Efficacy of Praziquantel against Schistosoma mekongi and Opisthorchis viverrini: A Randomized, Single-Blinded Dose-Comparison Trial

Background: Schistosomiasis and opisthorchiasis are of public health importance in Southeast Asia. Praziquantel (PZQ) is the drug of choice for morbidity control but few dose comparisons have been made. Methodology: Ninety-three schoolchildren were enrolled in an area of Lao PDR where Schistosoma mekongi and Opisthorchis viverrini coexist for a PZQ dose-comparison trial. Prevalence and intensity of infections were determined by a rigorous diagnostic effort (3 stool specimens, each examined with triplicate Kato-Katz) before and 28–30 days after treatment. Ninety children with full baseline data were randomized to receive PZQ: the 40 mg/kg standard single dose (n = 45) or a 75 mg/kg total dose (50 mg/kg+25 mg/kg, 4 hours apart; n = 45). Adverse events were assessed at 3 and 24 hours posttreatment. Principal Findings: Baseline infection prevalence of S. mekongi and O. viverrini were 87.8% and 98.9%, respectively. S. mekongi cure rates were 75.0% (95% confidence interval (CI): 56.6–88.5%) and 80.8% (95% CI: 60.6–93.4%) for 40 mg/kg and 75 mg/kg PZQ, respectively (P = 0.60). O. viverrini cure rates were significantly different at 71.4% (95% CI: 53.4–84.4%) and 96.6% (95% CI: not defined), respectively (P = 0.009). Egg reduction rates (ERRs) against O. viverrini were very high for both doses (>99%), but slightly lower for S. mekongi at 40 mg/kg (96.4% vs. 98.1%) and not influenced by increasing diagnostic effort. O. viverrini cure rates would have been overestimated and no statistical difference between doses found if efficacy was based on a minimum sampling effort (single Kato-Katz before and after treatment). Adverse events were common (96%), mainly mild with no significant differences between the two treatment groups. Conclusions/Significance: Cure rate from the 75 mg/kg PZQ dose was more efficacious than 40 mg/kg against O. viverrini but not against S. mekongi infections, while ERRs were similar for both doses. Trial Registration: Controlled-Trials.com ISRCTN57714676 Author Summary: Parasitic worm infections are of public health importance in Southeast Asia. Particularly, the blood-dwelling Schistosoma mekongi worm, which is acquired by skin contact with the infectious cercariae in freshwater, can lead to liver enlargement. An infection with Opisthorchis viverrini is obtained by consumption of undercooked freshwater fish, and this infection increases the risk of developing cholangiocarcinoma. A single oral dose of 40 mg/kg praziquantel is recommended for mass treatment of schistosomiasis and opisthorchiasis, while at the individual level, a total dose of 75 mg/kg divided into three doses, is currently common practice to treat O. viverrini infection. Diagnosis is based on stool examination under a microscope for detection of worm eggs, but is limited by the low sensitivity of the widely used Kato-Katz technique. In this study, we showed that a 75 mg/kg total dose of praziquantel (50 mg/kg+25 mg/kg given 4 hours apart) cleared significantly more O. viverrini infections than a single 40 mg/kg dose, but no difference was observed for S. mekongi. Solicited adverse event profiles were mainly mild and similar in both groups. Repeated stool examination before and after treatment was essential for an accurate assessment of drug efficacy in terms of cure rate, but showed no effect on assessing egg reduction rates.