title: Genomic resolution of an aggressive, widespread, diverse and expanding meningococcal serogroup B, C and W lineage.
abstract: OBJECTIVE
  Neisseria meningitidis is a leading cause of meningitis and septicaemia. The hyperinvasive ST-11 clonal complex (cc11) caused serogroup C (MenC) outbreaks in the US military in the 1960s and UK universities in the 1990s, a global Hajj-associated serogroup W (MenW) outbreak in 2000-2001, and subsequent MenW epidemics in sub-Saharan Africa. More recently, endemic MenW disease has expanded in South Africa, South America and the UK, and MenC cases have been reported among European and North American men who have sex with men (MSM). Routine typing schemes poorly resolve cc11 so we established the population structure at genomic resolution.
  
  
  METHODS
  Representatives of these episodes and other geo-temporally diverse cc11 meningococci (n = 750) were compared across 1546 core genes and visualised on phylogenetic networks.
  
  
  RESULTS
  MenW isolates were confined to a distal portion of one of two main lineages with MenB and MenC isolates interspersed elsewhere. An expanding South American/UK MenW strain was distinct from the 'Hajj outbreak' strain and a closely related endemic South African strain. Recent MenC isolates from MSM in France and the UK were closely related but distinct.
  
  
  CONCLUSIONS
  High resolution 'genomic' multilocus sequence typing is necessary to resolve and monitor the spread of diverse cc11 lineages globally.
authors.affiliation: Vaccine Evaluation Unit, Public Health England, Manchester Medical Microbiology Partnership, Second Floor, Clinical Sciences Building II, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WZ, UK. Electronic address: jay.lucidarme@phe.gov.uk.
authors.forename: Jay
authors.initials: J
authors.lastname: Lucidarme
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK. Electronic address: dorothea.hill@zoo.ox.ac.uk.
authors.forename: Dorothea M C
authors.initials: DM
authors.lastname: Hill
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK. Electronic address: holly.bratcher@zoo.ox.ac.uk.
authors.forename: Holly B
authors.initials: HB
authors.lastname: Bratcher
authors.affiliation: Meningococcal Reference Unit, Public Health England, Manchester Medical Microbiology Partnership, Second Floor, Clinical Sciences Building II, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WZ, UK. Electronic address: Steve.Gray@phe.gov.uk.
authors.forename: Steve J
authors.initials: SJ
authors.lastname: Gray
authors.affiliation: Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, National Health Laboratory Service, 1 Modderfontein Road, Sandringham, Johannesburg, 2131, South Africa. Electronic address: mignond@nicd.ac.za.
authors.forename: Mignon
authors.initials: M
authors.lastname: du Plessis
authors.affiliation: National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, MB R3E 3R2, Canada. Electronic address: Raymond.Tsang@phac-aspc.gc.ca.
authors.forename: Raymond S W
authors.initials: RS
authors.lastname: Tsang
authors.affiliation: Reference Laboratory for Meningococci, Institute of Health Carlos III, Majadahonda, Spain. Electronic address: julioavazquez@gmail.com.
authors.forename: Julio A
authors.initials: JA
authors.lastname: Vazquez
authors.affiliation: Institut Pasteur, Unité des Infections Bactériennes invasives, Département Infection et Epidémiologie, Paris, France. Electronic address: muhamed-kheir.taha@pasteur.fr.
authors.forename: Muhamed-Kheir
authors.initials: MK
authors.lastname: Taha
authors.affiliation: Faculty of Medicine, Hacettepe University, Ankara, Turkey. Electronic address: mceyhan@hacettepe.edu.tr.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Ceyhan
authors.affiliation: Servicio Bacteriología Clínica, Departamento de Bacteriología, Instituto Nacional de Enfermedades Infecciosas-ANLIS «Dr. Carlos G. Malbrán», Ciudad Autónoma de Buenos Aires, Argentina. Electronic address: amefron@anlis.gov.ar.
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Efron
authors.affiliation: Division of Medical Biology, Bacteriology Department, Adolfo Lutz Institute, São Paulo 01246-902, Brazil. Electronic address: mcgorla@ial.sp.gov.br.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Gorla
authors.affiliation: Vaccine Evaluation Unit, Public Health England, Manchester Medical Microbiology Partnership, Second Floor, Clinical Sciences Building II, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WZ, UK. Electronic address: Jamie.Findlow@phe.gov.uk.
authors.forename: Jamie
authors.initials: J
authors.lastname: Findlow
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK. Electronic address: keith.jolley@zoo.ox.ac.uk.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Jolley
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
authors.affiliation: Vaccine Evaluation Unit, Public Health England, Manchester Medical Microbiology Partnership, Second Floor, Clinical Sciences Building II, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WZ, UK; Meningococcal Reference Unit, Public Health England, Manchester Medical Microbiology Partnership, Second Floor, Clinical Sciences Building II, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WZ, UK. Electronic address: Ray.Borrow@phe.gov.uk.
authors.forename: Ray
authors.initials: R
authors.lastname: Borrow
mesh_terms: D004196:Disease Outbreaks; D019353:Endemic Diseases; D005602:France / Q000453:epidemiology; D018451:Homosexuality, Male; D006801:Humans; D008297:Male; D008589:Meningococcal Infections / Q000453:epidemiology* / Q000382:microbiology*; D058885:Multilocus Sequence Typing; D009345:Neisseria meningitidis / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D038541:Neisseria meningitidis, Serogroup B / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D038542:Neisseria meningitidis, Serogroup C / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D009656:North America / Q000453:epidemiology; D010802:Phylogeny; D065288:Serogroup; D012703:Serotyping; D013019:South Africa / Q000453:epidemiology; D013020:South America / Q000453:epidemiology; D006113:United Kingdom / Q000453:epidemiology
keywords: Genome; Meningococcal; ST-11 clonal complex; Serogroup C; Serogroup W