Erhunse Nekpen, Sahal Dinkar
Malaria Drug Discovery Research Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, 110067, India.
Department of Biochemistry, Faculty of Life Sciences, University of Benin, Benin City, Edo-State, Nigeria.
J Pharm Anal. 2021 Oct;11(5):541-554. doi: 10.1016/j.jpha.2020.07.005. Epub 2020 Aug 9.
Having faced increased clinical treatment failures with dihydroartemisinin-piperaquine (DHA-PPQ), Cambodia swapped the first line artemisinin-based combination therapy (ACT) from DHA-PPQ to artesunate-mefloquine given that parasites resistant to piperaquine are susceptible to mefloquine. However, triple mutants have now emerged, suggesting that drug rotations may not be adequate to keep resistance at bay. There is, therefore, an urgent need for alternative treatment strategies to tackle resistance and prevent its spread. A proper understanding of all contributors to artemisinin resistance may help us identify novel strategies to keep artemisinins effective until new drugs become available for their replacement. This review highlights the role of the key players in artemisinin resistance, the current strategies to deal with it and suggests ways of protecting future antimalarial drugs from bowing to resistance as their predecessors did.
鉴于双氢青蒿素哌喹（DHA-PPQ）面临越来越多的临床治疗失败情况，柬埔寨将一线青蒿素联合疗法（ACT）从DHA-PPQ换成了青蒿琥酯甲氟喹，因为对哌喹耐药的寄生虫对甲氟喹敏感。然而，现在已经出现了三重突变体，这表明药物轮换可能不足以控制耐药性。因此，迫切需要替代治疗策略来应对耐药性并防止其传播。正确理解青蒿素耐药性的所有促成因素可能有助于我们确定新的策略，以保持青蒿素的有效性，直到有新药可供替代。本综述强调了青蒿素耐药性中关键因素的作用、当前应对耐药性的策略，并提出了保护未来抗疟药物不重蹈其前辈覆辙而屈服于耐药性的方法。
