title: Impact of 13-valent pneumococcal conjugate vaccination in invasive pneumococcal disease incidence and mortality.
abstract: BACKGROUND
  The impact of the 13-valent pneumococcal conjugate vaccine (PCV13) at the population level is unclear. We explored PCV13's effect in reducing invasive pneumococcal disease (IPD)-related morbidity and mortality, and whether serotype-specific changes were attributable to vaccination or expected as a part of natural, cyclical variations.
  
  
  METHODS
  This was a Danish nationwide population-based cohort study based on the linkage of laboratory surveillance data and the Danish Civil Registration System. Changes in IPD incidence and mortality during baseline (2000-2007), 7-valent pneumococcal conjugate vaccine (PCV7) (2008-2010), and PCV13 (2011-2013) periods were estimated. Predicted incidences of serotypes were estimated controlling for cyclical trends from historical patterns observed during the past 20 years.
  
  
  RESULTS
  We observed a 21% reduction (95% confidence interval [CI], 17%-25%) in IPD incidence in the total population after PCV13's introduction, and a 71% reduction (95% CI, 62%-79%) in children aged <2 years, considered as the vaccine effectiveness. We estimated a 28% reduction (95% CI, 18%-37%) in IPD-related 30-day mortality, from 3.4 deaths (95% CI, 3.2-3.6) per 100 000 population in the pre-PCV period to 2.4 (95% CI, 2.2-2.7) in the PCV13 period. The decline in mortality was observed across all age groups but was mainly related to mortality reductions in the nonvaccinated population. For serotypes 1 and 3, there were no significant changes in incidence beyond what would be expected from natural cyclical patterns. Serotype 19A significantly increased following PCV7's introduction, but the incidence declined toward baseline in 2012.
  
  
  CONCLUSIONS
  PCV13 has brought greater benefits than we had expected in our setting. We observed a further decline on IPD incidence shortly after the shift from PCV7 to PCV13 in the national immunization program. This decline was accompanied by a substantial population-level decline in pneumococcal-related mortality of nearly 30% among nonvaccinated persons.
authors.affiliation: National Neisseria and Streptococcus Reference Laboratory, Department of Microbiology and Infection Control, Statens Serum Institut Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Denmark.
authors.forename: Zitta Barrella
authors.initials: ZB
authors.lastname: Harboe
authors.affiliation: National Neisseria and Streptococcus Reference Laboratory, Department of Microbiology and Infection Control, Statens Serum Institut.
authors.forename: Tine
authors.initials: T
authors.lastname: Dalby
authors.affiliation: Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Weinberger
authors.affiliation: Department of Infectious Diseases Clinical Research Centre, Copenhagen University Hospital, Hvidovre Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen.
authors.forename: Thomas
authors.initials: T
authors.lastname: Benfield
authors.affiliation: Department of Infectious Disease Epidemiology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Kåre
authors.initials: K
authors.lastname: Mølbak
authors.affiliation: National Neisseria and Streptococcus Reference Laboratory, Department of Microbiology and Infection Control, Statens Serum Institut.
authors.forename: Hans Christian
authors.initials: HC
authors.lastname: Slotved
authors.affiliation: Department of Infectious Disease Epidemiology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Camilla H
authors.initials: CH
authors.lastname: Suppli
authors.affiliation: National Neisseria and Streptococcus Reference Laboratory, Department of Microbiology and Infection Control, Statens Serum Institut.
authors.forename: Helle Bossen
authors.initials: HB
authors.lastname: Konradsen
authors.affiliation: Department of Infectious Disease Epidemiology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Palle
authors.initials: P
authors.lastname: Valentiner-Branth
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016470:Bacteremia / Q000453:epidemiology* / Q000517:prevention & control; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D016920:Meningitis, Bacterial / Q000453:epidemiology* / Q000517:prevention & control; D008875:Middle Aged; D011008:Pneumococcal Infections / Q000453:epidemiology* / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification / Q000302:isolation & purification*; D016019:Survival Analysis; D055815:Young Adult
chemical_list: C538862:13-valent pneumococcal vaccine; D022242:Pneumococcal Vaccines
keywords: IPD; incidence; indirect effect; mortality; pneumococcal conjugate vaccination