Prevention of community-acquired pneumonia among a cohort of hospitalized elderly: Benefit due to influenza and pneumococcal vaccination not demonstrated
Introduction
Influenza and 23-valent pneumococcal polysaccharide (23vPPV) vaccines have been shown to reduce invasive pneumococcal disease and laboratory confirmed influenza in persons aged ≥65 years [1], [2]. However, uncertainty remains regarding their effectiveness against community acquired pneumonia in this age group. A recent Cochrane review of pneumococcal vaccine effectiveness (VE) in adults was unable to demonstrate a significant benefit against pneumonia [1]. VE was 23% (95%CI 2–42%) when data were combined from 14 clinical trials, dropping to 16% (95%CI 8–35%) with the exclusion of one trial from the 1940s [3]. The few trials showing benefit [3], [4], [5], [6], [7] were conducted among institutionalized, predominantly non-elderly populations and/or had methodological problems such as lack of radiological confirmation of pneumonia and inadequate concealment of randomization [4], or presentation of interim results only [5]. These data are unlikely to be generalisable to the healthy elderly. Prior to 2002, non-experimental studies of 23vPPV with pneumonia as an outcome were limited to high-risk populations [8] or reported only interim data without adjustment for confounders [9]. Studies since 2002 have produced conflicting results [10], [11], [12], [13].
Although some studies have shown benefit from influenza vaccination against pneumonia for elderly persons who live in the community, a degree of controversy still exists. A recent systematic review found a small benefit that did not reach statistical significance in this population (RR 0.88, 95%CI 0.64–1.20), in addition to those in long-term care facilities where environmental and vaccine viral strain match is poor or unknown [14]. Similarly, two recent cohort studies conducted among community-based elderly in Japan and the Netherlands also found benefit against hospitalisation for influenza and pneumonia [15] and pneumonia [16], respectively, that was not statistically signficant. While Voordouw et al. more recently reported benefit against pneumonia for hospitalised subjects (HR 0.29, 95%CI 0.10–0.96), this was based upon the occurrence of three pneumonia cases [17].
Recent criticism of observational studies showing benefit cites biased estimates of effect in favor of vaccination due to preferential vaccination of healthy subjects [18].
In Australia, funding of influenza vaccine for all persons ≥65 years commenced in 1998 and for 23vPPV in 2005. Prior to this national program, the state of Victoria was the only jurisdiction to provide 23vPPV free to persons ≥65 years from 1998 [19]. This created a unique setting where relatively high vaccine coverage enabled estimation of effectiveness of influenza vaccine and 23vPPV against hospitalization for community-acquired pneumonia (HCAP).
Section snippets
Design
A case–cohort study was chosen as the best design to estimate VE. An experimental design was impossible because the vaccines were in widespread use, while a prospective cohort study was not feasible because of the resources required to follow a large number of elderly subjects for the outcome of interest, the lack of data on covariates in existing databases and potential for considerable loss to follow-up. The case–cohort design is an accepted method for evaluating VE [20] and a variant of the
Description of eligible subjects
There were 1952 first selected episodes of HCAP (see Fig. 1). A random sample of 3204/49,692 (6%) eligible separations was selected for the cohort, of whom 2927 remained for analysis after further exclusions (Fig. 2). 107 (4%) of these were also cases. Cases and cohort subjects differed for a number of baseline characteristics (Table 1) which were included in subsequent regression models.
3534 (74% of 4772) selected subjects consented to participate in the questionnaire and 4166 (87%) consented
Discussion
While both 23vPPV and influenza vaccine have proven benefit against other outcomes, during a period of typical disease rates due to S. pneumoniae and influenza, our study did not find benefit from either vaccine for the prevention of HCAP. However, we cannot exclude the possibility of small protective effects of less than 19 and 16%, respectively. The study had a number of strengths compared with some previous non-experimental studies. Results were consistent across all adjusted and unadjusted,
Acknowledgments
This study was supported by research assistants responsible for data collection: Anne-Marie Woods, Carol Roberts, Caroline Watts and Joy Turner, with data entry by Thao Nguyen and Jason Zhu. Graham Byrnes is supported by a National Health and Medical Research Council Capacity Building Grant in Population Health (251533). This study was jointly funded by the Victorian Government Department of Human Services and the National Health and Medical Research Council. The sponsors of the study had no
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