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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.

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.

In response to Theilacker et al. we explain that we consider the point estimate as well as the confidence bounds in our interpretation of the study results and do not treat confidence intervals as a dichotomous signal. We refute that the proposed calculation of vaccine preventable disease incidence is more valuable than calculation of vaccine efficacy. Finally we remain at our conclusion that 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.

Pneumokokkeninfecties komen frequent voor en vormen wereldwijd een belangrijke oorzaak van morbiditeit en mortaliteit. De incidentie is het hoogst onder jonge kinderen en ouderen; bij deze groepen is bovendien het risico op sterfte of complicaties ten gevolge van de infectie het grootst. Behandeling wordt gecompliceerd door stijgende resistentie van pneumokokken voor de meest gebruikte antibiotische middelen. Sinds 2006 worden in Nederland baby’s via het Rijksvaccinatieprogramma gevaccineerd tegen pneumokokken, waarbij ook een beschermend effect te verwachten is op andere risicogroepen. In een recente grote Nederlandse vaccinatietrial (CAPiTA) bleek pneumokokkenvaccinatie effectief in het voorkomen van pneumokokkenpneumonie en invasieve pneumokokkenziekte bij ouderen.

Background We aimed to evaluate health status and associated factors in community-dwelling elderly in the Netherlands. Methods Participants from a placebo-controlled double-blind randomized controlled trial conducted in the Netherlands were invited at the time of enrolment to participate in this study. Data were collected on comorbidities, socio-demographic background and health status, using EQ-5D-3L instrument. EQ-5D-3L summary index values (EQ-5D-indices) was derived using Dutch tariff. Regression analysis was conducted to identify factors associated with EQ-5D-indices and visual analogue scale (EQ-VAS). Results 48,634 elderly (≥65 years) were included. The most frequently reported complaint was pain/discomfort (29.4%), but for the elder elderly (i.e. ≥85 years) it was mobility (52.9%). The proportion of persons reporting (multiple) problems increased with age from 31.5% for 65–69 years old subjects to 65.9% for elder elderly. The mean EQ-5D-indices and EQ-VAS decreased with age from 0.94 and 84, respectively in those 65 to 69 years old to 0.86 and 76, respectively, in ≥85 years old subjects. Increasing age, female gender, low education, geographic factors and comorbidities were associated with impaired health status. Conclusions Within community-dwelling elderly large differences in health status exist. Impairment increases rapidly with age, but health status is also associated with socio-demographic variables and comorbidities. Trial registration ClinicalTrials.gov, NCT00812084. Electronic supplementary material The online version of this article (doi:10.1186/s12955-016-0577-5) contains supplementary material, which is available to authorized users.

BACKGROUND: Herd protection from infant pneumococcal conjugate vaccination is well established for invasive pneumococcal disease (IPD) but not for non-IPD pneumococcal community-acquired pneumonia (PCAP). We assessed the contribution of vaccine-serotypes in non-IPD PCAP in adults 65 years and older in the period 2008-2013. METHODS: This is a post hoc analysis of two prospective studies from the Netherlands. Serotype specific urinary antigen detection and routine microbiological testing were used to categorize episodes as IPD or non-IPD PCAP caused by 7-valent pneumococcal conjugate vaccine (PCV7), PCV10-7 (three additional PCV10 serotypes), PCV13-10 (three additional PCV13 serotypes), and non-PCV13 serotypes. Proportions per vaccine-serotype group were assessed per year from June 1st to May 31st. Time trends were compared to national IPD data. RESULTS: Of 270 non-IPD PCAP episodes with known serotype, PCV7 serotypes decreased from 28% in 2008/2009 to 7% in 2012/2013 (p-value for trend

