EFFICACY OF PRAZIQUANTEL FOR TREATMENT OF REPEAT INFECTION OF Opisthorchis viverrini IN HAMSTER

Sophita  Thongsen; Sirikajorn  Tangkawattana; Banchob  Sripa; Paul J.  Brindley; Thewarach  Laha

Authors

Sophita Thongsen Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
Sirikajorn Tangkawattana Department of Veterinary Pathobiology, Faculty of Veterinary Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
Banchob Sripa Tropical Disease Research Laboratory, Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
Paul J. Brindley Department of Microbiology, Immunology and Tropical Medicine, and Research Center for Neglected Diseases of Poverty, School of Medicine & Health Sciences, George Washington University, Washington, DC 20037, USA.
Thewarach Laha Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.

Keywords:

Opisthorchis viverrini, praziquantel, cholangiocarcinoma, hamster, hepatobiliary

Abstract

The human liver fluke, Opisthorchis viverrini infects several million people in Thailand.Chronic opisthorchiasis combined with nitrosamine ingested with food frequently leadsbile duct cancer, cholangiocarcinoma (CCA). Repeated infection by O. viverrini increases hepatobiliary disease as well as increases the risk of CCA. Praziquantel (PZQ) is the drugof choice for treatment of opisthorchiasis. Whereas PZQ is considered safe to use, recentreports have cautioned that repeated use might influence the risk of liver fluke infectioninducedCCA. Therefore, the efficacy of repeated treatment with PZQ warrantedevaluation. Here the efficacy of PZQ treatment was investigated in hamsters repeatedly infected with O. viverrini and in hamsters both infected with O. viverrini and exposed to the carcinogen dimethylnitrosamine (DMN). Experimental hamsters were infected withO. viverrini and treated two times with 300 mg/kg of PZQ. Other hamsters were infected with O. viverrini as well as provided with drinking water that contained 12.5 ppm DMN,following by two treatments with PZQ. As controls, uninfected hamsters, uninfected hamsters treated with PZQ, and uninfected hamsters treated with both PZQ with DMNwere included. Histopathology of hepatobiliary tissues was examined, specifically forinfiltration of white blood cells, proliferation of cholangiocytes and fibrosis. The pathology including inflammation, bile duct cell proliferation and liver fibrosis decreased.

References

Bhamarapravati, N., Thammavit, W., and Vajrasthira, S.(1978). Liver changes in hamsters infected with aliver fluke of man, Opisthorchis viverrini. Am. J.Trop. Med. Hyg., 27(4):787-794.

Bunnag, D. and Harinasuta, T. (1980). Studies on the chemotherapy of human opisthorchiasis in Thailand: I. Clinical trial of praziquantel. SE. AsianJ. Trop. Med., 11(4):528-531.

Boonmars, T., Srisawangwong, T., Srirach, P., Kaewsamut,B., Pinlaor, S., and Sithithaworn, P. (2007).Apoptosis-related gene expressions in hamsters reinfected with Opisthorchis viverrini and re-treatedwith praziquantel. Parasitol. Res., 102(1):57-62.

Day, T.A., Bennett, J.L., and Pax, R.A. (1992). Praziquantel:The enigmatic antiparasitic. Parasitol. Today, 8(10):342-344.

Greenberg, R.M. (2005). Ca2+ signalling, voltage-gatedCa2+ channels and praziquantel in flatwormneuromusculature. Parasitol., 131:97-108.

Harnett, W. (1988). The anthelmintic action of praziquantel.Parasitol. Today, 4(5):144-146.

Honjo, S., Srivatanakul, P., Sriplung, H., Kikukawa, H.,Hanai, S., Uchida, K., Todoroki, T., Jedpiyawongse,A., Kittiwatanachot, P., Sripa, B., Deerasamee, S.,and Miwa, M. (2005). Genetic and environmentaldeterminants of risk for cholangiocarcinoma viaOpisthorchis viverrini in a densely infested area inNakhon Phanom, northeast Thailand. Int. J. Cancer,117(5):854-860.

IARC. (1994). Infection with liver flukes (Opisthorchisviverrini, Opisthorchis felineus and Clonorchissinensis). IARC Monographs on the Evaluation ofCarcinogenic Risks to Humans, 61:121-175.

