JMIR Publications

ABSTRACT

Background:

Hand, foot, and mouth disease (HFMD) remains a major childhood infection in China. After monovalent enterovirus 71 (EV71) vaccine introduction in 2016 and the subsequent COVID-19 disruption, routine surveillance data need careful interpretation because etiological typing is incomplete and testing practices may change over time.

Objective:

This study aimed to describe long-term HFMD burden, typed serotype composition, and ecological counterfactual surveillance signals in Anhui Province, China, while explicitly separating routine-surveillance signals from causal vaccine-effect estimates.

Methods:

We analysed HFMD surveillance data from Anhui Province from January 2008 to December 2023. Analyses included descriptive epidemiology, prefecture-level incidence mapping, county-level typed-serotype dominance mapping with masking where annual typed samples were fewer than 10, joinpoint regression, spatiotemporal scan statistics, and ITS counterfactual models. Sensitivity analyses evaluated typing-fraction adjustment, baseline-window choice excluding the 2010-2012 laboratory scale-up period, and severity-driven sampling bias.

Results:

Anhui reported 1,302,675 HFMD cases, of which 47,990 (3.68%) had etiological typing. Among typed cases, EV71 declined from 45.69% before June 2016 to 8.51% in June 2016-December 2019 and 3.41% in 2020-2023, while other enteroviruses increased from 29.60% to 61.84% and 81.80%, respectively. ITS models showed sustained negative divergence of typed EV71 from counterfactual trajectories in 2017-2019; in 2019, 63 EV71 cases were observed versus 210 predicted (95% prediction interval 54-828). This direction persisted when the vaccine-era baseline excluded 2010-2012. During 2021-2023, the share of cases in children aged 4 years or older increased from 18.98% in 2017-2019 to 29.07%, supporting but not proving a post-pandemic age-shift pattern.

Conclusions:

Routine surveillance in Anhui suggests a post-2016 shift in the typed HFMD profile away from EV71 and toward other enteroviruses, followed by COVID-19-related disruption and rebound. Because the typing fraction was low, vaccination histories and province-wide vaccine coverage data were unavailable, and testing practice may have changed, these findings should be interpreted as ecological surveillance signals rather than causal estimates of vaccine effectiveness or definitive serotype replacement. Strengthened sentinel molecular typing, multiplex PCR where feasible, and complementary wastewater surveillance would improve post-licensure HFMD monitoring.