Location: Zoonotic and Emerging Disease Research
Project Number: 3022-32000-021-007-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Aug 22, 2022
End Date: Apr 30, 2027
The emergence of high-impact zoonotic viruses causing severe and often fatal infections is a serious threat to animal and human health across the globe. The dramatic impact of pathogens like Crimean-Congo hemorrhagic fever virus (CCHFV) and Nipah (NiV) and Hendra-like henipa-paramyxoviruses on domesticated livestock production can rapidly lead to the collapse of markets for live animals and lead to transboundary trade restrictions. CCHFV and NiV are a NIH/NIAID Category A pathogen with broad mammalian host range. Both diseases are marked by rapid and severe progression in humans with high fatality ratios. Domestic introduction of CCHFV or henipaviruses could lead to massive impacts across the animal health and value-chain due to concerns over food safety and security and pose a direct threat to human health. CCHFV (genus Orthonairovirus, family Nairoviridae) is a tick-borne zoonotic pathogen. The majority of detected human cases are found in the Mediterranean and Middle East regions where there is active surveillance for the disease. Cases are often linked to exposure to the primary tick vector (Hyalomma spp.). The contribution of other tick species and other potential mammal hosts to the ecological maintenance of the virus is poorly understood. NiV and Hendra viruses (HeV) (genus Henipavirus, family Paramyxoviridae) are maintained in nature among frugivorous bat reservoir hosts (Pteropus spp.) and are found across broad swathes of South Asia, the Indo-Pacific region and East Afica. Studies have indicated that across the African continent highly diverse henipaviruses are present, but yet to be linked with significant livestock or human disease. Spillover of infectious virus from the reservoir host can occur through contact with fomites, contact with intermediate livestock hosts such as pigs (NiV) or horses (HeV), and infectious droplets and aerosols. In both livestock and humans, henipavirus infections can rapidly progress to fatal encephalitic and respiratory complex disease. This proposed project is an extension of previous work and will be conducted in partnership with the UC Los Angeles (UCLA), the University of Texas Medical Branch (UTMB), and three UC Davis specific partners–the Sokoine University of Agriculture (SUA) and the Ifakara Health Institute (IHI) in Tanzania, and the University of Makeni in Sierra Leone (UNIMAK) and NBAF to specifically address research goals of NBAF including building scientific workforce capacities through training in vector and wildlife sampling and surveillance for high-priority zoonotic pathogens. The effort will expand existing work on CCHF in the region. Investigators will utilize existing study sites to explore the presence of heninipahviruses in Africa while identifying other potential study sites internationally and domestically.
Aim 1: Longitudinal monitoring of CCHFV and henipavirus prevalence. Previously, a total of 37 sites were investigated (17 Tanzania, 20 Sierra Leone) to assess the prevalence of CCHFV infection among cattle (RT-PCR and serology) and ticks (RT-PCR). Initial laboratory testing revealed approximately 30% seropositivity in cattle in Tanzania. From this initial data set, a total of 4 sites per country will be selected for more intensive sampling of livestock (cattle, sheep, goats) and where feasible other wildlife in close contact with livestock herds (e.g., rodents, birds, and bats). Archived specimens will be assessed for presence of henipaviruses using serological approaches. For investigations of henipaviruses, as funding allows, targeted collection of blood, oral, urogenital, and rectal specimens from insect and fruit eating bats and other wildlife will be tested to determine potential zoonotic risk at high-risk interfaces for human and wildlife contact. Our consortium of partners will work to share representative specimens collected from ticks, livestock, wildlife, and humans where possible with the collaborating partner laboratories at UTMB and NBAF for further characterization and virus isolation attempts. Aim 2. Integration and harmonization of wildlife and humans. In coordination with partners at the UC Los Angeles (UCLA), the Cooperator OHI will provide technical assistance and training of in-country staff to achieve program deliverables and study aims regarding wildlife sampling in accordance with best practices to promote safe and humane animal capture, handling, and non-lethal specimen collection techniques. UCLA will provide technical assistance and training where necessary to ensure that human surveillance activities are harmonized across all international study sites to reduce variability and allow for robust cross-project data analyses. Aim 3: Development and assessment of field deployable diagnostic technologies. In partnership with UTMB and other USDA-ARS NBAF partners, the Cooperator OHI will use existing and pilot test novel diagnostic modalities to enable rapid detection and–where possible–sequence confirmation of CCHFV and henipaviruses among collected specimens using a variety of approaches including rapid point-of-care RT-PCR approaches, next-generation sequencing and species agnostic serological testing approaches (e.g., antibody binding reporter assays). Aim 4: Identification of field study sites within the United States and internationally. Potential studies sites that would enable sampling and training activities will be identified. The use of existing long-term surveillance sites and other novel sites will be considered including key factors such as wildlife biodiversity, ecological characteristics, land-use patterns, and proximity to livestock and/or humans that may enhance potential of zoonotic virus spillover. Internationally 1-2 study sites in areas of active henipahvirus infections will be identified. Aim 5. Develop and parameterize ecological and epidemiological models. Niche models will be developed to characterize virus risk using publicly available and project-derived environmental and virus infection data.