Efficacy of PPV23 in Preventing Pneumococcal Pneumonia in Adults at Increased Risk – A Systematic Review and Meta-Analysis

BACKGROUND: Pneumococcal community-acquired pneumonia (pCAP) is the most frequent form of pneumonia. The elderly and adults with underlying diseases are at an increased risk of developing pCAP. The 23-valent pneumococcal polysaccharide vaccine (PPV23) was licensed over 30 years ago and is recommended as the standard intervention in many countries across the globe, although its efficacy continues to be debated. We performed a meta-analysis of randomized controlled trials (RCTs) to investigate the effect of PPV23 for preventing pCAP in adults ≥60 years of age. METHODS: An existing Cochrane Review was updated to Oct 2014 using a systematic literature search to select appropriate RCTs. DerSimonian and Laird random-effects meta-analyses were performed and odd ratios (OR) with 95%-confidence intervals (CI) and p-values were calculated for the descriptive analyses. Reasons for heterogeneity were explored by subgroup analyses. RESULTS: Meta-analysis of PPV23 efficacy included four studies. Three of them did not demonstrate efficacy for PPV23. The body of evidence indicated statistically significant heterogeneity (I(2) = 78%, p = 0.004) that could be explained by subgroup analysis by “study setting”. Further effect modifiers for pCAP were “continent of trial” (p<0.01), and “method of pneumococcal diagnostics” (p = 0.001). Subgroup analyses revealed that the only study showing efficacy for PPV23 was an outlier. Overall, the validity of the meta-analytic PPV23 efficacy assessment was confirmed by the meta-analysis of all-cause CAP including six studies. DISCUSSION: Inconsistencies in PPV23 treatment effects to prevent pCAP could solely be explained by one outlier study that was performed in nursing homes in Japan. The effect modifier “method of pneumococcal diagnostics” should be interpreted carefully, since methodological weaknesses are not restricted to one special method only, which would justify the exclusion of certain studies. Overall, we conclude from our meta-analysis that to date there is no proof that PPV23 can prevent pCAP in a general, community-dwelling elderly population.