Pathogenesis, Carcinogenesis and Ecology of Opisthorchiasis in Thailand

这项TMRC申请涉及一种被忽视的热带疾病--尾棘虫病，这种疾病是由鱼传播的吸虫寄生虫Opisthorchis viverrini感染引起的。慢性后遗症通常会导致胆管癌，即胆道癌。这项TMRC申请是在泰国东北部科拉特高原的昆康省进行的。这项研究汇集了一支不同的研究团队，他们拥有癌症发生学、分子和免疫寄生虫学、发病机制、生物统计学、流行病学和传播模型方面的专业知识。这项拟议的研究包括三个科学项目和两个核心，解决了我们目前对致癌、宿主易感性和弧菌传播生态学的主要空白。虽然我们的研究重点是华支睾吸虫，但这项研究对控制其他致癌肝吸虫，特别是华支睾吸虫也有意义。在东南亚、中国和朝鲜，估计有4500万人感染了这些寄生虫，感染和相关的恶性肿瘤集中在农村贫困人口中。 该提案包括三个科学项目和两个核心。该TMRC的科学目标包括表征感染的人所表现出的人类表型标志物，这些人有患由绿僵菌引起的胆管癌的风险。特别是，我们将比较和对比肝脏(门脉周围)纤维化在使用吡喹酮清除寄生虫感染的药物治疗后消退或不消退的免疫学和炎症特征。可以预测，这些比较可以提供一些标志物，预测数百万感染华支睾吸虫的人会发展为晚期肝纤维化，甚至是胆管癌，或许还会有数百万感染相关肝吸虫的人，包括越南的华支睾吸虫、中国和韩国。

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.