Mechanisms of resistance to the partner drugs of artemisinin in the malaria parasite

Current Opinion in Pharmacology
Rowena E MartinSashika N Richards

Abstract

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.

Citations

Sep 5, 2019·The New England Journal of Medicine·Jigang WangChengchao Xu
Feb 6, 2019·Tropical Medicine and Infectious Disease·Christian Nsanzabana
Aug 9, 2020·Nature Communications·Sarah H ShafikRowena E Martin
Nov 9, 2019·Biological Reviews of the Cambridge Philosophical Society·Rowena E Martin
Jun 6, 2021·International Journal for Parasitology. Drugs and Drug Resistance·Faiza Amber SiddiquiLiwang Cui

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