EMERGING VIRUSES ARE AN UNDERESTIMATED CAUSE OF UNDIAGNOSED FEBRILE ILLNESS IN UGANDA

Abstract

Intro: Viruses that cause acute febrile illness (AFI) in sub-Saharan Africa (SSA) lead to a spectrum of clinical disease from mild to life-threatening. Viral infection is often undiagnosed, resulting in onward transmission of high consequence pathogens. Routine diagnostics are currently insufficient to capture the breadth and diversity of viral pathogens occurring in SSA. Methods: 1281 patients with fever of 2-7 days were prospectively recruited as part of the CDC-UVRI AFI Study and screened with enhanced diagnostics. Plasma samples from 233 undiagnosed patients were retrospectively sequenced using metagenomic next generation sequencing (mNGS). Data was analysed bioinformatically to identify evidence of viral genomes in the samples and confirmed by serology or PCR. Findings: Thirty-eight viral pathogens were identified by mNGS in 36 of 233 (15.4%) undiagnosed patients. Four high-consequence arboviruses were found in six patients; Crimean-Congo haemorrhagic fever virus, Rift Valley Fever virus, dengue virus and yellow fever virus. Respiratory and gastrointestinal pathogens were frequently detected, including measles, Hepatitis -A, -B, -E, HIV, Rhinovirus, HHV6B, Respirovirus and Enteroviruses. Le Dantec virus, a rhabdovirus last reported in 1969, was detected and confirmed by seroconversion in an affected patient and a contact of the patient. The majority of patients (30/36; 83%) identified with a viral infection in this study were treated with antibiotics. Discussion: This highlights an unaddressed risk to public health, the need for improved vigilance and extensive estimation of the true disease burden in the region. In partnership with UVRI, we subsequently conducted a One-Health virus discovery study; the Arboviral Infection (AVI) Study. We used mNGS to identify circulating viruses in patients, community, animal reservoirs and vectors. We also tested serological exposure to high-consequence viruses in occupational risk groups. Conclusion: Viruses consequential to global health are circulating under the radar in Uganda. Increased surveillance and diagnostics are essential towards better preparedness for future outbreaks of disease.