title: Indirect effects of childhood pneumococcal conjugate vaccination on invasive pneumococcal disease: a systematic review and meta-analysis.
abstract: The full extent to which childhood pneumococcal conjugate vaccines (PCV) can indirectly reduce illness in unvaccinated populations is not known. We aimed to estimate the magnitude and timing of indirect effects of PCVs on invasive pneumococcal disease.
  
  
  
  In this systematic review and meta-analysis, we searched bibliographic databases for non-randomised quasi-experimental or observational studies reporting invasive pneumococcal disease changes following PCV introduction in unvaccinated populations (studies published Sept 1, 2010, to Jan 6, 2016), updating the previous systematic review of the same topic (studies published Jan 1, 1994, to Sept 30, 2010). Two reviewers extracted summary data by consensus. We used a Bayesian mixed-effects model to account for between-study heterogeneity to estimate temporal indirect effects by pooling of invasive pneumococcal disease changes by serotype and serogroup.
  
  
  
  Data were extracted from 70 studies included in the previous review and 172 additional studies, covering 27 high-income and seven middle-income countries. The predicted mean times to attaining a 90% reduction in invasive pneumococcal disease were 8·9 years (95% credible interval [CrI] 7·8-10·3) for grouped serotypes contained in the seven-valent PCV (PCV7), and 9·5 years (6·1-16·6) for the grouped six additional serotypes contained in the 13-valent PCV (PCV13) but not in PCV7. Disease due to grouped serotypes contained in the 23-valent pneumococcal polysaccharide vaccine (PPV23) decreased at similar rates per year in adults aged 19-64 years (relative risk [RR] 0·85, 95% CrI 0·75-0·95) and 65 years and older (0·87, 0·84-0·90). However, we noted no changes in either group in invasive pneumococcal disease caused by the additional 11 serotypes covered by PPV23 but not PCV13.
  
  
  
  Population childhood PCV programmes will lead, on average, to substantial protection across the whole population within a decade. This large indirect protection should be considered when assessing vaccination of older age groups.
  
  
  
  Policy Research Programme of the Department of Health, England.
authors.affiliation: Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, UK. Electronic address: t.shiri@warwick.ac.uk.
authors.forename: Tinevimbo
authors.initials: T
authors.lastname: Shiri
authors.affiliation: WIDER group, Warwick Mathematics Institute, Warwick Medical School, University of Warwick, Coventry, UK.
authors.forename: Samik
authors.initials: S
authors.lastname: Datta
authors.affiliation: Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, UK.
authors.forename: Jason
authors.initials: J
authors.lastname: Madan
authors.affiliation: Population Evidence and Technologies, Warwick Medical School, University of Warwick, Coventry, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Tsertsvadze
authors.affiliation: Population Evidence and Technologies, Warwick Medical School, University of Warwick, Coventry, UK.
authors.forename: Pamela
authors.initials: P
authors.lastname: Royle
authors.affiliation: WIDER group, Warwick Mathematics Institute, Warwick Medical School, University of Warwick, Coventry, UK.
authors.forename: Matt J
authors.initials: MJ
authors.lastname: Keeling
authors.affiliation: Population Evidence and Technologies, Warwick Medical School, University of Warwick, Coventry, UK.
authors.forename: Noel D
authors.initials: ND
authors.lastname: McCarthy
authors.affiliation: Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, UK.
authors.forename: Stavros
authors.initials: S
authors.lastname: Petrou
mesh_terms: D019049:Developed Countries; D006801:Humans; D011008:Pneumococcal Infections / Q000276:immunology* / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage; D065288:Serogroup; D014611:Vaccination / Q000379:methods*; D018074:Vaccines, Conjugate / Q000008:administration & dosage
chemical_list: C538862:13-valent pneumococcal vaccine; C414006:23-valent pneumococcal capsular polysaccharide vaccine; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate