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Background: Clinical trials and meta-analyses have produced conflicting results of the efficacy of unconjugated pneumococcal polysaccharide vaccine in adults. We sought to evaluate the vaccine's efficacy on clinical outcomes as well as the methodologic quality of the trials. Methods:We searched several databases and all bibliographies of reviews and meta-analyses for clinical trials that compared pneumococcal polysaccharide vaccine with a control. We examined rates of pneumonia and death, taking the methodologic quality of the trials into consideration. Results:We included 22 trials involving 101 507 participants: 11 trials reported on presumptive pneumococcal pneumonia, 19 on all-cause pneumonia and 12 on allcause mortality. The current 23-valent vaccine was used in 8 trials. The relative risk (RR) was 0.64 (95% confidence interval [CI] 0.43-0.96) for presumptive pneumococcal pneumonia and 0.73 (95% CI 0.56-0.94) for all-cause pneumonia. There was significant heterogeneity between the trials reporting on presumptive pneumonia (I 2 = 74%, p < 0.001) and between those reporting on all-cause pneumonia (I 2 = 90%, p < 0.001). The RR for all-cause mortality was 0.97 (95% CI 0.87-1.09), with moderate heterogeneity between trials (I 2 = 44%, p = 0.053). Trial quality, especially regarding double blinding, explained a substantial proportion of the heterogeneity in the trials reporting on presumptive pneumonia and all-cause pneumonia. There was little evidence of vaccine protection in trials of higher methodologic quality (RR 1.20, 95% CI 0.75-1.92, for presumptive pneumonia; and 1.19, 95% CI 0.95-1.49, for allcause pneumonia in double-blind trials; p for heterogeneity > 0.05). The results for all-cause mortality in double-blind trials were similar to those in all trials combined. There was little evidence of vaccine protection among elderly patients or adults with chronic illness in analyses of all trials (RR 1.04, 95% CI 0.78-1.38, for presumptive pneumococcal pneumonia; 0.89, 95% CI 0.69-1.14, for all-cause pneumonia; and 1.00, 95% CI 0.87-1.14, for all-cause mortality).Interpretation: Pneumococcal vaccination does not appear to be effective in preventing pneumonia, even in populations for whom the vaccine is currently recommended.

SummaryBackgroundA serogroup A meningococcal polysaccharide–tetanus toxoid conjugate vaccine (PsA–TT, MenAfriVac) was licensed in India in 2009, and pre-qualified by WHO in 2010, on the basis of its safety and immunogenicity. This vaccine is now being deployed across the African meningitis belt. We studied the effect of PsA–TT on meningococcal meningitis and carriage in Chad during a serogroup A meningococcal meningitis epidemic.MethodsWe obtained data for the incidence of meningitis before and after vaccination from national records between January, 2009, and June, 2012. In 2012, surveillance was enhanced in regions where vaccination with PsA–TT had been undertaken in 2011, and in one district where a reactive vaccination campaign in response to an outbreak of meningitis was undertaken. Meningococcal carriage was studied in an age-stratified sample of residents aged 1–29 years of a rural area roughly 13–15 and 2–4 months before and 4–6 months after vaccination. Meningococci obtained from cerebrospinal fluid or oropharyngeal swabs were characterised by conventional microbiological and molecular methods.FindingsRoughly 1·8 million individuals aged 1–29 years received one dose of PsA–TT during a vaccination campaign in three regions of Chad in and around the capital N'Djamena during 10 days in December, 2011. The incidence of meningitis during the 2012 meningitis season in these three regions was 2·48 per 100 000 (57 cases in the 2·3 million population), whereas in regions without mass vaccination, incidence was 43·8 per 100 000 (3809 cases per 8·7 million population), a 94% difference in crude incidence (p<0·0001), and an incidence rate ratio of 0·096 (95% CI 0·046–0·198). Despite enhanced surveillance, no case of serogroup A meningococcal meningitis was reported in the three vaccinated regions. 32 serogroup A carriers were identified in 4278 age-stratified individuals (0·75%) living in a rural area near the capital 2–4 months before vaccination, whereas only one serogroup A meningococcus was isolated in 5001 people living in the same community 4–6 months after vaccination (adjusted odds ratio 0·019, 95% CI 0·002–0·138; p<0·0001).InterpretationPSA–TT was highly effective at prevention of serogroup A invasive meningococcal disease and carriage in Chad. How long this protection will persist needs to be established.FundingThe Bill & Melinda Gates Foundation, the Wellcome Trust, and Médecins Sans Frontères.