Investigating the role of whole genome sequencing in syphilis epidemiology: an English case study
Investigating the role of whole genome sequencing in syphilis epidemiology: an English case study
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调查全基因组测序在梅毒流行病学中的作用：英国案例研究
DOI：
10.1101/2022.12.02.22283031
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Beale M
中科院分区：
文献类型：
--
作者：
Beale M
梅毒是由梅毒螺旋体（Treponemapallidumsubspecies pallidum）引起的性传播细菌感染，全球每年约有630万例梅毒病例。在过去的十年中，梅毒发病率在许多高收入国家急剧上升，包括英格兰，增长超过150%。虽然这种增加与同性恋，双性恋和其他与男性发生性关系的男性（GBMSM）的高风险性活动有关，但异性恋男性和女性的病例正在增加，现在每年都会看到先天性梅毒病例。GBMSM和异性恋者的性网络内和之间的传输动态还没有很好地understood.MethodsTo确定是否可以使用全基因组测序来识别离散的传输模式，我们将国家患者的人口统计，地理空间和行为元数据的wholeT。苍白球基因组序列先前从2012年至2018年期间从英格兰各地收集的237名患者样本中生成。在英国检测到的苍白球亚系占主导地位。这些占主导地位的亚系表现出不同的时空趋势与人口统计学或行为，这表明他们代表不同的性网络：亚系1被发现在整个英格兰和所有的患者群体，而亚系14主要发生在老年GBMSM和缺席从英格兰北部测序的样本。通过集中在英格兰的不同地区，我们能够区分一个本地的异性传播集群之间GBMSM.InterpretationThese研究结果表明，尽管非常密切的遗传关系之间的T。尽管在全球范围内对苍白球基因组进行了研究，但基因组学仍然可以用于确定流行病学随访的假定传播集群，因此在为公共卫生干预提供信息方面发挥作用。（#206194和108413/A/15/D），UKRI和NIHR（COV0335; MR/V027956/1，NIHR 200125），EDCTP（RIA2018D-249），和UKHSA。本研究之前的背景证据研究详细的基因组分析调查密螺旋体的流行病学和传播动力学由于临床标本中的低细菌载量和细菌培养的困难，苍白球是具有挑战性的。我们使用检索词“梅毒螺旋体”或“梅毒螺旋体”和“基因组”或“基因组”或“测序”检索PubMed，直到2022年8月9日，发现23项描述T全基因组测序的研究。pallidumsubspeciespallidum，其中两个使用全基因组遗传学来调查性网络流行病学，其中一个主要在澳大利亚的维多利亚进行的性网络的大型研究，其特征在于该环境中的两个主要循环亚系，以及具有不同性行为特征和网络之间潜在桥接的假定性传播网络。我们把国家监控数据和T联系起来。pallidumgenomes，并使用来自整个国家的样本，在欧洲环境（英格兰）中描述了梅毒的传播动力学。整合国家一级的社会人口，时空和基因组数据允许划定假定的性网络在国家和地区两级，并揭示了以前没有检测到的模式，使用流行病学或基因组数据单独。所有可用的证据的影响我们的研究结果是一致的，在澳大利亚的研究结果表明基因组...
BackgroundSyphilis is a sexually transmitted bacterial infection caused byTreponema pallidumsubspeciespallidum, with approximately 6.3 million annual cases globally. Over the last decade, syphilis rates have risen dramatically in many high-income countries, including in England, which has seen a greater than 150% increase. Although this increase is known to be associated with high risk sexual activity in gay, bisexual and other men who have sex with men (GBMSM), cases are rising in heterosexual men and women, and congenital syphilis cases are now seen annually. The transmission dynamics within and between sexual networks of GBMSM and heterosexuals are not well understood.MethodsTo determine if whole genome sequencing could be used to identify discrete patterns of transmission, we linked national patient demographic, geospatial and behavioural metadata to wholeT. pallidumgenome sequences previously generated from 237 patient samples collected from across England between 2012 and 2018.FindingsPhylogenomic analysis and clustering revealed two of the eightT. pallidumsublineages detected in England dominated. These dominant sublineages exhibited different spatiotemporal trends linked to demography or behaviour, suggesting they represent different sexual networks: sublineage 1 was found throughout England and across all patient groups, whereas sublineage 14 occurred predominantly in older GBMSM and was absent from samples sequenced from the North of England. By focussing on different regions of England we were able to distinguish a local heterosexual transmission cluster from a background of transmission amongst GBMSM.InterpretationThese findings demonstrate that despite extremely close genetic relationships betweenT. pallidumgenomes globally, genomics can still be used to identify putative transmission clusters for epidemiological follow-up, and therefore has a role to play in informing public health interventions.FundingWellcome funding to the Sanger Institute (#206194 and 108413/A/15/D), UKRI and NIHR (COV0335; MR/V027956/1, NIHR200125), the EDCTP (RIA2018D-249), and UKHSA.Research in ContextEvidence before this studyDetailed phylogenomic analyses investigating the epidemiology and transmission dynamics ofTreponema pallidumare challenging due to low bacterial loads in clinical specimens, and difficulty in culturing the bacteria. We searched PubMed until August 9th2022 using the search terms “Syphilis” or “Treponema pallidum” and “genomic” or “genome(s)” or “sequencing”, finding 23 studies describing whole genome sequencing ofT. pallidumsubspeciespallidum, of which two used whole genome phylogenies to investigate sexual network epidemiology, with one large study of sexual networks conducted primarily in Victoria, Australia which characterised two major circulating sublineages in that setting, as well as putative sexual transmission networks with distinct sexual behavioural characteristics and potential bridging between networks.Added value of this studyIn this study, we linked national surveillance data toT. pallidumgenomes, and characterised the transmission dynamics of syphilis using samples from across a whole country, in a European setting (England). Integration of national-level sociodemographic, spatiotemporal and genomic data allowed the delineation of putative sexual networks at both the national and region levels, and revealed patterns not previously detected using epidemiological or genomic data alone.Implications of all the available evidenceOur findings are consistent with findings in Australia that demonstrate genomics …
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影响因子：
3.1
作者：
Chesson, HW;Dee, TS;Aral, SO
通讯作者：
Aral, SO
DOI：
10.1086/656533
发表时间：
2010-11-01
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Marra C;Sahi S;Tantalo L;Godornes C;Reid T;Behets F;Rompalo A;Klausner JD;Yin Y;Mulcahy F;Golden MR;Centurion-Lara A;Lukehart SA
通讯作者：
Lukehart SA
影响因子：
1.4
作者：
P. Acheson;M. McGivern;P. Frank;E. Kunonga;I. Simms;S. Tayal;E. Thody;Alison Waldram;J. Kibirige
通讯作者：
J. Kibirige
传染性梅毒。
DOI：
--
发表时间：
1994
期刊：
Seminars in Dermatology
影响因子：
--
作者：
Harry Pariser
通讯作者：
Harry Pariser
影响因子：
28.3
作者：
Arora, Natasha;Schuenemann, Verena J.;Bagheri, Homayoun C.
通讯作者：
Bagheri, Homayoun C.