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 #
5P50AI098639-03
Application #
8711253
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
2014-08-01
Budget End
2015-07-31
Support Year
3
Fiscal Year
2014
Total Cost
$307,383
Indirect Cost
$22,769
Name
Khon Kaen University
Department
Type
DUNS #
659454446
City
Khon Kaen
State
Country
Thailand
Zip Code
40002
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
Sripa, Banchob; Echaubard, Pierre (2017) Prospects and Challenges towards Sustainable Liver Fluke Control. Trends Parasitol 33:799-812
Khoontawad, Jarinya; Pairojkul, Chawalit; Rucksaken, Rucksak et al. (2017) Differential Protein Expression Marks the Transition From Infection WithOpisthorchis viverrinito Cholangiocarcinoma. Mol Cell Proteomics 16:911-923
Sripa, Banchob; Tangkawattana, Sirikachorn; Sangnikul, Thinnakorn (2017) The Lawa model: A sustainable, integrated opisthorchiasis control program using the EcoHealth approach in the Lawa Lake region of Thailand. Parasitol Int 66:346-354
Sereerak, Piya; Upontain, Songkaid; Tangkawattana, Prasarn et al. (2017) Efficacious and safe dose of praziquantel for the successful treatment of feline reservoir hosts with opisthorchiasis. Parasitol Int 66:448-452
Teimoori, Salma; Arimatsu, Yuji; Laha, Thewarach et al. (2017) Chicken IgY-based coproantigen capture ELISA for diagnosis of human opisthorchiasis. Parasitol Int 66:443-447
Saltykova, Irina V; Ogorodova, Ludmilla M; Ivanov, Vladimir V et al. (2017) Carbonyl stress phenomena during chronic infection with Opisthorchis felineus. Parasitol Int 66:453-457
Gouveia, Maria João; Pakharukova, Maria Y; Laha, Thewarach et al. (2017) Infection with Opisthorchis felineus induces intraepithelial neoplasia of the biliary tract in a rodent model. Carcinogenesis 38:929-937
Surapaitoon, Arpa; Suttiprapa, Sutas; Mairiang, Eimorn et al. (2017) Subsets of Inflammatory Cytokine Gene Polymorphisms are Associated with Risk of Carcinogenic Liver Fluke Opisthorchis viverrini-Associated Advanced Periductal Fibrosis and Cholangiocarcinoma. Korean J Parasitol 55:295-304

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