IHRC Inc., Atlanta, Georgia, USA.
CDC Foundation, Atlanta, Georgia, USA.
mSphere. 2020 Apr 8;5(2):e00197-20. doi: 10.1128/mSphere.00197-20.
In 2015 and 2016, meningococcal carriage evaluations were conducted at two universities in the United States following mass vaccination campaigns in response to serogroup B (NmB) disease outbreaks. A simultaneous carriage evaluation was also conducted at a university near one of the outbreaks, where no NmB cases were reported and no mass vaccination occurred. A total of ten cross-sectional carriage evaluation rounds were conducted, resulting in 1,514 meningococcal carriage isolates collected from 7,001 unique participants; 1,587 individuals were swabbed at multiple time points (repeat participants). All isolates underwent whole-genome sequencing. The most frequently observed clonal complexes (CC) were CC198 (27.3%), followed by CC1157 (17.4%), CC41/44 (9.8%), CC35 (7.4%), and CC32 (5.6%). Phylogenetic analysis identified carriage isolates that were highly similar to the NmB outbreak strains; comparative genomics between these outbreak and carriage isolates revealed genetic changes in virulence genes. Among repeat participants, 348 individuals carried meningococcal bacteria during at least one carriage evaluation round; 50.3% retained carriage of a strain with the same sequence type (ST) and CC across rounds, 44.3% only carried in one round, and 5.4% acquired a new strain between rounds. Recombination, point mutations, deletions, and simple sequence repeats were the most frequent genetic mechanisms found in isolates collected from hosts carrying a strain of the same ST and CC across rounds. Our findings provide insight on the dynamics of meningococcal carriage among a population that is at higher risk for invasive meningococcal disease than the general population. U.S. university students are at a higher risk of invasive meningococcal disease than the general population. The responsible pathogen, , can be carried asymptomatically in the oropharynx; the dynamics of meningococcal carriage and the genetic features that distinguish carriage versus disease states are not completely understood. Through our analyses, we aimed to provide data to address these topics. We whole-genome sequenced 1,514 meningococcal carriage isolates from individuals at three U.S. universities, two of which underwent mass vaccination campaigns following recent meningococcal outbreaks. We describe the within-host genetic changes among individuals carrying a strain with the same molecular type over time, the primary strains being carried in this population, and the genetic differences between closely related outbreak and carriage strains. Our results provide detailed information on the dynamics of meningococcal carriage and the genetic differences in carriage and outbreak strains, which can inform future efforts to reduce the incidence of invasive meningococcal disease.
2015 年和 2016 年，在美国两所大学针对 B 群（NmB）疾病爆发开展大规模疫苗接种活动后，进行了脑膜炎球菌带菌评估。在其中一个爆发点附近的一所大学也同时进行了带菌评估，该大学没有报告 NmB 病例，也没有进行大规模疫苗接种。共进行了十轮横断面带菌评估，从 7001 名独特参与者中收集了 1514 株脑膜炎球菌带菌分离株；1587 人在多个时间点接受了拭子检测（重复参与者）。所有分离株均进行了全基因组测序。最常观察到的克隆复合体（CC）是 CC198（27.3%），其次是 CC1157（17.4%）、CC41/44（9.8%）、CC35（7.4%）和 CC32（5.6%）。系统发育分析确定了与 NmB 爆发菌株高度相似的带菌分离株；对这些爆发和带菌分离株进行比较基因组学分析，揭示了毒力基因的遗传变化。在重复参与者中，348 人在至少一轮带菌评估中携带脑膜炎球菌细菌；50.3%的人在各轮中保留了相同序列型（ST）和 CC 的带菌，44.3%的人仅在一轮中携带，5.4%的人在各轮之间获得了新的菌株。重组、点突变、缺失和简单重复序列是在各轮中携带相同 ST 和 CC 的宿主中分离出的菌株中最常见的遗传机制。我们的研究结果提供了有关在比普通人群更容易发生侵袭性脑膜炎球菌病的人群中脑膜炎球菌带菌动态的见解。美国大学生比普通人群更容易发生侵袭性脑膜炎球菌病。病原体 ，可无症状地携带在鼻咽部；脑膜炎球菌带菌的动态以及区分带菌与疾病状态的遗传特征尚不完全清楚。通过我们的分析，我们旨在提供数据来解决这些问题。我们对来自美国三所大学的 1514 名脑膜炎球菌带菌者的分离株进行了全基因组测序，其中两所大学在最近的脑膜炎球菌爆发后进行了大规模疫苗接种活动。我们描述了随时间推移，同一分子型菌株在个体中携带的遗传变化，该人群主要携带的菌株，以及密切相关的爆发和带菌菌株之间的遗传差异。我们的研究结果提供了关于脑膜炎球菌带菌动态以及带菌和爆发菌株遗传差异的详细信息，这可为减少侵袭性脑膜炎球菌病的发生提供信息。
