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青蒿素和耐多药恶性疟原虫——对疟疾控制和消除的威胁。

Artemisinin and multidrug-resistant Plasmodium falciparum - a threat for malaria control and elimination.

机构信息

Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

出版信息

Curr Opin Infect Dis. 2021 Oct 1;34(5):432-439. doi: 10.1097/QCO.0000000000000766.

Abstract

PURPOSE OF REVIEW

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.

RECENT FINDINGS

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.

SUMMARY

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.

摘要

综述目的:在全球范围内,青蒿素类复方疗法(ACTs)是治疗无并发症恶性疟原虫感染的一线药物,且在未来几年内不会有新的化合物问世。十余年前,在大湄公河次区域(GMS)出现了对青蒿素具有耐药性的恶性疟原虫,再加上 ACT 联合用药的耐药性,导致 ACT 治疗失败的情况显著增加。本综述就青蒿素耐药性的流行病学、耐药机制以及应对多重耐药性恶性疟原虫感染的方法进行了更新。

最新发现:GMS 地区实施的一项积极的疟疾消除计划有助于防止耐药性传播到邻国。然而,现在在亚洲、非洲和南美洲的多个其他地区,也独立出现了携带恶性疟原虫 Kelch13 基因(pfk13)中与青蒿素耐药相关突变的寄生虫。值得注意的是,携带 pfk13 R561H 突变的青蒿素耐药感染已经在卢旺达出现并传播。

总结:加强耐药性监测的地理覆盖范围将是关键,以确保及时发现新出现的耐药性,从而毫不拖延地实施有效的应对措施。必须考虑制定旨在预防多药耐药性出现和传播的治疗策略,包括使用三药联合疗法和多种一线疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ef7/8452334/ea1b508f8cee/coidi-34-432-g001.jpg

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