In 2006, the Senegalese National Malaria Control Programme recommended artemisinin-based combination therapy (ACT) with artemether–lumefantrine as the first-line treatment for uncomplicated Plasmodium falciparum malaria. To date, multiple mutations associated with artemisinin delayed parasite clearance have been described in Southeast Asia in the Pfk13 gene, such as Y493H, R539T, I543T and C580Y. Even though ACT remains clinically and parasitologically efficacious in Senegal, the spread of resistance is possible as shown by the earlier emergence of resistance to chloroquine in Southeast Asia that subsequently spread to Africa. Therefore, surveillance of artemisinin resistance in malaria endemic regions is crucial and requires the implementation of sensitive tools, such as next-generation sequencing (NGS) which can detect novel mutations at low frequency. Here, an amplicon sequencing approach was used to identify mutations in the Pfk13 gene in eighty-one P. falciparum isolates collected from three different regions of Senegal. In total, 10 SNPs around the propeller domain were identified; one synonymous SNP and nine non-synonymous SNPs, and two insertions. Three of these SNPs (T478T, A578S and V637I) were located in the propeller domain. A578S, is the most frequent mutation observed in Africa, but has not previously been reported in Senegal. A previous study has suggested that A578S could disrupt the function of the Pfk13 propeller region. As the genetic basis of possible artemisinin resistance may be distinct in Africa and Southeast Asia, further studies are necessary to assess the new SNPs reported in this study.

中文翻译：

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来自塞内加尔的恶性疟原虫分离物中 kelch13 的扩增子深度测序。

2006 年，塞内加尔国家疟疾控制计划推荐青蒿素为基础的联合疗法 (ACT) 与蒿甲醚-苯芴醇作为无并发症恶性疟原虫疟疾的一线治疗方法。迄今为止，在东南亚的 Pfk13 基因中已经描述了与青蒿素延迟寄生虫清除相关的多个突变，例如 Y493H、R539T、I543T 和 C580Y。尽管 ACT 在塞内加尔的临床和寄生虫学上仍然有效，但正如较早出现的东南亚氯喹耐药性随后传播到非洲所表明的那样，耐药性的传播是可能的。因此，在疟疾流行地区监测青蒿素耐药性至关重要，需要实施敏感工具，例如下一代测序（NGS），它可以检测低频率的新突变。在这里，扩增子测序方法用于鉴定从塞内加尔三个不同地区收集的 81 个恶性疟原虫分离株中 Pfk13 基因的突变。总共确定了围绕螺旋桨域的 10 个 SNP；一个同义 SNP 和九个非同义 SNP，以及两个插入。其中三个 SNP（T478T、A578S 和 V637I）位于螺旋桨域中。A578S 是在非洲观察到的最常见的突变，但之前在塞内加尔没有报道过。之前的一项研究表明，A578S 可能会破坏 Pfk13 螺旋桨区域的功能。由于可能的青蒿素耐药性的遗传基础在非洲和东南亚可能不同，