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Editorials

Pneumococcal polysaccharide vaccine in high risk adults

BMJ 2010; 340 doi: https://doi.org/10.1136/bmj.c1139 (Published 08 March 2010) Cite this as: BMJ 2010;340:c1139
  1. Sarah A Moberley, epidemiologist1,
  2. Paul Torzillo, senior respiratory and intensive care physician2
  1. 1Acute Respiratory Infections, Papua New Guinea Institute of Medical Research, PO Box 60, Goroka, 441 EHP, Papua New Guinea
  2. 2Department of Respiratory Medicine, Royal Prince Alfred Hospital, Camperdown, Sydney, NSW 2050, Australia
  1. sarah.moberley{at}gmail.com

    Evidence of efficacy against pneumonia is still limited

    Streptococcus pneumoniae continues to cause a substantial burden of disease and death in adults, despite nearly 100 years of research into disease prevention and the availability of a licensed vaccine. To date, uptake of the vaccine has generally been limited to older adults and those with chronic illness in high income countries. Coverage has been generally suboptimal, perhaps because of the continued controversy about the vaccine’s efficacy against various clinical end points and within different populations.

    In the linked randomised controlled trial (doi:10.1136/bmj.c1004), Maruyama and colleagues assess the effects of the 23-valent pneumococcal polysaccharide vaccine in 1006 nursing home residents in Japan.1 This is the first trial of this type for many years, and the first to show that this vaccine protects against all cause pneumonia (vaccine efficacy 44.8%, 95% confidence interval 22.4 to 60.8) and pneumococcal pneumonia (vaccine efficacy 63.8%, 32.1 to 80.7) in older adults.

    Pneumonia is the most common presentation of pneumococcal disease in adults, and it was outbreaks of pneumococcal pneumonia in otherwise healthy men in barrack accommodation that provided the impetus for vaccine trials in the 1940s.2 Later trials of vaccines of various valency in South African miners and in Papua New Guinea during the 1970s found reductions in bacteraemic pneumonia, all cause pneumonia, mortality from pneumonia, and all cause mortality (listed in the order of the level of protective efficacy).3 4 5 A 14-valent pneumococcal polysaccharide vaccine was subsequently licensed in 1977, then replaced by the higher valency (23-valent) but lower antigen content vaccine in 1983 without additional trials before licensing.6

    Trials in high income countries after licensing of the 23-valent vaccine have been plagued by problems. Outcomes vary depending on which end point measurement—invasive disease (vaccine serotype or not), presumptive pneumococcal pneumonia, all cause pneumonia, mortality from pneumonia, or all cause mortality—is selected. These measures require large sample sizes if attack rates are low. In older patients and those with chronic illness, randomised controlled trials have failed to find evidence of efficacy against pneumonia or mortality, although these trials were generally underpowered.7 In addition, the reporting of these later studies was of higher quality than in the earlier studies.8 Large observational studies have consistently reported vaccine effectiveness against invasive disease in populations in which the vaccine has been used. A recent systematic review shows that for otherwise healthy older adults the vaccine significantly reduced invasive disease but had no effect on other outcomes.7

    The limitations of Maruyama and colleagues’ study make it unlikely that the debate about vaccine efficacy against non-bacteraemic pneumonia in older adults will be quelled. The incidence of pneumonia was high (72.8/1000 person years), and this was not supported by the earlier study that they cite, which did not provide incidence data. The trial was limited by the classification and causes of pneumonia because the authors did not use a standard definition for radiological confirmation. Most cases of pneumococcal pneumonia were diagnosed by urinary antigen, which does not have well defined sensitivity and specificity. However, evidence of a positive effect of vaccination was strengthened by the absence of invasive pneumococcal disease in the intervention group.

    The authors claim that the 23-valent vaccine improved survival; however, despite the apparent protective efficacy against all cause pneumonia and pneumonia related mortality (0 in the vaccine group v 13 in the control group), this did not translate into a reduction in all cause mortality (even though pneumonia accounted for 26 of 80 (32.5%) deaths in the control group). The overall rate of death did not differ significantly between the vaccine group and the control group.

    Existing evidence strongly supports immunising elderly people living in nursing homes. These institutions continue to experience outbreaks of pneumococcal disease with high case fatality rates in poorly vaccinated populations. The evidence for vaccinating elderly people living at home or those with chronic illness remains contentious. However, the vaccine is safe and probably effective against invasive disease, so clinicians should consider using it in patients who fit these categories.

    The greatest burden of pneumococcal disease is in low income countries, and the role of the 23-valent vaccine and other pneumococcal vaccine formulations in these settings needs to be researched. In high income countries, new trials are needed to provide data on preventing pneumococcal disease in high risk adults. However, these studies need to be large and may be too costly. It is unclear whether the conjugate vaccine can overcome the limitations of serotype coverage by providing enhanced protection against disease end points compared with the polysaccharide vaccine. Future research also needs to include better ways to diagnose pneumococcal pneumonia and a standardised definition of radiological pneumonia in adults.

    Notes

    Cite this as: BMJ 2010;340:c1139

    Footnotes

    • Research, doi:10.1136/bmj.c1004
    • Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: (1) No financial support for the submitted work from anyone other than their employer; (2) No financial relationships with commercial entities that might have an interest in the submitted work; (3) No spouses, partners, or children with relationships with commercial entities that might have an interest in the submitted work; (4) No Non-financial interests that may be relevant to the submitted work.

    • Provenance and peer review: Commissioned; not externally peer reviewed.

    References

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