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 muM) 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 muM mefloquine for a period of 10 days was parasiticidal, as determined by murine bioassays, while treatment with 12 muM 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.
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机译：肺泡棘球co病（AE）是由狐狸tape虫多虫棘球the虫的前肠阶段引起的，它在人的肝脏中甚至在其他器官中引起严重的疾病，如果治疗不成功，则是致命的。当前针对AE的化学疗法基于甲苯咪唑和阿苯达唑。已发现阿苯达唑治疗在某些情况下无效，是抗寄生虫药而不是杀寄生虫药，通常涉及终身服用大剂量药物。因此，迫切需要新的治疗方案。在这项研究中，我们研究了甲氟喹对多叶大肠杆菌的代谢产物的体外和体内功效。使用甲氟喹（20μM）进行抗鞘细胞体外培养的处理导致数小时内生发层的大部分从层压层的内表面快速，完全脱离。甲氟喹的体外活性取决于剂量。通过鼠类生物测定法确定，在24μM甲喹喹存在下10天内在体外进行灭顶螨的体外培养是杀虫的，而用12μM的处理则不是。在多支叶猴感染的小鼠中口服甲氟喹（25 mg / kg体重，每周两次，共8周）对降低寄生虫体重无效，而使用阿苯达唑（200 mg / kg / kg天）非常有效。但是，当腹膜内使用相同的甲氟喹剂量时，寄生虫重量的减少与口服阿苯达唑的减少相似。两种药物的联合应用并未增加治疗效果。总之，甲氟喹是治疗AE的一种有趣的候选药物，这些结果应在适当的体内研究中进行随访。
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