title: Genomic epidemiology of age-associated meningococcal lineages in national surveillance: an observational cohort study.
abstract: BACKGROUND
  Invasive meningococcal disease (IMD) is a worldwide health issue that is potentially preventable with vaccination. In view of its sporadic nature and the high diversity of Neisseria meningitidis, epidemiological surveillance incorporating detailed isolate characterisation is crucial for effective control and understanding the evolving epidemiology of IMD. The Meningitis Research Foundation Meningococcus Genome Library (MRF-MGL) exploits whole-genome sequencing (WGS) for this purpose and presents data on a comprehensive and coherent IMD isolate collection from England and Wales via the internet. We assessed the contribution of these data to investigating IMD epidemiology.
  
  
  METHODS
  WGS data were obtained for all 899 IMD isolates available for England and Wales in epidemiological years 2010-11 and 2011-12. The data had been annotated at 1720 loci, analysed, and disseminated online. Information was also available on meningococcal population structure and vaccine (Bexsero, GlaxoSmithKline, Brentford, Middlesex, UK) antigen variants, which enabled the investigation of IMD-associated genotypes over time and by patients' age groups. Population genomic analyses were done with a hierarchical gene-by-gene approach.
  
  
  RESULTS
  The methods used by MRF-MGL efficiently characterised IMD isolates and information was provided in plain language. At least 20 meningococcal lineages were identified, three of which (hyperinvasive clonal complexes 41/44 [lineage 3], 269 [lineage 2], and 23 [lineage 23]) were responsible for 528 (59%) of IMD isolates. Lineages were highly diverse and showed evidence of extensive recombination. Specific lineages were associated with IMD in particular age groups, with notable diversity in the youngest and oldest individuals. The increased incidence of IMD from 1984 to 2010 in England and Wales was due to successive and concurrent epidemics of different lineages. Genetically, 74% of isolates were characterised as encoding group B capsules: 16% group Y, 6% group W, and 3% group C. Exact peptide matches for individual Bexsero vaccine antigens were present in up to 26% of isolates.
  
  
  CONCLUSIONS
  The MRF-MGL represents an effective, broadly applicable model for the storage, analysis, and dissemination of WGS data that can facilitate real-time genomic pathogen surveillance. The data revealed information crucial to effective deployment and assessment of vaccines against N meningitidis.
  
  
  BACKGROUND
  Meningitis Research Foundation, Wellcome Trust, Public Health England, European Union.
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK.
authors.forename: Dorothea M C
authors.initials: DM
authors.lastname: Hill
authors.affiliation: Meningococcal Reference Unit, Public Health England, Manchester Royal Infirmary, Manchester, UK.
authors.forename: Jay
authors.initials: J
authors.lastname: Lucidarme
authors.affiliation: Meningococcal Reference Unit, Public Health England, Manchester Royal Infirmary, Manchester, UK.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Gray
authors.affiliation: Meningococcal Reference Unit, Public Health England, Manchester Royal Infirmary, Manchester, UK.
authors.forename: Lynne S
authors.initials: LS
authors.lastname: Newbold
authors.affiliation: Scottish Haemophilus, Legionella, Meningococcus and Pneumococcus Reference Laboratory, Glasgow Royal Infirmary, Glasgow, UK.
authors.forename: Roisin
authors.initials: R
authors.lastname: Ure
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK.
authors.forename: Carina
authors.initials: C
authors.lastname: Brehony
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK.
authors.forename: Odile B
authors.initials: OB
authors.lastname: Harrison
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK.
authors.forename: James E
authors.initials: JE
authors.lastname: Bray
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Jolley
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK.
authors.forename: Holly B
authors.initials: HB
authors.lastname: Bratcher
authors.affiliation: Wellcome Trust Sanger Institute, Cambridge, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
authors.forename: Christoph M
authors.initials: CM
authors.lastname: Tang
authors.affiliation: Meningococcal Reference Unit, Public Health England, Manchester Royal Infirmary, Manchester, UK.
authors.forename: Ray
authors.initials: R
authors.lastname: Borrow
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK. Electronic address: martin.maiden@zoo.ox.ac.uk.
authors.forename: Martin C J
authors.initials: MC
authors.lastname: Maiden
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004739:England / Q000453:epidemiology; D062665:Epidemiological Monitoring; D005260:Female; D016680:Genome, Bacterial; D015698:Genomic Library; D005838:Genotype; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D008585:Meningitis, Meningococcal / Q000453:epidemiology* / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D008589:Meningococcal Infections / Q000453:epidemiology* / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000008:administration & dosage; D008875:Middle Aged; D017720:Molecular Epidemiology; D009345:Neisseria meningitidis / Q000145:classification / Q000235:genetics* / Q000276:immunology; D010802:Phylogeny; D065288:Serogroup; D014611:Vaccination; D014852:Wales / Q000453:epidemiology
chemical_list: D022401:Meningococcal Vaccines