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法国 W 群侵袭性脑膜炎奈瑟菌分离株中的克隆替换和扩增。

Clonal replacement and expansion among invasive meningococcal isolates of serogroup W in France.

机构信息

Institut Pasteur, National Reference Centre for Meningococci and Invasive Bacterial Infections Unit, F-75724, Paris, France.

Sante publique France, French National Public Health Agency, F-94415, Saint-Maurice, France.

出版信息

J Infect. 2018 Feb;76(2):149-158. doi: 10.1016/j.jinf.2017.10.015. Epub 2017 Nov 10.

Abstract

BACKGROUND

Neisseria meningitidis group W (NmW) belonging to the clonal complex ST-11 (NmW/cc11) spread in Europe and in France in 2000 and declined thereafter. In France, invasive meningococcal disease (IMD) due to NmW increased again in 2012 and thereafter since 2015. Several sub-lineages of NmW/cc11 are circulating worldwide with successive epidemic waves. We aimed to describe recent epidemiological trends of NmW in France and to explore the microbiological and epidemiological characteristics associated with different NmW/cc11 sub-lineages.

METHODS

The epidemiology of NmW was described based on data collected through mandatory notification of IMD and strain typing data for culture-confirmed and PCR-confirmed cases for the period 2000-2016. All culture-confirmed cases due to NmW from the period 2010-2016 were characterised by whole genome sequencing (WGS). A detailed epidemiological analysis was performed for culture-confirmed cases on the basis of WGS data.

FINDINGS

During the period 2010-2016, genotyping was obtained for 148 cases including all the 132 culture-confirmed cases, among which 127 were matched with epidemiological data, and 16 PCR-confirmed cases (out of a total of 47 PCR-confirmed cases). An increase in IMD was observed in 2012 and was linked to isolates belonging to the "Anglo-French-Hajj" sub-lineage. These isolates have decreased significantly since 2013 and have been replaced by NmW/cc11 isolates related to the "South American - UK" sub-lineage which caused a marked increase in the number of cases of NmW in 2016. In this sub-lineage, the "original UK strain" was first detected in 2012 and increased thereafter, followed by the recently described "UK 2013-strain". Isolates related to the "South American-UK" sub-lineage represented 45% of all NmW cultured isolates from the whole period 2010-2016 but were the most frequent isolates in 2016, representing 76% of the total NmW typed isolates and 94% of the typed NmW/cc11 isolates. A changing pattern in the epidemiology of NmW has been observed in 2015-2016 in relation to the spread of the "UK 2013-strain" with a sharp increase in the number of cases among persons aged 15 years and over and a high case fatality rate (CFR). Among cases due to the "UK 2013-strain", 94% of cases were aged 15 years and over and the CFR was 28%.

INTERPRETATION

Our data suggest a recent clonal replacement among NmW/cc11 isolates with the expansion of the "South American-UK" sub-lineage in France and particularly the "UK 2013-strain" which was predominant in 2015 and 2016. A shift in the age-distribution of IMD due to NmW to older ages and the high CFR are consistent with the expansion of a new virulent clone in a naive population. These data may have an impact on tailoring vaccination strategies against NmW.

摘要

背景

奈瑟菌属脑膜炎球菌组 W(NmW)属于克隆复合体 ST-11(NmW/cc11),在欧洲和法国传播,2000 年后有所减少。此后,法国侵袭性脑膜炎球菌病(IMD)再次增加,2012 年以后一直持续增加。全球范围内有几个 NmW/cc11 的亚谱系在传播,并相继出现了流行波。我们旨在描述法国近期 NmW 的流行病学趋势,并探索与不同 NmW/cc11 亚谱系相关的微生物学和流行病学特征。

方法

通过强制性报告 IMD 和培养确诊及 PCR 确诊病例的菌株分型数据,描述了 NmW 的流行病学情况。2010-2016 年期间所有培养确诊的 NmW 病例均进行全基因组测序(WGS)。根据 WGS 数据对培养确诊病例进行了详细的流行病学分析。

结果

2010-2016 年期间,共对 148 例病例进行了基因分型,其中包括所有 132 例培养确诊病例,其中 127 例与流行病学数据相匹配,16 例为 PCR 确诊病例(共 47 例 PCR 确诊病例)。2012 年 IMD 增加,与属于“英法-朝觐”亚谱系的分离株有关。自 2013 年以来,这些分离株的数量显著减少,取而代之的是与“南美-英国”亚谱系相关的 NmW/cc11 分离株,2016 年 NmW 病例数明显增加。在这个亚谱系中,首先检测到“原始英国株”,随后在 2012 年增加,随后是最近描述的“英国 2013 株”。2010-2016 年期间,所有培养的 NmW 分离株中,与“南美-英国”亚谱系相关的分离株占 45%,但在 2016 年是最常见的分离株,占 NmW 总分型分离株的 76%,占 NmW/cc11 分型分离株的 94%。2015-2016 年,NmW 的流行病学模式发生了变化,与“英国 2013 株”的传播有关,15 岁及以上人群的病例数急剧增加,病死率(CFR)较高。在“英国 2013 株”引起的病例中,94%的病例年龄在 15 岁及以上,CFR 为 28%。

结论

我们的数据表明,NmW/cc11 分离株最近发生了克隆替代,法国“南美-英国”亚谱系特别是“英国 2013 株”的扩张,2015 年和 2016 年占据主导地位。NmW 引起的 IMD 年龄分布向老年转移,CFR 较高,这与新的毒力克隆在无免疫力人群中的扩展一致。这些数据可能对调整针对 NmW 的疫苗接种策略产生影响。

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