Community-Acquired Pneumonia Immunization Trial In Adults Research Articles

PCV13 Vaccination of Adults against Pneumococcal Disease: What We Have Learned from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA).

The Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA) evaluated older adult pneumococcal vaccination and was one of the largest vaccine clinical trials ever conducted. Among older adults aged ≥65 years, the trial established 13-valent pneumococcal conjugate vaccine (PCV13) efficacy in preventing first episodes of bacteremic and nonbacteremic pneumococcal vaccine serotype (VT) community acquired pneumonia (CAP), and of vaccine serotype invasive pneumococcal disease (VT-IPD). Since the publication of the original trial results, 15 additional publications have extended the analyses. In this review, we summarize and integrate the full body of evidence generated by these studies, contextualize the results in light of their public health relevance, and discuss their implications for the assessment of current and future adult pneumococcal vaccination. This accumulating evidence has helped to better understand PCV13 efficacy, serotype-specific efficacy, efficacy in subgroups, the interpretation of immunogenicity data, and the public health value of adult PCV vaccination.

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

ObjectivesThe 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. MethodsCommunity-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. ResultsIn 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%). ConclusionsPCV13 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.

Confounding by indication of the safety of de-escalation in community-acquired pneumonia: Asimulation study embedded in a prospective cohort.

Observational studies have demonstrated that de-escalation of antimicrobial therapy is independently associated with lower mortality. This most probably results from confounding by indication. Reaching clinical stability is associated with the decision to de-escalate and with survival. However, studies rarely adjust for this confounder. We quantified the potential confounding effect of clinical stability on the estimated impact of de-escalation on mortality in patients with community-acquired pneumonia. Data were used from the Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA). The primary outcome was 30-day mortality. We performed Cox proportional-hazards regression with de-escalation as time-dependent variable and adjusted for baseline characteristics using propensity scores. The potential impact of unmeasured confounding was quantified through simulating a variable representing clinical stability on day three, using data on prevalence and associations with mortality from the literature. Of 1,536 included patients, 257 (16.7%) were de-escalated, 123 (8.0%) were escalated and in 1156 (75.3%) the antibiotic spectrum remained unchanged. Crude 30-day mortality was 3.5% (9/257) and 10.9% (107/986) in the de-escalation and continuation groups, respectively. The adjusted hazard ratio of de-escalation for 30-day mortality (compared to patients with unchanged coverage), without adjustment for clinical stability, was 0.39 (95%CI: 0.19–0.79). If 90% to 100% of de-escalated patients were clinically stable on day three, the fully adjusted hazard ratio would be 0.56 (95%CI: 0.27–1.12) to 1.04 (95%CI: 0.49–2.23), respectively. The simulated confounder was substantially stronger than any of the baseline confounders in our dataset. Quantification of effects of de-escalation on patient outcomes without proper adjustment for clinical stability results in strong negative bias. This study suggests the effect of de-escalation on mortality needs further well-designed prospective research to determine effect size more accurately.

1439. The Cost-Effectiveness of Vaccinating Adults at Increased Risk of Pneumococcal Disease Against Pneumococcal Disease in The Netherlands