Kamsa-ard, S., Laopaiboon, M., Luvira, V., andBhudhisawasdi, V. (2013). Association between praziquantel and cholangiocarcinoma in patientsinfected with Opisthorchis viverrini: a systematicreview and meta-analysis. Asian Pac. J. CancerPrev., 14(11):7011-7016.

Mairiang, E. and Mairiang, P. (2003). Clinical manifestation of opisthorchiasis and treatment. Acta Trop.,88(3):221-227.

Pinlaor, S., Hiraku, Y., Yongvanit, P., Tada-Oikawa, S.,Ma, N., Pinlaor, P., Sithithaworn, P., Sripa, B.,Murata, M., Oikawa, S., and Kawanishi, S. (2006).iNOS-dependent DNA damage via NF-kappa expression in hamsters infected with Opisthorchisviverrini and its suppression by the antihelminthicdrug praziquantel. Int. J. Cancer, 119(5):1067-1072.

Pinlaor, S., Prakobwong, S., Hiraku, Y., Kaewsamut, B.,Dechakhamphu, S., Boonmars, T., Sithithaworn, P.,Pinlaor, P., Ma, N., Yongvanit, P., and Kawanishi,S. (2008). Oxidative and nitrative stress in Opisthorchis viverrini-infected hamsters: anindirect effect after praziquantel treatment. Am. J.Trop. Med. Hyg., 78(4):564-573.

Riganti, M., Pungpak, S., Punpoowong, B., Bunnag, D.,and Harinasuta, T. (1989). Human pathology of Opisthorchis viverrini infection: a comparison of adults and children. SE J. Trop. Med., 20(1):95-100.

Sithithaworn, P., Pipitgool, V., Srisawangwong, T.,Elkins, D.B., and Haswell-Elkins, M.R. (1997).Seasonal variation of Opisthorchis viverriniinfection in cyprinoid fish in north-east Thailand:implications for parasite control and food safety.Bull. World Health Organ., 75(2):125-131.

Sithithaworn, P., Andrews, R.H., Nguyen, V.D., Wongsaroj,T., Sinuon, M., Odermatt, P., Nawa, Y., Liang, S.,Brindley, P.J., and Sripa, B. (2012). The currentstatus of opisthorchiasis and clonorchiasis in theMekong Basin. Parasitol. Int., 61(1):10-16.

Sripa, B. (2003). Pathobiology of opisthorchiasis: an update. Acta Trop., 88(3):209-220.

Sripa, B., Yongvanit, P., and Pairojkul, C. (2005). Etiologyand Pathogenesis of Cholangiocarcinoma: Introduction to the Association with Liver Fluke Infection.Srinagarind Med. J., 20(3):122-134.

Sripa, B., Kaewkes, S., Sithithaworn, P., Mairiang, E.,Laha, T., Smout, M., Pairojkul, C., Bhudhisawasdi,V., Tesana, S., Thinkamrop, B., Bethony, J.M.,Loukas, A., and Brindley, P.J. (2007). Liver flukeinduces cholangiocarcinoma. PLOS Med., 4(7):201.

Sripa, B., Bethony, J.M., Sithithaworn, P., Kaewkes, S.,Mairiang, E., Loukas, A., Mulvenna, J., Laha, T., Hotez,P.J., and Brindley, P.J. (2011). Opisthorchiasis and Opisthorchis-associated cholangiocarcinoma in Thailand and Laos. Acta Trop., 120(1):158-168.

Sripa, B., Brindley, P.J., Mulvenna, J., Laha, T., Smout,M.J., Mairiang, E., Bethony, J.M., and Loukas, A.(2012). The tumorigenic liver fluke Opisthorchisviverrini-multiple pathways to cancer. TrendsParasitol., 28(10):395-407.

Thamavit, W., Bhamarapravati, N., Sahaphong, S.,Vajrasthira, S., and Angsubhakorn, S. (1978).Effects of dimethylnitrosamine on induction of cholangiocarcinoma in Opisthorchis viverriniinfectedSyrian golden hamsters. Cancer Res.,38(12):4634-4639.

Watanapa, P. and Watanapa, W.B. (2002). Liver flukeassociatedcholangiocarcinoma. Brit. J. Surg.,89(8):962-970.