In vitro and in vivo efficacy of mefloquine-based treatment against alveolar echinococcosis

Alveolar echinococcosis (AE) is caused by the metacestode stage of the fox tapeworm Echinococcus multilocularis and causes severe disease in the human liver and occasionally other organs, which is fatal if treatment is unsuccessful. The present chemotherapy of AE is based on mebendazole and albendazole. Albendazole treatment has been found to be ineffective in some instances, parasitostatic rather than parasiticidal, and usually involves the lifelong uptake of large doses of drugs. Thus, new treatment options are urgently needed. In this study we investigated the in vitro and in vivo efficacy of mefloquine against E. multilocularis metacestodes. Mefloquine treatment of in vitro cultures of metacestodes at 20 muM resulted in rapid and complete detachment of large parts of the germinal layer from the inner surface of the laminated layer within a few hours. The in vitro activity of mefloquine was dose-dependent. In vitro culture of metacestodes in the presence of 24 muM mefloquine for a period of 10 days was parasiticidal as determined by bioassay in mice, while treatment with 12 muM was not. Oral application of mefloquine (25mg/kg body weight, twice a week for a period of 8 weeks) in E. multilocularis-infected mice was ineffective in achieving any reduction of parasite weight, while treatment with albendazole (200mg/kg/day) was highly effective. However, when the same mefloquine dosage was applied intraperitoneally, the reduction in parasite weight was similar to oral albendazole application. Combined application of both drugs did not increase the treatment efficacy. In conclusion, mefloquine represents an interesting drug candidate for the treatment of AE, and these results should be followed up in appropriate in vivo studies