尼日利亚西北部卡诺Murtala Muhammad专科医院成年疟疾患者恶性疟原虫耐多药-1 (pfmdr1)基因突变

I.U. Muhammad, A.A. Imam, S. Khadijah
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摘要

由于怀疑以青蒿素为基础的联合疗法(目前是全世界疟疾的一线治疗方法)有效性不足,尼日利亚西北部的卡诺州非官方地使用了替代抗疟药物,包括氯喹和磺胺多辛/乙胺嘧啶。为促进基于证据的耐药管理,研究了恶性疟原虫多药耐药-1 (pfmdr1)基因的抗疟耐药突变。研究招募了100名成年患者,包括43名男性和57名女性。参与者的平均年龄为36.4岁,最小年龄为16岁,最大年龄为60岁,其中41%的参与者年龄在16 - 30岁之间。然后用显微镜分析血液分离物是否存在疟原虫,结果显示受试者中恶性疟原虫感染率很高(30%)。Pfmdr1基因是青蒿素耐药性的分子标记,已在从招募的参与者收集的100株恶性疟原虫分离株中的21株中成功测序。19.5%(4/33)的分离样本中发现Pfmdr1突变。Pfmdr1 N86Y等位基因在4份样本中普遍存在,而Y184F和D1246Y等位基因未检出。共检测到4个密码子N86Y的非同义突变。这些突变的存在凸显了尼日利亚西北部卡诺州使用甲醚甲苯胺、甲氟喹、阿莫地喹、奎宁和甲苯胺等抗疟药物治疗疟疾所面临的挑战。
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Plasmodium falciparum Multidrug Resistance-1 (pfmdr1) Gene Mutation in Adults Malaria Patients Attending Murtala Muhammad Specialist Hospital Kano, Northwest Nigeria
Suspicion of failure in the effectiveness of artemisinin-based combination therapies (currently the first-line treatment of malaria, worldwide) is leading to the unofficial use of alternative antimalarials, including chloroquine and sulfadoxine/pyrimethamine in Kano state northwestern Nigeria. To facilitate evidence-based resistance management, antimalarial resistance mutations were investigated in Plasmodium falciparum multidrug resistance-1 (pfmdr1) gene. Hundred adult patients comprising 43 males and 57 females were recruited for the study. The mean age of participants is 36.4 years, minimum and maximum ages were 16 and 60 years respectively, while 41% of them fall within the range of 16 to 30 years. Blood isolates were then analyzed for the presence of malaria parasite using microscopy, the results show a high prevalence of P. falciparum infection in the subject (30%). Pfmdr1 gene, a molecular marker of artemisinin resistance, was successfully sequenced in 21 out of 100 P. falciparum isolates collected from recruited participants. Pfmdr1 mutations were found in 19.5% (4/33) of the samples isolated. The prevalence of the Pfmdr1 N86Y allele was found in 4 samples whilst Y184F and D1246Y were not detected. A total of 4 non-synonymous mutations at codon N86Y were detected. The presence of these mutations highlights the challenges for malaria treatment in Kano state, northwestern Nigeria using antimalarials such as artemether lumefantrine, mefloquine, amodiaquine quinine and lumefantrine.
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