Dose-response relationships and tegumental surface alterations in Opisthorchis viverrini following treatment with mefloquine in vivo and in vitro.
The treatment and control of opisthorchiasis relies on a single drug, praziquantel; hence, there is a need to develop novel opisthorchicidal drugs. We investigated the in vitro and in vivo activity of the antimalarial mefloquine against Opisthorchis viverrini. Hamsters infected with O. viverrini for 2 weeks (juvenile infections) and 4 weeks (adult infections) were treated orally with single 200-400-mg/kg oral mefloquine. Worm burden reductions were assessed against untreated control hamsters. Worms were incubated in the presence of 10 and 100 microg/ml mefloquine. Scanning electron microscopy was used to examine adult O. viverrini after recovery from hamsters and following in vitro incubation. A single oral dose of 300-mg/kg mefloquine resulted in worm burden reductions of 88.5% (juvenile infection) and 96.0% (adult infections), respectively. Incubation with 10 and 100 microg/ml mefloquine resulted in rapid death of O. viverrini. Extensive tegumental disruption such as blebbing, sloughing, and furrowing was seen on worms incubated in vitro and on flukes recovered 48 h posttreatment. In conclusion, we have documented promising opisthorchicidal activities in hamsters and in vitro with the tegument being an important drug target. Proof-of-concept studies with mefloquine could be considered in opisthorchiasis patients.
Keiser
Jennifer
J
Department of Medical Parasitology and Infection Biology, Swiss Tropical Institute, Basel, Switzerland. jennifer.keiser@unibas.ch
Odermatt
Peter
P
Tesana
Smarn
S
D000284:Administration, Oral; D000825:Animal Structures / Q000187:drug effects; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D015767:Mefloquine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D008647:Mesocricetus / Q000469:parasitology; D008855:Microscopy, Electron, Scanning; D009889:Opisthorchiasis / Q000188:drug therapy / Q000469:parasitology / Q000662:veterinary*; D009891:Opisthorchis / Q000187:drug effects* / Q000648:ultrastructure; D016019:Survival Analysis
D000871:Anthelmintics; D015767:Mefloquine