The burden of hand‒foot‒mouth disease in China affected by compound temperature and humidity events: A nationwide study

Climate change has increased the frequency of extreme temperature and humidity events. Although the association between temperature and hand ‒ foot ‒ mouth disease (HFMD) is well-established, evidence regarding the synergistic amplification of risk driven by compound temperature‒humidity events remain limited. This study aims to investigate the temperature‒humidity synergistic effects on the HFMD risk and burden across China based on daily HFMD surveillance records and meteorological data from 302 cities during the period 2011–2019. Temperature‒humidity interactions are evaluated using generalized additive models (GAMs). Bivariate compound events are defined based on multiple temperature‒humidity percentile combinations. Exposure‒lag‒response relationships between temperature‒humidity compound events and HFMD risk are quantified using distributed lag nonlinear models (DLNMs) to identify high-risk thresholds with extreme characteristics. The HFMD burden is assessed through attributable case calculations. In over 18 million cases, we identified substantial synergistic effects between high temperature and humidity ( S = 1.328, 95% CI: 1.286–1.370). Concurrent exposure above the 70th temperature percentile and 80th humidity percentile constituted high-risk conditions for HFMD (RR: 1.298, 95% CI: 1.222–1.379) at the national level, yet specific thresholds and associated risks exhibited spatial heterogeneity across regions. Subgroup analysis further identified preschool children and regions with economic disadvantages as vulnerable populations. The frequency of high HFMD risk compound events increased by 24% during 2017–2019 compared with 2011–2013. We identified 464,823 HFMD cases attributable to high-risk compound events across China, with the burden increasing most substantially in Northeast and North China. These findings provide a scientific basis for developing climate-adaptive early-warning systems and targeted interventions.