Insights on Population Structure and Within-Host Genetic Changes among Meningococcal Carriage Isolates from U.S. Universities

Abstract

In 2015 and 2016, meningococcal carriage evaluations were conducted at two universities in the United States following mass vaccination campaigns in response to Neisseria meningitidis 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 N. meningitidis carriage of a strain with the same sequence type (ST) and CC across rounds, 44.3% only carried N. meningitidis in one round, and 5.4% acquired a new N. meningitidis 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. IMPORTANCE U.S. university students are at a higher risk of invasive meningococcal disease than the general population. The responsible pathogen, Neisseria meningitidis, 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.

The genomic epidemiology of Neisseria meningitidis carriage from a randomised controlled trial of 4CMenB vaccination in an asymptomatic adolescent population

“…Capsule switching in meningococci, along with extended recombination events and horizontal gene transfer, has lent support to the hypothesis that multiple meningococcal variants may be carried simultaneously in asymptomatic carriers. 27 , 28 Given that a single colony was chosen for sequencing from the culture plates, this study could not consider strain heterogeneity within an individual; however, our data demonstrated genomic heterogeneity at the population level. Specifically, genogroup B isolates from our study were phylogenetically diverse despite having the same capsular biosynthesis genes.…”

Prevalence and Characteristics of Carriage of Neisseria meningitidis Among Young Israeli Adults

“…The dominant CCs among genogroup B isolates were CC32 and CC41/44, while CC23 accounted for 97% of genogroup Y isolates. These CCs were previously found to be hyperinvasive [ 23 ]. Interestingly, in a national survey of IMD, CC32, CC23, and CC41/44 were reported to cause >61% of IMD cases in Israel between 1998 and 2017 [ 7 ].…”

“…Several CCs are considered hyperinvasive lineages, such as CC23, CC32, and CC41/44 and CC11 [ 20 , 22 ]. CCs found among asymptomatic carriers are more diverse, and carried isolates are commonly associated with STs that rarely cause invasive disease [ 20 , 23 ].…”

“…For example, WGS was an essential tool in elucidating the epidemiology of serogroup W ST11 strains after the 2000 Hajj pilgrim outbreak [ 20 , 24 ]. Moreover, the use of genomic epidemiology provides insight into the carriage dynamics among populations and the link between host characteristics and carriage, thus shedding light on the risk of IMD among carriers [ 23 ].…”