Efficacy of pneumococcal polysaccharide vaccine in immunocompetent adults: a meta-analysis of randomized trials
Introduction
Illnesses related to Streptococcus pneumoniae cause substantial morbidity and mortality in the elderly and people with predisposing conditions or underlying diseases. In Western Europe, 175,000 to 290,000 old people were hospitalized for a pneumococcal pneumonia in 1998 [1]. Mortality due to pneumococcal pneumonia is estimated to be between 6000 and 13,000 deaths per year in France and 20,000 deaths per year in the USA [2], [3]. Streptococcus pneumoniae is responsible for 30 to 50% of all community-acquired pneumonia [2]. Curative care of these diseases includes hospitalization, although death sometimes occurs despite prompt and appropriate anti-microbial therapy [4], [5], [6]. Antibiotic resistance among pneumococcal strains is increasing world-wide, making the prevention of pneumococcal infections by vaccination appear an attractive option. The first 14-serotype pneumococcal polysaccharide vaccine has existed since 1981, and the 23-serotype vaccine has been marketed since 1983 and contains about 90% of the serotypes of Streptococcus pneumoniae, including the penicillin resistant serotypes 6, 14, 19, 23 [7]. Some physicians and health authorities seem to have doubts about its efficacy, and in some countries its use is not widespread [3]. Several randomized clinical trials and meta-analyses with conflicting conclusions have been published, [8], [9], [10]. In a meta-analysis published in 1994, Fine et al. found a reduction in the incidence of definitive pneumococcal pneumonia, Odds Ratio (OR) 0.34; confidence interval (CI) 95%[0.24–0.48] and of presumptive pneumococcal pneumonia, OR 0.47; CI 95%[0.35–0.63] after immunization with the polysaccharide pneumococcal vaccine (PPV), but not in all-cause pneumonia and death from pneumonia. Two randomized trials have been published since then [11], [12]. More recently, Moore et al. have published a meta-analysis, which is updated, and analyzed in two separate subgroups, ‘immunocompromised or elderly’ (including healthy elderly in a home for old people, patients with bronchogenic carcinoma, obstructive pulmonary diseases, and HIV positive males), and ‘young immunocompetent subjects’, a subgrouping which could appear not very relevant, especially in the first group, and concluded to an absence of efficacy of the 23-valent PPV. The purpose of this study is to perform an updated, systematic review of all randomized trials in immunocompetent adults.
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Eligible trials
To avoid as much as possible the possibility of biases, trials were eligible for inclusion in the meta-analysis if they: (1) were randomized, with a precisely described randomization process ensuring that the next treatment cannot be guessed, and comprise at least a PPV and a control group (placebo, a control vaccine, or no vaccine); (2) targeted immunocompetent adults (aged over 18); and (3) assessed one or more of the following clinical outcomes: definite pneumococcal pneumonia, defined as
Literature search
We found 1835 articles with relevant titles. From this list, 11 pertinent randomized trials were identified. One trial performed in HIV positive subjects was not included in this analysis, and one quasi randomized study was also retrieved but not included because the vaccine allocation was based on the year of birth and could therefore be anticipated, which might introduce biases [16], [17]. Three articles reported results of two sub-studies, with distinct vaccine and control groups [18], [19],
Discussion
The aim of this meta-analysis was to evaluate the efficacy of PPV in preventing clinically relevant outcomes in immunocompetent adults, i.e. in adults free from diseases affecting the immune system.
The populations of three of the trials were made up of young male workers, one in a community of adults in Papua New Guinea, without age limit, and together represent more than 50% of the patients [25], [19]. Considering that the main target population for PPV in western countries is the elderly
Conclusion
This meta-analysis confirms unambiguously the high efficacy of PPV in reducing definite (bacteremic) pneumococcal pneumonia by 71%, and presumptive pneumococcal pneumonia by 40%, with a possible 27% reduction in mortality due to pneumonia. It did not reach sufficient power to show any efficacy of the vaccine in preventing these diseases in elderly patients, the actual target population for PPV. For this reason, and also because the populations tested up until now may not represent the target
Acknowledgements
The authors wish to thank Alison Foote for correcting the English of the manuscript, and the scientists and correspondents in the pharmaceutical firms commercializing vaccines for their replies to our enquiries. Date of Analysis: 1999-10-30. Financial sources: Aventis Pasteur MSD, Lyon, France.
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