Selection of N86F184D1246 haplotype of Pfmrd1 gene by artemether-lumefantrine drug pressure on Plasmodium falciparum populations in Senegal.
Selection of N86F184D1246 haplotype of Pfmrd1 gene by artemether-lumefantrine drug pressure on Plasmodium falciparum populations in Senegal.
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DOI：
10.1186/s12936-016-1490-4
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发表时间：
2016-08-25
期刊：
影响因子：
3
通讯作者：
Ndiaye D
中科院分区：
文献类型：
--
作者：
Mbaye A;Dieye B;Ndiaye YD;Bei AK;Muna A;Deme AB;Yade MS;Diongue K;Gaye A;Ndiaye IM;Ndiaye T;Sy M;Diallo MA;Badiane AS;Ndiaye M;Seck MC;Sy N;Koita O;Krogstad DJ;Nwakanma D;Ndiaye D
使用青蒿素作为单一疗法导致2005年东南亚出现了青蒿素耐药性。监测青蒿素联合疗法对于发现和预防耐药性在流行地区的传播至关重要。体外研究和耐药分子标记的基因分型可作为这一常规监测策略的一部分。恶性疟原虫多药耐药蛋白1 （pfmdr1）基因与某些ACT伴侣耐药有关。本研究的目的是通过离体试验和对目前用于治疗的ACT药物成分耐药的分子标记分型，评估塞内加尔thi<s:1>地区恶性疟原虫种群的药物敏感性。采用DAPI法测定170株恶性疟原虫对氯喹、阿莫地喹、氨苯曲明、青蒿琥酯和蒿甲醚的体外敏感性。采用高分辨率熔融技术对pfmdr1基因在密码子86、184和1246处进行基因分型。2012 - 2013年，阿莫地喹的IC50值从13.84降至6.484，氨苯曲明的IC50值从173.4降至113.2，氯喹的IC50值从39.72降至18.29。野生单倍型NYD增加，突变单倍型NFD减少（分别为79%和62.26%）。pfmdr1野生型等位基因Y184与除阿莫地喹外的所有药物的高IC50均存在相关性。该研究表明，在两个传播季节中，以pfmdr1的WT等位基因增加为标志，敏感性增加。持续监测用于治疗简单疟疾的青蒿素联合疗法将是有益的。
The use of artemisinin as a monotherapy resulted in the emergence of artemisinin resistance in 2005 in Southeast Asia. Monitoring of artemisinin combination therapy (ACT) is critical in order to detect and prevent the spread of resistance in endemic areas. Ex vivo studies and genotyping of molecular markers of resistance can be used as part of this routine monitoring strategy. One gene that has been associated in some ACT partner drug resistance is the Plasmodium falciparum multidrug resistance protein 1 (pfmdr1) gene. The purpose of this study was to assess the drug susceptibility of P. falciparum populations from Thiès, Senegal by ex vivo assay and typing molecular markers of resistance to drug components of ACT currently used for treatment. The ex vivo susceptibility of 170 P. falciparum isolates to chloroquine, amodiaquine, lumefantrine, artesunate, and artemether was determined using the DAPI ex vivo assay. The high resolution melting technique was used to genotype the pfmdr1 gene at codons 86, 184 and 1246. A significant decrease in IC50 values was observed between 2012 and 2013: from 13.84 to 6.484 for amodiaquine, 173.4 to 113.2 for lumefantrine, and 39.72 to 18.29 for chloroquine, respectively. Increase of the wild haplotype NYD and the decrease of the mutant haplotype NFD (79 and 62.26 %) was also observed. A correlation was observed between the wild type allele Y184 in pfmdr1 and higher IC50 for all drugs, except amodiaquine. This study has shown an increase in sensitivity over the span of two transmission seasons, marked by an increase in the WT alleles at pfmdr1. Continuous the monitoring of the ACT used for treatment of uncomplicated malaria will be helpful.
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影响因子：
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作者：
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