained using data from January 2008 through December 2019. Secondary analyses assessed spatial, temporal, and age patterns. Vaccine coverage histories, individual vaccination records, specimen submission metadata, and laboratory platform-change metadata were unavailable; therefore, models estimated calendar-based surveillance deviations rather than vaccine effectiveness.

resultsAnhui reported 1,292,579 HFMD cases from 2008 to 2023, including 47,990 (3.7%) typed cases. EV71 declined from 45.8% (8479/18,534) of typed cases before vaccine introduction to 3.4% (578/16,930) during COVID-19, while other enteroviruses increased from 29.6% (5487/18,534) to 81.8% (13,848/16,930). There were 123 deaths from 2008 to 2023, corresponding to 9.52 deaths per 100,000 reported cases; no deaths were recorded from 2020 to 2023. In primary vaccine-era ITS models, typed EV71 counts remained below the predicted trajectory in 2017 to 2019: 470 observed vs 659 predicted cases (95% prediction interval [PI] 467-933) in 2017, 181 vs 531 (95% PI 379-798) in 2018, and 63 vs 427 (95% PI 305-662) in 2019. All reported HFMD cases were not uniformly below the vaccine-era counterfactual. During the COVID-19 pandemic, all reported HFMD cases remained below prediction through 2023, with the largest relative difference in 2022 (28,385 observed vs 175,601 predicted; 95% PI 111,465-268,202). The proportion of reported children aged ≥4 years increased from 19% (50,503/266,132) during 2017 to 2019 to 29.1% (44,133/151,795) during 2021 to 2023 (odds ratio 1.75, 95% CI 1.72-1.78; P<.001).

conclusionsTyped EV71 surveillance signals declined after EV71 vaccine introduction, and overall HFMD burden was strongly disrupted during the COVID-19 pandemic. However, sparse typing, unavailable vaccination and testing policy metadata, and the aggregated other enteroviruses category limit causal interpretation. These findings should be read as surveillance signals, not as direct estimates of population-level serotype replacement or individual-level vaccine protection.