Polymorphisms in the K13-Propeller Gene in Artemisinin-Susceptible Plasmodium falciparum Parasites from Bougoula-Hameau and Bandiagara, Mali
Polymorphisms in the K13-Propeller Gene in Artemisinin-Susceptible Plasmodium falciparum Parasites from Bougoula-Hameau and Bandiagara, Mali
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DOI：
10.4269/ajtmh.14-0605
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发表时间：
2015-06-01
影响因子：
3.3
通讯作者：
Djimde, Abdoulaye A.
中科院分区：
文献类型：
--
作者：
Ouattara, Amed;Kone, Aminatou;Djimde, Abdoulaye A.
抗青蒿素恶性疟原虫已在东南亚被记录在案，并可能已经在该地区传播。分子标记是监测抗疟药耐药性传播的重要工具。近年来，体内和体外研究表明，PF3D7_1343700海带推进器(K13-推进器)区域的单核苷酸多态(SNPs)与青蒿素耐药性有关。K13螺旋桨突变的流行情况和作用在撒哈拉以南非洲地区知之甚少。通过对马里使用以青蒿素为基础的联合疗法(ACT)作为一线治疗前后的治疗前恶性疟疾感染患者的干血点进行直接测序，对K13螺旋体突变进行了基因分型。尽管在柬埔寨没有发现以前与寄生虫清除延迟有关的K13螺旋体突变，但在最近的样本和ACT前感染中都发现了26个K13螺旋体突变。带有非同义K13螺旋桨突变的感染和具有参考等位基因的感染之间的寄生虫清除时间相当。这些发现表明，在对青蒿素敏感的寄生虫中存在K13螺旋体突变，并且这些突变先于ACTS在马里的广泛使用。
Artemisinin-resistant Plasmodium falciparum malaria has been documented in southeast Asia and may already be spreading in that region. Molecular markers are important tools for monitoring the spread of antimalarial drug resistance. Recently, single-nucleotide polymorphisms (SNPs) in the PF3D7_1343700 kelch propeller (K13-propeller) domain were shown to be associated with artemisinin resistance in vivo and in vitro. The prevalence and role of K13-propeller mutations are poorly known in sub-Saharan Africa. K13-propeller mutations were genotyped by direct sequencing of nested polymerase chain reaction (PCR) amplicons from dried blood spots of pre-treatment falciparum malaria infections collected before and after the use of artemisinin-based combination therapy (ACT) as first-line therapy in Mali. Although K13-propeller mutations previously associated with delayed parasite clearance in Cambodia were not identified, 26 K13-propeller mutations were identified in both recent samples and pre-ACT infections. Parasite clearance time was comparable between infections with non-synonymous K13-propeller mutations and infections with the reference allele. These findings suggest that K13-propeller mutations are present in artemisinin-sensitive parasites and that they preceded the wide use of ACTs in Mali.