Issa Ibrahima, Lamine Mahaman Moustapha, Hubert Veronique, Ilagouma Amadou, Adehossi Eric, Mahamadou Aboubacar, Lobo Neil F, Sarr Demba, Shollenberger Lisa M, Sandrine Houze, Jambou Ronan, Laminou Ibrahim Maman
Centre de Recherche Médicale et Sanitaire, Niamey P.O. Box 10887, Niger.
Faculty of Sciences, University of Zinder, Zinder P.O. Box 656, Niger.
Trop Med Infect Dis. 2022 Jul 29;7(8):155. doi: 10.3390/tropicalmed7080155.
The effectiveness of artemisinin-based combination therapies (ACTs) depends not only on that of artemisinin but also on that of partner molecules. This study aims to evaluate the prevalence of mutations in the , and genes from isolates collected during a clinical study. genomic DNA samples extracted from symptomatic malaria patients from Dogondoutchi, Niger, were sequenced by the Sanger method to determine mutations in the (codons 51, 59, 108, and 164), (codons 436, 437, 540, 581, and 613), and (codons 86, 184, 1034, and 1246) genes. One hundred fifty-five (155) pre-treatment samples were sequenced for the and genes. A high prevalence of mutations in the gene was observed at the level of the N51I (84.97%), C59R (92.62%), and S108N (97.39%) codons. The key K540E mutation in the gene was not observed. Only one isolate was found to harbor a mutation at codon I431V. The most common mutation on the gene was Y184F in 71.43% of the mutations found, followed by N86Y in 10.20%. The triple-mutant haplotype N51I/C59R/S108N (IRN) was detected in 97% of the samples. Single-mutant (ICS and NCN) and double-mutant (IRS, NRN, and ICN) haplotypes were prevalent at 97% and 95%, respectively. Double-mutant haplotypes of the (581 and 613) and (86 and 184) were found in 3% and 25.45% of the isolates studied, respectively. The study focused on the molecular analysis of the sequencing of the , and genes. Although a high prevalence of mutations in the gene have been observed, there is a lack of sulfadoxine pyrimethamine resistance. There is a high prevalence of mutation in the codon associated with resistance to amodiaquine. These data will be used by Niger's National Malaria Control Program to better monitor the resistance of to partner molecules in artemisinin-based combination therapies.
以青蒿素为基础的联合疗法（ACTs）的有效性不仅取决于青蒿素，还取决于其配伍分子。本研究旨在评估在一项临床研究中收集的分离株中，、和基因的突变流行情况。通过桑格法对从尼日尔多贡杜奇有症状疟疾患者中提取的基因组DNA样本进行测序，以确定（密码子51、59、108和164）、（密码子436、437、540、581和613）和（密码子86、184、1034和1246）基因中的突变。对155份治疗前样本的和基因进行了测序。在N51I（84.97%）、C59R（92.62%）和S108N（97.39%）密码子水平观察到基因中的高突变率。未观察到基因中的关键K540E突变。仅发现1株分离株在密码子I431V处存在突变。基因中最常见的突变是Y184F，占发现突变的71.43%，其次是N86Y，占10.20%。在97%的样本中检测到三重突变单倍型N51I/C59R/S108N（IRN）。单突变（ICS和NCN）和双突变（IRS、NRN和ICN）单倍型的流行率分别为97%和95%。在分别3%和25.45%的研究分离株中发现了（581和613）和（86和184）的双突变单倍型。该研究聚焦于对、和基因测序的分子分析。尽管观察到基因中的高突变率，但不存在磺胺多辛-乙胺嘧啶耐药性。与阿莫地喹耐药相关的密码子中存在高突变率。这些数据将被尼日尔国家疟疾控制项目用于更好地监测对以青蒿素为基础的联合疗法中配伍分子的耐药性。
