'Understanding viral zoonotic spillover through an integrated eco-epidemiological approach, using Crimean Congo Haemorrhagic Fever virus (CCHFV) in Ug

Viral zoonoses represent an important reservoir for emerging and remerging viral infections, resulting in significant health and economic costs through spillover events causing human infection. These spillover events are the result of a complex combination of virological, socioeconomic and ecological factors and understanding and predicting spillover requires a multidisciplinary approach encompassing human, animal and environmental health. There is also an urgency to understand how ongoing global environmental changes will impact upon the risk of zoonotic spillover. Uganda has been identified as a potential high-risk area for emerging infections due to its rich biodiversity and other specific ecological and social features of the region, that remain poorly understood. CCHFV is an orthonairovirus; it undergoes a silent sylvatic cycle in nature which includes ixodes ticks as both the principal virus reservoir and vector and wild mammals acting as important amplifying hosts. In endemic areas, livestock are commonly infected and may act as bridging hosts, enabling human spillover events. Infection in humans causes a spectrum of disease; ranging from subclinical infection to severe haemorrhagic disease with a mortality rate of up to 40%. Humans are infected through tick bites or exposure to blood from infected animals, however the wider factors determining spillover and severity of human disease remain poorly understood. CCHFV has been detected in ticks, livestock and humans in Uganda, and previous small seroprevalence studies have indicated high levels of exposure in livestock and at-risk human populations. However, the true burden of disease is unknown due to lack of systematic surveillance and underdiagnosis of acute infection. CCHFV is known to demonstrate significant geographic genetic diversity which may have implications for transmission, disease severity, diagnostic testing and breadth of immunity between strains. My thesis will bring together field epidemiology, serology, next generation sequencing and bioinformatics and ecological methods, to better understand the risk of CCHFV in Uganda. This will directly inform future surveillance and prevention strategies and lessons learnt from this combined approach can be applied to other zoonotic and vector borne infections.