Nature Communications (Mar 2025)

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

  • Shirin Ashraf,
  • Hanna Jerome,
  • Daniel Lule Bugembe,
  • Deogratius Ssemwanga,
  • Timothy Byaruhanga,
  • John Timothy Kayiwa,
  • Robert Downing,
  • Jesus F. Salazar-Gonzalez,
  • Maria G. Salazar,
  • James G. Shepherd,
  • Craig Wilkie,
  • Chris Davis,
  • Nicola Logan,
  • Sreenu B. Vattipally,
  • Gavin S. Wilkie,
  • Ana da Silva Filipe,
  • Alfred Ssekagiri,
  • Prossy Namuwulya,
  • Henry Bukenya,
  • Brian K. Kigozi,
  • Weronika Witkowska McConnell,
  • Brian J. Willett,
  • Stephen Balinandi,
  • Julius Lutwama,
  • Pontiano Kaleebu,
  • Josephine Bwogi,
  • Emma C. Thomson

DOI
https://doi.org/10.1038/s41467-025-57696-8
Journal volume & issue
Vol. 16, no. 1
pp. 1 – 12

Abstract

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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.