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同域分布的恶性疟原虫和间日疟原虫种群的基因组流行病学对比。

Contrasting genomic epidemiology between sympatric Plasmodium falciparum and Plasmodium vivax populations.

机构信息

Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

出版信息

Nat Commun. 2024 Sep 30;15(1):8450. doi: 10.1038/s41467-024-52545-6.

Abstract

The malaria parasites Plasmodium falciparum and Plasmodium vivax differ in key biological processes and associated clinical effects, but consequences on population-level transmission dynamics are difficult to predict. This co-endemic malaria study from Guyana details important epidemiological contrasts between the species by coupling population genomics (1396 spatiotemporally matched parasite genomes, primarily from 2020-21) with sociodemographic analysis (nationwide patient census from 2019). We describe how P. falciparum forms large, interrelated subpopulations that sporadically expand but generally exhibit restrained dispersal, whereby spatial distance and patient travel statistics predict parasite identity-by-descent (IBD). Case bias towards working-age adults is also strongly pronounced. P. vivax exhibits 46% higher average nucleotide diversity (π) and 6.5x lower average IBD. It occupies a wider geographic range, without evidence for outbreak-like expansions, only microgeographic patterns of isolation-by-distance, and weaker case bias towards adults. Possible latency-relapse effects also manifest in various analyses. For example, 11.0% of patients diagnosed with P. vivax in Greater Georgetown report no recent travel to endemic zones, and P. vivax clones recur in 11 of 46 patients incidentally sampled twice during the study. Polyclonality rate is also 2.1x higher than in P. falciparum, does not trend positively with estimated incidence, and correlates uniquely to selected demographics. We discuss possible underlying mechanisms and implications for malaria control.

摘要

疟原虫恶性疟原虫和间日疟原虫在关键的生物学过程和相关的临床影响上有所不同,但对人群传播动态的影响却难以预测。这项来自圭亚那的地方性疟疾研究通过结合种群基因组学(1396 个时空匹配的寄生虫基因组,主要来自 2020-21 年)和社会人口分析(2019 年全国范围内的患者普查),详细描述了这两个物种之间的重要流行病学对比。我们描述了恶性疟原虫如何形成大的、相互关联的亚群,这些亚群偶尔会扩张,但通常表现出受限制的扩散,因此空间距离和患者旅行统计数据可以预测寄生虫的血缘关系(IBD)。成人病例的偏向也非常明显。间日疟原虫的平均核苷酸多样性(π)高出 46%,平均 IBD 低 6.5 倍。它占据了更广泛的地理范围,没有暴发样扩张的证据,只有隔离距离的微地理模式,以及对成人的病例偏向较弱。潜伏期复发效应也在各种分析中表现出来。例如,在大乔治敦地区被诊断为间日疟原虫的 11.0%的患者报告最近没有到流行区旅行,在研究期间两次偶然抽样的 46 名患者中有 11 名再次出现间日疟原虫克隆。多克隆率也比恶性疟原虫高 2.1 倍,与估计的发病率没有正相关关系,并且与特定的人口统计学因素相关。我们讨论了可能的潜在机制及其对疟疾控制的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/204a/11442626/5376d6062c01/41467_2024_52545_Fig1_HTML.jpg

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