Wade Alioune, Sene Seynabou D, Caspar Emanuelle, Diallo Fatoumata, Platon Lucien, Thiebaut Lucas, Pouye Mariama N, Ba Aboubacar, Thiam Laty Gaye, Fall Magal, Sadio Bacary Djilocalisse, Desamours Ife, Guerra Noemi, Hagadorn Kelly, Amambua-Ngwa Alfred, Bei Amy K, Vigan-Womas Ines, Ménard Didier, Mbengue Alassane
Institut Pasteur de Dakar, Immunophysiopathology and Infectious Diseases Department, G4-Malaria Experimental Genetic Approaches and Vaccines Unit, Dakar, Senegal.
Institut Pasteur de Dakar, Immunophysiopathology and Infectious Diseases Department, Dakar, Senegal.
J Antimicrob Chemother. 2025 Mar 3;80(3):828-839. doi: 10.1093/jac/dkaf006.
Since 2006, artemisinin-based combination therapies (ACTs) have been introduced in Senegal in response to chloroquine resistance (CQ-R) and have shown high efficacy against Plasmodium falciparum. However, the detection of the PfKelch13R515K mutation in Kaolack, which confers artemisinin resistance in vitro, highlights the urgency of strengthening antimalarial drug surveillance to achieve malaria elimination by 2030.
To assess the proportion of P. falciparum parasites carrying molecular signatures associated with antimalarial resistance (PfKelch13, Pfmdr1, Pfcrt, dhfr and dhps) in isolates collected at Kédougou using multiplex amplicon deep sequencing.
Venous blood samples were collected from patients diagnosed with P. falciparum infection over a 3-year period (2021, 2022 and 2023). Parasite DNA was extracted, and multiplex amplicon sequencing was used to investigate gene polymorphisms.
Analysis of PfKelch13 did not reveal any non-synonymous mutations. Pfcrt mutations were present in 45% of the samples, mainly K76T (44%) and I356T (36%). The dominant Pfmdr-1 allele was Y184F (62%). The sextuple mutant 51I/59R/108N + 436A/437G/613S dhfr/dhps was observed in 10% of the samples.
The absence of PfKelch13 mutants suggests that ACT efficacy remains uncompromised, although clinical outcome studies are required to confirm this. Analysis of Pfcrt and Pfmdr-1 shows that CQ-R alleles, probably from previous CQ use, are slowly decreasing. Likewise, the detection of the dhfr/dhps sextuple mutant highlights the need to monitor sulfadoxine-pyrimethamine resistance and the emergence of 581G. There is therefore a need for continued antimalarial resistance surveillance in Senegal.
自2006年以来，塞内加尔为应对氯喹耐药性（CQ-R）引入了以青蒿素为基础的联合疗法（ACTs），并已显示出对恶性疟原虫的高效性。然而，在考拉克检测到体外具有青蒿素抗性的PfKelch13R515K突变，凸显了加强抗疟药物监测以在2030年前实现疟疾消除的紧迫性。
使用多重扩增子深度测序评估在凯杜古收集的分离株中携带与抗疟抗性相关分子特征（PfKelch13、Pfmdr1、Pfcrt、dhfr和dhps）的恶性疟原虫寄生虫比例。
在3年期间（2021年、2022年和2023年）从被诊断为恶性疟原虫感染的患者中采集静脉血样本。提取寄生虫DNA，并使用多重扩增子测序研究基因多态性。
对PfKelch13的分析未发现任何非同义突变。45%的样本中存在Pfcrt突变，主要是K76T（44%）和I356T（36%）。主要的Pfmdr-1等位基因是Y184F（62%）。在10%的样本中观察到六重突变体51I/59R/108N + 436A/437G/613S dhfr/dhps。
PfKelch13突变体的缺失表明ACT的疗效仍然未受影响，尽管需要临床结局研究来证实这一点。对Pfcrt和Pfmdr-1的分析表明，可能来自先前使用氯喹的CQ-R等位基因正在缓慢减少。同样，dhfr/dhps六重突变体的检测凸显了监测磺胺多辛-乙胺嘧啶抗性和581G出现的必要性。因此，塞内加尔需要持续进行抗疟抗性监测。
