Spatio-temporal occurrence, burden, risk factors and modelling methods for estimating scrub typhus burden from global to subnational resolutions: a systematic review protocol [version 2; peer review: 2 approved]

Background Scrub typhus is a neglected life-threatening vector-borne disease mainly caused by the bacterium Orientia tsutsugamushi, which is occasionally transmitted to humans during feeding of larval mites. It has been estimated that more than 1 billion persons are potentially threatened and 1 million clinical cases occur annually across the world; however, it is unclear how this estimate was computed (and what the original source was) and much remains unknown regarding its global burden and risk factors. This systematic review aims to provide a comprehensive overview of the spatial-temporal distribution of scrub typhus, associated burden and risk factors at global, national and subnational resolutions, and to review the burden estimation models used at those different scales. Methods A systematic search for literature on scrub typhus occurrence, risk factors and modelling methods will be conducted. PubMed and five other databases will be searched for published literature, and Google Scholar and nine other databases will be used to search for grey literatures. All titles/abstracts of the searched records will be separately assessed by two reviewers, who will then screen the full-text of potential records to decide eligibility. A pre-formatted spreadsheet will be used by one reviewer to extract data from qualifying research, with a second reviewer checking the results. Data will be tabulated, synthesized descriptively, and summarized narratively for each review question. Where appropriate, meta-analyses will be conducted. The risk of bias will be assessed, and potential publication bias will be detected. Discussion This review will provide a comprehensive understanding of the current occurrence, spatial-temporal distribution, and burden of scrub typhus, identify associated risk factors from global to subnational resolutions, consolidate the best practice modeling framework(s) to estimate the burden of scrub typhus at various geographic/temporal resolutions, and decompose the relative contributions of various risk factors at scale. PROSPERO Registration CRD42022315209