Efficacy and Safety of Praziquantel Against Light Infections of Opisthorchis viverrini: A Randomized Parallel Single-Blind Dose-Ranging Trial.
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 × 25 mg/kg for individual treatment, is the drug of choice, yet information on the nature of the dose-response relationship is lacking.



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 × 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 Emax models.



Two-hundred seventeen O. viverrini–infected patients were assigned to the 5 treatment arms. The majority (94.3%) of patients harbored light infections. The Emax 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 × 25 mg/kg) than in the single-dose treatment arms.



Single-dose praziquantel appears to be as efficacious as the standard 3 × 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.



Randomized Controlled Trials (ISRCTN77186750).
National Institute of Public Health, Ministry of Health, Vientiane, Lao People's Democratic Republic.
Somphou
S
Sayasone
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel|University of Basel, Switzerland
Isabel
I
Meister
Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, California.
Jason R
JR
Andrews
University of Basel, Switzerland|Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland
Peter
P
Odermatt
University of Health Sciences, Ministry of Health, Vientiane, Lao People's Democratic Republic.
Youthanavanh
Y
Vonghachack
National Institute of Public Health, Ministry of Health, Vientiane, Lao People's Democratic Republic.
Syda
S
Xayavong
National Institute of Public Health, Ministry of Health, Vientiane, Lao People's Democratic Republic.
Kanpaseuth
K
Senggnam
National Institute of Public Health, Ministry of Health, Vientiane, Lao People's Democratic Republic.
Khampheng
K
Phongluxa
University of Basel, Switzerland|Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland
Jan
J
Hattendorf
Divisions of General Internal Medicine and Infectious Diseases, University Health Network|Department of Medicine, University of Toronto, Ontario, Canada
Isaac I
II
Bogoch
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel|University of Basel, Switzerland
Jennifer
J
Keiser
D000328:Adult; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage* / Q000009:adverse effects; D060085:Coinfection; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009889:Opisthorchiasis / Q000188:drug therapy* / Q000469:parasitology*; D009891:Opisthorchis; D010270:Parasite Egg Count; D059208:Parasite Load; D011223:Praziquantel / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D000871:Anthelmintics; D011223:Praziquantel