One-Health Approach to Study Human Fasciola hepatica Transmission and Inform Strategic Control

项目总结/摘要 片形吸虫病是一种重要的人畜共患传染病，分布于世界各地。这是一个重大的公共卫生问题 在南美洲、中东、亚洲和非洲国家的贫困农村社区。学龄儿童熊 贫血和生长发育迟缓等疾病的不成比例的负担。片形吸虫引起大量 发达国家和发展中国家畜牧业生产的经济损失。它有复杂的流行病学 源于其感染多种最终宿主和30多种蜗牛的能力， 多种环境。尽管片形吸虫病被列入世卫组织被忽视的热带病名单， 在寄生虫防治方面取得了进展。大规模治疗一直是首选的控制干预措施， 人和牲畜。然而，一个单一的药物，三氯苯达唑，建议用于治疗和控制， 人类和牲畜的首选。三氯苯达唑疗效降低的担忧已经在 流行国家。预测片形吸虫病风险和指导预防干预措施的工具主要集中在牲畜上。 大多数模型忽略了人类感染风险和与脆弱性相关的因素，如治疗失败， 贫穷和易感性。我们的TMRC申请建议使用全面的“一个健康”方法， 在秘鲁高地的两个地点研究片形吸虫的人类传播。我们的方法将考虑 片形吸虫病在蜗牛中间宿主、牲畜、人类和 环境重要的是，我们将包括研究，以解决改变人类感染风险的因素， 例如天气和土地使用，阻碍了诊断和监测，例如缺乏简单的诊断测试， 在所有宿主中的使用，以及慢性感染对治疗反应和感染易感性的潜在影响。 我们将使用基于代理的建模来确定传播的关键步骤和潜在的干预领域 这一问题可以在对传播产生重大影响和对环境产生较小影响同时加以解决 和药物有效性。在我们的TMRC结束时，我们希望获得对人类片形吸虫的实质性了解 传播和确定潜在的综合控制干预措施，简单敏感的诊断工具， 监测感染，以及药物有效性和感染易感性背后的免疫机制。

PROJECT SUMMARY/ABSTRACT Fascioliasis in an important zoonic infection with a worldwide distribution. It is a significant public health problem in poor rural communities in countries of South America, Middle East, Asia, and Africa. School age children bear a disproportionate burden of the diseases suffering from anemia and stunted growth. Fasciola causes substantial economic losses in livestock production in developed and developing countries. It has a complex epidemiology stemming from its capacity to infect multiple definitive hosts and more than 30 species of snails and adapt to multiple environments. Despite Fasciola’s inclusion in the WHO neglected tropical diseases list very little progress in parasite control has been achieved. Mass treatment has been the preferred control intervention in human and livestock. However, a single drug, triclabendazole, is recommended for treatment and control in humans and preferred for livestock. Concerns for decreasing efficacy of triclabendazole have been raised in endemic countries. Tools to predict fascioliasis risk and guide preventive interventions have focused on livestock. Most models have ignored human infection risk and factor 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 human such as weather and land use, 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 agent-based modeling to identify crucial steps in transmission and potential areas of intervention that could be address simultaneous 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 Fasciola transmission and to identify potential integrated control interventions, simple sensitive tools to diagnose and surveil infection, and immune mechanisms behind drug effectiveness and infection susceptibility.