Precision Solutions for Controlling Fasciolosis in Sheep

肝吸虫是一种极具破坏性的常见寄生虫，感染全球很大比例的羊群和牛群。据估计，在欧洲，由于产奶量、生育力和生长率下降以及死亡率和兽医治疗费用增加，这种寄生虫每年给畜牧业造成6.35亿欧元的损失。由于气候变化和寄生虫对治疗的耐药性不断增加，持续控制肝吸虫极具挑战性。肝吸虫在感染牲畜之前必须先感染泥螺，这一特性意味着在这种蜗牛居住的农场中存在特定的感染风险区域。然而，我们对泥蜗牛分布的了解很差，这进一步阻碍了农民通过放牧和土地管理来管理动物感染风险的能力。此外，农民和兽医诊断肝吸虫感染的工具有限。这使得准确治疗肝吸虫感染变得困难，并导致吸虫治疗药物的过度使用和随后肝吸虫群体的耐药性发展。我们的研究将致力于通过开发和部署环境DNA和蛋白质工具来开发控制肝吸虫的新解决方案，这些工具可以确定农场的肝吸虫感染风险区域。我们将通过一系列访谈，初步评估农民对肝吸虫感染风险领域的了解，这也将突出未来教育计划的知识差距。然后，我们将使用eDNA调查绘制农田泥蜗牛的分布图，这将为研究农民提供吸虫感染风险区域的信息，并将增强我们对泥蜗牛生态，泥蜗牛栖息地及其典型特征的基本了解。该项目的这一方面将直接与农民和兽医合作，他们将共同创建一个农民/兽医教育计划，该计划将由我们的研究成果和初步确定的知识差距推动。该项目还将确定与肝吸虫感染状况相关的动物行为和性能特征。我们将使用可穿戴行为传感器技术监测实验感染和自然感染肝吸虫的羔羊的行为。监测的行为变化将包括活动和动作，以及说谎的频率和时间。我们假设这些行为在感染羔羊和未感染羔羊之间会有所不同，并且感染羔羊的行为会随着肝吸虫感染的进展而改变。我们还将监测自然感染肝吸虫的羔羊的生长速度，目的是确定羔羊的表现是否可以表明需要治疗肝吸虫。我们在这里假设，通过控制草的可用性和质量，羔羊低于一定的性能阈值将受益于治疗肝吸虫。最后，我们将研究在环境中发现的不同肝吸虫阶段分泌的蛋白质。这些生命阶段包括卵、幼虫（感染泥蜗牛的幼虫）以及尾蚴和囊蚴（可以感染牲畜的幼虫阶段）。我们假设传染性肝吸虫幼虫会分泌独特的蛋白质，并且我们可以在从农场的泥蜗牛栖息地收集的水样中检测到这些蛋白质。检测这些独特的传染性吸虫幼虫蛋白的存在和能力，将使牧场上的肝脏吸虫感染风险立即得到确定，从而为最佳实践提供信息，并增强我们对吸虫感染风险的理解。这项研究将通过开发工具和知识使农民受益，这些工具和知识将加强他们农场对肝吸虫的控制。该项目还将增强我们对寄生虫生物学、动物行为和泥蜗牛生态学的基本理解，这些信息可以帮助研究人员进一步优化全球寄生虫和疾病控制。

The liver fluke is a highly damaging and common parasite that infects a high proportion of sheep flocks and cattle herds globally. In Europe, it is estimated that this parasite costs the livestock industry 635 million annually due to decreased milk yields, fertility and growth rates, and increases in mortality and veterinary treatment costs. Sustainable control of liver fluke is extremely challenging because of climate change and increasing rates of parasite resistance to treatment. Liver fluke must infect a mud snail before infecting livestock, a trait which means that specific infection risk areas are present on farms where this snail resides. However, our understanding of mud snail distribution is poor which further hinders a farmer's ability to manage infection risk in animals through grazing and land management. Furthermore, limited tools are available to farmers and vets to diagnose liver fluke infection. This makes accurately treating liver fluke infections difficult and has led to the overuse of fluke treatment drugs and subsequent resistance development in liver fluke populations.Our research will aim to develop new solutions for liver fluke control by developing and deploying environmental DNA and protein tools that can determine liver fluke infection risk areas on farms. We will initially assess farmer understanding of liver fluke infection risk areas though a series of interviews, which will also highlight knowledge gaps for future education programmes. We will then use eDNA surveys to map the distribution of mud snails on farmland, which will inform study farmers of fluke infection risk areas and will enhance our fundamental understanding of mud snail ecology, mud snail habitats and their typical characteristics. This aspect of the project will directly engage and collaborate with farmers and veterinarians who will co-create a farmer/veterinarian education programme that will be driven by our research findings and initially identified knowledge gaps. This project will also identify animal behaviour and performance traits associated with liver fluke infection status. We will monitor the behaviour of lambs experimentally infected and naturally infected with liver fluke using wearable behaviour sensor technologies. Behaviour changes monitored will include activity and motion, as well as lying rates and time. We hypothesise that these behaviours will vary between infected and non-infected lambs and that infected lamb behaviour will change as liver fluke infection progresses. We will also monitor the growth rates of lambs naturally infected with liver fluke with the aim of identifying if lamb performance can be indicative of the need to treat against liver fluke. We hypothesise here that by controlling for grass availability and quality, that lambs falling below a certain threshold of performance will be the ones that benefit from treatment against liver fluke. Finally, we will investigate which proteins are secreted by various liver fluke stages that are found in the environment. These life stages include eggs, miracidia (larvae that infect mud snails) and cercariae and metacercariae (larval stages that can infect livestock). We hypothesise that unique proteins will be secreted by infective liver fluke larvae and that we can detect these proteins in water samples collected from mud snail habitats on farms. The presence and ability to detect these unique infective fluke larva proteins would allow immediate liver fluke infection risk on pastures to be determined, subsequently informing best practise and enhancing our understanding of fluke infection risk. This research will benefit farmers by developing tools and knowledge that will enhance the control of liver fluke on their farms. The project will also enhance our fundamental understanding of parasite biology, animal behaviour and mud snail ecology, information that can assist researchers to further optimise parasite and disease control globally.