2017 年塞内加尔的体外 RSA 和 pfkelch13 靶向扩增子深度测序显示寄生虫对青蒿素的敏感性。
Ex vivo RSA and pfkelch13 targeted-amplicon deep sequencing reveal parasites susceptibility to artemisinin in Senegal, 2017.
机构信息
Laboratory of Parasitology-Mycology, Aristide le Dantec Hospital, Université Cheikh Anta Diop, Dakar, Senegal.
International Research Training Center on Genomics and Health Surveillance (CIGASS), Dakar, Senegal.
出版信息
Malar J. 2023 May 26;22(1):167. doi: 10.1186/s12936-023-04588-1.
BACKGROUND
Malaria control is highly dependent on the effectiveness of artemisinin-based combination therapy (ACT), the current frontline malaria curative treatment. 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.
METHODS
Here, ex vivo susceptibility to dihydroartemisinin (DHA) was evaluated from 38 Plasmodium falciparum isolates collected in 2017 in Thiès (Senegal) expressed in the Ring-stage Survival Assay (RSA). Both major and minor variants were explored in the three conserved-encoding domains of the pfkelch13 gene, the main determinant of ART resistance using a targeted-amplicon deep sequencing (TADS) approach.
RESULTS
All samples tested in the ex vivo RSA were found to be susceptible to DHA (parasite survival rate < 1%). The non-synonymous mutations K189T and K248R in pfkelch13 were observed each in one isolate, as major (99%) or minor (5%) variants, respectively.
CONCLUSION
The results suggest that ART is still fully effective in the Thiès region of Senegal in 2017. Investigations combining ex vivo RSA and TADS are a useful approach for monitoring ART resistance in Africa.
背景
疟疾控制高度依赖于青蒿素类复方疗法（ACT）的有效性，这是目前治疗疟疾的一线药物。不幸的是，东南亚和南美洲青蒿素衍生物耐药性寄生虫的出现和传播，以及最近在卢旺达和乌干达（东非）的出现，使其在撒哈拉以南非洲地区的长期使用受到影响，而大多数疟疾死亡都发生在该地区。
方法
本研究采用环体生存检测（RSA）评估了 2017 年在塞内加尔的蒂埃斯采集的 38 株恶性疟原虫分离株对二氢青蒿素（DHA）的体外敏感性。使用靶向扩增子深度测序（TADS）方法，在 pfkelch13 基因的三个保守编码域中探索了主要和次要变异体，该基因是青蒿素耐药的主要决定因素。
结果
RSA 体外检测的所有样本均对 DHA 敏感（寄生虫存活率<1%）。pfkelch13 基因中的非 synonymous 突变 K189T 和 K248R 分别在一个分离株中被观察到，分别为主要（99%）或次要（5%）变体。
结论
研究结果表明，2017 年，ART 在塞内加尔的蒂埃斯地区仍然非常有效。将体外 RSA 和 TADS 相结合的研究是监测非洲地区 ART 耐药性的一种有效方法。
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