Background Substantial outbreaks of scrub typhus, coupled with the discovery of this vector-borne disease in new areas, suggest that the disease remains remarkably neglected. The objectives of this study were to map the contemporary and potential transmission risk zones of the disease and to provide novel insights into the health burden imposed by scrub typhus in southern China. Methods Based on the assembled data sets of annual scrub typhus cases and maps of environmental and socioeconomic correlates, a boosted regression tree modeling procedure was used to identify the environmental niche of scrub typhus and to predict the potential infection zones of the disease. Additionally, we estimated the population living in the potential scrub typhus infection areas in southern China. Results Spatiotemporal patterns of the annual scrub typhus cases in southern China between 2007 and 2017 reveal a tremendous, wide spread of scrub typhus. Temperature, relative humidity, elevation, and the normalized difference vegetation index are the main factors that influence the spread of scrub typhus. In southern China, the predicted highest transmission risk areas of scrub typhus are mainly concentrated in several regions, such as Yunnan, Guangxi, Guangdong, Hainan, and Fujian. We estimated that 162 684 million people inhabit the potential infection risk zones in southern China. Conclusions Our results provide a better understanding of the environmental and socioeconomic factors driving scrub typhus spread, and estimate the potential infection risk zones beyond the disease’s current, limited geographical extent, which enhances our capacity to target biosurveillance and help public health authorities develop disease control strategies.

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