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

Author

Listed:
  • Shirin Ashraf

    ((CVR))

  • Hanna Jerome

    ((CVR))

  • Daniel Lule Bugembe

    ((UVRI)
    (MRC-UVRI))

  • Deogratius Ssemwanga

    ((UVRI)
    (MRC-UVRI))

  • Timothy Byaruhanga

    ((UVRI)
    (APHA))

  • John Timothy Kayiwa

    ((UVRI))

  • Robert Downing

    ((UVRI))

  • Jesus F. Salazar-Gonzalez

    ((MRC-UVRI)
    (NIH))

  • Maria G. Salazar

    ((MRC-UVRI))

  • James G. Shepherd

    ((CVR))

  • Craig Wilkie

    (University of Glasgow)

  • Chris Davis

    ((CVR))

  • Nicola Logan

    ((CVR))

  • Sreenu B. Vattipally

    ((CVR))

  • Gavin S. Wilkie

    ((CVR))

  • Ana Silva Filipe

    ((CVR))

  • Alfred Ssekagiri

    ((CVR)
    (UVRI))

  • Prossy Namuwulya

    ((CVR)
    (UVRI))

  • Henry Bukenya

    ((UVRI))

  • Brian K. Kigozi

    ((UVRI))

  • Weronika Witkowska McConnell

    ((CVR))

  • Brian J. Willett

    ((CVR))

  • Stephen Balinandi

    ((UVRI))

  • Julius Lutwama

    ((UVRI))

  • Pontiano Kaleebu

    ((UVRI)
    (LSHTM))

  • Josephine Bwogi

    ((UVRI))

  • Emma C. Thomson

    ((CVR)
    (LSHTM))

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.

Suggested Citation

  • 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, 2025. "Uncovering the viral aetiology of undiagnosed acute febrile illness in Uganda using metagenomic sequencing," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57696-8
    DOI: 10.1038/s41467-025-57696-8
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    References listed on IDEAS

    as
    1. Antonia Ho & Richard Orton & Rachel Tayler & Patawee Asamaphan & Vanessa Herder & Chris Davis & Lily Tong & Katherine Smollett & Maria Manali & Jay Allan & Konrad Rawlik & Sarah E. McDonald & Elen Vin, 2023. "Adeno-associated virus 2 infection in children with non-A–E hepatitis," Nature, Nature, vol. 617(7961), pages 555-563, May.
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