Modeling malaria genomics reveals transmission decline and rebound in Senegal

Modeling malaria genomics reveals transmission decline and rebound in Senegal
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DOI:
10.1073/pnas.1505691112
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发表时间:
2015-06-02
影响因子:
11.1
通讯作者:
Wirth, Dyann F.
Wirth, Dyann F.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Daniels, Rachel F.;Schaffner, Stephen F.;Wirth, Dyann F.

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为了研究疟疾控制干预措施对寄生虫种群基因组学的影响,我们检查了2006年至2013年在塞内加尔捷斯收集的1,007份疟疾寄生虫恶性疟原虫样本。使用24个SNP的分子条形码对寄生虫样品进行基因分型。大约35%的样本被分成具有相同条形码的子集,这些子集的大小因年份而异,有时会持续多年。条形码还形成了相关群体的网络。对164个完全测序的寄生虫的分析显示了基因组区域的广泛共享。在至少两个案例中,我们发现父母的第一代重组后代的基因组与样本中的基因组相似或相同。追踪寄生虫基因型的流行病学模型可以重现观察到的条形码子集模式。模型中的可能性量化强烈表明,2006-2010年传播减少,2012-2013年显著反弹。Thies的发病率数据直接证实了传播和反弹的减少。这些发现意味着,控制疟疾的密集干预措施会导致寄生虫种群基因组学发生快速而显著的变化。研究结果还表明,基因组学与流行病学建模相结合,可以提供及时,连续和具有成本效益的跟踪疟疾消除的进展。
To study the effects of malaria-control interventions on parasite population genomics, we examined a set of 1,007 samples of the malaria parasite Plasmodium falciparum collected in Thies, Senegal between 2006 and 2013. The parasite samples were genotyped using a molecular barcode of 24 SNPs. About 35% of the samples grouped into subsets with identical barcodes, varying in size by year and sometimes persisting across years. The barcodes also formed networks of related groups. Analysis of 164 completely sequenced parasites revealed extensive sharing of genomic regions. In at least two cases we found first-generation recombinant offspring of parents whose genomes are similar or identical to genomes also present in the sample. An epidemiological model that tracks parasite genotypes can reproduce the observed pattern of barcode subsets. Quantification of likelihoods in the model strongly suggests a reduction of transmission from 2006-2010 with a significant rebound in 2012-2013. The reduced transmission and rebound were confirmed directly by incidence data from Thies. These findings imply that intensive intervention to control malaria results in rapid and dramatic changes in parasite population genomics. The results also suggest that genomics combined with epidemiological modeling may afford prompt, continuous, and cost-effective tracking of progress toward malaria elimination.