Igbasi Uche Thecla, Oyibo Wellington Aghoghavia, Chen Jun-Hu, Quan Hong, Omilabu Sunday Aremu, Chen Shen-Bo, Shen Hai-Mo, Zhou Xiao-Nong
Centre for Infectious Disease Research, Microbiology Department, Nigerian Institute of Medical Research, 6 Edmund Crescent, Yaba, Lagos, Nigeria.
Centre for Malaria Diagnosis, NTD Research, Training, and Policy/ANDI Centre of Excellence for Malaria Diagnosis, College of Medicine, University of Lagos, Lagos, Nigeria.
Biochem Genet. 2025 Jan 22. doi: 10.1007/s10528-025-11022-5.
Drug resistance resulting from mutations in Plasmodium falciparum, that caused the failure of previously effective malaria drugs, has continued to threaten the global malaria elimination goal. This study describes the profiles of P. falciparum chloroquine resistance transporter (Pfcrt) and P. falciparum multidrug resistance 1 (Pfmdr1), the genetic markers associated with 4-aminoquinoline resistance, among P. falciparum isolates from Lagos, Nigeria. Genomic DNA was extracted from the dried blood spot samples obtained from individuals with microscopically confirmed P. falciparum infection in health facilities and communities in Lagos State, Nigeria. The DNA was amplified using nested polymerase chain reaction, and sequence analysis was performed to identify single nucleotide polymorphisms in the pfcrt and pfmdr1 genes. The study showed that 82.4% (178) of the isolates had pfmdr1 wild-type, while mutations were observed at codons N86Y (11.6%) and D1246Y (3.2%). Other mutations seen were at codons Y23S (0.5%), E130K (2.3%), and S149P (0.5%). 30.8% (64) of the isolates had pfcrt wild-type (CVMNK), while 62.0% (129) had CVIET (mutant) haplotype. Other pfcrt haplotypes detected include; CVIDT (1.9%); CVMDT (1.4%); CVIKT (1.0%); CVINT (0.5%); CVMET (0.5%); CVMKT (0.5%); CVMNT (1.0%); and CVMEK (0.5%). The findings underscore the presence of uncommon pfcrt haplotypes and a high prevalence of drug-resistant pfcrt haplotypes (CVIET), alongside a high prevalence of wild-type pfmdr in Lagos. This study highlights the need for ongoing surveillance of these genetic markers to provide data that can inform decisions on malaria case management and preserve the efficacy of artemisinin combination therapies (ACTs) in Nigeria.
恶性疟原虫的基因突变导致耐药性产生，致使先前有效的疟疾药物失效，这持续威胁着全球疟疾消除目标。本研究描述了来自尼日利亚拉各斯的恶性疟原虫分离株中，与4-氨基喹啉耐药性相关的遗传标记——恶性疟原虫氯喹抗性转运蛋白（Pfcrt）和恶性疟原虫多药耐药蛋白1（Pfmdr1）的特征。从尼日利亚拉各斯州卫生设施和社区中经显微镜确诊为恶性疟原虫感染的个体所采集的干血斑样本中提取基因组DNA。使用巢式聚合酶链反应扩增DNA，并进行序列分析以鉴定pfcrt和pfmdr1基因中的单核苷酸多态性。研究表明，82.4%（178株）的分离株为pfmdr1野生型，而在密码子N86Y（11.6%）和D1246Y（3.2%）处观察到突变。其他观察到的突变位于密码子Y23S（0.5%）、E130K（2.3%）和S149P（0.5%）。30.8%（64株）的分离株为pfcrt野生型（CVMNK），而62.0%（129株）具有CVIET（突变）单倍型。检测到的其他pfcrt单倍型包括：CVIDT（1.9%）；CVMDT（1.4%）；CVIKT（1.0%）；CVINT（0.5%）；CVMET（0.5%）；CVMKT（0.5%）；CVMNT（1.0%）；以及CVMEK（0.5%）。这些发现强调了在拉各斯存在不常见的pfcrt单倍型以及耐药性pfcrt单倍型（CVIET）的高流行率，同时pfmdr野生型的高流行率。本研究强调了持续监测这些遗传标记的必要性，以便提供可为尼日利亚疟疾病例管理决策提供信息的数据，并维持青蒿素联合疗法（ACTs）的疗效。
