The spatial heterogeneity of the associations between relative humidity and pediatric hand, foot and mouth disease: Evidence from a nation-wide multicity study from mainland China

Background: Hand, foot, and mouth disease (HFMD) remains a serious health threat to young children in East and Southeast Asia. The humidity is crucial for the survival of enterovirus, but the evidence of the humidity-HFMD association is inconsistent. In this study we investigated the spatial heterogeneity of humidity-HFMD associations and related effect modifiers. Methods: We retrieved the daily surveillance data of childhood HFMD counts and meteorological variables from 143 cities in mainland China between 2009 and 2014 and then adopted a three-stage time series analysis. We first fitted a common distributed lag nonlinear model (DLNM) for each of the 143 cities separately to obtain the city-specific estimates of humidity-HFMD association. Then, we pooled the city-specific estimates through multivariate meta-regression with city-level characteristics as potential effect modifiers to study the reasons for heterogeneity. Finally, we applied a region-specific analysis to verify our findings and to better visualize our results. Results: We found that the overall pooled humidity-HFMD relationship was shown as an approximately U-shaped curve with substantial spatial heterogeneity (I2 = 77.8%). Taking the reference relative humidity as 70%, the minimum relative risk (RR) was obtained at 45% with a value of 0.83 (0.79, 0.87), while the maximum RR was found to be at both 20% and over 85% separately with a value of 1.10 (1.05, 1.15). The spatial heterogeneity can be well explained by the climatic, social characteristics and terrains among cities. The modification effects can be roughly classified into two types, including change in the overall slope and the shape of the curve. Conclusions: Due to substantial spatial heterogeneity, caution should be taken when interpreting the weather-HFMD association in a single-site study and to avoid generalizing its findings to another site. Our study also implied the existence of interactions among meteorological factors given that climatic factors can modify the weather-HFMD association. (C) 2019 Elsevier B.V. All rights reserved.