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.
Highlights
Neisseria meningitidis is present in the nasopharynx of 10–35% of young adults in an asymptomatic ‘carriage’ state (Coureuil et al, 2012)
In order to determine whether the 11-fold expansion of the N. meningitidis MenW sequence type (ST)-11 clone among University of Nottingham (UoN) students was due to localized clusters and rapid genome evolution, we analyzed wholegenome sequencing (WGS) data for the 54 MenW isolates obtained from this crosssectional carriage study (Oldfield et al, 2018)
Analysis of 3,034 core genomic loci identified 603 gene alleles with 1–2 variant nucleotides. Genetic variability in these carriage isolates is similar to that seen in United Kingdom disease isolates from the same clone and time period
Summary
Neisseria meningitidis is present in the nasopharynx of 10–35% of young adults in an asymptomatic ‘carriage’ state (Coureuil et al, 2012). Invasive meningococcal disease (IMD) occurs when meningococci traverse the epithelial and endothelial barriers leading to septicaemia and cerebrospinal meningitis. IMD can be endemic, with rates of ∼1 cases/100,000 individuals, or epidemic, as occurs in sub-Saharan Africa (Caugant and Maiden, 2009). Starting in 2009, the United Kingdom was subject to consistent yearly increase in IMD due to hyper-virulent. MenW sequence type (ST) 11 strains (Ladhani et al, 2015). A sub-variant appeared in 2013 and rapidly became the dominant cause of MenW IMD. In 2015, combatting of these infections in the United Kingdom was initiated with provision of MenACWY conjugate vaccines to adolescents and first year university students (Campbell et al, 2015)
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