Artemisinin Action and Resistance in Plasmodium falciparum.

Artemisinin Action and Resistance in Plasmodium falciparum.
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青蒿素在恶性疟原虫中的作用及耐药性。

DOI:
10.1016/j.pt.2016.05.010
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发表时间:
2016-09
影响因子:
9.6
通讯作者:
Fidock DA
Fidock DA
中科院分区:
医学1区
文献类型:
--
作者:
Tilley L;Straimer J;Gnädig NF;Ralph SA;Fidock DA

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近年来,在世界范围内使用以青蒿素为基础的联合疗法,大大减少了恶性疟原虫疟疾造成的死亡人数。然而,对青蒿素的耐药性已经在东南亚出现。临床上,耐药性的定义是接受青蒿素衍生物或青蒿素类联合疗法治疗的患者的寄生虫清除率较慢。这些缓慢的清除率与体外短暂暴露于双氢青蒿素的环期寄生虫的存活率提高有关。我们描述了最近在确定青蒿素耐药性的分子基础方面取得的进展,其中确定了恶性疟原虫K13蛋白的主要作用。利用K13突变作为分子标记,流行病学研究正在追踪青蒿素耐药性的出现和传播。机械研究提出了克服耐药性的潜在方法。
The worldwide use of artemisinin-based combination therapies (ACTs) has contributed in recent years to a substantial reduction in deaths resulting from Plasmodium falciparum malaria. Resistance to artemisinins, however, has emerged in Southeast Asia. Clinically, resistance is defined as a slower rate of parasite clearance in patients treated with an artemisinin derivative or an ACT. These slow clearance rates associate with enhanced survival rates of ring-stage parasites briefly exposed in vitro to dihydroartemisinin. We describe recent progress made in defining the molecular basis of artemisinin resistance, which has identified a primary role for the P. falciparum K13 protein. Using K13 mutations as molecular markers, epidemiological studies are now tracking the emergence and spread of artemisinin resistance. Mechanistic studies suggest potential ways to overcome resistance.
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