title: Impact of pneumococcal conjugate vaccines on nasopharyngeal carriage and invasive disease among unvaccinated people: review of evidence on indirect effects.
abstract: BACKGROUND
  Invasive disease due to Streptococcus pneumoniae remains an important worldwide cause of morbidity and mortality, particularly in young children and the elderly. The development and use of pneumococcal conjugate vaccines (PCVs) have had a dramatic impact on rates of vaccine-type invasive pneumococcal disease (IPD) not only in the pediatric population targeted for vaccination but in non-vaccinated age-groups as well. This indirect effect is directly mediated by a reduction of vaccine-type nasopharyngeal carriage and thus transmission by vaccinated children. Current PCV licensing procedures do not take into consideration nasopharyngeal carriage impact, and thus the indirect effect. This review summarizes the evidence for the indirect effect of PCV on vaccine-type disease and its correlation with changes in carriage among unvaccinated populations, to assess the basis for inclusion of carriage in the PCV licensing process.
  
  
  METHODS
  Randomized controlled trials, surveillance and other observational studies published between 1994 and 2013 were systematically identified from global, regional and review databases and conference abstracts. We included as primary evidence, studies in non-vaccinated groups addressing changes in both vaccine-type IPD and carriage between pre- and post-PCV introduction periods; studies missing one of these four components were included as supporting rather than primary evidence.
  
  
  RESULTS
  We identified studies from 14 countries, nearly all developed countries. Vaccine-type IPD and carriage in non-targeted populations consistently decreased after PCV introduction, with the magnitude of decrease growing over time. Where IPD and carriage were observed in the same population, VT-decreases occurred contemporaneously. These relationships held true across age-groups and between indigenous and non-indigenous populations in the US and Australia.
  
  
  CONCLUSIONS
  Indirect PCV impact on VT-IPD and VT-carriage has been significant. Impact on carriage should be considered for inclusion in the PCV licensure process as a predictor of indirect effects.
authors.affiliation: International Vaccine Access Center, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Davis
authors.affiliation: International Vaccine Access Center, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
authors.forename: Maria
authors.initials: M
authors.lastname: Deloria-Knoll
authors.affiliation: International Vaccine Access Center, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States.
authors.forename: Hilina T
authors.initials: HT
authors.lastname: Kassa
authors.affiliation: International Vaccine Access Center, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States; Center for American Indian Health, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States. Electronic address: klobrien@jhsph.edu.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: O'Brien
mesh_terms: D002353:Carrier State / Q000453:epidemiology*; D014943:Global Health; D006801:Humans; D009305:Nasopharynx / Q000276:immunology / Q000382:microbiology*; D011008:Pneumococcal Infections / Q000453:epidemiology* / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000276:immunology*
chemical_list: D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate
keywords: Indirect effect; Nasopharyngeal carriage; Nasopharyngeal colonization; Pneumococcal conjugate vaccine; Pneumococcus