Vaccines to Prevent Pneumococcal Community-Acquired Pneumonia

Streptococcus pneumoniae is the most frequent pathogen in community-acquired pneumonia and also causes invasive diseases like bacteremia and meningitis. Young children and elderly are especially at risk for pneumococcal diseases and are, therefore, eligible for pneumococcal vaccination in most countries. This reviews provides an overview of the current epidemiology of pneumococcal infections, history and evidence of available pneumococcal polysaccharide and conjugate vaccines, and current recommendations

The scrutiny of identifying community-acquired pneumonia episodes quantified bias in absolute effect estimation in a population-based pneumococcal vaccination trial

Objectives To determine the accurateness of detecting community-acquired pneumonia (CAP) in the Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA), a community-based, double-blind, randomized placebo-controlled trial in which the needed to treat (NNT) for prevention of vaccine-type pneumococcal CAP was 1,007 [95% confidence interval (CI): 613, 2,646]. Study Design and Setting Study participants developing pneumonia were identified in 58 participating hospitals by research nurses (RNs) using local-adapted protocols. In addition, general practitioner (GP) records were screened for hospital referrals for suspected pneumonia. Two independent reviewers determined reasons for not identifying pneumonia episodes, and the NNT adjusted for missed episodes was estimated. Results Of 2,183 hospital referrals with suspected pneumonia detected in GP records, 232 (11%) were admitted outside established screening routes and 102 (5%) were not suspected of pneumonia on admission. Of the remaining 1,849 episodes, 1,374 (63% of all episodes and 74% of identifiable episodes) were identified by RNs. Several causes of missing episodes were identified. After adjustment for missed episodes, the NNT reduced to 634 (95% CI: 386, 1,675). Conclusion With the screening procedure, 63% of suspected pneumonia episodes were identified, and the estimated NNT reduced from 1,007 to 634. Root cause analysis of unidentified episodes provides guidance for improving pneumonia detection in future trials

The impact of community-acquired pneumonia on the health-related quality-of-life in elderly

BACKGROUND: The sustained health-related quality-of-life of patients surviving community-acquired pneumonia has not been accurately quantified. The aim of the current study was to quantify differences in health-related quality-of-life of community-dwelling elderly with and without community-acquired pneumonia during a 12-month follow-up period. METHODS: In a matched cohort study design, nested in a prospective randomized double-blind placebo-controlled trial on the efficacy of the 13-valent pneumococcal vaccine in community-dwelling persons of ≥65 years, health-related quality-of-life was assessed in 562 subjects hospitalized with suspected community-acquired pneumonia (i.e. diseased cohort) and 1145 unaffected persons (i.e. non-diseased cohort) matched to pneumonia cases on age, sex, and health status (EQ-5D-3L-index). Health-related quality-of-life was determined 1-2 weeks after hospital discharge/inclusion and 1, 6 and 12 months thereafter, using Euroqol EQ-5D-3L and Short Form-36 Health survey questionnaires. One-year quality-adjusted life years (QALY) were estimated for both diseased and non-diseased cohorts. Separate analyses were performed for pneumonia cases with and without radiologically confirmed community-acquired pneumonia. RESULTS: The one-year excess QALY loss attributed to community-acquired pneumonia was 0.13. Mortality in the post-discharge follow-up year was 8.4% in community-acquired pneumonia patients and 1.2% in non-diseased persons (p < 0.001). During follow-up health-related quality-of-life was persistently lower in community-acquired pneumonia patients, compared to non-diseased persons, but differences in health-related quality-of-life between radiologically confirmed and non-confirmed community-acquired pneumonia cases were not statistically significant. CONCLUSIONS: Community-acquired pneumonia was associated with a six-fold increased mortality and 16% lower quality-of-life in the post-discharge year among patients surviving hospitalization for community-acquired pneumonia, compared to non-diseased persons. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00812084

The Impact of Age on the Efficacy of 13-valent Pneumococcal Conjugate Vaccine in Elderly

In a post hoc analysis of the Community-Acquired Pneumonia (CAP) immunization Trial in Adults the model-predicted 13-valent pneumococcal conjugate vaccine efficacy for preventing vaccine-type specific CAP and Invasive Pneumococcal Disease declined from 65% to 40% for subjects being 65 and 75 year olds at the time of vaccination, respectively

