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Research Project: Ecological and Epidemiological Investigations of High-consequence Zoonotic Pathogens at the Livestock, Wildlife and Human Interface

Location: ZOONOTIC AND EMERGING DISEASE RESEARCH

Project Number: 3022-32000-027-001-S
Project Type: Non-Assistance Cooperative Agreement

Start Date: Aug 22, 2022
End Date: Aug 22, 2025

Objective:
The increasing frequency of outbreaks of emerging and re-emerging diseases reflects the interconnected nature of human, animal, and environmental health. Local and regional outbreaks present a greater threat to human and animal health everywhere. Species in close contact at the human-animal nexus, namely humans and the animals they raise, represent high-risk populations for cross-species spillover events. Crimean-Congo Hemorrhagic Fever virus (CCHFV) and Henipaviruses are two key examples of emerging infectious diseases that represent a threat to livestock, wildlife and humans with complicated zoonotic origins. CCHFV is a tick-borne virus known to cause hemorrhagic fever with a case fatality rate ranging from 9-50%. The geographic distribution of this virus remains only partially characterized with cases found across the mediterranean through central Africa and China. As wild and domesticated animals such as cattle, goats, and sheep are amplifying hosts for the virus, those who work closely with these animals are at high occupational risk for the virus. Similarly, henipaviruses are rare but fatal viruses spread via bats to livestock animals which in turn infect the people who care for them. Hendravirus, observed in Australia in 1994 was spread from flying fox bats to horses and then to seven individuals, and caused high fatality among both groups. Nipahvirus shares a similar trajectory from wild bats to domesticated animals and eventually to humans. Nipahvirus was first discovered in 1999 on a pig farm in Malaysia. Both viruses can cause encephalitis and case fatality rates from 40-75%. Despite limited surveillance and diagnostic capacity there have been three confirmed cases of CCHF– two in 1956 and one in 2008 (3,4). In western Africa, Liberia has not detected a CCHF case, but other counties in this region, including neighboring Sierra Leone. The piecemeal and sporadic reporting of cases across Africa speaks to the deficits of current viral surveillance work in the region and has likely resulted in gross underestimates of the true risk of CCHF to animals and humans. Similarly, though human cases of henipaviruses have been confined to Australia and southeast Asia, molecular evidence of henipaviruses in bats, livestock, and humans has been found in Africa suggesting these viruses or closely related are circulating in the region. The Cooperator in partnership with the United States Department of Agriculture - Agricultural Research Service will leverage long-standing research relationships in the Democratic Republic of the Congo and Liberia. The efforts will synergize with ongoing work being performed by the Cooperator's institute with universities. It will begin to address specific research questions and goals of the National Agro and Bio-Defense Facility (NBAF) high-consequence zoonotic threats as part of the objectives and specific aims as outlined in this partnership.

Approach:
Aim 1: Harmonization of surveillance and sampling strategies with DRC, Liberia, Sierra Leone and Tanzania in coordination with the Cooperator, the Cooperator will provide technical assistance and training of in-country staff to achieve program deliverables and study aims. This sampling will take place in accordance with best practices to promote safe and humane animal capture, handling, and non-lethal specimen collection techniques. To better assess the frequency of spillovers, primates (humans and/or apes) in close contact with livestock will be sampled for serologic evidence of exposure. Sampling of primates will provide insight into the cumulative risk of spillover events over time, given the potential turnover of livestock, which could result in underestimates of seroprevalence for viruses of interest. Year 1 will focus on the development of approval collection protocols as well as materials for community education and informed consents for human sampling. The Cooperator will harmonize protocols across sites and provide subject matter expertise to respective teams. Aim 2: Selection of selected sites and Longitudinal monitoring of CCHFV and Henipavirus and other emerging zoonotic threats. Potential study sites will be identified in DRC and Liberia. A target of 5-20 sites will be identified with the technical support and procedural methodology of Cooperator. Criteria for site selection will include use function (eg, animal husbandry), endemicity of vector species, wildlife and primate density, and geographic locations. Limited samples will be collected for serologic screening using available assays. Sites will be down-selected for a target of 4-6 that will undergo longitudinal data collection. Down-selection will be based on pilot serologic samples (aim 2), location, and size, as well as other factors including diversity of ecological parameters and presence of wildlife. Entomological assessments of active CCHFV infection will be conducted using RT-PCR. Deep sequencing will be performed on a subset of samples. Where possible sampling of wildlife in close contact with herds of livestock will be. Samples will be collected every 6-12 months. Samples are suspected to contain live viruses will be stored until isolations can be performed at NBAF or a partner lab. Aim 3: Evaluation of diagnostics for detection of Henipaviruses and CCHF. Novel diagnositcs and research assays being developed by ARS and other partners will be evaluated at established study sites. This cross matrixing will allow real world testing of assays. Aim 4: Identification and evaluation of surveillance sites in other locations. Potential study sites will be identified in Madagascar, Bangladesh and the Philippines. Where possible, we will partner with other USG entities and researchers working in the area. If feasible sites would allow for collection of samples from live livestock, wildlife, and humans in close contact with reported Nipah virus infections. To evaluate the domestic risk of spillover from bats domestic sites with large bat colonies and swine are geographically co-located be identified and site feasibility assessed.