Antimalarial drug resistance in the Central and Adamawa regions of Cameroon: Prevalence of mutations in P. falciparum crt, Pfmdr1, Pfdhfr and Pfdhps genes.
Antimalarial drug resistance in the Central and Adamawa regions of Cameroon: Prevalence of mutations in P. falciparum crt, Pfmdr1, Pfdhfr and Pfdhps genes.
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DOI：
10.1371/journal.pone.0256343
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Nsango SE
中科院分区：
文献类型：
--
作者：
Tuedom AGB;Sarah-Matio EM;Moukoko CEE;Feufack-Donfack BL;Maffo CN;Bayibeki AN;Awono-Ambene HP;Ayong L;Berry A;Abate L;Morlais I;Nsango SE
恶性疟原虫耐药寄生虫的传播仍然是撒哈拉以南非洲控制和消除疟疾的主要挑战之一。监测赋予不同抗疟药耐药性的分子标记对于跟踪耐药寄生虫的传播和优化现有药物的治疗寿命非常重要。本研究旨在评估喀麦隆两种不同流行病学环境中耐药基因Pfcrt、Pfmdr1、Pfdhfr和Pfdhps已知突变的流行程度。采用2018年和2019年采集的无症状个体干血点进行DNA提取，然后采用pcr检测疟原虫感染状况。采用巢式PCR检测snp，然后进行等位基因特异性限制性分析（ASRA）。使用卡方检验和Fisher精确检验比较各基因型的流行率。Pfcrt K76野生型等位基因在两个位点均有较高的流行率（分别为88.5%和62.29%，P< 0.0001）。Pfmdr1 86Y和1246Y突变在mfu的患病率分别为55.83%和1.45%，在Tibati的患病率分别为45.87和5.97%，研究地区间差异有统计学意义（P<0.0001）。总体而言，Pfdhfr三突变基因型（51I/59R/108N）非常普遍（bb0 96%），但在密码子164处未检测到SNP。在Pfdhps中，437G突变的患病率达到90%，在mfu中频率更高（P< 0.0001）。总体而言，Pfdhps突变540E和581G较少见（分别为0.33%和3.26%）。四重耐药基因型（Pfdhfr 51I/59R/108N+Pfdhp437G）占90%。野生型基因型（Pfdhfr N51/C59/S108/164I+Pfdhps A437/K540/A581）未被发现，而六重突变型（Pfdhfr 51I/59R/108N+Pfdhp437G/540E/581G）在Tibati的两份样本中出现超耐药。这些发现表明，对4-氨基喹啉类药物，特别是氯喹产生耐药性的突变的流行率呈下降趋势。然而，检测到与SP耐药相关的恶性疟原虫基因的高水平突变，这引起了对喀麦隆IPTp-SP和SMC未来疗效的关注。
The spread of Plasmodium falciparum resistant parasites remains one of the major challenges for malaria control and elimination in Sub Saharan Africa. Monitoring of molecular markers conferring resistance to different antimalarials is important to track the spread of resistant parasites and to optimize the therapeutic lifespan of current drugs. This study aimed to evaluate the prevalence of known mutations in the drug resistance genes Pfcrt, Pfmdr1, Pfdhfr and Pfdhps in two different epidemiological settings in Cameroon. Dried blood spots collected in 2018 and 2019 from asymptomatic individuals were used for DNA extraction and then the Plasmodium infection status was determined byPCR. Detection of SNPs was performed by nested PCR followed by allele-specific restriction analysis (ASRA). The prevalence of each genotype was compared between sites using the Chi square and Fisher’s exact tests. A high prevalence of the Pfcrt K76 wild type allele was found in both sites (88.5 and 62.29% respectively; P< 0,0001). The prevalence of Pfmdr1 mutations 86Y and 1246Y was respectively 55.83 and 1.45% in Mfou and 45.87 and 5.97% in Tibati, with significant difference between the studied areas (P<0.0001). Overall, the Pfdhfr triple-mutant genotype (51I/59R/108N) was highly prevalent (> 96%), however no SNP was detected at codon 164. In Pfdhps, the prevalence of the 437G mutation reached (90%) and was at higher frequency in Mfou (P< 0.0001). Overall, the Pfdhps mutations 540E and 581G were less common (0.33 and 3.26%, respectively). The quadruple resistant genotype (Pfdhfr 51I/59R/108N+Pfdhp437G) was found almost 90% of the samples. The wild-type genotype (Pfdhfr N51/C59/S108/164I+Pfdhps A437/K540/A581) was never identified and the sextuple mutant (Pfdhfr 51I/59R/108N+Pfdhp437G/540E/581G), kwon as super resistant appeared in two samples from Tibati. These findings demonstrate declining trends in the prevalence of mutations conferring resistance to 4-aminoquinolines, especially to chloroquine. However, a high level of mutations in P. falciparum genes related to SP resistance was detected and this raises concerns about the future efficacy of IPTp-SP and SMC in Cameroon.
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作者：
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