Integrated Clinical, Climate, and Environmental Prediction Modeling for Diagnosis of Spotted Fever Group Rickettsioses in northern Tanzania.

Spotted fever group rickettsioses (SFGR) pose a global threat as emerging zoonotic infectious diseases; however, timely and cost-effective diagnostic tools are currently limited. While traditional clinical prediction models focus on individual patient-level parameters, we hypothesize that for infectious diseases, the inclusion of location-specific parameters such as climate data may improve predictive ability. To create a prediction model, we used data from 449 patients presenting to two hospitals in northern Tanzania between 2007 to 2008, of which 71 (15.8%) met criteria for acute SFGR based on ≥4-fold rise in antibody titers between acute and convalescent serum samples. We fit random forest classifiers by incorporating clinical and demographic data from hospitalized febrile participants as well as satellite-derived climate predictors from the Kilimanjaro Region. In cross-validation, a prediction model combining clinical, climate, and environmental predictors (20 predictors total) achieved a statistically non-significant increase in the area under the receiver operating characteristic curve (AUC) compared to clinical predictors alone [AUC: 0.72 (95% CI:0.57-0.86) versus AUC: 0.64 (95% CI:0.48-0.80)]. In conclusion, we derived and internally-validated a diagnostic prediction model for acute SFGR, demonstrating that the inclusion of climate variables alongside clinical variables improved model performance, though this difference was not statistically significant. Novel strategies are needed to improve the diagnosis of acute SFGR, including the identification of diagnostic biomarkers that could enhance clinical prediction models. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was supported by the International Studies on AIDS Associated Co-infections, United States National Institutes of Health (U01 AI062563 to J.A.C. and V.P.M, K24 AI166087 to D.T.L., and R38 HL143605 to R.J.W. through Utah Stimulating Access to Research in Residency (StARR)). We acknowledge the Hubert-Yeargan Center for Global Health at Duke University for critical infrastructure support for the Kilimanjaro Christian Medical Centre-Duke University Collaboration. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The primary study was approved by the Kilimanjaro Christian Medical University College Health Research Ethics Committee, the Tanzania National Institutes for Medical Research National Health Research Ethics Coordinating Committee, and Institutional Review Boards of Duke University Medical Center, and the US CDC. The secondary data analysis was reviewed by the Institutional Review Board of the University of Utah and determined to be exempt (IRB_00164810). All minors had written informed consent given from a parent or guardian, and all adult participants provided their own written informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors