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

项目摘要/摘要 肝片吸虫病是一种重要的人畜共患传染病，在全球范围内分布。这是一个重大的公共卫生问题。 在南美、中东、亚洲和非洲国家的贫困农村社区。学龄儿童承担 患有贫血和发育迟缓的疾病造成了不成比例的负担。片吸虫导致大量 发达国家和发展中国家畜牧业的经济损失。它有复杂的流行病学。 源于它能够感染多个最终宿主和30多种蜗牛，并适应 多个环境。尽管片吸虫被列入世界卫生组织被忽视的热带病名单，但很少有 在寄生虫控制方面取得了进展。大规模治疗一直是艾滋病患者首选的控制干预措施 人和牲畜。然而，一种单一的药物三氯苯达唑被推荐用于治疗和控制 人类和家畜的首选。人们对三氯苯达唑药效下降的担忧已于#年提出。 地方病流行国家。预测肝片吸虫病风险和指导预防性干预的工具侧重于牲畜。 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。OUT TMRC应用程序建议使用全面的One Health方法来 在秘鲁高地的两个地点研究片状吸虫的人类传播。我们的方法将考虑 钉螺中间宿主、家畜、人和人的肝片吸虫病的时空相关性 环境。重要的是，我们将包括处理改变人类感染风险的因素的研究。 如天气和土地利用，阻碍诊断和监测，如缺乏简单的诊断测试 在所有宿主中使用，以及慢性感染对治疗反应和感染敏感性的潜在影响。 我们将使用基于代理的建模来确定传播中的关键步骤和潜在的干预领域 可以同时解决这一问题，同时对输电造成较大影响，对环境造成较小影响 以及药物的有效性。在我们的TMRC结束时，我们希望对人类片吸虫有更深入的了解 传播和确定潜在的综合控制干预措施、简单、敏感的诊断和 监测感染，以及药物有效性和感染敏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.