ArticlesRandomised trial of 23-valent pneumococcal capsular polysaccharide vaccine in prevention of pneumonia in middle-aged and elderly people
Introduction
Polyvalent pneumococcal capsular polysaccharide vaccine is effective in the prevention of invasive pneumococcal disease in immunocompetent people,1, 2, 3, 4 and of pneumococcal pneumonia in healthy young men.5, 6 However, the vaccine's protective efficacy against pneumococcal pneumonia in middle-aged and elderly people remains unknown. Most randomised controlled studies have shown no benefit from vaccination among older, high-risk adults7, 8, 9 possibly because there were too few participants or the estimated frequency of pneumococcal pneumonia in the study populations was too high.10
About 10 years ago, Clemens and Shapiro11 argued that randomised clinical trials were unlikely to resolve the question of the vaccine's efficacy. Although a randomised trial is a powerful method, ethical objections to random allocation of a licensed and potentially life-saving vaccine, and the enormous sample size required, called for studies that were observational and, in particular, case-controlled.
In Sweden, no recommendation concerning the use of the pneumococcal vaccine existed until the end of 1994, and because the earlier use had been very limited (roughly 1500 doses per year in a population of nearly 9 million) no ethical objections to randomised clinical trials were raised before that time. One way to reduce the sample size needed is to study a population at high risk of pneumonia. Patients treated in hospital, for any cause, have a high probability of readmission with pneumonia within 5 years.12 In patients admitted to hospital with a diagnosis of pneumonia, the risk of readmission with the same diagnosis is even higher.13
We therefore undertook a prospective, multicentre, double-blind, randomised, placebo-controlled trial of the 23-valent pneumococcal vaccine in middle-aged and elderly patients without known immunosuppression, who had been discharged from hospital after treatment for pneumonia. Our primary objective was to assess the effectiveness of the pneumococcal vaccine in the prevention of pneumococcal pneumonia and pneumonia overall.
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Study design
Patients who had been treated in hospital for community-acquired pneumonia (CAP) were randomly assigned in equal proportions to receive 23-valent pneumococcal capsular polysaccharide vaccine (Pneumovax, MSD, NJ, USA) 0·5 mL (25 μg each capsular type) or placebo (sodium chloride) 0·5 mL intramuscularly, in a double-blind, multicentre study. Patients on anticoagulant treatment received the vaccine subcutaneously.
Randomisation was done by the vaccine manufacturer (MSD) and the code was not
Definitions
Primary and secondary endpoints—Primary endpoints were pneumonia, defined as acute clinical symptoms or signs compatible with a lower-respiratory-tract infection and a new infiltrate on chest radiography; and pneumococcal pneumonia, defined as pneumonia and a positive culture from blood, pleural fluid, or sputum (≥105 colony-forming units per mL in a purulent sample) or a positive pneumococcal antibody test. Secondary endpoints were bacteraemic pneumococcal pneumonia and death from all causes.
Results
Consecutive eligible patients treated for CAP between January, 1991, and January, 1994, were reviewed for inclusion. Of 1549 reviewed, 894 (58%) patients were excluded (figure 1). “Presumed poor compliance” included patients who were unable, for practical reasons (eg, distance, transport difficulties), to contact the hospital in case of a suspected recurrent pneumonia (191 patients); patients with mental impairment or severe chronic alcoholism (187 patients); and patients bed-ridden owing to a
Discussion
We found the polyvalent pneumococcal polysaccharide vaccine to be safe, with no serious adverse events. This finding is consistent with previous research.22 We were unable to show that the vaccine was effective in the prevention of pneumonia overall or of pneumococcal pneumonia, despite a high incidence of these diseases in the study population. Nor could we find any difference in death rates between the study groups. However, a higher (though not significant) rate of bacteraemia occurred in
References (30)
- et al.
Pneumococcal infection and immunologic response to pneumococcal vaccine in chronic obstructive pulmonary disease: a pilot study
Chest
(1987) - et al.
Risk of pneumonia in patients previously treated in hospital for pneumonia
Lancet
(1992) - et al.
Measurement of antibody responses to Pneumolysin: a promising method for the presumptive etiological diagnosis of pneumococcal pneumonia
J Infect
(1989) - et al.
Demonstration of pneumolysin antibodies in circulating immune complexes: a new diagnostic method for pneumococcal pneumonia
Serodiagn Immunother Infect Dis
(1990) - et al.
Hospital-study of adult community-acquired pneumonia
Lancet
(1982) - et al.
Inefficacy of pneumococcal vaccine in a high-risk population
Am J Med
(1987) - et al.
The clinical effectiveness of pneumococcal vaccine in the elderly
Ann Intern Med
(1988) - et al.
The protective efficacy of polyvalent pneumococcal polysaccharide vaccine
N Engl J Med
(1991) - et al.
Pneumococcal polysaccharide vaccine efficacy
JAMA
(1993) - et al.
Preventing pneumococcal bacteremia in patients at risk
Arch Intern Med
(1995)
Prevention of pneumococcal pneumonia by vaccination
Trans Assoc Am Physicians
Protective efficacy of pneumococcal polysaccharide vaccines
JAMA
Efficacy of pneumococcal vaccine in high-risk patients
N Engl J Med
Efficacy of pneumococcal vaccine in severe chronic obstructive pulmonary disease
Can Med Assoc J
Pneumococcal vaccine after 15 years of use
Arch Intern Med
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