Genetic diversity of Plasmodium falciparum in human malaria cases in Mali.
Genetic diversity of Plasmodium falciparum in human malaria cases in Mali.
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DOI：
10.1186/s12936-016-1397-0
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发表时间：
2016-07-11
期刊：
影响因子：
3
通讯作者：
Piarroux R
中科院分区：
文献类型：
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作者：
Nabet C;Doumbo S;Jeddi F;Konaté S;Manciulli T;Fofana B;L'Ollivier C;Camara A;Moore S;Ranque S;Théra MA;Doumbo OK;Piarroux R
在马里，恶性疟原虫疟疾高度流行，尽管采取了各种疟疾控制措施，但仍保持稳定。了解全国范围内的恶性疟原虫种群结构差异可以为指导疟疾控制规划提供新的见解。在这项研究中，分析了马里不同疟疾传播模式地区的恶性疟原虫遗传多样性和种群结构。在马里四个不同地点的人口监测调查（2012 年 12 月至 2013 年 3 月、2013 年 10 月）期间，通过定量 PCR (qPCR) 筛查了滤纸上吸附的总共 648 个血液分离株是否存在恶性疟原虫。然后使用八个微卫星标记对阳性 qPCR 样本进行多位点可变串联重复序列分析 (MLVA)。然后分析完整基因型的遗传多样性、遗传分化和连锁不平衡。在 156 个 qPCR 阳性样本中，完成了 112 个样本的基因分型。寄生虫种群表现出高度的遗传多样性（平均 He = 0.77），这与马里的高水平疟疾传播一致。即使在相距约 900 公里的地点之间，遗传分化也很低（FST < 0.02），从而说明寄生虫种群之间存在显着的基因流动。缺乏连锁不平衡进一步揭示了局部克隆扩张的缺失，这得到了基因型关系结果的证实。与全国观察到的稳定的遗传多样性水平相反，平均感染复数从北到南增加（从 1.4 到 2.06），并且当地观察到的疟疾传播水平与之平行。在马里，恶性疟原虫种群中高水平的遗传多样性和显着的基因流动可能是控制疟疾的障碍。事实上，研究结果表明，寄生虫种群具有足够的多态性，足以适应宿主并抵消抗疟疾疫苗接种等干预措施。此外，恐慌性寄生虫种群结构意味着抗性特征可以从一个地区自由传播到另一个地区，从而使得在地方一级实施的控制措施无效。本文的在线版本 (doi:10.1186/s12936-016-1397-0) 包含补充材料，可供授权用户使用。
In Mali, Plasmodium falciparum malaria is highly endemic and remains stable despite the implementation of various malaria control measures. Understanding P. falciparum population structure variations across the country could provide new insights to guide malaria control programmes. In this study, P. falciparum genetic diversity and population structure in regions of varying patterns of malaria transmission in Mali were analysed. A total of 648 blood isolates adsorbed onto filter papers during population surveillance surveys (December 2012–March 2013, October 2013) in four distinct sites of Mali were screened for the presence of P. falciparum via quantitative PCR (qPCR). Multiple loci variable number of tandem repeats analysis (MLVA) using eight microsatellite markers was then performed on positive qPCR samples. Complete genotypes were then analysed for genetic diversity, genetic differentiation and linkage disequilibrium. Of 156 qPCR-positive samples, complete genotyping of 112 samples was achieved. The parasite populations displayed high genetic diversity (mean He = 0.77), which was consistent with a high level of malaria transmission in Mali. Genetic differentiation was low (FST < 0.02), even between sites located approximately 900 km apart, thereby illustrating marked gene flux amongst parasite populations. The lack of linkage disequilibrium further revealed an absence of local clonal expansion, which was corroborated by the genotype relationship results. In contrast to the stable genetic diversity level observed throughout the country, mean multiplicity of infection increased from north to south (from 1.4 to 2.06) and paralleled malaria transmission levels observed locally. In Mali, the high level of genetic diversity and the pronounced gene flux amongst P. falciparum populations may represent an obstacle to control malaria. Indeed, results suggest that parasite populations are polymorphic enough to adapt to their host and to counteract interventions, such as anti-malarial vaccination. Additionally, the panmictic parasite population structure imply that resistance traits may disseminate freely from one area to another, making control measures performed at a local level ineffective. The online version of this article (doi:10.1186/s12936-016-1397-0) contains supplementary material, which is available to authorized users.