Uncovering the viral aetiology of undiagnosed acute febrile illness in Uganda using metagenomic sequencing.

Ashraf, Shirin; Jerome, Hanna; Bugembe, Daniel Lule; Ssemwanga, Deogratius; Byaruhanga, Timothy; Kayiwa, John Timothy; Downing, Robert; Salazar-Gonzalez, Jesus F; Salazar, Maria G; Shepherd, James G; +17 more... Wilkie, Craig; Davis, Chris; Logan, Nicola; Vattipally, Sreenu B; Wilkie, Gavin S; da Silva Filipe, Ana; Ssekagiri, Alfred; Namuwulya, Prossy; Bukenya, Henry; Kigozi, Brian K; McConnell, Weronika Witkowska; Willett, Brian J; Balinandi, Stephen; Lutwama, Julius; Kaleebu, Pontiano; Bwogi, Josephine; Thomson, Emma C; (2025) Uncovering the viral aetiology of undiagnosed acute febrile illness in Uganda using metagenomic sequencing. Nature communications, 16 (1). 2844-. ISSN 2041-1723 DOI: https://doi.org/10.1038/s41467-025-57696-8

Abstract

Viruses associated with acute febrile illness in Africa cause a spectrum of clinical disease from mild to life-threatening. Routine diagnostic methods are insufficient to identify all viral pathogens in this region. In this study, 1281 febrile Ugandan patients were prospectively recruited as part of the CDC-UVRI Acute Febrile Illness Study and pre-screened for common pathogens. 210/1281 undiagnosed samples, and 20 additional samples from viral outbreaks were subjected to metagenomic sequencing. Viral pathogens were identified in 44/230 (19%), including respiratory, hepatitis, blood-borne, gastrointestinal and vector-borne viruses. Importantly, one case of Crimean-Congo haemorrhagic fever and two cases each of Rift Valley fever, dengue and yellow fever were detected in 7/230 (3%) of cases. Le Dantec virus, last reported in 1969, was also identified in one patient. The presence of high-consequence and (re-)emerging viruses of public health concern highlights the need for enhanced population-based diagnostic surveillance in the African region.

Additional Information

Item Type	Article
Faculty and Department	MRC Uganda > UG-HIV Care Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
PubMed ID	40122843
Elements ID	238412
Official URL	https://doi.org/10.1038/s41467-025-57696-8