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[恶性疟原虫对青蒿素类复方疗法(ACTs)的耐药性:对广泛耐药的担忧]

[Plasmodium falciparum resistance to artemisinin-based combination therapies (ACTs): Fears of widespread drug resistance].

作者信息

Benoit-Vical Françoise, Paloque Lucie, Augereau Jean-Michel

出版信息

Bull Acad Natl Med. 2016 Mar;200(3):477-89; discussion 490.

Abstract

Malaria treatment with ACTs (Artemisinin-based Combination Therapies), combining a chemical derivative of artemisinin, and a partner drug has, for more than 15 years, produced a notable decrease in the mortality in tropical and subtropical areas. However, since 2008, a serious threat has emerged in western Cambodia, where the clinical efficacy of artemisinins has significantly declined, with a delayed parasite clearance rate and high recrudescence rates in the following weeks. Resistance of Plasmodium to artemisinins is now reported in several countries in South-East Asia. ACTs remain effective as long as the partner drug retains its activity but more and more clinical failures related to parasite resistance to both resistant parasites in sub-Saharan Africa, the continent most affected by malaria, as was the case in the past with other antimalarial treatments. It is therefore essential to better understand, from phenotypic and genotypic points of view, the mechanisms of resistance developed by the parasite Plasmodium falciparum face artemisinin and its derivatives in order to offer new therapeutic tools.

摘要

使用青蒿素联合疗法(ACTs,即基于青蒿素的联合疗法,将青蒿素的一种化学衍生物与一种辅助药物相结合)治疗疟疾,在超过15年的时间里,已使热带和亚热带地区的死亡率显著下降。然而,自2008年以来,柬埔寨西部出现了一个严重威胁,青蒿素的临床疗效显著下降,寄生虫清除率延迟,且在接下来的几周内复发率很高。目前在东南亚的几个国家都报告了疟原虫对青蒿素产生耐药性。只要辅助药物保持其活性,ACTs仍然有效,但越来越多与寄生虫对两种药物均产生耐药性相关的临床治疗失败情况在撒哈拉以南非洲出现,该地区是受疟疾影响最严重的大陆,过去其他抗疟治疗也曾出现过这种情况。因此,从表型和基因型角度更好地了解恶性疟原虫对青蒿素及其衍生物产生耐药性的机制至关重要,以便提供新的治疗手段。

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