title: Systematic review of the indirect effect of pneumococcal conjugate vaccine dosing schedules on pneumococcal disease and colonization.
abstract: BACKGROUND
  To aid decision making for pneumococcal conjugate vaccine (PCV) use in infant national immunization programs, we summarized the indirect effects of PCV on clinical outcomes among nontargeted age groups.
  
  
  METHODS
  We systematically reviewed the English literature on infant PCV dosing schedules published from 1994 to 2010 (with ad hoc addition of 2011 articles) for outcomes on children >5 years of age and adults including vaccine-type nasopharyngeal carriage (VT-NP), vaccine-type invasive pneumococcal disease (VT-IPD) and syndromic pneumonia.
  
  
  RESULTS
  Of 12,980 citations reviewed, we identified 21 VT-IPD, 6 VT-NP and 9 pneumonia studies. Of these 36, 21 (58%) included 3 primary doses plus PCV or pneumococcal polysaccharide vaccine (PPV23) booster schedule (3+1 or 3+PPV23), 5 (14%) 3+0, 9 (25%) 2+1 and 1 (3%) 2+0. Most (95%) were PCV7 studies. Among observational VT-IPD studies, all schedules (2+1, 3+0 and 3+1) demonstrated reductions in incidence among young adult groups. Among syndromic pneumonia observational studies (2+1, 3+0 and 3+1), only 3+1 schedules showed significant indirect impact. Of 2 VT-NP controlled trials (3+0 and 3+1) and 3 VT-NP observational studies (2+1, 3+1 and 3+PPV23), 3+1 and 3+PPV23 schedules showed significant indirect effect. The 1 study to directly compare between schedules was a VT-NP study (2+0 vs. 2+1), which found no indirect effect on older siblings and parents of vaccinated children with either schedule.
  
  
  CONCLUSIONS
  Indirect benefit of a 3+1 infant PCV dosing schedule has been demonstrated for VT-IPD, VT-NP and syndromic pneumonia; 2+1 and 3+0 schedules have demonstrated indirect effect only for VT-IPD. The choice of optimal infant PCV schedule is limited by data paucity on indirect effects, especially a lack of head-to-head studies and studies of PCV10 and PCV13.
authors: From the *Respiratory Diseases Branch, Division of Bacterial Diseases, National Center for Immunizations and Respiratory Diseases; †Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, GA; ‡International Vaccine Access Center, Johns Hopkins Bloomberg School of Public Health, Baltimore; §Westat Inc., Rockville, MD; and ¶Institute of Child Health, University College London, London, United Kingdom.
authors: Jennifer D
authors: JD
authors: Loo
authors: Laura
authors: L
authors: Conklin
authors: Katherine E
authors: KE
authors: Fleming-Dutra
authors: Maria Deloria
authors: MD
authors: Knoll
authors: Daniel E
authors: DE
authors: Park
authors: Jennifer
authors: J
authors: Kirk
authors: David
authors: D
authors: Goldblatt
authors: Katherine L
authors: KL
authors: O'Brien
authors: Cynthia G
authors: CG
authors: Whitney
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002353:Carrier State / Q000517:prevention & control*; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D008875:Middle Aged; D009305:Nasopharynx / Q000382:microbiology*; D064887:Observational Studies as Topic; D011008:Pneumococcal Infections / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology; D016032:Randomized Controlled Trials as Topic; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology; D055815:Young Adult
chemical_list: D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate