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.

Keywords: Infants; Nasopharyngeal carriage; Non-typeable haemophilus influenzae; Otitis media; Pneumococcal conjugate vaccine; Streptococcus pneumoniae.