Pathogenesis, Carcinogenesis and Ecology of Opisthorchiasis in Thailand

本TMRC申请涉及被忽视的热带病——蛇胸虫病，该病由鱼源性吸虫感染引起。慢性胆胸病常以胆管癌（胆管癌）为高潮。这个TMRC申请发生在泰国东北部的呵叻高原上的孔敬省。这项研究汇集了一个在致癌、分子和免疫寄生虫学、发病机制、生物统计学、流行病学和传播建模方面具有专业知识的不同研究人员团队。拟议的研究包括三个科学项目和两个核心，解决了我们目前对O. viverrini传播的致癌性，宿主易感性和生态学理解的主要空白。虽然我们的研究主要集中在O. viverrini上，但该研究对其他致癌性肝吸虫的控制也有意义，特别是华支睾吸虫。在东南亚、中国和朝鲜，这些寄生虫总共感染了大约4500万人，感染和相关恶性肿瘤集中在农村贫困人口中。

This TMRC application deals with the neglected tropical disease, opisthorchiasis, caused by infection with the fish-borne trematode parasite, Opisthorchis viverrini. Chronic opisthorchiasis often culminates cholangiocarcinoma, cancer of the bile ducts. This TMRC application takes place in Khon Kaen Province, on the Khorat Plateau in northeastern Thailand. The research draws together a diverse team of researchers with expertise in carcinogenesis, molecular and immuno-parasitology, pathogenesis, biostatistics, epidemiology and transmission modeling. The proposed research, which includes three scientific projects and two cores, addresses major gaps in our current understanding of carcinogenesis, host-susceptibility and the ecology of O. viverrini transmission. While our research focuses specifically on O. viverrini, the research has implications for the control of other carcinogenic liver flukes, particularly, Clonorchis sinensis. Together, these parasites infec an estimated 45 million people in Southeast Asia, China and the Koreas, with infections and associated malignancies concentrated in the rural poor. The proposal includes three scientific projects and two cores. The scientific goals of this TMRC involve characterizing human phenotypic markers displayed by infected humans who are at risk of cholangiocarcinoma caused by O. viverrini. In particular, we will compare and contrast immunological and inflammatory profiles of individuals whose liver (periportal) fibrosis do or does not resolve after medication with praziquantel to remove the parasite infection. These comparisons can be predicted to deliver markers that predict progression to advanced liver fibrosis and indeed cholangiocarcinoma from among the millions of persons infected with O. viverrini, and perhaps also from the many millions more infected with related liver flukes, including Clonorchis sinensis in Vietnam, China and the Koreas.