Background The Community Acquired Pneumonia immunization Trial in Adults (CAPiTA) was conducted to evaluate 13-valent pneumococcal conjugate vaccine (PCV13) for the prevention of vaccine-type community-acquired pneumonia (VT-CAP) and vaccine-type invasive pneumococcal disease (VT-IPD) in adults aged ⩾65 years. Plotting the cumulative number of episodes against time from vaccination demonstrated that efficacy was evident soon after vaccination and persisted throughout the duration of the study. This post hoc analysis was performed to quantify the persistence of vaccine efficacy (VE) of PCV13. Methods This was a parallel-group, randomized, placebo-controlled, double-blind trial. Subjects were enrolled between September 15, 2008 and January 30, 2010 at 101 sites in the Netherlands and randomized 1:1 to receive a single dose of PCV13 or placebo. The observed accumulation of episodes for VT-CAP, nonbacteremic/noninvasive VT-CAP (NB/NI-VT-CAP), and VT-IPD over the course of the study after vaccination was assessed. Post hoc time-to-event analyses of primary and secondary endpoints were performed. VE behavior over time was derived and effects of treatment, time, and time by treatment interactions were estimated. Results A total of 84,496 individuals were enrolled (PCV13, n = 42,240; placebo, n = 42,256). Cases of VT-CAP, NB/NI-VT-CAP, and VT-IPD were greater among placebo recipients compared with PCV13 recipients throughout the postvaccination observation period with a periodic rise in cases in the placebo group that was consistent with varied exposure and ensuing disease over time. There was a significant difference in disease-free survival among PCV13 recipients compared with placebo recipients for VT-CAP (log-rank test P = 0.0005), NB/NI VT-CAP ( P = 0.0051), and VT-IPD ( P = 0.0004). VE ranged from 42.9% to 50.0% for VT-CAP, 36.2% to 48.5% for NB/NI-VT-CAP, and 66.7% to 75.0% for VT-IPD. Conclusions The results of this post hoc analysis of the persistence of PCV13 VE in adults ⩾65 years, indicate that PCV13 was protective over the 5-year duration of the study, with no waning of efficacy observed. ClinicalTrials.gov identifier NCT00744263

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.

Pneumococcal polysaccharide conjugate vaccines prevent pneumococcal disease in infants, but their efficacy against pneumococcal community-acquired pneumonia in adults 65 years of age or older is unknown.In a randomized, double-blind, placebo-controlled trial involving 84,496 adults 65 years of age or older, we evaluated the efficacy of 13-valent polysaccharide conjugate vaccine (PCV13) in preventing first episodes of vaccine-type strains of pneumococcal community-acquired pneumonia, nonbacteremic and noninvasive pneumococcal community-acquired pneumonia, and invasive pneumococcal disease. Standard laboratory methods and a serotype-specific urinary antigen detection assay were used to identify community-acquired pneumonia and invasive pneumococcal disease.In the per-protocol analysis of first episodes of infections due to vaccine-type strains, community-acquired pneumonia occurred in 49 persons in the PCV13 group and 90 persons in the placebo group (vaccine efficacy, 45.6%; 95.2% confidence interval [CI], 21.8 to 62.5), nonbacteremic and noninvasive community-acquired pneumonia occurred in 33 persons in the PCV13 group and 60 persons in the placebo group (vaccine efficacy, 45.0%; 95.2% CI, 14.2 to 65.3), and invasive pneumococcal disease occurred in 7 persons in the PCV13 group and 28 persons in the placebo group (vaccine efficacy, 75.0%; 95% CI, 41.4 to 90.8). Efficacy persisted throughout the trial (mean follow-up, 3.97 years). In the modified intention-to-treat analysis, similar efficacy was observed (vaccine efficacy, 37.7%, 41.1%, and 75.8%, respectively), and community-acquired pneumonia occurred in 747 persons in the PCV13 group and 787 persons in placebo group (vaccine efficacy, 5.1%; 95% CI, -5.1 to 14.2). Numbers of serious adverse events and deaths were similar in the two groups, but there were more local reactions in the PCV13 group.Among older adults, PCV13 was effective in preventing vaccine-type pneumococcal, bacteremic, and nonbacteremic community-acquired pneumonia and vaccine-type invasive pneumococcal disease but not in preventing community-acquired pneumonia from any cause. (Funded by Pfizer; CAPITA ClinicalTrials.gov number NCT00744263.).

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 ⩾65 years, 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 .

In een redactioneel commentaar (juli 2015) wordt gesteld dat de resultaten van de CAPiTA trial niet voldoende realistisch zijn gepresenteerd, dat er geen statistische effecten op sterfte zijn en dat de betrokkenheid van Pfizer een genuanceerde weergave van de resultaten in de weg heeft gestaan.1

Old Age: Results from an Exploratory Analysis of the CAPiTA Trial Cornelis H VanWerkhoven, MD; Susanne MHuijts, MD; Marieke Bolkenbaas, MD; Chris Webber, MD, PhD; Beate Schmoele-Thoma, MD; Scott D. Patterson, PhD; William Gruber, MD; Diederick E. Grobbee, MD, PhD; Marc Bonten, MD PhD; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands; Pfizer Vaccine Clinical Research, Maidenhead, United Kingdom; Pfizer Pharma GmbH, Berlin, Germany; Pfizer Vaccine Clinical Research, Collegeville, PA; Pfizer Vaccine Clinical Research, Pearl River, NY; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, Netherlands