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

The human liver fluke, Opisthorchis viverrini infects several million people in Thailand. Chronic opisthorchiasis combined with nitrosamine ingested with food frequently leads bile duct cancer, cholangiocarcinoma (CCA). Repeated infection by O. viverrini increases hepatobiliary disease as well as increases the risk of CCA. Praziquantel (PZQ) is the drug of choice for treatment of opisthorchiasis. Whereas PZQ is considered safe to use, recent reports have cautioned that repeated use might influence the risk of liver fluke infection-induced CCA. Therefore, the efficacy of repeated treatment with PZQ warranted evaluation. 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 with O. 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 DMN were included. Histopathology of hepatobiliary tissues was examined, specifically for infiltration of white blood cells, proliferation of cholangiocytes and fibrosis. The pathology including inflammation, bile duct cell proliferation and liver fibrosis decreased significantly by one week following treatment with PZQ. Following repeated infection with O. viverrini and exposure to DMN, and treatment with PZQ, disease was less marked compared to hamsters infected twice with O. viverrini but without treatment with PZQ. Severe disease manifested in hamsters with repeated liver fluke infection without PZQ treatment. Differences in pathology were not evident among the control hamsters - noninfected hamsters, uninfected hamster receiving PZQ only and uninfected hamsters treated with both PZQ with DMN. These findings confirmed the efficacy of PZQ for treatment of opisthorchiasis.