Research School of Biology, Australian National University, Canberra 2601, Australia.
Research School of Biology, Australian National University, Canberra 2601, Australia.
Curr Opin Pharmacol. 2018 Oct;42:71-80. doi: 10.1016/j.coph.2018.07.010. Epub 2018 Aug 22.
The deployment of artemisinin-based combination therapies (ACTs) has been, and continues to be, integral to reducing the number of malaria cases and deaths. However, their efficacy is being increasingly jeopardized by the emergence and spread of parasites that are resistant (or partially resistant) to the artemisinin derivatives and to their partner drugs, with the efficacy of the latter being especially crucial for treatment success. A detailed understanding of the genetic determinants of resistance to the ACT partner drugs, and the mechanisms by which they mediate resistance, is required for the surveillance of molecular markers and to optimize the efficacy and lifespan of the partner drugs through resistance management strategies. We summarize new insights into the molecular basis of parasite resistance to the ACTs, such as recently-uncovered determinants of parasite susceptibility to the artemisinin derivatives, piperaquine, lumefantrine, and mefloquine, and outline the mechanisms through which polymorphisms in these determinants may be conferring resistance.
青蒿素类复方疗法（ACTs）的应用对于减少疟疾病例和死亡人数至关重要。然而，随着对青蒿素衍生物和联合用药产生抗药性（或部分抗药性）的寄生虫的出现和传播，其疗效正受到越来越大的威胁，而后者的疗效对于治疗成功尤为关键。为了监测分子标记物并通过耐药管理策略优化联合用药的疗效和寿命，需要深入了解对 ACT 联合用药产生抗药性的遗传决定因素，以及它们介导抗药性的机制。我们总结了有关寄生虫对 ACTs 产生抗药性的分子基础的新见解，例如最近发现的寄生虫对青蒿素衍生物、哌喹、咯萘啶和甲氟喹敏感性的决定因素，并概述了这些决定因素中的多态性可能导致抗药性的机制。
