Pneumococcal polysaccharide vaccine: a systematic review of clinical effectiveness in adults

Abstract

Pneumococcal polysaccharide vaccine is recommended in western countries for individuals at high risk of pneumococcal illness. We undertook a systematic review of randomised controlled trials of pneumococcal vaccine in adults, to determine the effects on clinical outcomes. Results: In industrialised populations, no benefit was detected for outcomes other than pneumococcal bacteraemia, and this did not reach statistical significance. In non-industrial populations, clear benefit was demonstrated for mortality and all-cause pneumonia. Conclusion: Benefit from pneumococcal vaccination depends on the baseline risk of infection and characteristics of a given population. Evidence from randomised trials for widespread adult vaccination in industrial countries is lacking.

Introduction

Pneumococcal illness remains a serious public health problem around the world despite medical advances [1]. It is a major cause of pneumonia, meningitis and septicaemia, as well as less serious infections, in developed and developing populations, and mortality remains high. The most vulnerable groups are the very young, the very old and those with predisposing co-morbidities, including immunosuppression and chronic organ dysfunction [2].

The pneumococcal polysaccharide vaccine has been licensed for twenty years in the US and UK. The vaccine contains 23 of the commoner serotypes of pneumococcal infection, covering around 90% of invasive infections. Its overall efficacy is quoted as ‘probably 60–70%’ in preventing pneumococcal pneumonia, but less in the presence of immunosuppression or in children under 2 years [3]. The US Advisory Committee on Immunisation Practices (ACIP) recommend use of pneumococcal polysaccharide vaccine in people over 65, as well as persons at high risk of pneumococcal infection due to co-morbidity [4], [5]. In the UK, vaccination is recommended for patients with chronic organ dysfunction and immunosuppression [3]. Around 8% of the UK population fulfils this definition. Immunisation rates in adults in the UK have been low, but have increased in the past few years [6].

Much of the evidence for the efficacy of the vaccine has been derived from ecological and observational studies [7], [8], [9]. Meta-analyses have produced inconsistent recommendations: Fine and colleagues failed to find definitive evidence of vaccine efficacy in ‘high risk’ groups [10], but Hutchison et al. [11] concluded that the vaccine was efficacious against the specific serotypes included in the preparation, with no evidence of poorer efficacy in immunocompromised subjects. This conflicting evidence led us to re-examine the evidence of effectiveness of the vaccine by conducting an updated systematic review and meta-analysis, with a focus firstly on those groups in which vaccination is recommended in UK and US guidance, and secondly on endpoints which are clinically relevant, rather than proxy indicators. We also wished to examine whether differences in the epidemiology of pneumococcal infection in industrialised and less industrialised countries appeared to affect vaccine effectiveness [12], [13], [14].