Menard Didier, Dondorp Arjen
Malaria Molecular Epidemiology Unit, Institut Pasteur in Cambodia, Phnom Penh 12201, Cambodia.
Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 73170, Thailand.
Cold Spring Harb Perspect Med. 2017 Jul 5;7(7):a025619. doi: 10.1101/cshperspect.a025619.
Increasing antimalarial drug resistance once again threatens effective antimalarial drug treatment, malaria control, and elimination. Artemisinin combination therapies (ACTs) are first-line treatment for uncomplicated falciparum malaria in all endemic countries, yet partial resistance to artemisinins has emerged in the Greater Mekong Subregion. Concomitant emergence of partner drug resistance is now causing high ACT treatment failure rates in several areas. Genetic markers for artemisinin resistance and several of the partner drugs have been established, greatly facilitating surveillance. Single point mutations in the gene coding for the Kelch propeller domain of the K13 protein strongly correlate with artemisinin resistance. Novel regimens and strategies using existing antimalarial drugs will be needed until novel compounds can be deployed. Elimination of artemisinin resistance will imply elimination of all falciparum malaria from the same areas. In vivax malaria, chloroquine resistance is an increasing problem.
日益增加的抗疟药物耐药性再次威胁到有效的抗疟药物治疗、疟疾控制及消除。在所有疟疾流行国家，青蒿素联合疗法（ACTs）是无并发症恶性疟的一线治疗方法，但在大湄公河次区域已出现对青蒿素的部分耐药性。同时，伙伴药物耐药性的出现正导致多个地区ACT治疗失败率居高不下。青蒿素耐药性及几种伙伴药物的基因标志物已确定，极大地促进了监测工作。编码K13蛋白Kelch螺旋桨结构域的基因中的单点突变与青蒿素耐药性密切相关。在能够部署新型化合物之前，将需要使用现有抗疟药物的新型治疗方案和策略。消除青蒿素耐药性意味着在同一地区消除所有恶性疟。在间日疟方面，氯喹耐药性问题日益严重。
