Effectiveness of pneumococcal vaccines in preventing pneumonia in adults, a systematic review and meta-analyses of observational studies

Abstract

Introduction: S. pneumoniae can cause a wide spectrum of diseases, including invasive pneumococcal disease and pneumonia. Two types of pneumococcal vaccines are indicated for use in adults: 23-valent pneumococcal polysaccharide vaccines (PPV23) and a 13-valent pneumococcal conjugate vaccine (PCV13).

Objective: To systematically review the literature assessing pneumococcal vaccine effectiveness (VE) against community-acquired pneumonia (CAP) in adults among the general population, the immunocompromised and subjects with underlying risk factors in real-world settings.

Methods: We searched for peer-reviewed observational studies published between 1980 and 2015 in Pubmed, SciELO or LILACS, with pneumococcal VE estimates against CAP, pneumococcal CAP or nonbacteremic pneumococcal CAP. Meta-analyses and meta-regression for VE against CAP requiring hospitalization in the general population was performed.

Results: 1159 unique articles were retrieved of which 33 were included. No studies evaluating PCV13 effectiveness were found. Wide ranges in PPV23 effectiveness estimates for any-CAP were observed among adults ≥65 years (-143% to 60%). The meta-analyzed VE estimate for any-CAP requiring hospitalization in the general population was 10.2% (95%CI: -12.6; 33.0). The meta-regression indicates that VE against any-CAP requiring hospitalization is significantly lower in studies with a maximum time since vaccination ≥60 months vs. <60 months and in countries with the pediatric PCV vaccine available on the private market. However, these results should be interpreted cautiously due to the high influence of two studies. The VE estimates for pneumococcal CAP hospitalization ranged from 32% (95%CI: -18; 61) to 51% (95%CI: 16; 71) in the general population.

Conclusions: Wide ranges in PPV23 effectiveness estimates for any-CAP were observed, likely due to a great diversity of study populations, circulation of S. pneumoniae serotypes, coverage of pediatric pneumococcal vaccination, case definition and time since vaccination. Despite some evidence for short-term protection, effectiveness of PPV23 against CAP was not consistent in the general population, the immunocompromised and subjects with underlying risk factors.

Fig 1. Flowchart of selection procedure.

The flowchart was based on the flowchart from the PRISMA group [17]. *Invasive pneumococcal disease (n = 11), not a primary research article (n = 7), vaccine or vaccinated group not of interest (n = 5), study protocol or rationale without results (n = 4), study design not of interest (n = 4), data from same source was presented in another article (n = 4), inadequate comparison group (n = 3), no relevant information (n = 3), data in children (n = 2), safety endpoint (n = 1), impact (n = 1). **Outcome other than any community-acquired pneumonia (CAP), pneumococcal CAP (pCAP) or nonbacteremic pCAP (n = 18), no vaccine effectiveness estimate provided (n = 7), estimates comparing receipt of both PPV23 and influenza vaccine with the receipt of influenza vaccine only (n = 2), CAP data from same source was presented in another article (n = 1).

Fig 2. VE with most adjusted estimates for any-CAP in the general population, comparing PPV23 vaccinated with unvaccinated.

Fig 3. Meta-analysis, stratified by availability of pediatric pneumococcal vaccine (PCV): VE with most adjusted estimates for hospitalization due to any-CAP in the general population, comparing PPV23 vaccinated with unvaccinated.

# weights from the random-effects model; *>70% for at least one dose; **45–64 years; ***65+ years.

Fig 4. Meta-analysis, stratified by maximum time since vaccination: VE with most adjusted estimates for hospitalization due to any-CAP in the general population, comparing PPV23 vaccinated with unvaccinated.

*weights from the random-effects model; **45–64 years; ***65+ years.