In Vitro and In Vivo Efficacies of Mefloquine-Based Treatment against Alveolar Echinococcosis
In Vitro and In Vivo Efficacies of Mefloquine-Based Treatment against Alveolar Echinococcosis
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DOI：
10.1128/aac.01392-10
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发表时间：
2011-02-01
影响因子：
4.9
通讯作者：
Hemphill, Andrew
中科院分区：
文献类型：
--
作者：
Kuester, Tatiana;Stadelmann, Britta;Hemphill, Andrew
泡状棘球蚴病（AE）是由狐狸绦虫多房棘球蚴的后绦虫阶段引起的，并在人类肝脏中引起严重疾病，偶尔在其他器官中引起，当治疗不成功时是致命的。目前治疗AE的化疗药物主要是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，是抑制寄生虫而不是杀寄生虫的，并且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大肠杆菌的体外和体内疗效。多房后囊虫用甲氟喹（20 μ M）对后绦虫体外培养物进行处理，在几小时内导致大部分的germinal层从层压层的内表面快速和完全分离。甲氟喹的体外活性与剂量有关。在体外培养的后绦虫在24 μ M的甲氟喹的存在下，为期10天的寄生虫是杀的，由小鼠生物测定法确定，而治疗与12 μ M没有。口服甲氟喹（25 mg/kg体重，每周两次，共8周）。多室疟原虫感染的小鼠在实现寄生虫重量的任何减少方面是无效的，而用阿苯达唑（200 mg/kg/天）治疗是高度有效的。然而，当腹腔注射相同剂量的甲氟喹时，寄生虫重量的减少与口服阿苯达唑的减少相似。两种药物联合应用不增加治疗效果。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。
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 mu M) 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 mu M mefloquine for a period of 10 days was parasiticidal, as determined by murine bioassays, while treatment with 12 mu M 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.