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Background  Numerous studies have demonstrated the potential association between rainfall and hand, foot and mouth disease (HFMD), but the results are inconsistent. This study aimed to quantify the relationship between rainfall and HFMD based on a multicity study and explore the potential sources of spatial heterogeneity.    Methods  We retrieved the daily counts of childhood HFMD and the meteorological variables of the 143 cities in mainland China between 2009 and 2014. A common time series regression model was applied to quantify the association between rainfall and HFMD for each of the 143 cities. Then, we adopted the meta-regression model to pool the city-specific estimates and explore the sources of heterogeneity by incorporating city-specific characteristics.    Results  The overall pooled estimation suggested a nonlinear exposure-response relationship between rainfall and HFMD. Once rainfall exceeded 15 mm, the HFMD risk stopped increasing linearly and began to plateau with the excessive risk ratio (ERR) peaking at 21 mm of rainfall (ERR = 3.46, 95% CI: 2.05, 4.88). We also found significant heterogeneity in the rainfall-HFMD relationships ( I   2   = 52.75%,  P  < 0.001). By incorporating the city-specific characteristics into the meta-regression model, temperature and student density can explain a substantial proportion of spatial heterogeneity with  I   2   statistics that decreased by 5.29 and 6.80% at most, respectively.    Conclusions  Our findings verified the nonlinear association between rainfall and HFMD. The rainfall-HFMD relationship also varies depending on locations. Therefore, the estimation of the rain-HFMD relationship of one location should not be generalized to another location.

Short-term effects of rainfall on childhood hand, foot and mouth disease and related spatial heterogeneity: evidence from 143 cities in mainland China