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东非恶性疟原虫种群动态及肯尼亚-乌干达边境的基因组监测。

Plasmodium falciparum population dynamics in East Africa and genomic surveillance along the Kenya-Uganda border.

机构信息

Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.

School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan.

出版信息

Sci Rep. 2024 Aug 5;14(1):18051. doi: 10.1038/s41598-024-67623-4.

Abstract

East African countries accounted for ~ 10% of all malaria prevalence worldwide in 2022, with an estimated 23.8 million cases and > 53,000 deaths. Despite recent increases in malaria incidence, high-resolution genome-wide analyses of Plasmodium parasite populations are sparse in Kenya, Tanzania, and Uganda. The Kenyan-Ugandan border region is a particular concern, with Uganda confirming the emergence and spread of artemisinin resistant P. falciparum parasites. To establish genomic surveillance along the Kenyan-Ugandan border and analyse P. falciparum population dynamics within East Africa, we generated whole-genome sequencing (WGS) data for 38 parasites from Bungoma, Western Kenya. These sequences were integrated into a genomic analysis of available East African isolate data (n = 599) and revealed parasite subpopulations with distinct genetic structure and diverse ancestral origins. Ancestral admixture analysis of these subpopulations alongside isolates from across Africa (n = 365) suggested potential independent ancestral populations from other major African populations. Within isolates from Western Kenya, the prevalence of biomarkers associated with chloroquine resistance (e.g. Pfcrt K76T) were significantly reduced compared to wider East African populations and a single isolate contained the PfK13 V568I variant, potentially linked to reduced susceptibility to artemisinin. Overall, our work provides baseline WGS data and analysis for future malaria genomic surveillance in the region.

摘要

东非国家在 2022 年占全球疟疾流行率的约 10%,估计有 2380 万例病例和超过 5.3 万人死亡。尽管疟疾发病率最近有所上升,但肯尼亚、坦桑尼亚和乌干达对疟原虫种群进行高分辨率全基因组分析的情况仍然很少。肯尼亚-乌干达边境地区尤其令人担忧,因为乌干达已确认出现并传播了对青蒿素耐药的恶性疟原虫寄生虫。为了在肯尼亚-乌干达边境建立基因组监测,并分析东非内部的恶性疟原虫种群动态,我们对来自肯尼亚西部邦戈马的 38 个寄生虫进行了全基因组测序(WGS)。这些序列被整合到对东非现有分离株数据(n=599)的基因组分析中,揭示了具有不同遗传结构和不同祖先起源的寄生虫亚群。对这些亚群与来自非洲各地的分离株(n=365)进行的祖先混合分析表明,它们可能来自其他主要非洲人群的独立祖先群体。在来自肯尼亚西部的分离株中,与氯喹耐药相关的生物标志物(例如 Pfcrt K76T)的流行率与更广泛的东非人群相比显著降低,并且单个分离株含有 PfK13 V568I 变异体,可能与对青蒿素的敏感性降低有关。总体而言,我们的工作为该地区未来的疟疾基因组监测提供了基线 WGS 数据和分析。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b01/11300580/7f1f4321d9cc/41598_2024_67623_Fig1_HTML.jpg

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