In vitro and in vivo efficacies 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 in other organs, that is fatal when treatment is unsuccessful. The present chemotherapy against AE is based on mebendazole and albendazole. Albendazole treatment has been found to be ineffective in some instances, is 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. Treatment using mefloquine (20 μM) against in vitro cultures of metacestodes 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 dependent on the dosage. In vitro culture of metacestodes in the presence of 24 μM mefloquine for a period of 10 days was parasiticidal, as determined by murine bioassays, while treatment with 12 μM was not. Oral application of mefloquine (25 mg/kg of body weight administered twice a week for a period of 8 weeks) in E. multilocularis-infected mice was ineffective in achieving any reduction of parasite weight, whereas treatment with albendazole (200 mg/kg/day) was highly effective. However, when the same mefloquine dosage was applied intraperitoneally, the reduction in parasite weight was similar to the reduction seen with 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.
Institute of Parasitology, Vetsuisse Faculty, University of Berne, Berne, Switzerland.
Tatiana
T
Küster
Britta
B
Stadelmann
Corina
C
Hermann
Sabrina
S
Scholl
Jennifer
J
Keiser
Andrew
A
Hemphill
D015766:Albendazole / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000977:Antiparasitic Agents / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004443:Echinococcosis; D004444:Echinococcosis, Hepatic / Q000188:drug therapy / Q000469:parasitology; D048210:Echinococcus multilocularis / Q000187:drug effects / Q000254:growth & development / Q000648:ultrastructure; D005260:Female; D006801:Humans; D015767:Mefloquine / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D021261:Parasitic Sensitivity Tests; D016896:Treatment Outcome
D000977:Antiparasitic Agents; D015766:Albendazole; D015767:Mefloquine