Levine, Zoë CSene, AitaMkandawire, WinnieDeme, Awa BNdiaye, TollaSy, MouhamadGaye, AmyDiedhiou, YounoussMbaye, Amadou MNdiaye, Ibrahima MGomis, JulesNdiop, MédouneSene, DoudouFaye Paye, MarietouMacInnis, Bronwyn LSchaffner, Stephen FPark, Daniel JBadiane, Aida SColubri, AndrésNdiaye, MouhamadouSy, NgayoSabeti, Pardis CNdiaye, DaoudaSiddle, Katherine J2024-02-272024-02-272024-01-25Levine ZC, Sene A, Mkandawire W, Deme AB, Ndiaye T, Sy M, Gaye A, Diedhiou Y, Mbaye AM, Ndiaye IM, Gomis J, Ndiop M, Sene D, Faye Paye M, MacInnis BL, Schaffner SF, Park DJ, Badiane AS, Colubri A, Ndiaye M, Sy N, Sabeti PC, Ndiaye D, Siddle KJ. Investigating the etiologies of non-malarial febrile illness in Senegal using metagenomic sequencing. Nat Commun. 2024 Jan 25;15(1):747. doi: 10.1038/s41467-024-44800-7. PMID: 38272885; PMCID: PMC10810818.2041-172310.1038/s41467-024-44800-738272885https://hdl.handle.net/20.500.14038/53099The worldwide decline in malaria incidence is revealing the extensive burden of non-malarial febrile illness (NMFI), which remains poorly understood and difficult to diagnose. To characterize NMFI in Senegal, we collected venous blood and clinical metadata in a cross-sectional study of febrile patients and healthy controls in a low malaria burden area. Using 16S and untargeted sequencing, we detected viral, bacterial, or eukaryotic pathogens in 23% (38/163) of NMFI cases. Bacteria were the most common, with relapsing fever Borrelia and spotted fever Rickettsia found in 15.5% and 3.8% of cases, respectively. Four viral pathogens were found in a total of 7 febrile cases (3.5%). Sequencing also detected undiagnosed Plasmodium, including one putative P. ovale infection. We developed a logistic regression model that can distinguish Borrelia from NMFIs with similar presentation based on symptoms and vital signs (F1 score: 0.823). These results highlight the challenge and importance of improved diagnostics, especially for Borrelia, to support diagnosis and surveillance.enOpen Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/ licenses/by/4.0/. © The Author(s) 2024Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/GenomicsInfectious diseasesMicrobial geneticsJournal ArticleNature communications