Efficacy and safety of praziquantel against light infections of Opisthorchis viverrini : a randomised parallel single blind dose-ranging trial

Background. The liver fluke Opisthorchis viverrini, highly prevalent in Southeast Asia, is an important public health burden, including a risk factor for developing an aggressive bile duct cancer, cholangiocarcinoma, in chronically infected patients. Praziquantel, administered at a single 40 mg/kg dose in preventive chemotherapy programs and 3 x 25 mg/kg for individual treatment, is the drug of choice, yet information on the nature of the dose-response relationship is lacking.Methods. We performed a randomized, parallel, single-blind dose-ranging phase 2 trial in the Lao People's Democratic Republic in O. viverrini-infected adults. Patients were randomly assigned to 30 mg/kg, 40 mg/kg, 50 mg/kg, or 3 x 25 mg/kg praziquantel or placebo. Adverse events were recorded at baseline, 3 hours, and 24 hours posttreatment. Cure rates (CRs) and egg reduction rates (ERRs) were estimated 3 weeks after drug administration using available case analysis. Dose-response curves were predicted using E-max models.Results. Two-hundred seventeen O. viverrini-infected patients were assigned to the 5 treatment arms. The majority (94.3%) of patients harbored light infections. The E-max model predicted a high efficacy among the observed dose range. We observed CRs ranging from 92.7% to 95.5% and ERRs > 99.5% for all praziquantel treatment groups. Adverse events were mild but higher in the standard treatment group (3 x 25 mg/kg) than in the single-dose treatment arms.Conclusions. Single-dose praziquantel appears to be as efficacious as the standard 3 x 25 mg/kg regimen for the treatment of O. viverrini infections, while presenting fewer adverse events. Further studies are necessary in moderate and heavy O. viverrini infections.