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首页> 外文期刊>MBio >Relapse after Treatment with Miltefosine for Visceral Leishmaniasis Is Associated with Increased Infectivity of the Infecting Leishmania donovani Strain
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Relapse after Treatment with Miltefosine for Visceral Leishmaniasis Is Associated with Increased Infectivity of the Infecting Leishmania donovani Strain

机译：Miltefosine治疗内脏利什曼病后的复发与感染性利什曼原虫donovani菌株的感染性增加有关

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Leishmania donovani is an intracellular protozoan parasite that causes leishmaniasis, which can range from a self-healing cutaneous disease to a fatal visceral disease depending on the infecting species. Miltefosine is currently the latest and only oral antileishmanial that came out of drug discovery pipelines in the past few decades, but recent reports indicate a significant decline in its efficacy against visceral leishmaniasis (also known as kala-azar) in the Indian subcontinent. This relapse rate of up to 20% within 12?months after treatment was shown not to be related to reinfection, drug quality, drug exposure, or drug-resistant parasites. We therefore aimed to assess other phenotypes of the parasite that may affect treatment outcome and found a significant association between the number of metacyclic parasites, parasite infectivity, and patient treatment outcome in the Indian subcontinent. Together with previous studies on resistance of L.?donovani against pentavalent antimonials, these data suggest that the infectivity of the parasite, or related phenotypes, might be a more determinant factor for treatment failure in visceral leishmaniasis than drug susceptibility, warranting a reassessment of our current view on treatment failure and drug resistance in leishmaniasis and beyond. >IMPORTANCE The high miltefosine relapse rate poses a major challenge for the current Kala-Azar Elimination Program in the Indian subcontinent and other leishmaniasis control programs worldwide. This relapse rate could not be related to reinfection, drug-resistant parasites, or reduced treatment quality. Here we report that an increased infectivity of the parasite is associated with miltefosine relapse of visceral leishmaniasis (VL) patients. These results supplement those obtained with antimonial-resistant L.?donovani where an increased infectivity was also observed. This challenges the current view of Leishmania drug susceptibility being the biggest parasitic factor that contributes to treatment failure in leishmaniasis. These selected more infectious parasites may pose an additional burden to leishmaniasis control programs, highlighting the importance of multifaceted control measures to achieve leishmaniasis elimination in the Indian subcontinent and other regions where leishmaniasis is endemic.
机译： Leishmania donovani 是引起利什曼病的细胞内原生动物寄生虫，根据感染物种的不同，其范围从自我修复的皮肤病到致命的内脏疾病。 Miltefosine是过去几十年来从药物研发渠道中获得的最新且唯一的口服抗衰老药物，但最近的报道表明，其在印度次大陆对内脏利什曼病（也称为黑热病）的功效显着下降。治疗后12个月内这种高达20％的复发率与再感染，药物质量，药物暴露或耐药性寄生虫无关。因此，我们旨在评估可能影响治疗结果的其他寄生虫表型，并发现印度次大陆中的元环寄生虫数量，寄生虫感染性和患者治疗结果之间存在显着关联。连同以前对 L.donovani 对五价锑抗药性的研究，这些数据表明，与药物相比，寄生虫或相关表型的感染性可能是决定内脏利什曼病治疗失败的更主要因素。易感性，有必要重新评估我们对利什曼病及其他疾病治疗失败和耐药性的当前观点。 >重要性：高miltefosine复发率对当前印度次大陆的Kala-Azar消除计划和全球其他利什曼病控制计划构成了重大挑战。该复发率可能与再感染，耐药性寄生虫或治疗质量下降无关。在这里，我们报告该寄生虫的传染性增加与内脏利什曼病（VL）患者的miltefosine复发相关。这些结果补充了对抗生素耐药的 L.donovani 所获得的结果，其中还观察到了感染性的增加。这挑战了目前对利什曼原虫药物敏感性的观点，后者是导致利什曼原虫病治疗失败的最大寄生因素。这些选择的更具传染性的寄生虫可能给利什曼病控制计划带来额外负担，突出了在印度次大陆和利什曼病流行的其他地区采取多方面控制措施以消除利什曼病的重要性。

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