Background Diarrheal disease remains a leading cause of childhood illness and mortality and Shigella is a major etiological contributor for which a vaccine may soon be available. This study aimed to model the spatiotemporal variation in pediatric Shigella infection and map its predicted prevalence across low- and middle-income countries (LMICs).

Methods Independent participant data on Shigella positivity in stool samples collected from children aged ≤59 months were sourced from multiple LMIC-based studies. Covariates included household- and subject-level factors ascertained by study investigators and environmental and hydrometeorological variables extracted from various data products at georeferenced child locations. Multivariate models were fitted, and prevalence predictions obtained by syndrome and age stratum.

Findings 20 studies from 23 countries contributed 66,563 sample results. Age, symptom status, and study design contributed most to model performance followed by temperature, wind speed, relative humidity, and soil moisture. Shigella probability exceeded 20% when both precipitation and soil moisture were above average and had a 43% peak in uncomplicated diarrhea cases at 33°C temperatures, above which it decreased. Improved sanitation and open defecation decreased Shigella odds by 19% and 18% respectively compared to unimproved sanitation.

Interpretation The distribution of Shigella is more sensitive to climatological factors like temperature than previously recognized. Conditions in much of sub-Saharan Africa are particularly propitious for Shigella transmission, though hotspots also occur in South and Central America, the Ganges–Brahmaputra Delta, and New Guinea. These findings can inform prioritization of populations for future vaccine trials and campaigns.

Funding NASA 16-GEO16-0047; NIH-NIAID 1R03AI151564-01; BMGF OPP1066146.

Drs. Gaensbauer and Melgar report grants from PanTheryx, Inc, during the conduct of the study; Dr. Page reports grants from GlaxoSmithKline, during the conduct of the study; the remaining authors have no competing interests to disclose.

The research presented in this article was supported financially by NASA's Group on Earth Observations Work Programme (16-GEO16-0047), the National Institutes of Health's National Institute of Allergy and Infectious Diseases grant 1R03AI151564-01, and the Department of Internal Medicine and the Division of Infectious Diseases and International Health of the University of Virginia. Further funding was obtained from the BMGF under OPP1066146 to MNK. AJP is funded by Wellcome (108065/Z/15/Z). The funders played no role in the design and implementation of the study or the analysis and interpretation of the results.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethical approval for this study was given by the University of Virginia Institutional Review Board for Health Sciences Research (IRB-HSR #21544) and the Johns Hopkins University Homewood Institutional Review Board (Study# HIRB0011882).

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.

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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).

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I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

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The epidemiological data used in this analysis contains identifiable human subject data, which cannot be disseminated under the terms of the IRB and data use agreements with contributing institutions. Investigators from contributing studies may be contacted with reasonable request for data access. Data from the MAL-ED and GEMS studies are available from the ClinEpiDB website.72 GLDAS data is disseminated as part of the mission of NASA's Earth Science Division and archived and distributed by the Goddard Earth Sciences (GES) Data and Information Services Center (DISC).73 Other input data is available from the sources cited in the supplementary appendix. Processed versions in raster/TIFF format are available upon reasonable request to the corresponding author as is statistical source code. Output model predictions of probabilities and standard errors are available for each of nine age groups/symptom stratum combinations at the following GitHub repository https://github.com/joshcolston/Badr_Shigella_predictions.

https://github.com/joshcolston/Badr_Shigella_predictions