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

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Specialized Center (P50)
Project #
4P50AI098639-02
Application #
8494466
Study Section
Special Emphasis Panel (ZAI1-AWA-M (J1))
Program Officer
Rao, Malla R
Project Start
2012-08-01
Project End
2017-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
2
Fiscal Year
2013
Total Cost
$342,515
Indirect Cost
$21,743
Name
Khon Kaen University
Department
Type
DUNS #
659454446
City
Khon Kaen
State
Country
Thailand
Zip Code
40002
Chaiyadet, Sujittra; Smout, Michael; Laha, Thewarach et al. (2017) Proteomic characterization of the internalization of Opisthorchis viverrini excretory/secretory products in human cells. Parasitol Int 66:494-502
Deenonpoe, Raksawan; Mairiang, Eimorn; Mairiang, Pisaln et al. (2017) Elevated prevalence of Helicobacter species and virulence factors in opisthorchiasis and associated hepatobiliary disease. Sci Rep 7:42744
van Tong, Hoang; Brindley, Paul J; Meyer, Christian G et al. (2017) Parasite Infection, Carcinogenesis and Human Malignancy. EBioMedicine 15:12-23
Sripa, Banchob; Deenonpoe, Raksawan; Brindley, Paul J (2017) Co-infections with liver fluke and Helicobacter species: A paradigm change in pathogenesis of opisthorchiasis and cholangiocarcinoma? Parasitol Int 66:383-389
Kim, Christina Sunyoung; Smith, John F; Suwannatrai, Apiporn et al. (2017) Role of socio-cultural and economic factors in cyprinid fish distribution networks and consumption in Lawa Lake region, Northeast Thailand: Novel perspectives on Opisthorchis viverrini transmission dynamics. Acta Trop 170:85-94
Echaubard, Pierre; León, Tomas; Suwanatrai, Kulwadee et al. (2017) Experimental and modelling investigations of Opisthorchis viverrini miracidia transmission over time and across temperatures: implications for control. Int J Parasitol 47:257-270
Vinh, Hoang Quang; Phimpraphai, Waraphon; Tangkawattana, Sirikachorn et al. (2017) Risk factors for Clonorchis sinensis infection transmission in humans in northern Vietnam: A descriptive and social network analysis study. Parasitol Int 66:74-82
Van, Chinh Dang; Doungchawee, Galayanee; Suttiprapa, Sutas et al. (2017) Association between Opisthorchis viverrini and Leptospira spp. infection in endemic Northeast Thailand. Parasitol Int 66:503-509
Hanpanich, Petcharakorn; Laha, Thewarach; Sripa, Banchob et al. (2017) Decreased risk of cholangiocarcinogenesis following repeated cycles of Opisthorchis viverrini infection-praziquantel treatment: Magnetic Resonance Imaging (MRI) and histopathological study in a hamster model. Parasitol Int 66:464-470
Maksimova, Galina A; Pakharukova, Maria Y; Kashina, Elena V et al. (2017) Effect of Opisthorchis felineus infection and dimethylnitrosamine administration on the induction of cholangiocarcinoma in Syrian hamsters. Parasitol Int 66:458-463

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