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.

Public Health Relevance

This project offers to shed light on the cause and mechanism of pathogenesis and carcinogenesis caused by infection with the liver fluke (Opisthorchis viverrini) and also providing means to sustainably reduce O. viverrini infection prevalence and associated morbidity in endemic countries in Southeast Asia as well as China and Korea where the other liver fluke (Clonorchis sinensis) is also a public health problem

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Specialized Center (P50)
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Special Emphasis Panel (ZAI1-AWA-M (J1))
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Rao, Malla R
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Khon Kaen University
Khon Kaen
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Thanasuwan, Sirikanda; Piratae, Supawadee; Brindley, Paul J et al. (2014) Suppression of aquaporin, a mediator of water channel control in the carcinogenic liver fluke, Opisthorchis viverrini. Parasit Vectors 7:224
Thi Phung, Luyen; Loukas, Alex; Brindley, Paul J et al. (2014) Retrotransposon OV-RTE-1 from the carcinogenic liver fluke Opisthorchis viverrini: potential target for DNA-based diagnosis. Infect Genet Evol 21:443-51
Plieskatt, Jordan L; Rinaldi, Gabriel; Feng, Yanjun et al. (2014) Distinct miRNA signatures associate with subtypes of cholangiocarcinoma from infection with the tumourigenic liver fluke Opisthorchis viverrini. J Hepatol 61:850-8
Plieskatt, Jordan L; Deenonpoe, Raksawan; Mulvenna, Jason P et al. (2013) Infection with the carcinogenic liver fluke Opisthorchis viverrini modifies intestinal and biliary microbiome. FASEB J 27:4572-84
Saichua, Prasert; Sithithaworn, Paiboon; Jariwala, Amar R et al. (2013) Microproteinuria during Opisthorchis viverrini infection: a biomarker for advanced renal and hepatobiliary pathologies from chronic opisthorchiasis. PLoS Negl Trop Dis 7:e2228