Dose-response relationships and tegumental surface alterations in Opisthorchis viverrini following treatment with mefloquine in vivo and in vitro

Keiser, Jennifer ; Odermatt, Peter ; Tesana, Smarn

In: Parasitology Research, 2009, vol. 105, no. 1, p. 261-266

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    Summary
    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 2weeks (juvenile infections) and 4weeks (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 100µg/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 100µg/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 48h 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