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基因监测显示,圣多美和普林西比存在低水平且持续的疟疾传播,并伴有克隆取代现象。

Genetic surveillance reveals low, sustained malaria transmission with clonal replacement in Sao Tome and Principe.

作者信息

Chen Ying-An, Ng Peng-Yin, Garcia Daniel, Elliot Aaron, Palmer Brian, Assunção Carvalho Ronalg Mendes Costa d', Tseng Lien-Fen, Lee Cheng-Sheng, Tsai Kun-Hsien, Greenhouse Bryan, Chang Hsiao-Han

机构信息

EPPIcenter Research Program, Division of HIV, Infectious Diseases and Global Medicine, Department of Medicine, University of California, San Francisco, United States.

Institute of Bioinformatics and Structural Biology, College of Life Sciences and Medicine, National Tsing Hua University, Hsinchu, Taiwan.

出版信息

medRxiv. 2024 Jul 16:2024.07.15.24309968. doi: 10.1101/2024.07.15.24309968.

DOI:10.1101/2024.07.15.24309968
PMID:39072035
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11275696/
Abstract

Despite efforts to eliminate malaria in Sao Tome and Principe (STP), cases have recently increased. Understanding residual transmission structure is crucial for developing effective elimination strategies. This study collected surveillance data and generated amplicon sequencing data from 980 samples between 2010 and 2016 to examine the genetic structure of the parasite population. The mean multiplicity of infection (MOI) was 1.3, with 11% polyclonal infections, indicating low transmission intensity. Temporal trends of these genetic metrics did not align with incidence rates, suggesting that changes in genetic metrics may not straightforwardly reflect changes in transmission intensity, particularly in low transmission settings where genetic drift and importation have a substantial impact. While 88% of samples were genetically linked, continuous turnover in genetic clusters and changes in drug-resistance haplotypes were observed. Principal component analysis revealed some STP samples were genetically similar to those from Central and West Africa, indicating possible importation. These findings highlight the need to prioritize several interventions such as targeted interventions against transmission hotspots, reactive case detection, and strategies to reduce the introduction of new parasites into this island nation as it approaches elimination. This study also serves as a case study for implementing genetic surveillance in a low transmission setting.

摘要

尽管圣多美和普林西比(STP)已努力消除疟疾,但近期病例数仍有所增加。了解残余传播结构对于制定有效的消除策略至关重要。本研究收集了监测数据,并生成了2010年至2016年间980份样本的扩增子测序数据,以研究疟原虫种群的遗传结构。平均感染复数(MOI)为1.3,11%为多克隆感染,表明传播强度较低。这些遗传指标的时间趋势与发病率不一致,这表明遗传指标的变化可能无法直接反映传播强度的变化,特别是在遗传漂变和输入影响较大的低传播环境中。虽然88%的样本存在遗传联系,但观察到遗传簇的持续更替和耐药单倍型的变化。主成分分析显示,一些圣多美和普林西比的样本在基因上与中非和西非的样本相似,表明可能存在输入情况。这些发现凸显了需要优先采取多种干预措施,如针对传播热点的靶向干预、反应性病例检测,以及在这个岛国接近消除疟疾时减少新疟原虫引入的策略。本研究还作为在低传播环境中实施基因监测的案例研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e09/11275696/cb1a569ea306/nihpp-2024.07.15.24309968v1-f0006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e09/11275696/7cf5c277b1af/nihpp-2024.07.15.24309968v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e09/11275696/bbc006c49595/nihpp-2024.07.15.24309968v1-f0002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e09/11275696/9766e760eb21/nihpp-2024.07.15.24309968v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e09/11275696/6e0d0c4ea0c1/nihpp-2024.07.15.24309968v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e09/11275696/cb1a569ea306/nihpp-2024.07.15.24309968v1-f0006.jpg

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MOIRE: a software package for the estimation of allele frequencies and effective multiplicity of infection from polyallelic data.Moire:用于从多等位基因数据中估计等位基因频率和有效多重感染率的软件包。
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Strong isolation by distance and evidence of population microstructure reflect ongoing transmission in Zanzibar.强的距离隔离和种群微结构的证据反映了在桑给巴尔岛持续的传播。
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