Location: Zoonotic and Emerging Disease Research
Project Number: 3022-32000-021-018-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Jul 15, 2025
End Date: Jul 31, 2026
Objective:
Infectious disease emergence is a clear and imminent threat to humanity. Anthropogenic biodiversity loss has been implicated as a central driver of the global increase in disease emergence, but the direction and mechanisms that connect biodiversity with disease emergence are controversial.
In the current work on Crimean-Congo hemorragic fever virus (CCHFV) and related East African nairoviruses, the investigators offer a novel perspective, hypothesizing that the loss of pathogen biodiversity may contribute to disease emergence risk. They posit that exposure to diverse related pathogens prompts hosts to establish multivalent cross-reactive antibody portfolios, which can (i) prevent severe disease, (ii) reduce transmission, and ultimately (iii) limit the risk of pathogen emergence. This work has important implications for assessing the risks associated with introduction of CCHFV and its tick vectors in the US. Such an introduction would place CCHFV in a novel ecological context that lacks a diverse community of common, closely related nairoviral species, potentially leading to more extensive transmission and severe infection outcomes than those observed in its current endemic range.
Approach:
This study takes a classic One Health approach to understand the distribution of nairovirus disease in East Africa. Specifically, it will test the idea that infection in livestock may occur predominantly in areas where vectors and hosts are abundant, but nairoviral pathogen diversity is low. As such, the investigators will survey nairovirus diversity and Crimean-Congo hemorragic fever virus (CCHFV) prevalence in tick vectors in Uganda, where CCHFV is endemic, and compare regional nairovirus diversity to seroprevalence of CCHFV in livestock.
Site selection: They classified 12 eco-zones in Uganda, based on physical habitat characteristics, land use, population and livestock density variables, to define ecological zones in Uganda that are likely to differ in host, vector and nairovirus diversity and abundance. Current funding level allows them to include 7 of the 12 ecozones in the study design. It is proposed to expand our sampling to all 12 ecozones, ensuring that we include major ecological gradients in our design. This will allow the investigators to identify the relevant tick vectors for CCHFV across Uganda, establish the prevalence of CCHFV and other nairoviruses across vector species and regions; and understand relationships between pathogen abundance in vectors and livestock hosts.
Cross-sectional survey of nairovirus diversity and abundance in ticks: Hard and soft ticks will be collected at each study site via environmental dragging and flagging, CO2 and pitfall traps, and direct collection from domestic animal species (cattle, goats and sheep). The range of collection methods reflects the variety of host seeking behaviors by different tick genera and will maximize the diversity of ticks collected. Tick pools will be made according to their collection sites, species, life stage, and the environmental or host animal source, and screened by RT-PCR using pan- nairovirus primers. Pools deemed positive for nairovirus species will be further investigated by target enrichment (TE) next generation sequencing (NGS). To establish infection prevalence, ticks from positive pools will be extracted individually and tested by PCR for CCHFV and related viruses. This will allow the prevalence to to be investigated in different tick species, helping us identify likely reservoirs of infection in endemic settings. Serosurvey of nairoviruses in livestock: Blood samples will be collected from livestock (cattle, goats, sheep) during the cross-sectional study. The study will test (a) whether CCHFV seroprevalence is lower in study sites with higher nairovirus diversity, and (b) whether individual hosts with co-exposure to other nairoviruses have lower sero-prevalence of CCHFV. Towards this aim, all sera will be tested for antibodies against CCHFV, and related nairoviruses: Nairobi sheep disease virus (NSDV) Dugbe, Macira and any other locally common nairoviruses detected in the ticks.
This work will assess the prevalence of CCHF in vector and animal hosts in Uganda, providing key information to improve understanding of CCHF epidemiology and the role of ticks in maintaining reservoirs of infection in endemic settings.