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用利什曼原虫 - 巨噬细胞体外模型检测埃塞俄比亚利什曼原虫临床分离株对米替福新、巴龙霉素、两性霉素 B 和葡萄糖酸锑钠的敏感性。

Susceptibility of clinical isolates of Leishmania aethiopica to miltefosine, paromomycin, amphotericin B and sodium stibogluconate using amastigote-macrophage in vitro model.

机构信息

Department of Microbiology, Immunology and Parasitology, School of Medicine, Addis Ababa University, P.O. Box 1237, Code 1110, Addis Ababa, Ethiopia.

出版信息

Exp Parasitol. 2013 May;134(1):68-75. doi: 10.1016/j.exppara.2013.01.022. Epub 2013 Feb 19.

DOI:10.1016/j.exppara.2013.01.022
PMID:23434530
Abstract

Cutaneous Leishmaniasis (CL) caused by Leishmania aethiopica is a public health and social problem with a sequel of severe and mutilating skin lesions. It is manifested in three forms: localized CL (LCL), mucosal CL (MCL) and diffuse CL (DCL). Unresponsiveness to sodium stibogluconate (Sb(V)) is common in Ethiopian CL patients. Using the amastigote-macrophage in vitro model the susceptibility of 24 clinical isolates of L. aethiopica derived from untreated patients was investigated. Eight strains of LCL, 9 of MCL, and 7 of DCL patients together with a reference strain (MHOM/ET/82/117/82) were tested against four antileishmanial drugs: amphotericin B, miltefosine, Sb(V) and paromomycin. In the same order of drugs, IC(50) (μg/ml±SD) values for the 24 strains tested were 0.16±0.18, 5.88±4.79, 10.23±8.12, and 13.63±18.74. The susceptibility threshold of isolates originating from the 3 categories of patients to all 4 drugs was not different (p>0.05). Maximal efficacy was superior for miltefosine across all the strains. Further susceptibility test could validate miltefosine as a potential alternative drug in cases of sodium stibogluconate treatment failure in CL patients.

摘要

埃塞俄比亚利什曼原虫引起的皮肤利什曼病(CL)是一个公共卫生和社会问题,会导致严重和毁容性皮肤损伤。它表现为三种形式:局限性 CL(LCL)、黏膜 CL(MCL)和弥漫性 CL(DCL)。埃塞俄比亚 CL 患者对葡萄糖酸锑钠(Sb(V))无反应的情况很常见。使用无鞭毛体-巨噬细胞体外模型,研究了来自未经治疗的患者的 24 株利什曼原虫临床分离株的易感性。对 8 株 LCL、9 株 MCL 和 7 株 DCL 患者以及参考株(MHOM/ET/82/117/82)进行了 4 种抗利什曼原虫药物的测试:两性霉素 B、米替福新、Sb(V)和巴龙霉素。按照药物顺序,24 株受试菌株的 IC50(μg/ml±SD)值分别为 0.16±0.18、5.88±4.79、10.23±8.12 和 13.63±18.74。来自这 3 类患者的分离株对所有 4 种药物的敏感性阈值没有差异(p>0.05)。米替福新对所有菌株的疗效最大。进一步的药敏试验可以验证米替福新作为 CL 患者葡萄糖酸锑钠治疗失败时的潜在替代药物。

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