Transmission pathways of the food-borne carcinogen Opisthorchis viverrini

描述（由申请人提供）：致癌性肝吸虫是一种食源性寄生虫，感染大约1000万人，主要是东南亚的低收入人群。人们在食用生的或未煮熟的淡水鱼时受到感染，淡水鱼携带有弧菌囊蚴，感染可导致胆管癌。拟议的研究将描述弧菌的传播途径，重点关注鱼类运动和食物分配网络在将弧菌寄生虫传播给人类中的作用。这项研究将在泰国东北部三个相连的湖泊及其周围进行，该地区是世界上由O. viverrini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焦点（例如，传播在湖泊尺度上受到限制），或者是否存在广泛的基因流动，表明寄生虫容易在湖泊和村庄之间传播。我们将描述收获的鱼类分配网络。使用以渔民为目标的基于智能手机的暴露评估协议，我们将量化整个研究区域的源湖和村庄之间的连接，以评估这些连接是否构成区域传输网络。此外，我们评估了鱼类运动在传播寄生虫方面的潜在作用-在第一个中间蜗牛宿主中感染O. viverrini是罕见的（通常，患病率<2%），但鱼类感染是常见的（在某些地区超过90%），这表明鱼类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。我们将研究弧菌感染在鱼类中的分布，从湖泊内和湖泊之间的不同地点取样，以检验弧菌感染因湖泊而异的假设，

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.