title: The short-term impact of each primary dose of pneumococcal conjugate vaccine on nasopharyngeal carriage: Systematic review and meta-analyses of randomised controlled trials.
abstract: BACKGROUND
  Early onset of persistent otitis media is a priority issue for Australian Indigenous populations. The objective is to determine the direct and short-term impact of one, two and three doses of any pneumococcal conjugate vaccine (PCV) formulation on nasopharyngeal (NP) carriage of Streptococcus pneumoniae (Spn) and non-typeable Haemophilus influenzae (NTHi), the otopathogens targeted by current PCVs.
  
  
  METHODS
  We searched MEDLINE (PubMed) and CENTRAL (Cochrane Library) to 29 September 2015. We also scanned reference lists of recent reviews and contacted authors. We included randomised controlled trials (RCTs) with a PCV schedule commencing ≤3 months of age that reported controlled non-cumulative group-specific prevalence data for carriage of Spn or NTHi at age<12 months. We performed a standard risk of bias assessment. We estimated the pooled relative risk (RR) and 95% confidence interval (95%CI) for each vaccine dose on NP carriage by meta-analysis.
  
  
  RESULTS
  We included 16 RCTs involving 14,776 participants. The PCVs were conjugated to diphtheria toxin CRM197, diphtheria toxoid, tetanus toxoid or NTHi protein D and varied in valency (4-13). Controls were non-PCVs, placebo or no vaccine. The earliest carriage outcome was from 2 to 9 months of age. Compared to controls, there were no significant differences between one or two doses of PCV on vaccine-type (VT) pneumococcal carriage at ∼4 and ∼6 months respectively. However, VT carriage was significantly lower at ∼7 months RR 0.67 95%CI 0.56-0.81 from 9 studies and 7613 infants and non-vaccine type (NVT) carriage was higher RR 1.23 95%CI 1.09-1.40 from 8 studies and 5861 infants. No impact on overall pneumococcal or NTHi carriage was found.
  
  
  CONCLUSIONS
  The primary PCV schedule had no significant short-term impact on overall pneumococcal or NTHi NP carriage and a limited impact on VT pneumococcal carriage before the third dose.
authors.affiliation: Menzies School of Health Research, Charles Darwin University, John Matthews Building (58), Royal Darwin Hospital Campus, Darwin 0810, NT, Australia.
authors.forename: Thomas Rodger
authors.initials: TR
authors.lastname: Nicholls
authors.affiliation: Menzies School of Health Research, Charles Darwin University, John Matthews Building (58), Royal Darwin Hospital Campus, Darwin 0810, NT, Australia. Electronic address: amanda.leach@menzies.edu.au.
authors.forename: Amanda Jane
authors.initials: AJ
authors.lastname: Leach
authors.affiliation: Menzies School of Health Research, Charles Darwin University, John Matthews Building (58), Royal Darwin Hospital Campus, Darwin 0810, NT, Australia.
authors.forename: Peter Stanley
authors.initials: PS
authors.lastname: Morris
mesh_terms: D002353:Carrier State / Q000453:epidemiology* / Q000382:microbiology; D006801:Humans; D007223:Infant; D009305:Nasopharynx / Q000382:microbiology; D011008:Pneumococcal Infections / Q000453:epidemiology* / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D013296:Streptococcus pneumoniae / Q000302:isolation & purification*; D018074:Vaccines, Conjugate / Q000008:administration & dosage
chemical_list: D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate
keywords: Infants; Nasopharyngeal carriage; Non-typeable haemophilus influenzae; Otitis media; Pneumococcal conjugate vaccine; Streptococcus pneumoniae