Yade Mamadou Samb, Dièye Baba, Coppée Romain, Mbaye Aminata, Diallo Mamadou Alpha, Diongue Khadim, Bailly Justine, Mama Atikatou, Fall Awa, Thiaw Alphonse Birane, Ndiaye Ibrahima Mbaye, Ndiaye Tolla, Gaye Amy, Tine Abdoulaye, Diédhiou Younouss, Mbaye Amadou Mactar, Doderer-Lang Cécile, Garba Mamane Nassirou, Bei Amy Kristine, Ménard Didier, Ndiaye Daouda
Centre International de Recherche et de Formation en Génomique Appliquée, et de Surveillance Sanitaire (CIGASS), Cheikh Anta Diop University of Dakar.
Université Paris Cité and Sorbone Paris Nord, Inserm, IAME.
Res Sq. 2023 Feb 6:rs.3.rs-2538775. doi: 10.21203/rs.3.rs-2538775/v1.
Malaria control is highly dependent on the effectiveness of artemisinin-based combination therapies (ACTs), the current frontline malaria curative treatments. Unfortunately, the emergence and spread of parasites resistant to artemisinin (ART) derivatives in Southeast Asia and South America, and more recently in Rwanda and Uganda (East Africa), compromise their long-term use in Sub-Saharan Africa where most malaria deaths occur.
Here, we evaluated susceptibility to dihydroartemisinin (DHA) from 38 isolates collected in 2017 in Thiès (Senegal) expressed with the Ring-stage Survival Assay (RSA). We explored major and minor variants in the full gene, the main determinant of ART resistance using a targeted-amplicon deep sequencing (TADS) approach.
All samples tested in the RSA were found to be susceptible to DHA. Both non-synonymous mutations K189T and K248R were observed each in one isolate, as major (99%) or minor (5%) variants, respectively.
Altogether, investigations combining RSA and TADS are a useful approach for monitoring ART resistance in Africa.
疟疾控制高度依赖于以青蒿素为基础的联合疗法（ACTs）的有效性，这是目前治疗疟疾的一线疗法。不幸的是，东南亚和南美洲，以及最近在卢旺达和乌干达（东非）出现并传播了对青蒿素（ART）衍生物耐药的寄生虫，这危及了它们在撒哈拉以南非洲的长期使用，而撒哈拉以南非洲是疟疾死亡人数最多的地区。
在此，我们使用环期存活测定法（RSA）评估了2017年在塞内加尔捷斯采集的38株分离株对双氢青蒿素（DHA）的敏感性。我们采用靶向扩增子深度测序（TADS）方法，探究了全长基因中的主要和次要变异，全长基因是ART耐药性的主要决定因素。
在RSA中测试的所有样本均被发现对DHA敏感。在一个分离株中分别观察到非同义突变K189T和K248R，分别作为主要（99%）或次要（5%）变异。
总之，将RSA和TADS相结合的调查是监测非洲ART耐药性的一种有用方法。
