A spatiotemporal mixed model to assess the influence of environmental and socioeconomic factors on the incidence of hand, foot and mouth disease

Background: As a common infectious disease, hand, foot and mouth disease (HFMD) is affected by multiple environmental and socioeconomic factors, and its pathogenesis is complex. Furthermore, the transmission of HFMD is characterized by strong spatial clustering and autocorrelation, and the classical statistical approach may be biased without consideration of spatial autocorrelation. In this paper, we propose to embed spatial characteristics into a spatiotemporal additive model to improve HFMD incidence assessment. Methods: Using incidence data (6439 samples from 137 monitoring district) for Shandong Province, China, along with meteorological, environmental and socioeconomic spatial and spatiotemporal covariate data, we proposed a spatiotemporal mixed model to estimate HFMD incidence. Geo-additive regression was used to model the non-linear effects of the covariates on the incidence risk of HFMD in univariate and multivariate models. Furthermore, the spatial effect was constructed to capture spatial autocorrelation at the sub-regional scale, and clusters (hotspots of high risk) were generated using spatiotemporal scanning statistics as a predictor. Linear and non-linear effects were compared to illustrate the usefulness of non-linear associations. Patterns of spatial effects and clusters were explored to illustrate the variation of the HFMD incidence across geographical sub-regions. To validate our approach, 10-fold cross-validation was conducted. Results: The results showed that there were significant non-linear associations of the temporal index, spatiotemporal meteorological factors and spatial environmental and socioeconomic factors with HFMD incidence. Furthermore, there were strong spatial autocorrelation and clusters for the HFMD incidence. Spatiotemporal meteorological parameters, the normalized difference vegetation index (NDVI), the temporal index, spatiotemporal clustering and spatial effects played important roles as predictors in the multivariate models. Efron's cross-validation R-2 of 0.83 was acquired using our approach. The spatial effect accounted for 23% of the R2, and notable patterns of the posterior spatial effect were captured. Conclusions: We developed a geo-additive mixed spatiotemporal model to assess the influence of meteorological, environmental and socioeconomic factors on HFMD incidence and explored spatiotemporal patterns of such incidence. Our approach achieved a competitive performance in cross-validation and revealed strong spatial patterns for the HFMD incidence rate, illustrating important implications for the epidemiology of HFMD.