Uncovering the viral aetiology of undiagnosed acute febrile illness in Uganda using metagenomic sequencing
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.
Authors
- Emma C. Thomson (ORCID: https://orcid.org/0000-0003-1482-0889)
- Alfred Ssekagiri (ORCID: https://orcid.org/0000-0002-6549-3550)
- Pontiano Kaleebu (ORCID: https://orcid.org/0000-0001-9706-2977)
- Prossy Namuwulya (ORCID: https://orcid.org/0000-0002-9468-1788)
- Jesus F. Salazar-Gonzalez (ORCID: https://orcid.org/0000-0003-4626-6448)
- Christopher Davis (ORCID: https://orcid.org/0000-0002-7317-3266)
- Daniel Lule Bugembe (ORCID: https://orcid.org/0000-0002-5616-515X)
- John Kayiwa (ORCID: https://orcid.org/0000-0002-1840-1801)
- Stephen Karabyo Balinandi (ORCID: https://orcid.org/0000-0002-3057-0755)
- Shirin Ashraf (ORCID: https://orcid.org/0000-0002-6468-0258)
- Vattipally B. Sreenu (ORCID: https://orcid.org/0000-0001-6673-4697)
- Weronika Witkowska McConnell (ORCID: https://orcid.org/0000-0002-8925-1791)
- Craig Wilkie (ORCID: https://orcid.org/0000-0003-0805-0195)
- Nicola Logan (ORCID: https://orcid.org/0000-0001-6895-6015)
- Julius J. Lutwama (ORCID: https://orcid.org/0000-0002-3210-722X)
- H. Kim Jerome
- James G. Shepherd (ORCID: https://orcid.org/0000-0003-3915-048X)
- Gavin S. Wilkie (ORCID: https://orcid.org/0000-0002-2025-1937)
- Josephine Bwogi (ORCID: https://orcid.org/0000-0001-6975-7106)
- Ana da Silva Filipe (ORCID: https://orcid.org/0000-0002-9442-2903)
- Henry Bukenya
- Brian J. Willett (ORCID: https://orcid.org/0000-0001-8912-3266)
- Timothy Byaruhanga (ORCID: https://orcid.org/0000-0003-2024-9172)
- Deogratius Ssemwanga (ORCID: https://orcid.org/0000-0001-9675-4234)
- Brian K. Kigozi (ORCID: https://orcid.org/0000-0003-1066-687X)
- Robert Downing (ORCID: https://orcid.org/0000-0001-5692-8981)
- Maria G. Salazar (ORCID: https://orcid.org/0000-0003-0823-7697)
Institutions
- Animal and Plant Health Agency (GB)
- London School of Hygiene & Tropical Medicine (GB)
- National Institute of Allergy and Infectious Diseases (US)
- MRC University of Glasgow Centre for Virus Research (GB)
- University of Glasgow (GB)
- Uganda Virus Research Institute (UG)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-03-23
- DOI
- https://doi.org/10.1038/s41467-025-57696-8
- Citations
- 6
- Primary Topic
- Viral Infections and Vectors
- Type
- article
- Field-Weighted Citation Impact
- 8.38
Funders
- Wellcome
- Medical Research Council