title: Resolution of a Protracted Serogroup B Meningococcal Outbreak with Whole-Genome Sequencing Shows Interspecies Genetic Transfer.
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.
authors.affiliation: Irish Meningitis and Sepsis Reference Laboratory, Temple Street Children's University Hospital, Dublin, Republic of Ireland robert.mulhall@cuh.ie.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Mulhall
authors.affiliation: Department of Zoology, University of Oxford, Oxford, England, United Kingdom.
authors.forename: Carina
authors.initials: C
authors.lastname: Brehony
authors.affiliation: Department of Public Health, HSE East, Dr Steevens' Hospital, Dublin, Republic of Ireland.
authors.forename: Lois
authors.initials: L
authors.lastname: O'Connor
authors.affiliation: Irish Meningitis and Sepsis Reference Laboratory, Temple Street Children's University Hospital, Dublin, Republic of Ireland.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Meyler
authors.affiliation: Department of Zoology, University of Oxford, Oxford, England, United Kingdom.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Jolley
authors.affiliation: Department of Zoology, University of Oxford, Oxford, England, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Bray
authors.affiliation: Irish Meningitis and Sepsis Reference Laboratory, Temple Street Children's University Hospital, Dublin, Republic of Ireland.
authors.forename: Desiree
authors.initials: D
authors.lastname: Bennett
authors.affiliation: Department of Zoology, University of Oxford, Oxford, England, United Kingdom.
authors.forename: Martin C J
authors.initials: MC
authors.lastname: Maiden
authors.affiliation: Irish Meningitis and Sepsis Reference Laboratory, Temple Street Children's University Hospital, Dublin, Republic of Ireland.
authors.forename: Robert
authors.initials: R
authors.lastname: Cunney
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004196:Disease Outbreaks; D022761:Gene Transfer, Horizontal / Q000235:genetics; D016680:Genome, Bacterial / Q000235:genetics; D006801:Humans; D007223:Infant; D008589:Meningococcal Infections / Q000453:epidemiology* / Q000382:microbiology / Q000635:transmission*; D058885:Multilocus Sequence Typing; D042806:Neisseria lactamica / Q000235:genetics / Q000302:isolation & purification*; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics / Q000302:isolation & purification*; D011156:Population Density; D055815:Young Adult