Ex vivo susceptibility and genotyping of Plasmodium falciparum isolates from Pikine, Senegal.
Ex vivo susceptibility and genotyping of Plasmodium falciparum isolates from Pikine, Senegal.
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DOI：
10.1186/s12936-017-1897-6
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发表时间：
2017-06-14
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;Gaye A;Dieye B;Ndiaye YD;Bei AK;Affara M;Deme AB;Yade MS;Diongue K;Ndiaye IM;Ndiaye T;Sy M;Sy N;Koita O;Krogstad DJ;Volkman S;Nwakanma D;Ndiaye D
监测恶性疟原虫对抗疟药物的敏感性是有效管理疟疾病例的必要条件。该物种的特点是对抗疟疾药物有很强的抵抗力。在塞内加尔，1988年在达喀尔地区报告了第一例氯喹耐药性病例，发病率接近7%，到1990年达到47%。正是在这种情况下，在2006年采用青蒿素综合疗法之前，磺胺嘧啶-乙胺嘧啶在2003年暂时取代氯喹作为一线治疗。本研究的目的是评估来自Pikine的恶性疟原虫种群对不同抗疟疾药物的体外敏感性。2014年，在皮金的Deggo卫生中心从2至20岁的非并发性疟疾患者中收集了54份样本。采用4 '，6-二脒基-2-苯基吲哚（DAPI）染色寄生虫的试验来研究分离株对氯喹、阿莫地喹、哌喹、乙胺嘧啶和双氢青蒿素的离体敏感性。高分辨率熔解用于pfdhps、pfdhfr、pfmdr 1和pfcrt基因的基因分型。氯喹、阿莫地喹、哌喹、双氢青蒿素和乙胺嘧啶的平均IC 50分别为39.44、54.02、15.28、2.23和64.70 nM。pfdhfr基因和pfdhps基因第437位密码子发生耐药突变，pfdhps基因第540位无突变。pfcrt的密码子K76 T和pfmdr 1的密码子N86 Y的突变分别在51%和11%的人群患病率中观察到。发现K76 T和N86 Y突变与离体氯喹抗性之间存在关系。观察到分离株对氯喹的敏感性增加。观察到对双氢青蒿素的高敏感性;而在来自Pikine的寄生虫种群中观察到对乙胺嘧啶的敏感性降低。
The monitoring of Plasmodium falciparum sensitivity to anti-malarial drugs is a necessity for effective case management of malaria. This species is characterized by a strong resistance to anti-malarial drugs. In Senegal, the first cases of chloroquine resistance were reported in the Dakar region in 1988 with nearly 7% population prevalence, reaching 47% by 1990. It is in this context that sulfadoxine–pyrimethamine temporarily replaced chloroquine as first line treatment in 2003, pending the introduction of artemisinin-based combination therapy in 2006. The purpose of this study is to assess the ex vivo sensitivity to different anti-malarial drugs of the P. falciparum population from Pikine. Fifty-four samples were collected from patients with non-complicated malaria and aged between 2 and 20 years in the Deggo health centre in Pikine in 2014. An assay in which parasites are stained with 4′, 6-di-amidino-2-phenylindole (DAPI), was used to study the ex vivo sensitivity of isolates to chloroquine, amodiaquine, piperaquine, pyrimethamine, and dihydroartemisinin. High resolution melting was used for genotyping of pfdhps, pfdhfr, pfmdr1, and pfcrt genes. The mean IC50s of chloroquine, amodiaquine, piperaquine, dihydroartemisinin, and pyrimethamine were, respectively, 39.44, 54.02, 15.28, 2.23, and 64.70 nM. Resistance mutations in pfdhfr gene, in codon 437 of pfdhps gene, and an absence of mutation at position 540 of pfdhps were observed. Mutations in codons K76T of pfcrt and N86Y of pfmdr1 were observed at 51 and 11% population prevalence, respectively. A relationship was found between the K76T and N86Y mutations and ex vivo resistance to chloroquine. An increase in sensitivity of isolates to chloroquine was observed. A high sensitivity to dihydroartemisinin was observed; whereas, a decrease in sensitivity to pyrimethamine was observed in the parasite population from Pikine.