Artemisinin-induced parasite dormancy: a plausible mechanism for treatment failure.
Artemisinin-induced parasite dormancy: a plausible mechanism for treatment failure.
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DOI：
10.1186/1475-2875-10-56
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发表时间：
2011-03-08
期刊：
影响因子：
3
通讯作者：
Gatton ML
中科院分区：
文献类型：
--
作者：
Codd A;Teuscher F;Kyle DE;Cheng Q;Gatton ML
青蒿素联合疗法是治疗单纯性恶性疟疾的一种非常有效的疗法，但青蒿素（ART）单药治疗后寄生虫复发的报道很常见。休眠恢复假说已被提出来解释这一现象，这是不同的较慢的寄生虫清除时间报告的第一个证据的发展ART的阻力。在这项研究中，对现有的恶性疟原虫感染模型进行了修改，以纳入休眠假设。已发表的体外数据描述的休眠寄生虫的特点是用来探讨是否休眠单独可以负责使用单药治疗的田间研究中观察到的高复发率。模拟几种治疗方案和休眠率，以调查治疗后的临床和寄生虫学失败率。模型输出表明，在使用ART进行单次治疗后，分别高达77%和67%的模拟发生寄生虫学和临床失败。这些速率随着重复处理而迅速下降，并且对假定的休眠速率敏感。治疗3天和7天后的模拟寄生虫学和临床治疗失败率与几项田间试验报告的结果相当。虽然需要进一步的研究来证实体内休眠，但这项理论研究为这一假设提供了支持，突出了这种寄生虫亚群在单药治疗失败后的潜在作用，并加强了ART与其他抗疟药联合使用的重要性。
Artemisinin-combination therapy is a highly effective treatment for uncomplicated falciparum malaria but parasite recrudescence has been commonly reported following artemisinin (ART) monotherapy. The dormancy recovery hypothesis has been proposed to explain this phenomenon, which is different from the slower parasite clearance times reported as the first evidence of the development of ART resistance. In this study, an existing P. falciparum infection model is modified to incorporate the hypothesis of dormancy. Published in vitro data describing the characteristics of dormant parasites is used to explore whether dormancy alone could be responsible for the high recrudescence rates observed in field studies using monotherapy. Several treatment regimens and dormancy rates were simulated to investigate the rate of clinical and parasitological failure following treatment. The model output indicates that following a single treatment with ART parasitological and clinical failures occur in up to 77% and 67% of simulations, respectively. These rates rapidly decline with repeated treatment and are sensitive to the assumed dormancy rate. The simulated parasitological and clinical treatment failure rates after 3 and 7 days of treatment are comparable to those reported from several field trials. Although further studies are required to confirm dormancy in vivo, this theoretical study adds support for the hypothesis, highlighting the potential role of this parasite sub-population in treatment failure following monotherapy and reinforcing the importance of using ART in combination with other anti-malarials.