Ouattara Amed, Kone Aminatou, Adams Matthew, Fofana Bakary, Maiga Amelia Walling, Hampton Shay, Coulibaly Drissa, Thera Mahamadou A, Diallo Nouhoum, Dara Antoine, Sagara Issaka, Gil Jose Pedro, Bjorkman Anders, Takala-Harrison Shannon, Doumbo Ogobara K, Plowe Christopher V, Djimde Abdoulaye A
Department of Epidemiology of Parasitic Diseases, University of Science, Techniques and Technologies of Bamako, Bamako, Mali; Vanderbilt University Medical Center, Nashville, Tennessee; Howard Hughes Medical Institute, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Department of Physiology and Pharmacology, Karolinska University Hospital/Karolinska Institutet, Stockholm, Sweden; Drug Resistance and Pharmacogenetics, Center for Biodiversity, Functional and Integrative Genomics, Faculdade de Ciências, Universidade de Lisboa, Lisbon, Portugal; The Harpur College of Arts and Sciences, Binghamton University, The State University of New York, Binghamton, New York.
Department of Epidemiology of Parasitic Diseases, University of Science, Techniques and Technologies of Bamako, Bamako, Mali; Vanderbilt University Medical Center, Nashville, Tennessee; Howard Hughes Medical Institute, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Department of Physiology and Pharmacology, Karolinska University Hospital/Karolinska Institutet, Stockholm, Sweden; Drug Resistance and Pharmacogenetics, Center for Biodiversity, Functional and Integrative Genomics, Faculdade de Ciências, Universidade de Lisboa, Lisbon, Portugal; The Harpur College of Arts and Sciences, Binghamton University, The State University of New York, Binghamton, New York
Am J Trop Med Hyg. 2015 Jun;92(6):1202-6. doi: 10.4269/ajtmh.14-0605. Epub 2015 Apr 27.
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.
东南亚已出现对青蒿素耐药的恶性疟原虫疟疾，且可能已在该地区传播。分子标记是监测抗疟药耐药性传播的重要工具。最近，PF3D7_1343700 Kelch螺旋桨（K13螺旋桨）结构域中的单核苷酸多态性（SNP）被证明与体内外青蒿素耐药性相关。在撒哈拉以南非洲，K13螺旋桨突变的流行情况和作用鲜为人知。在马里，以青蒿素为基础的联合疗法（ACT）作为一线疗法使用前后，通过对预处理的恶性疟原虫感染干血斑进行巢式聚合酶链反应（PCR）扩增子直接测序，对K13螺旋桨突变进行基因分型。虽然未发现先前在柬埔寨与寄生虫清除延迟相关的K13螺旋桨突变，但在近期样本和ACT治疗前的感染中均发现了26种K13螺旋桨突变。非同义K13螺旋桨突变感染与参考等位基因感染之间的寄生虫清除时间相当。这些发现表明，K13螺旋桨突变存在于对青蒿素敏感的寄生虫中，且在马里广泛使用ACT之前就已存在。
