Rosenthal Philip J, Asua Victor, Bailey Jeffrey A, Conrad Melissa D, Ishengoma Deus S, Kamya Moses R, Rasmussen Charlotte, Tadesse Fitsum G, Uwimana Aline, Fidock David A
Department of Medicine, University of California, San Francisco, CA, USA.
Infectious Diseases Research Collaboration, Kampala, Uganda; University of Tübingen, Tübingen, Germany.
Lancet Infect Dis. 2024 Sep;24(9):e591-e600. doi: 10.1016/S1473-3099(24)00141-5. Epub 2024 Mar 26.
Malaria remains one of the most important infectious diseases in the world, with the greatest burden in sub-Saharan Africa, primarily from Plasmodium falciparum infection. The treatment and control of malaria is challenged by resistance to most available drugs, but partial resistance to artemisinins (ART-R), the most important class for the treatment of malaria, was until recently confined to southeast Asia. This situation has changed, with the emergence of ART-R in multiple countries in eastern Africa. ART-R is mediated primarily by single point mutations in the P falciparum kelch13 protein, with several mutations present in African parasites that are now validated resistance mediators based on clinical and laboratory criteria. Major priorities at present are the expansion of genomic surveillance for ART-R mutations across the continent, more frequent testing of the efficacies of artemisinin-based regimens against uncomplicated and severe malaria in trials, more regular assessment of ex-vivo antimalarial drug susceptibilities, consideration of changes in treatment policy to deter the spread of ART-R, and accelerated development of new antimalarial regimens to overcome the impacts of ART-R. The emergence of ART-R in Africa is an urgent concern, and it is essential that we increase efforts to characterise its spread and mitigate its impact.
疟疾仍然是世界上最重要的传染病之一,在撒哈拉以南非洲负担最重,主要由恶性疟原虫感染所致。疟疾的治疗和控制面临着对大多数现有药物耐药性的挑战,但对青蒿素的部分耐药性(ART-R),这一治疗疟疾最重要的药物类别,直到最近还仅限于东南亚地区。随着非洲东部多个国家出现ART-R,这种情况已经发生了变化。ART-R主要由恶性疟原虫kelch13蛋白中的单点突变介导,非洲寄生虫中存在几种突变,根据临床和实验室标准,这些突变现在已被确认为耐药性介导因子。目前的主要优先事项包括在整个非洲大陆扩大对ART-R突变的基因组监测,在试验中更频繁地测试基于青蒿素的治疗方案对非复杂性和重症疟疾的疗效,更定期地评估体外抗疟药物敏感性,考虑改变治疗政策以阻止ART-R的传播,以及加速开发新的抗疟治疗方案以克服ART-R的影响。非洲出现ART-R是一个紧迫问题,我们必须加大力度来描述其传播情况并减轻其影响。
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