Brhane Bokretsion G, Fola Abebe A, Nigussie Helen, Leonetti Alec, Kassa Moges, Hailgiorgis Henok, Wuletaw Yonas, Abera Adugna, Mohammed Hussein, Sime Heven, G/Tsadik Abeba, Assefa Gudissa, Solomon Hiwot, Tasew Geremew, Tollera Getachew, Hailu Mesay, Juliano Jonathan J, Assefa Ashenafi, Parr Jonathan B, Bailey Jeffrey A
Ethiopian Public Health Institute, Addis Ababa, Ethiopia.
Department of Microbial Sciences and Genetics, Addis Ababa University, Addis Ababa, Ethiopia.
Commun Med (Lond). 2025 Jul 18;5(1):297. doi: 10.1038/s43856-025-01008-0.
Ethiopia aims to eliminate local malaria transmission by 2030, but rising malaria cases, due to different factors, present a challenge. Understanding the prevalence and distribution of artemisinin partial resistance (ART-R) and other markers related to partner drugs as well as parasite connectivity in Ethiopia can greatly inform malaria control.
We analyzed 1199 clinical Plasmodium falciparum infections from 12 sentinel sites across five regions in Ethiopia, collected between 2019 and 2023. Using two molecular inversion probe (MIP) panels targeting key drug resistance genes and genome-wide SNPs, we assessed the prevalence of resistance-associated mutations, complexity of infection (COI), and parasite relatedness through identity-by-descent (IBD) and principal component analysis (PCA).
The most prevalent k13 R622I mutation appears in 15.7% of samples, with marked regional variation. Three validated ART-R mutations (P441L, P574L, A675V) are detected in Ethiopia for the first time, as far as we are aware, with A675V found exclusively in a Gambella clinic serving refugees from Sudan and South Sudan. Additionally, polymorphisms associated with resistance to partner drugs, including those in crt, mdr1, dhps, and dhfr genes, are nearly fixed. Most samples (87.2%) consist of monogenomic infections (COI = 1), and mutant parasites show high local genetic relatedness at the health facility level, suggesting clonal transmission. PCA reveals regional clustering, particularly in Gambella, highlighting the influence of local drug pressure, regional transmission dynamics, and importation as drivers of the observed drug resistance patterns.
The increasing prevalence of k13 R622I and the emergence of additional ART-R mutations underscore the urgent need for enhanced ACT efficacy monitoring. Early detection of partner drug resistance and ACT failure will be essential to address malaria resurgence and support Ethiopia's elimination goals.
埃塞俄比亚旨在到2030年消除本地疟疾传播，但由于不同因素导致疟疾病例不断增加，这带来了挑战。了解埃塞俄比亚青蒿素部分耐药性（ART-R）及其他与联合用药相关标志物的流行情况和分布，以及寄生虫的连通性，可为疟疾控制提供重要信息。
我们分析了2019年至2023年期间从埃塞俄比亚五个地区的12个哨点收集的1199例临床恶性疟原虫感染病例。使用两个针对关键耐药基因和全基因组单核苷酸多态性（SNP）的分子倒置探针（MIP）面板，我们通过同源性（IBD）和主成分分析（PCA）评估了耐药相关突变的流行情况、感染复杂性（COI）和寄生虫亲缘关系。
最常见的k13 R622I突变出现在15.7%的样本中，存在明显的区域差异。据我们所知，在埃塞俄比亚首次检测到三个经过验证的ART-R突变（P441L、P574L、A675V），其中A675V仅在一家为来自苏丹和南苏丹的难民服务的甘贝拉诊所中发现。此外，与联合用药耐药性相关的多态性，包括crt、mdr1、dhps和dhfr基因中的多态性，几乎是固定的。大多数样本（87.2%）为单基因组感染（COI = 1），突变寄生虫在医疗机构层面显示出高度的本地遗传相关性，表明存在克隆传播。PCA显示出区域聚类，特别是在甘贝拉，突出了本地药物压力、区域传播动态和输入作为观察到的耐药模式驱动因素的影响。
k13 R622I的流行率不断上升以及其他ART-R突变的出现，凸显了加强青蒿琥酯-阿莫地喹疗效监测的迫切需求。早期检测联合用药耐药性和青蒿琥酯-阿莫地喹治疗失败对于应对疟疾卷土重来和支持埃塞俄比亚的消除目标至关重要。