The Impact of Age on the Efficacy of 13-valent Pneumococcal Conjugate Vaccine in Elderly

In a post hoc analysis of the Community-Acquired Pneumonia (CAP) immunization Trial in Adults the model-predicted 13-valent pneumococcal conjugate vaccine efficacy for preventing vaccine-type specific CAP and Invasive Pneumococcal Disease declined from 65% to 40% for subjects being 65 and 75 year olds at the time of vaccination, respectively

Post-hoc analysis of a randomized controlled trial : Diabetes mellitus modifies the efficacy of the 13-valent pneumococcal conjugate vaccine in elderly

BACKGROUND: The 13-valent pneumococcal conjugate-vaccine (PCV13) was effective in preventing vaccine-type Community-Acquired Pneumonia (VT-CAP) and Invasive Pneumococcal Disease (VT-IPD) in elderly subjects, but vaccine efficacy (VE) in patients with comorbidities at time of vaccination is unknown. METHODS: This is a post hoc analysis of the CAPiTA study, a double blind, randomized controlled trial with 84,496 immunocompetent participants aged ⩾65years, receiving PCV13 or placebo vaccination. Presence of diabetes mellitus (DM), heart disease, respiratory disease, liver disease, asplenia, and smoking at the time of immunization was verified on medical records in 139 subjects developing the primary endpoint of VT-CAP. Presence of DM and respiratory disease based on International Classification of Primary Care (ICPC) coding was also determined in 40,427 subjects. FINDINGS: In the 139 subjects developing VT-CAP, DM caused significant effect modification (p-value 0.002), yielding VE of 89.5% (95%CI, 65.5-96.8) and 24.7% (95%CI, -10.4 to 48.7) for those with and without DM, respectively. Comparable effect modification (p-value 0.020) was found in the 40,427 subjects with and without ICPC-based classification of DM with VE of 85.6% (95%CI, 36.7-96.7) and of 7.0% (95%CI, -58.5 to 45.5) respectively. Effect modification through respiratory disease was not statistically significant, although the point estimate of VE was lower for those with respiratory disease in both analyses. There was no evidence of effect modification in subjects stratified by heart disease, smoking, and presence of any comorbidity. CONCLUSIONS: Among immunocompetent elderly, VE of PCV13 was modified by DM with higher VE among subjects with DM. Significant effect modification was not observed for subjects with heart disease, respiratory disease, smoking, or presence of any comorbidity. CAPiTA trial registration number: www.ClinicalTrials.gov; trial number NCT00744263

Effects of 13-valent pneumococcal conjugate vaccination of adults on lower respiratory tract infections and antibiotic use in primary care: secondary analysis of a double-blind randomized placebo-controlled study

Objectives: The efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) in adults to prevent community-acquired pneumonia (CAP) and lower respiratory tract infections (LRTI) not requiring hospitalization is unknown. We determined the effect of PCV13 on CAP, LRTI and antibiotic use in the primary care setting. Methods: Community-dwelling immunocompetent adults over 65 years of age were randomized to PCV13 or placebo as part of the double-blind Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA). CAP and LRTI episodes and antibiotic prescription data were extracted from general practitioner information systems of 40 426 individuals. Vaccine efficacy (VE) of PCV13 was determined using Poisson regression with robust standard errors, comparing CAP and non-CAP LRTI episodes, LRTI-specific and total antibiotic prescriptions. Results: In all, 20 195 participants received PCV13 and 20 231 received placebo. A total of 1564 and 1659 CAP episodes occurred in the PCV13 and placebo group, respectively; VE 5.5% (95% CI –2.6% to 13.0%). Non-CAP LRTI episodes occurred 7535 and 7817 times in the PCV13 and placebo groups, respectively; VE 3.4% (95% CI –2.0% to 8.5%). A total of 8835 and 9245 LRTI-related antibiotic courses were prescribed in the PCV13 and placebo arms, respectively; VE 4.2% (95% CI –1.0% to 9.1%). Antibiotic courses for any indication were prescribed 43 386 and 43 309 times, respectively; VE –0.4% (–4.9% to 3.9%). Conclusions: PCV13 vaccination in the elderly is unlikely to cause a relevant reduction in the incidence of CAP, LRTI, LRTI-related antibiotic use or total antibiotic use in primary care