One-Health Approach to Study Human Fasciola hepatica Transmission and Inform Strategic Control - PROJECT SUMMARY/ABSTRACT The highest human prevalence of fascioliasis has been reported in the Andes Mountains of Bolivia and Peru where up to 70 of children might be infected. Human fascioliasis is common in countries of Asia and Africa. France, Portugal, and Spain still report human infections. Autochthonous cases have been reported in California and Florida, while the Gulf Coast and Northwest states, Hawaii, and Puerto Rico are considered endemic areas in the United States. The highest number of human cases in the US is reported in immigrants, refugees, and returning travelers. However, fascioliasis is a major livestock parasite, affecting 30-80% of cattle herds in developed and developing countries causing massive losses to the livestock industry. According to the US National Beef Quality Audits, Fasciola related liver condemnation varies between 2-10% nationally. In addition, infected livestock will fail to gain weight, Tools to predict fascioliasis risk and guide preventive interventions have focused on livestock. Most models have ignored human infection risk and factors associated with vulnerability such as treatment failure, poverty, and susceptibility. Out TMRC application proposes using a comprehensive One Health approach to study human transmission of Fasciola in two sites of the Peruvian highlands. Our approach will consider the spatial and temporal association of fascioliasis in snail intermediate hosts, livestock, human, and the environment. Importantly we will include studies to tackle factors that modify the risk of infection among humans and livestock such as weather and land use, that hinder diagnosis and surveillance such as the lack of simple diagnostic tests to use in all hosts, and the potential effects of chronic infection on treatment response and infection susceptibility. We will use statistical, spatial, and agent-based modeling to identify crucial steps in transmission between human and livestock and potential areas of intervention that could be addressed simultaneously with a large impact on transmission and small impact on the environment and drug effectiveness. At the end of our TMRC, we expect to gain substantial insights into human and livestock Fasciola transmission, generate broadly applicable models and tools for surveillance and control of fascioliasis in multiple hosts and in developed and developing countries. Our novel integrated control interventions, simple sensitive tools to diagnose fascioliasis in human, livestock, and snails, and innovative surveillance techniques such as eDNA and drone based captured of environmental indexes will likely impact the prevalence of infection across hosts and decrease losses to industry in endemic countries including the US.