Persistence of chloroquine-resistant haplotypes of Plasmodium falciparum in children with uncomplicated Malaria in Lagos, Nigeria, four years after change of chloroquine as first-line antimalarial medicine.
Persistence of chloroquine-resistant haplotypes of Plasmodium falciparum in children with uncomplicated Malaria in Lagos, Nigeria, four years after change of chloroquine as first-line antimalarial medicine.
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DOI：
10.1186/s13000-015-0276-2
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发表时间：
2015-04-28
影响因子：
2.6
通讯作者：
Sutherland CJ
中科院分区：
文献类型：
--
作者：
Oladipo OO;Wellington OA;Sutherland CJ
在尼日利亚，尽管由于普遍存在氯喹耐药性，2005年国家疟疾药物政策改为青蒿素联合疗法（ACT），但氯喹（CQ）仍然广泛用于治疗疟疾，因为它价格便宜、负担得起且容易获得。目前正在推广使用 ACT 来治疗无并发症的疟疾。利用遗传标记来追踪循环中的抗氯喹寄生虫有助于阐明氯喹可能疗效不佳，特别是在不建议将其用于治疗单纯性恶性疟疾的情况下。这项研究确定了尼日利亚西南部商业城市拉各斯抗疟治疗政策从 CQ 改为 ACT 四年后 pfcrt 单倍型和 pfmdr1 基因点突变的流行情况。这是一项针对 12 岁以下儿童的无并发症疟疾的横断面研究，这些儿童出现发烧和其他提示疟疾的症状。从 251 名恶性疟原虫阳性儿童中的 119 名患者中提取了寄生虫 DNA，并进行了扩增。使用基于探针的 qPCR 研究了 pfcrt 基因中单倍型的发生，并使用巢式 PCR 研究了 pfmdr1 基因中的单核苷酸多态性。 119 名恶性疟原虫感染儿童中的一百零九 (109) 名 (91.6%) 携带带有突变 pfcrt 单倍型 (CVIET) 的寄生虫。其中，4.2% 包含编码 CVMNK 和 CVIET 的基因型混合物，而 4.2% 包含野生型 (CVMNK)。此外，pfmdr1 密码子 Y86 和 F184 的点突变频率分别为 62.2% 和 69.0%。 Pfmdr1 基因的密码子 1034、1042 和 1246 处没有突变。这些儿童中 CQ 抗性单倍型 (CVIET) 的高频率以及与恶性疟原虫 CQ 抗性相关的 Pfmdr1 突变表明，CQ 抗性寄生虫仍在传播。持续使用氯喹可能会继续增加 pfcrt 和 pfmdr1 基因的突变水平。国家药品监管机构国家食品药品监督管理局 (NAFDAC) 需要加强当前的病例管理工作，以促进 ACT 的使用，并紧急限制氯喹的获取。本文的虚拟幻灯片可以在这里找到：http://www.diagnosticpathology.diagnomx.eu/vs/2069472010142303
In Nigeria, despite the change in National malaria drug policy to artemisinin combination therapy (ACT) in 2005 due to widespread chloroquine resistance, chloroquine (CQ) is still widely used in the treatment of malaria because it is cheap, affordable and accessible. The use of ACT for the management of uncomplicated malaria is currently being promoted. The employment of genetic markers to track circulating chloroquine-resistant parasites are useful in elucidating likely poor efficacy of chloroquine, especially in settings where it is not recommended for the treatment of uncomplicated falciparum malaria. This study determined the prevalence of pfcrt haplotypes and point mutations in pfmdr1 genes four years after the change in antimalarial treatment policy from CQ to the ACTs in Lagos, a commercial city in South-West, Nigeria. This was a cross sectional study on uncomplicated malaria in children less than 12 years that presented with fever and other symptoms suggestive of malaria. Parasite DNA was extracted from 119 patients out of 251 children who were positive for Plasmodium falciparum by microscopy and amplified. The occurrence of haplotypes was investigated in pfcrt gene using probe-based qPCR and single nucleotide polymorphisms in pfmdr1 gene using nested PCR. One hundred and nine (109) of the 119 children with P falciparum infection (91.6%) harbourd parasites with the mutant pfcrt haplotype (CVIET). Out of this, 4.2% comprised a mixture of genotypes encoding CVMNK and CVIET, while 4.2% had the wild type (CVMNK). Furthermore, the frequency of point mutations in pfmdr1 was 62.2% and 69.0% for codons Y86 and F184 respectively. There were no mutations at codons 1034, 1042 and 1246 of the Pfmdr1 genes. The high frequency of the CQ-resistant haplotypes (CVIET) and mutations in Pfmdr1 associated with CQ resistance in P. falciparum among these children suggest that CQ-resistant parasites are still in circulation. Continuous use of chloroquine may continue to increase the level of mutations in pfcrt and pfmdr1genes. There is need to strengthen current case management efforts at promoting ACT use as well as urgently restricting access to chloroquine by the National drug regulatory agency, National Agency for Food Drug Administration and Control (NAFDAC). The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2069472010142303
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影响因子：
3.7
作者：
Andriantsoanirina V;Ratsimbasoa A;Bouchier C;Tichit M;Jahevitra M;Rabearimanana S;Raherinjafy R;Mercereau-Puijalon O;Durand R;Ménard D
通讯作者：
Ménard D
影响因子：
--
作者：
Khalil, IF;Alifrangis, M;Bygbjerg, IC
通讯作者：
Bygbjerg, IC
影响因子：
1.5
作者：
Basco, LK;LeBras, J;Wilson, CM
通讯作者：
Wilson, CM
影响因子：
4.9
作者：
Humphreys, G. S.;Merinopoulos, I.;Hallett, R. L.
通讯作者：
Hallett, R. L.
DOI：
10.4269/ajtmh.2003.69.558
发表时间：
2003-11-01
影响因子：
3.3
作者：
Djimdé, AA;Doumbo, OK;Plowe, CV
通讯作者：
Plowe, CV