In vitro Susceptibility of Leishmania donovani to Miltefosine in Indian Visceral Leishmaniasis

In vitro Susceptibility of Leishmania donovani to Miltefosine in Indian Visceral Leishmaniasis
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DOI:
10.4269/ajtmh.13-0096
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发表时间:
2013-10-01
影响因子:
3.3
通讯作者:
Sundar, Shyam
Sundar, Shyam
中科院分区:
医学4区
文献类型:
--
作者:
Prajapati, Vijay Kumar;Sharma, Smriti;Sundar, Shyam

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对印度内脏利什曼病患者接受MIL治疗的多诺瓦利什曼原虫分离株进行米特氟辛promastite (MIL)敏感性测试。在MIL治疗开始前、治疗完成后(第29天)或治疗失败时获得的分离株使用体外原mastigote assay进行筛选。预处理的MIL易感性隔离(N = 24日意味着IC50 + / - SEM = 3.74 + / - 0.38μM)明显高于治疗组(N = 26日意味着IC50 + / - SEM = 6.15 + / - 0.52μM; P = 0.0006),但类似的治愈病人(N = 22日意味着IC50 + / - SEM = 5.58 + / - 0.56μM)和那些失败的治疗(N = 28日意味着IC50 + / - SEM = 4.53 + / - 0.47μM)。因此,治疗前/治疗后的结果显示出2倍的差异,而从治愈患者和失败患者中分离出来的结果显示出相似的易感性,这表明这种更高的耐受性不是mil治疗失败的原因。我们的工作强调需要仔细监测MIL易感性,以便在国家VL消除规划中实施。
Promastigote miltefosine (MIL) susceptibility was performed on Leishmania donovani isolates from Indian patients with visceral leishmaniasis treated with MIL. Isolates that were obtained before the onset of MIL treatment, after completion of treatment (29th day), or at the time of treatment failure, were screened using in vitro promastigote assay. The MIL susceptibility of the pre-treatment isolates (N = 24, mean IC50 +/- SEM = 3.74 +/- 0.38 mu M) was significantly higher than that of the post-treatment group (N = 26, mean IC50 +/- SEM = 6.15 +/- 0.52 mu M; P = 0.0006) but was similar in the cured patients (N = 22, mean IC50 +/- SEM = 5.58 +/- 0.56 mu M) and those who failed treatment (N = 28, mean IC50 +/- SEM = 4.53 +/- 0.47 mu M). The pre/post-treatment results thus showed a 2-fold difference, whereas isolated from cured versus failed patients showed a similar susceptibility, suggesting that this higher tolerance is not responsible for MIL-treatment failure. Our work highlights the need for careful monitoring of MIL susceptibility for implementation in national VL elimination programs.