The impact of 13-valent pneumococcal conjugate vaccination on virus-associated community-acquired pneumonia in elderly: Exploratory analysis of the CAPiTA trial

Abstract

Objectives: Our objective was to evaluate whether vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) prevents the incidence of community-acquired pneumonia (CAP) caused by influenza (influenza-associated CAP, IA-CAP) or other respiratory viruses in the elderly.

Methods: This analysis was part of the Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA); a double blind, randomized, placebo-controlled trial in 84 496 immunocompetent individuals aged ≥65 years. CAP was defined by clinical and radiological criteria, and oropharyngeal swabs were collected from all individuals referred to a sentinel centre with a clinical suspicion of pneumonia. Presence of influenza A and B, parainfluenza 1, 2, 3 and 4, human adeno-, boca-, corona-, metapneumo-, rhino- and respiratory syncytial viruses was determined by real-time PCR.

Results: Of 3209 episodes of suspected pneumonia, viral aetiology was tested in 2917 and proportions with influenza virus, human metapneumovirus and respiratory syncytial virus were 4.6%, 2.5% and 3.1%, respectively. There were 1653 oropharyngeal swabs for PCR testing available from 1814 episodes that fulfilled criteria for CAP, yielding 23 first episodes of IA-CAP in the PCV13 and 35 in the in placebo group-vaccine efficacy for IA-CAP of 34.4% (95% CI -11.1% to 61.2%; p 0.117). Annual influenza vaccination was received by 672 (87.2%) in the PCV13 group and 719 (87.7%) in the placebo group of the confirmed CAP cases.

Conclusion: In a randomized study of 84 496 elderly individuals with a high uptake of influenza vaccination, PCV13 was not associated with a statistically significant reduction of influenza or virus-associated CAP. Overall incidence of non-influenza viral pneumonia was low.

Keywords: 13-valent pneumococcal conjugate vaccine; Community-acquired pneumonia; Influenza virus; Viral community-acquired pneumonia; Viral pneumonia.

Fig. 1

(a) Flow-chart of ‘confirmed CAP’ study population (n = 1653). ^$ No confirmed CAP = episodes not fulfilling the definition ‘confirmed CAP’, i.e. chest X-ray not consistent with pneumonia and/or less than two clinical symptoms. (b) Flow-chart of ‘suspected pneumonia’ study population (n = 2917). *Symptom onset <14 days after vaccination. Abbreviations used: PCV13, 13-valent pneumococcal conjugate vaccine; CAP, community-acquired pneumonia; UAD, urinary antigen detection assay.

Fig. 2

Diagram of available diagnostic methods for individuals with confirmed CAP and a oropharyngeal swab available (n = 1653). Abbreviations used: CAP, community-acquired pneumonia; UAD, urinary antigen detection assay; Culture, either a sterile (e.g. blood) or non-sterile (e.g. sputum) sample available for culture; pneumococcal UAD, either conventional pneumococcal urinary antigen detection assay (i.e. Binax) or serotype-specific urinary antigen detection assay. Please note that this diagram excludes 16 patients who did not have any of these diagnostic methods available (i.e. only an oropharyngeal swab for viral analyses).

Fig. 3

Proportion of IA-CAP among confirmed CAP episodes with swab (n = 1653), stratified by year. Abbreviations used: IA-CAP, influenza associated community-acquired pneumonia; INFL A, influenza A; INFL B, influenza B; Non-typ, non-typeable influenza, i.e. subtyping failed. The proportion represents the part of IA-CAP cases among all confirmed CAP cases with oropharyngeal swab available, admitted in that period. Year 2008/9 starts at 1 September 2008 until 31 August 2009, this also applies to the following years.