Abstract
The efficacy of PPV-23 vaccine on outcomes of pneumococcal disease in adults still remains controversial due mainly to the lack of consistency between the results obtained from observational studies(OSs) and those obtained from randomized controlled trials(RCTs). As a consequence, the complexity in the structure of evidence available, in turn, generates a challenge for combining disparate pieces of evidence quantitatively. In this regard, we used a hierarchical Bayesian inference-based evidence synthesis of RCTs and observational data using a two-stage approach (in addition to a traditional random-effects meta-analysis) to examine the effectiveness of PPV-23 in adults. To this end, 21 studies were included involving 826109 adult participants. By a two-stage Bayesian meta-analysis, which was directly used for combining studies of different designs, the overall log OR (95% credible interval) for IPDs was −0.1048 (−0.3920,−0.0250), indicating a significant protective effect of the vaccination against IPDs. No significant effect of PPV-23 was found on all-cause pneumonia, pneumococcal pneumonia, and death from pneumonia, which confirmed the results obtained by a traditional method followed by stratified and sensitivity analyses. The estimated overall log OR (95% credible interval) was −0.0002 (−0.0241,0.0142), −0.0002 (−0.0110,0.0122), and −6.3912 × 10−5 (−0.0219,0.0131), respectively. The PPV-23 vaccine might be effective in preventing the most severe invasive forms of pneumococcal diseases, but not effective in preventing other clinical outcomes, in the adult population of 18 years and older.
Highlights
There are two available pneumococcal preventive vaccines: the older Polysaccharide Vaccines (PPVs) that contain a purified capsular polysaccharide and the newer Conjugate Vaccines (PCVs) that include a conjugation of a carrier protein to capsular polysaccharide
Among the cohort/case-control studies that compared the 23-valent pneumococcal vaccinated with unvaccinated events, the pooled relative risk (RR) from a random-effects meta-analysis indicated a significant effect of PPV-23 on all-cause pneumonia (RR = 0.598, 95% confidence intervals (CIs); 0.386–0.927; P = 0.022), with no evidence of heterogeneity between studies (Cochran’s Q test P > 0.1, I2 = 54.397%)
The pooled RR showed a significant effect of PPV-23 on bacteremia, septicemia or invasive pneumococcal diseases (RR = 0.702, 95% CI; 0.555–0.887; P = 0.003), evidence of pronounced heterogeneity was found between studies (Cochran’s Q test P = 0, I2 = 75.072%; Table 4)
Summary
There are two available pneumococcal preventive vaccines: the older Polysaccharide Vaccines (PPVs) that contain a purified capsular polysaccharide and the newer Conjugate Vaccines (PCVs) that include a conjugation of a carrier protein to capsular polysaccharide. The pooled RR from a random-effects meta-analysis indicated no significant effect of PPV-23 on any of the clinical outcomes including all-cause pneumonia (RR = 1.009, 95% CI; 0.761–1.340; P = 0.948), pneumococcal pneumonia (RR = 0.837, 95% CI; 0.466–1.502; P = 0.550), death from pneumonia (RR = 0.606, 95% CI; 0.354–1.039; P = 0.068), and bacteremia, septicemia or invasive pneumococcal diseases (RR = 0.969, 95% CI; 0.496–1.891; P = 0.926; Table 3).
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