Overall, 428 of 1434 (29.8%) eligible participants reviewed in the 23 nursing homes were excluded (fig 1). Of the remaining 1006 participants, 502 were randomised to the 23-valent pneumococcal polysaccharide vaccine and 504 to placebo. Table 1 shows the baseline characteristics of the two groups. The exposure time was 1140 person years (mean 2.27 person years) in the vaccine group and 1149 (2.28) in the placebo group (fig 1).
Fig 1Flow diagram of trial
Table 1 Baseline characteristics of 1006 Japanese nursing home residents at randomisation to 23-valent pneumococcal polysaccharide vaccine or placebo (sodium chloride). Values are numbers (percentages) unless stated otherwise
During follow-up, one episode of pneumonia was diagnosed in 167 of the 1006 participants (16.6%), with 141 requiring admission to hospital (52 from the vaccine group, 89 from the placebo group). Although some of the participants had multiple episodes of pneumonia (18 had two and three had three), only the first episode was counted for statistical analysis. The incidence of pneumonia did not differ significantly among the 23 nursing homes, and none reported an outbreak of pneumonia.
Results were obtained from blood culture for 122 participants, sputum culture for 134, and urinary antigen test for 152. All cause pneumonia was diagnosed in 12.5% (63/502) of participants in the vaccine group and 20.6% (104/504) in the placebo group. Pneumococcal pneumonia was diagnosed in 51 participants (49 at the first episode and two at recurrences); of these, 49 cases were diagnosed by urinary antigen test, 41 were additionally diagnosed by sputum culture, and three by blood culture. In 97 of the 167 participants with pneumonia a full set of tests (sputum and blood cultures and urinary antigen test) was carried out. Causative pathogens were identified in 84 (50%) of the 167 participants. The causative agents of some non-pneumococcal pneumonia were Staphylococcus aureus (10/116, 9%), Enterobacteriaceae (8/116, 7%), Haemophilus influenzae (5/116, 4%), and Pseudomonas aeruginosa (3/116, 3%).
Pneumococcal pneumonia and all cause pneumonia were significantly more frequent in the placebo group than in the vaccine group during follow-up. Pneumococcal pneumonia was diagnosed in 2.8% (14/502) of participants in the vaccine group and 7.3% (37/504) in the placebo group. Invasive pneumococcal pneumonia (positive result on blood culture) was diagnosed in 0% of participants in the vaccine group and 0.6% (n=3) in the placebo group. Non-pneumococcal pneumonia was diagnosed in 9.8% (n=49) participants in the vaccine group and 13.3% (n=67) in the placebo group.
In the vaccine group the incidence of pneumococcal pneumonia per 1000 person years was reduced by 63.8% and all cause pneumonia by 44.8% (table 2). Survival curves in the vaccine group compared with the placebo group showed a significantly increased cumulative proportion of participants without pneumococcal pneumonia (fig 2) and all cause pneumonia (fig 3).
Table 2 Incidence and reduction of primary end points in Japanese nursing home residents assigned to 23-valent pneumococcal polysaccharide vaccine or placebo
Fig 2Kaplan-Meier survival curves of participants without pneumococcal pneumonia in vaccine and placebo groups
Fig 3Kaplan-Meier survival curves of participants without all cause pneumonia in vaccine and placebo groups
Significantly more participants with pneumococcal pneumonia died in the placebo group than in the vaccine group: 35.1% (13/37) v 0% (0/14) (table 3). The death rate for all cause pneumonia and non-pneumococcal pneumonia was the same in both groups (table 3). Among participants with all cause pneumonia, 20.6% (13/63) died in the vaccine group compared with 25.0% (26/104) in the placebo group. Among participants with non-pneumococcal pneumonia, 26.5% (13/49) died in the vaccine group compared with 19.4% (13/67) in the placebo group (table 3).
Table 3 Death rates among nursing home residents randomised to 23-valent pneumococcal polysaccharide vaccine or to placebo (sodium chloride). Values are numbers (percentages) unless stated otherwise
Overall, 89 participants in the vaccine group and 80 in the placebo group died from all causes—for example, pneumonia, cerebrovascular disease, ischaemic cardiomyopathy, renal failure, senility, and others. Deaths from all causes did not differ between the groups (fig 4).
Fig 4Kaplan-Meier survival curves of participants with different comorbidities, including pneumonia, in vaccine and placebo groups