title: Meningococcal carriage in Dutch adolescents and young adults; a cross-sectional and longitudinal cohort study.
abstract: OBJECTIVE
  Current information on rates and dynamics of meningococcal carriage is essential for public health policy. This study aimed to determine meningococcal carriage prevalence, its risk factors and duration in the Netherlands, where meningococcal C vaccine coverage is >90%. Several methods to identify serogroups of meningococcal carriage isolates among adolescent and young adults were compared.
  
  
  METHODS
  Oropharyngeal swabs were collected from 1715 participants 13-23 years of age in 2013-2014; 300 were prospectively followed over 8 months. Cultured isolates were characterized by Ouchterlony, real-time (rt-) PCR or whole-genome sequencing (WGS). Direct swabs were assessed by rt-PCR. Questionnaires on environmental factors and behaviour were also obtained.
  
  
  RESULTS
  A meningococcal isolate was identified in 270/1715 (16%) participants by culture. Of MenB isolates identified by whole genome sequencing, 37/72 (51%) were correctly serogrouped by Ouchterlony, 46/51 (90%) by rt-PCR of cultured isolates, and 39/51 (76%) by rt-PCR directly on swabs. A sharp increase in carriage was observed before the age of 15 years. The age-related association disappeared after correction for smoking, level of education, frequent attendance to crowded social venues, kissing in the previous week and alcohol consumption. Three participants carried the same strain identified at three consecutive visits in an 8-month period. In these isolates, progressively acquired mutations were observed.
  
  
  CONCLUSIONS
  Whole genome sequencing of culture isolates was the most sensitive method for serogroup identification. Based upon results of this study and risk of meningococcal disease, an adolescent meningococcal vaccination might include children before the age of 15 years to confer individual protection and potentially to establish herd protection.
authors.affiliation: Department of Immunology and Infectious diseases, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands; Research Centre Linnaeus Institute, Spaarne Hospital, Hoofddorp, The Netherlands.
authors.forename: M B
authors.initials: MB
authors.lastname: van Ravenhorst
authors.affiliation: Academic Medical Centre, Centre of Infection and Immunity Amsterdam (CINIMA), Department of Neurology, Amsterdam, The Netherlands.
authors.forename: M W
authors.initials: MW
authors.lastname: Bijlsma
authors.affiliation: Research Centre Linnaeus Institute, Spaarne Hospital, Hoofddorp, The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: van Houten
authors.affiliation: Research Centre Linnaeus Institute, Spaarne Hospital, Hoofddorp, The Netherlands.
authors.forename: V M D
authors.initials: VMD
authors.lastname: Struben
authors.affiliation: Pfizer Vaccine Research & Development, Pearl River, NY, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Anderson
authors.affiliation: Pfizer Vaccine Research & Development, Pearl River, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Eiden
authors.affiliation: Pfizer Vaccine Research & Development, Pearl River, NY, USA.
authors.forename: L
authors.initials: L
authors.lastname: Hao
authors.affiliation: Pfizer Vaccine Research & Development, Pearl River, NY, USA.
authors.forename: K U
authors.initials: KU
authors.lastname: Jansen
authors.affiliation: Pfizer Vaccine Research & Development, Pearl River, NY, USA.
authors.forename: H
authors.initials: H
authors.lastname: Jones
authors.affiliation: Pfizer Vaccine Research & Development, Maidenhead, UK.
authors.forename: N
authors.initials: N
authors.lastname: Kitchin
authors.affiliation: Pfizer Vaccine Research & Development, Pearl River, NY, USA.
authors.forename: L
authors.initials: L
authors.lastname: Pedneault
authors.affiliation: Department of Immunology and Infectious diseases, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: E A M
authors.initials: EAM
authors.lastname: Sanders
authors.affiliation: Academic Medical Centre, Centre of Infection and Immunity Amsterdam (CINIMA), Department of Medical Microbiology and the Netherlands Reference Laboratory for Bacterial Meningitis, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: A.vanderende@amc.uva.nl.
authors.forename: A
authors.initials: A
authors.lastname: van der Ende
mesh_terms: D000293:Adolescent; D002353:Carrier State / Q000453:epidemiology* / Q000382:microbiology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008589:Meningococcal Infections / Q000453:epidemiology* / Q000382:microbiology; D009345:Neisseria meningitidis / Q000145:classification / Q000302:isolation & purification*; D009426:Netherlands / Q000453:epidemiology; D009960:Oropharynx / Q000382:microbiology*; D015995:Prevalence; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D065288:Serogroup; D012703:Serotyping; D011795:Surveys and Questionnaires; D013997:Time Factors; D000073336:Whole Genome Sequencing; D055815:Young Adult
keywords: Adolescents; Carriage; Diagnostic tests; Longitudinal; Neisseria meningitidis; Risk factors