Transmission pathways of the food-borne carcinogen Opisthorchis viverrini

描述(申请人提供)：致癌肝吸虫是一种食源性寄生虫，感染约1000万人，主要在东南亚的低收入人群中。当人们食用生的或未煮熟的淡水鱼时，他们就会被感染，这些淡水鱼中含有稻瘟原虫囊虫，感染可能会导致胆管癌。这项拟议的研究将描述间日圆线虫的传播途径，重点是鱼的移动和食物分配网络在向人类群体传播间日圆线虫寄生虫方面的作用。这项研究将在泰国东北部的三个相连的湖泊及其周围进行，该地区是由绿僵菌引起的胆管癌发病率最高的地区。利用中性遗传标记，我们将评估研究区域内寄生虫的种群结构，以评估是否存在空间上不同的传播中心(例如，传播被限制在湖泊规模)，r如果整个区域存在广泛的基因流动，表明寄生虫很容易在湖泊和村庄之间传播。我们将描述捕捞的鱼类分销网络的特点。使用基于智能手机的针对渔民的暴露评估协议，我们将量化整个研究区域来源湖泊和村庄之间的连接，以评估这些连接是否构成区域传输网络。此外，我们还评估了鱼的移动在寄生虫分布中的潜在作用--在第一中间钉螺宿主中，鲜活的食线虫感染很少见(通常，患病率为2%)，但鱼的感染很常见(在某些地区超过90%的患病率)，这表明鱼可能从受感染的蜗牛中收集寄生虫，将感染分布在它们的范围内。我们将通过从不同地点和不同湖泊中采集鱼类样本，检查鱼中间日圆线虫感染的分布情况，以检验日圆线虫感染因湖泊而异的假设， 如果检测到，意味着鲤科宿主的运动受到湖泊几何形状的限制。我们最终将评估华氏血吸虫种群遗传结构与食物分配网络和鱼类感染的空间模式的一致性，使我们能够推断出限制或促进华氏血吸虫传播的关键传播途径。拟议的研究将 填补我们对这种被忽视的热带疾病的认识上的重大空白，这种疾病可以用来指导华支睾吸虫和相关寄生虫华支睾吸虫的感染预防计划和食品安全监测，据估计，华支睾吸虫感染了3500万人。更广泛地说，这一疾病系统提供了一个机会来评估食物分配系统和自然景观边界在确定传染病传播的空间尺度方面的作用。

DESCRIPTION (provided by applicant): The carcinogenic liver fluke Opisthorchis viverrini is a food-borne parasite that infects approximately 10 million people, primarily in low-income populations in Southeast Asia. People become infected when they consume raw or undercooked freshwater fish harboring O. viverrini metacercariae and infection can cause cholangiocarcinoma. The proposed research will characterize transmission pathways of O. viverrini, focusing on the role of fish movement and food-distribution networks in distributing O. viverrini parasites to human populations. The research will take place in and around three connected lakes in Northeast Thailand, an area with the highest incidence of O. viverrini-induced cholangiocarcinoma in the world. Using neutral genetic markers, we will assess the population structure of the parasite in the study region in order to assess whether there exist spatially distinct foci of transmission (e.g. transmission is constrained at the scale of a lake), r if there is widespread gene flow throughout the region, suggesting parasites are readily transported between lakes and villages. We will characterize harvested fish distribution networks. Using a smartphone-based exposure assessment protocol targeting fishermen, we will quantify connections between source lakes and villages throughout the study region in order to evaluate whether these connections constitute a regional transmission network. In addition, we evaluate the potential role of fish movement in distributing parasites- O. viverrini infections n the first intermediate snail host are rare (typically, prevalence is <2%) but fish infections are common (exceeding 90% prevalence in some areas), which suggests that fish may collect parasites from a patchwork of infected snails, distributing infections across their range. We will examine the distribution of O. viverrini infections in fish, sampling fish from different sites witin and between lakes in order to test the hypothesis that O. viverrini infections vary by lake, which, if detected, implies cyprinid host movements are constrained by lake geometry. We will ultimately evaluate the concordance of O. viverrini population genetic structure with the spatial patterns of food-distribution networks and fish infections, allowing us to infer key transmission pathways that act to constrain or facilitate the spread of O. viverrini. The proposed research will fill in crucial gaps in our understanding of this neglected tropical disease that can be used to guide infection prevention programs and food safety monitoring for O. viverrini and the related parasite, Clonorchis sinensis, which infects an estimated 35 million people. More generally, this disease system provides an opportunity to evaluate the role of food distribution systems and natural landscape boundaries in defining the spatial scale of infectious disease transmission.