Institut Pasteur, National Reference center for meningococci and Haemophilus influenzae, F-75724 Paris, France.
Santé publique France, French National Public Health Agency, F-94415, Saint-Maurice, France.
J Infect. 2020 May;80(5):519-526. doi: 10.1016/j.jinf.2020.01.020. Epub 2020 Feb 4.
The epidemiology of invasive meningococcal disease (IMD) is continuously changing in incidence, age distribution and/or the expansion of new strains of Neisseria meningitidis. The epidemiology of IMD due to group W (IMDW) has changed recently at a global level with the emergence of isolates belonging to the clonal complex ST-11 (CC11) derived from the South America-UK strain. A more recent change has been detected in France with the emergence of a new genotype distinct from CC11 that we aimed to analyse.
Epidemiological and microbiological surveillance data in France were used in combination with whole genome sequencing (WGS) to detect emerging phenotypes and genotypes of IMD causing strains, and their susceptibility to immunity induced by the 4CMenB vaccine. Transgenic mice expressing the human transferrin were used to analyse the virulence of emerging strain isolates by direct comparison with CC11 isolates.
Our data showed a local increase of IMDW isolates in north France since 2013. The isolates belonged to ST-9316 and few were ST-11 isolates. WGS clustered ST-9316 isolates together and were distantly separated from the isolates of the clonal complex ST-11 (CC11). Unlike cases due to W/CC11 isolates, cases due to W/ST-9316 isolates were mostly observed amongst infants under the age of 1 year but with lower mortality compared to W/CC11 cases. Genomic comparison showed that the W/ST-9316, unlike W/CC11 isolates, lacked the hmbR gene encoding the haemoglobin receptor that is a virulence factor involved in the acquisition of iron from haemoglobin. W/ST-9316 further showed lower virulence in mice compared to W/CC11 isolates.
We report the emergence of a novel sequence type (ST-9316) mostly associated with serogroup W, and exhibiting a lower virulence and a distinct age specific incidence profile than W/CC11 isolates. Surveillance requires powerful approaches combining WGS and pathophysiological analysis to adapt control measures.
侵袭性脑膜炎奈瑟菌病（IMD）的流行病学在发病率、年龄分布和/或新脑膜炎奈瑟菌菌株的扩展方面不断变化。全球范围内，W 群（IMDW）脑膜炎奈瑟菌的流行病学最近发生了变化，出现了源自南美-英国菌株的克隆复合体 ST-11（CC11）的分离株。在法国，最近发现了一个新的基因型，与 CC11 不同，我们旨在对此进行分析。
利用法国的流行病学和微生物学监测数据，并结合全基因组测序（WGS），检测引起 IMD 的新型表型和基因型菌株的出现，并检测其对 4CMenB 疫苗诱导的免疫的敏感性。通过与 CC11 分离株的直接比较，使用表达人转铁蛋白的转基因小鼠分析新型分离株的毒力。
我们的数据显示，自 2013 年以来，法国北部 IMDW 分离株的局部发病率有所增加。这些分离株属于 ST-9316，少数属于 ST-11 分离株。WGS 将 ST-9316 分离株聚类在一起，并与克隆复合体 ST-11（CC11）的分离株分离较远。与 W/CC11 分离株引起的病例不同，W/ST-9316 分离株引起的病例主要发生在 1 岁以下的婴儿中，但与 W/CC11 病例相比，死亡率较低。基因组比较表明，与 W/CC11 分离株不同，W/ST-9316 分离株缺乏编码血红蛋白受体的 hmbR 基因，该基因是一种从血红蛋白中获取铁的毒力因子。与 W/CC11 分离株相比，W/ST-9316 分离株在小鼠中的毒力较低。
我们报告了一种新型序列类型（ST-9316）的出现，该类型主要与血清群 W 相关，其毒力和特定年龄的发病特征与 W/CC11 分离株不同。监测需要结合 WGS 和病理生理学分析的强大方法，以调整控制措施。
