Reconstruction of Dispersal Patterns of Hypervirulent Meningococcal Strains of Serogroup C:cc11 by Phylogenomic Time Trees

Abstract

Neisseria meningitidis is one of the few commensal bacteria that can even cause large epidemics of invasive meningococcal disease (IMD). N. meningitis serogroup C belonging to the hypervirulent clonal complex 11 (cc11) represents an important public health threat worldwide. We reconstructed the dispersal patterns of hypervirulent meningococcal strains of serogroup C:cc11 by phylogenomic time trees. In particular, we focused the attention on the epidemic dynamics of C:P1.5.1,10-8:F3-6;ST-11(cc11) meningococci causing outbreaks, as occurred in the Tuscany region, Italy, in 2015 to 2016. A phylogeographic analysis was performed through a Bayesian method on 103 Italian and 208 foreign meningococcal genomes. The C:P1.5.1,10-8:F3-6;ST-11(cc11) genotype dated back to 1995 (1992 to 1998) in the United Kingdom. Two main clades of the hypervirulent genotype were identified in Italy. The Tuscany outbreak isolates were included in different clusters in a specific subclade which originated in the United Kingdom around 2011 and was introduced in Tuscany in 2013 to 2014. In this work, phylogeographic analysis allowed the identification of multiple introductions of these strains in several European countries and connections with extra-European areas. Whole-genome sequencing (WGS) combined with phylogeography enables us to track the dissemination of meningococci and their transmission. The C:P1.5.1,10-8:F3-6;ST-11(cc11) genotype analysis revealed how a hypervirulent strain may be introduced in previously naïve areas, causing a large and long-lasting outbreak.

Antimicrobial susceptibility profiles and genotyping of Neisseria meningitidis of serogroup C, Italy, 2000–2020

“…The study suggested a possible first introduction in our country between 2007 and 2011, where this variant was spreading among several European countries ( Lo Presti et al, 2019 ). The second possible introduction could be reconducted between 2013 and 2014 ( Lo Presti et al, 2019 ). It is likely that this strain has spread in Italy and remains stable as suggested by genomic and phylogenetic analysis, here reported.…”

“…Based on our previously study on MenC strains circulating in Italy ( Lo Presti et al, 2019 ), using a Bayesian method to reconstruct the epidemiological dynamics, the C:P1.5-1,10-8:F3-6:ST-11(cc11) genotype segregated into two distinct clades, both apparently originating from UK, but in a different time periods. The study suggested a possible first introduction in our country between 2007 and 2011, where this variant was spreading among several European countries ( Lo Presti et al, 2019 ). The second possible introduction could be reconducted between 2013 and 2014 ( Lo Presti et al, 2019 ).…”

Whole genome analysis of Neisseria meningitidis isolates from invasive meningococcal disease collected in the Czech Republic over 28 years (1993–2020)

“…the predominance of the hypervirulent clonal complex cc11 in MenC isolates from IMD, has been observed in a number of studies [31][32][33]. Phylogenetic analyses have shown that the hypervirulent strain C, cc11 (UK-strain) has spread in a number of European countries [34]. A study from the Republic of Ireland over a 19-year period (1996-2015) also demonstrated the homogeneity of MenC isolates from IMD, with a prevalence of cc8 and cc11 [30].…”

Improved Temporal Trends of Vaccination Coverage Rates in Childhood after the Mandatory Vaccination Act, Italy 2014–2019

“…As for N. meningitidis, there was a low incidence of invasive meningococcal diseases in Italy in 2017-2019, fluctuating around 0.3 cases/100,000 inhabitants, which may have led to a decrease in the attention of the public. Anyway, outbreaks due to N. meningitidis serogroup C occurred in Central and North Italy during 2015-2016 and 2019-2020, respectively [17,18].…”