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SUMMARYBackgroundViruses that cause acute febrile illness (AFI) in sub-Saharan Africa cause a spectrum of disease from mild to life-threatening. Viral infection is often undiagnosed, as routine diagnostics are insufficient to capture the diversity of circulating pathogens.Methods1281 patients with fever of 2-7 days were prospectively recruited from three sites in Uganda as part of the CDC-UVRI AFI Study and screened with enhanced diagnostics. Plasma from 233 undiagnosed patients was analysed using metagenomic next-generation sequencing (mNGS). Confirmatory testing was carried out by PCR and serology.FindingsThirty-eight viral pathogens were identified by mNGS in 35/233 (15%) undiagnosed patients including Measles, Hepatitis A/B/E viruses, Human immunodeficiency virus-1, Rhinovirus, Rotavirus-like virus, Human herpesvirus 6B, Human parainfluenza virus 3 and Enteroviruses. Four high-consequence arboviruses were found in six patients; Crimean-Congo haemorrhagic fever virus, Rift Valley fever virus, dengue virus and yellow fever virus. Le Dantec virus, last reported in 1969, was detected and confirmed by serology in one patient (and a contact of that patient). The majority of patients (23/30; 76%) diagnosed with an acute viral infection were treated with antibiotics and/or (12/30; 40%) antimalarials.InterpretationAFI in Uganda is commonly associated with undiagnosed viral infection, including high-consequence and rarely reported viruses. This highlights an ongoing risk to public health and the need for improved vigilance. MNGS alongside diagnostic serology is a powerful method for clinical surveillance to investigate circulating viral pathogens. Cost-effective diagnostic assays should be adapted according to regional needs for testing.FundingMedical Research Council and Wellcome Trust

The early diagnosis of active hepatitis C virus (HCV) infection remains a significant barrier to the treatment of the disease and to preventing the associated significant morbidity and mortality seen, worldwide. Current testing is delayed due to the high cost, long turnaround times and high expertise needed in centralised diagnostic laboratories. Here we demonstrate a user-friendly, low-cost pan-genotypic assay, based upon reverse transcriptase loop mediated isothermal amplification (RT-LAMP). We developed a prototype device for point-of-care use, comprising a LAMP amplification chamber and lateral flow nucleic acid detection strips, giving a visually-read, user-friendly result in, Current HCV nucleic acid-based diagnosis is largely performed in centralised laboratories. Here, the authors present a pan-genotypic RNA assay, based on reverse transcriptase loop mediated isothermal amplification and develop a low-cost prototype paper-based lateral flow device for point-of-care use, providing a visually read result within 40 min.