Rapid Transmission of a Hyper-Virulent Meningococcal Clone Due to High Effective Contact Numbers and Super Spreaders

Abstract

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 Neisseria meningitidis 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.

Vaccine Impact and Effectiveness of Meningococcal Serogroup ACWY Conjugate Vaccine Implementation in the Netherlands: A Nationwide Surveillance Study

“…It should, however, be taken into account that this study investigated a close-contact and thus high-risk setting. Also, a recent modeling study using the same carriage data showed that vaccination led to a carriage plateau, and the authors predicted that a higher coverage rate would have produced further reduction in carriage levels [ 31 ].…”

Using Neisseria meningitidis genomic diversity to inform outbreak strain identification

“…meningitidis isolates may arise from the higher rates of recombination and phase variation in the meningococcal genome [ 29 ], or from a prolonged divergence time if the N . meningitidis strain spreads among asymptomatic carriers prior to the outbreak [ 8 ].…”

“…Outbreaks involving other bacterial pathogens often exhibit fewer differences among isolates (24 SNPs for Staphylococcus aureus [28], 7 cgMLST alleles for Listeria monocytogenes [14]). The greater divergence among N. meningitidis isolates may arise from the higher rates of recombination and phase variation in the meningococcal genome [29], or from a prolonged divergence time if the N. meningitidis strain spreads among asymptomatic carriers prior to the outbreak [8].…”

“…Isolates collected during an outbreak are often clonal, with little genomic diversity, reflecting recent common ancestry [6][7][8]. Pulsed field gel electrophoresis (PFGE) was conventionally used to differentiate among isolates from outbreaks and other cases based on a quantitative similarity threshold [9].…”

“…PFGE is supplanted by whole genome sequence analysis, which provides high-resolution quantification of genome distances [10][11][12]. Genome sequencing also allows phylogenetic delineation of outbreak strains, based on whether the outbreak isolates form an outbreak-specific clade that includes their most recent common ancestor but excludes other N. meningitidis that were circulating prior to the outbreak; multiple clades indicate multiple introductions of meningococci into the population, with each clade accumulating diversity as it spreads among asymptomatic carriers [8]. The combination of phylogenetic topology with genome distance metrics has identified outbreak strains in multiple bacterial species, including Listeria spp.…”