The Clinical Effectiveness of Pneumococcal Conjugate Vaccines A Systematic Review and Meta-analysis of Randomized Controlled Trials

Background: Streptococcus pneumoniae is responsible for approximately 1.6 million yearly deaths worldwide. An up-to-date evidence base on the effects of pneumococcal conjugate vaccines (PCVs) on infectious diseases and mortality in any population or setting regardless of age or health status is currently lacking. Methods: We systematically searched MEDLINE and EMBASE for pertinent randomized controlled trials (RCTs). Two reviewers independently screened 9498 titles/abstracts and 430 full-text papers for eligible trials. The outcomes of our meta-analysis were pooled using relative risks (RRs) with a random effects model or Peto's odds ratios (ORs) if event rates were <1%. Results: 21 RCTs comprising 361 612 individuals were included. PCVs reduced the risk for invasive pneumococcal disease (odds ratio [OR]: 0.43, 95% confidence interval [CI]: [0.36; 0.51]), all-cause acute otitis media (AOM) (RR: 0.93, 95% CI: [0.86; 1.00]), pneumococcal AOM (RR: 0.57, 95% CI: [0.39; 0.83]), allcause pneumonia (RR: 0.93, 95% CI: [0.89; 0.97]), and pneumococcal pneumonia (RR: 0.78, 95% CI: [0.62; 0.97]). We found no significant effect of PCVs on all-cause mortality (RR: 0.95, 95% CI: [0.88; 1.03]) or recurrent AOM (RR: 0.87, 95% CI: [0.72; 1.05]). Conclusion: PCVs are associated with large risk reductions for pneumococcal infectious diseases, smaller risk reductions for infectious diseases from any cause, and no significant effect on all-cause mortality.