Intended for healthcare professionals


Polysaccharide pneumococcal vaccines

BMJ 2002; 325 doi: (Published 10 August 2002) Cite this as: BMJ 2002;325:292

Existing guidance is at variance with the evidence

  1. Tom Jefferson, coordinator (toj1{at},
  2. Vittorio Demicheli, coordinator (demichelivittorio{at}
  1. Cochrane Vaccines Field, and Health Reviews Ltd, Via Adige 28a, I-00061 Anguillara Sabazia, Rome, Italy
  2. Cochrane Vaccines Field, and Servizio Sovrazonale di Epidemiologia, ASL 20, 15100 Alessandria, Italy

    Infection with Streptococcus pneumoniae (pneumococcus) is a leading cause of illness in young children and of illness and death in elderly people and people with immune deficiencies and chronic illness. Pneumococcus causes a spectrum of disease: infections of the upper respiratory tract, otitis media, invasive infections such as bacteraemia and meningitis, and infections of the lower respiratory tract such as pneumonia.w1

    Polyvalent pneumococcal polysaccharide vaccines containing more than one capsular antigen of pneumococcus have been around since the 1940s. The current 23-valent pneumococcal polysaccharide vaccine was introduced in the United States in 1983.w2 Its antigenic composition reflects the incidence of the 23 serotypes in the causation of invasive disease, as well as coverage of themost prevalent serotypes.w2 As each of the many pneumococcal serotypes has a different epidemiology and probably invasiveness this combined vaccine has a very broad spectrum.w3

    Pneumococcal polysaccharide vaccine is recommended in the United States for use in all people aged 65 years or more and in people at risk aged 2 years or more.w1 In several other developed countries it is recommended for similar indications.w2 The evidence to support such indications for its use is, however, far from clear cut.1 w4 The decision to introduce a vaccine into an immunisation programme should be basedon an assessment of the importance of the target health problem, as well as the vaccine's impact on the problem, its safety record, economic profile, and acceptability to users.w5

    The epidemiology of pneumococcal disease seems to vary by serotype, population, age, and setting.w3 The incidence of confirmed pneumococcal disease in the control arms of trials of pneumococcal polysaccharide vaccines carried out in developed countries varied between 1.3% and 19%for pneumococcal pneumonias in people at high risk and between 0.31% and 2.4% in people aged 65 years or more.1 In England and Wales pneumococcal bacteraemia is rare (7/100 000 in the general population),w6 whereas up to 40% of hospital admissions for community acquired pneumonia are due to pneumococcus.w7 In developing countries the proportions may be higher, but difficulties of surveillance and serological diagnosis hinder quantification.w2

    Evidence of the effectiveness of pneumococcal polysaccharide vaccines comes from several trialscarried out in the past decades, which have been the subject of seven systematic reviews publishedbetween 1994 and 2002.17 The methodological quality of the reviews is variable. No review stratified its meta-analysis by valency of the vaccine and the outcomes by type of vaccine, population, or settings. Noneof six reviews found a statistically significant effect of pneumococcal polysaccharide vaccines onmortality in industrialised countries or on pneumoccoccal pneumonia in high risk and immunocompromised patients. Five of the six reviews reported a statistically significant reduction in pneumococcal pneumonia and bacteraemia among immunocompetent adults who were not otherwise at increased risk. The review by Watson et al reported a significant reduction in mortality (relative risk 0.79, 95% confidence interval 0.63 to 0.99) and all cause pneumonia (0.67, 0.52 to 0.87) in trials done in less industrialised countries.1 A Cochrane review of eighttrials of the effects of pneumococcal polysaccharide vaccines in children found an average protective efficacy of 10% against acute otitis media.6 The Cochrane review by Sheikh et al found limited evidence of the effectiveness of pneumococcal polysaccharide vaccines in children and adults with asthma.7

    The safety profile of pneumococcal polysaccharide vaccine is good, with transient erythema and induration appearing in up to 50% of recipients4 and, very rarely, high fever.1 Outcome data about safety were, however, seldom collected or reported in the trials. 1 4

    The acceptability of pneumococcal polysaccharide vaccines in elderly people seems good, especially if combined with influenza vaccines. Pneumococcal polysaccharide vaccines require revaccination, probably every five years, whereas the influenza vaccine needs to be administered every year.

    The economic profile of pneumococcal polysaccharide vaccines is affected by the uncertainties underlying the epidemiology of the disease, the effectiveness of pneumococcal polysaccharide vaccines, and the economic methods used.8 These problems are not specific to pneumococcal polysaccharide vaccines but affect a broad range of interventions and procedures that have been the subject of economic evaluations.w8 Although several economic evaluations have concluded in favour of vaccination, a systematic review of the evidence has found that the evaluations used optimistic estimates of effectiveness.8

    Given the diversity of epidemiological profiles of pneumococcal disease in different settings and populations and the consequent different vaccine performance, we believe that there is no generalisable answer to the question of whether and how to employ pneumococcal vaccine. It may be that protein conjugate pneumococcal vaccines show clearer effectiveness.w9

    Each decision making body must make it own evaluation based on known epidemiology of the disease, likely effectiveness and safety, cost, and fit with the existing immunisation programme. We are struck, however, by the apparent conflict between evidence of effectiveness of pneumococcal polysaccharide vaccines and existing recommendations for their use. Enhanced surveillance of pneumococcal disease and a systematic review of all comparative studies assessing the effects of pneumococcal polysaccharide vaccines may allow us to glimpse the stars through clearer skies.


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