Artemisinin and multidrug-resistant Plasmodium falciparum - a threat for malaria control and elimination.
Artemisinin and multidrug-resistant Plasmodium falciparum - a threat for malaria control and elimination.
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DOI：
10.1097/qco.0000000000000766
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发表时间：
2021-10-01
影响因子：
3.9
通讯作者：
Dondorp AM
中科院分区：
文献类型：
--
作者：
Dhorda M;Amaratunga C;Dondorp AM
以青蒿素为基础的综合疗法是全球治疗无并发症恶性疟疾的第一线疗法，今后几年内不会有新的化合物。十多年前在大湄公河次区域出现了对青蒿素具有抗药性的恶性疟原虫，再加上对青蒿素综合疗法伙伴药物的抗药性，导致青蒿素综合疗法治疗严重失败。本文综述了流行病学、青蒿素耐药机制以及对抗多重耐药恶性疟的方法的最新进展。大湄公河次区域一项积极的消灭疟疾方案有助于防止抗药性蔓延到邻国。然而，在恶性疟原虫Kelch13基因（pfk13）中携带青蒿素耐药性相关突变的寄生虫现在已经独立地出现在亚洲，非洲和南美洲的多个地方。值得注意的是，携带pfk13 R561H突变的寄生虫的青蒿素耐药性感染已经在卢旺达出现并蔓延。扩大耐药性监测的地理覆盖范围将是确保及时发现新出现的耐药性的关键，以便毫不拖延地实施有效的对策。必须考虑旨在预防多药耐药性出现和扩散的治疗策略，包括部署三联药物联合疗法和多种一线疗法。
Artemisinin-based combination therapies (ACTs) are globally the first-line treatment for uncomplicated falciparum malaria and new compounds will not be available within the next few years. Artemisinin-resistant Plasmodium falciparum emerged over a decade ago in the Greater Mekong Subregion (GMS) and, compounded by ACT partner drug resistance, has caused significant ACT treatment failure. This review provides an update on the epidemiology, and mechanisms of artemisinin resistance and approaches to counter multidrug-resistant falciparum malaria. An aggressive malaria elimination programme in the GMS has helped prevent the spread of drug resistance to neighbouring countries. However, parasites carrying artemisinin resistance-associated mutations in the P. falciparum Kelch13 gene (pfk13) have now emerged independently in multiple locations elsewhere in Asia, Africa and South America. Notably, artemisinin-resistant infections with parasites carrying the pfk13 R561H mutation have emerged and spread in Rwanda. Enhancing the geographic coverage of surveillance for resistance will be key to ensure prompt detection of emerging resistance in order to implement effective countermeasures without delay. Treatment strategies designed to prevent the emergence and spread of multidrug resistance must be considered, including deployment of triple drug combination therapies and multiple first-line therapies.