Holmes Jonathan C, Green Luke R, Oldfield Neil J, Turner David P J, Bayliss Christopher D
Department of Genetics and Genome Biology, University of Leicester, Leicester, United Kingdom.
School of Life Sciences, University of Nottingham, Nottingham, United Kingdom.
Front Genet. 2020 Dec 7;11:579411. doi: 10.3389/fgene.2020.579411. eCollection 2020.
Rapid transmission, a critical contributory factor in outbreaks of invasive meningococcal disease, requires naïve populations of sufficient size and intermingling. We examined genomic variability and transmission dynamics in a student population subject to an 11-fold increase in carriage of a hypervirulent serogroup W ST-11 clone. Phylogenetic clusters, mutation and recombination rates were derived by bioinformatic analyses of whole-genome sequencing data. Transmission dynamics were determined by combining observed carriage rates, cluster sizes and distributions with simple SIS models. Between 9 and 15 genetically-distinct clusters were detected and associated with seven residential halls. Clusters had low mutation accumulation rates and infrequent recombination events. Modeling indicated that effective contacts decreased from 10 to 2 per day between the start and mid-point of the university term. Transmission rates fluctuated between 1 and 4% while the R(t) for carriage decreased from an initial rate of 47 to 1. Decreases in transmission values correlated with a rise in vaccine-induced immunity. Observed carriage dynamics could be mimicked by populations containing 20% of super spreaders with 2.3-fold higher effective contact rates. We conclude that spread of this hypervirulent ST-11 meningococcal clone depends on the levels of effective contacts and immunity rather than genomic variability. Additionally, we propose that super-spreaders enhance meningococcal transmission and that a 70% MenACWY immunization level is sufficient to retard, but not fully prevent, meningococcal spread in close-contact populations.
快速传播是侵袭性脑膜炎球菌病暴发的一个关键促成因素,需要有足够规模的易感人群以及人群间的相互接触。我们研究了一个学生群体中的基因组变异性和传播动态,该群体中一个高毒力血清群W ST-11克隆的携带率增加了11倍。通过对全基因组测序数据进行生物信息学分析得出系统发育簇、突变率和重组率。通过将观察到的携带率、簇大小和分布与简单的SIS模型相结合来确定传播动态。检测到9至15个遗传上不同的簇,并与七个宿舍楼相关联。这些簇的突变积累率较低,重组事件很少。模型显示,在大学学期开始到中期之间,有效接触从每天10次降至2次。传播率在1%至4%之间波动,而携带的R(t)从初始的47降至1。传播值的下降与疫苗诱导的免疫力上升相关。观察到的携带动态可以由含有20%超级传播者的人群模拟,这些超级传播者的有效接触率高出2.3倍。我们得出结论,这种高毒力ST-11脑膜炎球菌克隆的传播取决于有效接触和免疫水平,而非基因组变异性。此外,我们提出超级传播者会增强脑膜炎球菌的传播,并且70%的ACWY脑膜炎球菌疫苗接种水平足以延缓但不能完全预防脑膜炎球菌在密切接触人群中的传播。