Abstract
A carriage study was undertaken (n = 112) to ascertain the prevalence of Neisseria spp. following the eighth case of invasive meningococcal disease in young children (5 to 46 months) and members of a large extended indigenous ethnic minority Traveller family (n = 123), typically associated with high-occupancy living conditions. Nested multilocus sequence typing (MLST) was employed for case specimen extracts. Isolates were genome sequenced and then were assembled de novo and deposited into the Bacterial Isolate Genome Sequencing Database (BIGSdb). This facilitated an expanded MLST approach utilizing large numbers of loci for isolate characterization and discrimination. A rare sequence type, ST-6697, predominated in disease specimens and isolates that were carried (n = 8/14), persisting for at least 44 months, likely driven by the high population density of houses (n = 67/112) and trailers (n = 45/112). Carriage for Neisseria meningitidis (P < 0.05) and Neisseria lactamica (P < 0.002) (2-sided Fisher's exact test) was more likely in the smaller, more densely populated trailers. Meningococcal carriage was highest in 24- to 39-year-olds (45%, n = 9/20). Evidence of horizontal gene transfer (HGT) was observed in four individuals cocolonized by Neisseria lactamica and Neisseria meningitidis. One HGT event resulted in the acquisition of 26 consecutive N. lactamica alleles. This study demonstrates how housing density can drive meningococcal transmission and carriage, which likely facilitated the persistence of ST-6697 and prolonged the outbreak. Whole-genome MLST effectively distinguished between highly similar outbreak strain isolates, including those isolated from person-to-person transmission, and also highlighted how a few HGT events can distort the true phylogenetic relationship between highly similar clonal isolates.
Highlights
Neisseria species, most of which reside in the nasopharynx, are considered harmless human commensal bacteria with two important exceptions: Neisseria gonorrhoeae, which inhabits the urogenital tract, and Neisseria meningitidis, a commensal bacterium which very rarely invades the nasopharyngeal epithelia and causes life-threatening septicemia and less frequently meningitis
Real-time PCR confirmed the presence of both meningococcal DNA and serogroup B capsular polysaccharide synthesis genes in all case-associated specimens received in the Irish Meningococcal and Meningitis Reference Laboratory (IMMRL)
A comparison of the ST6697 strains from this outbreak and the cc41/44 invasive isolates in the Meningitis Research Foundation Meningococcus Genome Library (MRF-MGL) revealed the rare nature of this sequence types (STs), where all outbreak-related isolates clustered together and branched off a clade composed of ST154 or ST154 variants (Fig. 1)
Summary
Most of which reside in the nasopharynx, are considered harmless human commensal bacteria with two important exceptions: Neisseria gonorrhoeae, which inhabits the urogenital tract, and Neisseria meningitidis, a commensal bacterium which very rarely invades the nasopharyngeal epithelia and causes life-threatening septicemia and less frequently meningitis. Lineages consist of many highly similar strains, or sequence types (STs), which arise as a consequence of both clonal decent and the high rates of horizontal gene transfer (HGT) observed in meningococci [6, 45]. Endemic strain disease incidence can be controlled by vaccines targeting the polysaccharide that defines the meningococcal serogroup, with the important exception of serogroup B, which is poorly immunogenic in humans [12]. Meningococcal outbreaks are less frequently observed than instances of endemic sporadic disease and tend to occur in environments where population densities are high, facilitating increases in both transmission rates and carriage and increasing the likelihood of persistent carriage
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