BackgroundThere is currently no data on the age- and risk-group-specific cost-effectiveness of the 13 valent pneumococcal vaccine (PCV13) compared with the 23 valent polysaccharide vaccine (PPV23). The aim of this study was to evaluate the cost-effectiveness of vaccinating these specific groups against pneumococcal disease.MethodsA previously published and independently validated (by The Dutch National Health-Care Institute) age-and risk-group-specific Markov-type model was used to compare the cost-effectiveness of PCV13 vaccination vs. PPV23 vaccination of all adults at increased risk of pneumococcal disease (i.e., adults with underlying disease and those ≥50 years). Efficacy estimates for PCV13 were extrapolated from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA). Efficacy estimates for PPV23 were based on systematic literature reviews and other published data.ResultsAt list price (€68.56 for PCV13 and €19.99 for PPV23), vaccination of all adults at increased risk of pneumococcal disease resulted in an ICER of €20,186/QALY, while vaccinating those with chronic medical conditions (moderate risk) and immunocompromising conditions (high risk) resulted in an ICER of <€10,000/QALY. Large differences in ICERs between age-and risk-groups were observed(table). Vaccinating, high-risk individuals with PCV13 was cost-saving for those aged less than 65 years of age compared with PPV23 while vaccinating those aged 85 years and older with PCV13 was moderate cost-effective with an ICER of €60,900/QALY. Vaccinating moderate risk individuals was highly cost-effective (<€20,000/QALY), while vaccinating those with low-risk of pneumococcal infection was cost-effective (<€50,000/QALY). However, within risk groups the ICER differed significantly between age groups. Sensitivity analysis showed that a proportional decrease in list price, such as common in national vaccination programs, decreased the ICER disproportionally in favor of PCV13.ConclusionVaccination all adults with PCV13 is cost effective compared with PPV23. There is a large variation in the cost-effectiveness between age and risk groups. Targeting individuals with underlying diseases aged less than 85 years would provide most value for money. Disclosures M. Rozenbaum, Pfizer: Employee and Shareholder, Salary.

Cost-effectiveness of alternative strategies for use of 13-valent pneumococcal conjugate vaccine (PCV13) in Canadian adults

ObjectivesThe Canadian National Advisory Committee on Immunization (NACI) recommends use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine in a sequential schedule (PCV13 → PPV23) among adults aged ≥ 65 years and those aged ≥ 18 years who are immunocompromised. In light of recent PCV13 efficacy data from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA), and new sero-epidemiology data on community-acquired pneumonia (CAP), we examined the economic implications of funding an expanded adult pneumococcal immunization program in Canada.MethodsA microsimulation model depicting expected lifetime risks, consequences, and costs of invasive pneumococcal disease (IPD) and CAP was developed. PPV23 effectiveness was based on published literature, and PCV13 effectiveness was based on CAPiTA; all other model parameters were based on published data or secondary sources. Herd effects from the PCV13 pediatric program were considered. Outcomes and costs were evaluated assuming use of PPV23 alone, and alternatively, use of PCV13 → PPV23 among (1) all adults aged ≥ 65 years (n = 5.4 M) and (2) immunocompromised and high-risk adults aged ≥ 65 years (n = 3.0 M).ResultsFor population no. 1, PCV13 → PPV23 reduced IPD cases by 1100, CAP cases by 7000, and disease costs by $135.8M; vaccination costs increased by $254.3M, and cost per QALY gained was $35,484. For population no. 2, PCV13 → PPV23 reduced IPD cases by 900, CAP cases by 6000, and disease costs by $120.3M; vaccination costs increased by $149.8M, and cost per QALY gained was $10,728.ConclusionExpanding use of PCV13 → PPV23 by funding PCV13 among Canadian adults aged ≥ 65 would be a cost-effective use of healthcare resources.

Post hoc analysis of the efficacy of the 13-valent pneumococcal conjugate vaccine against vaccine-type community-acquired pneumonia in at-risk older adults

BackgroundIndividuals with certain chronic medical conditions are at higher risk of developing pneumonia and pneumococcal disease than those without. Using data from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA), this post hoc analysis assessed the efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13) in adults aged ≥65 years with at-risk conditions. MethodsThe Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) was a double-blind, parallel-group, randomized, placebo-controlled study in the Netherlands in which adults aged ≥65 years received either PCV13 or placebo. Outcomes of interest were identified using prespecified clinical criteria, radiographic confirmation, routine microbiologic testing, and a serotype-specific urinary antigen detection assay.In this post hoc analysis, participants were classified by at-risk status based on self-reporting of any of the following chronic medical conditions: heart disease, lung disease, asthma, diabetes, liver disease, and smoking. The objective of this analysis was to assess PCV13 vaccine efficacy (VE) against a first episode of vaccine-serotype community-acquired pneumonia (VT-CAP) in at-risk participants. ResultsOf the 84,496 adults enrolled in the study, 41,385 (49.2%) were considered at risk owing to chronic medical conditions. Of the 139 VT-CAP cases, 115 (82.7%) occurred in these participants. VE of PCV13 against a first episode of VT-CAP among participants with at-risk conditions was 40.3% (95.2% CI: 11.4%, 60.2%). Average duration of follow-up since vaccination was 3.95 years for at-risk participants; protection did not wane over the study period. ConclusionsThis post hoc analysis of the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) showed significant and persistent efficacy of PCV13 against VT-CAP in at-risk older adults.ClinicalTrials.gov identifier: NCT00744263.

The Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Pneumococcal Carriage in the Community Acquired Pneumonia Immunization Trial in Adults (CAPiTA) Study.

The impact of pneumococcal conjugate vaccination on the prevalence of nasopharyngeal carriage with pneumococci and other bacteria in adults is unknown. The direct effects of the 13-valent pneumococcal conjugate vaccine (PCV13) in community dwelling older adults was investigated as part of the randomized controlled Community Acquired Pneumonia immunization Trial in Adults (CAPiTA). We determined the carriage of Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis before and 6, 12, and 24 months after vaccination using polymerase chain reaction (PCR)-based methods and conventional cultures of nasopharyngeal and oropharyngeal swab samples in 1006 PCV13 recipients and 1005 controls. Serotyping of the 13 vaccine-type (VT) pneumococci was performed by PCR targeting capsular synthesis genes and Quellung reaction of isolates. Before randomization and based on PCR, 339 of 1891 subjects had nasopharyngeal carriage with any pneumococci (17.9%), and 114 of 1891 (6.0%) carried VT pneumococci. At 6 months after vaccination, VT pneumococcal carriage was significantly lower in PCV13 recipients than in the placebo group (relative risk, 0.53; 95% confidence interval, .35-.80; P = .04). There was no difference between the groups at 12 and 24 months after vaccination. Carriage of non-VT pneumococci, S. aureus, H. influenzae, and M. catarrhalis did not change between groups. In community-dwelling adults aged ≥65 years, a single dose of PCV13 seems to elicit a small and temporary reduction in VT carriage 6 months after vaccination. Neither replacement by non-VT serotypes nor impact on other nasopharyngeal bacteria was observed.

Pneumococcal vaccination and chronic respiratory diseases.

Patients with COPD and other chronic respiratory diseases are especially vulnerable to viral and bacterial pulmonary infections, which are major causes of exacerbations, hospitalization, disease progression, and mortality in COPD patients. Effective vaccines could reduce the burden of respiratory infections and acute exacerbations in COPD patients, but what is the evidence for this? This article reviews and discusses the existing evidence for pneumococcal vaccination efficacy and its changing role in patients with chronic respiratory diseases, especially COPD. Specifically, the recent Community-Acquired Pneumonia Immunization Trial in Adults (CAPITA) showed the efficacy of pneumococcal conjugate vaccine in older adults, many of whom had additional risk factors for pneumococcal disease, including chronic lung diseases. Taken together, the evidence suggests that pneumococcal and influenza vaccinations can prevent community-acquired pneumonia and acute exacerbations in COPD patients, while pneumococcal vaccination early in the course of COPD could help maintain stable health status. Despite the need to prevent pulmonary infections in patients with chronic respiratory diseases and evidence for the efficacy of pneumococcal conjugate vaccine, pneumococcal vaccine coverage and awareness are low and need to be improved. Respiratory physicians need to communicate the benefits of vaccination more effectively to their patients who suffer from chronic respiratory diseases.

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

ObjectivesOur 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. MethodsThis 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. ResultsOf 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. ConclusionIn 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.

Immunogenicity of the 13-Valent Pneumococcal Conjugate Vaccine in Older Adults With and Without Comorbidities in the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA)

In the randomized controlled Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA), the efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13) against first episodes of vaccine-type community-acquired pneumonia in adults aged ≥65 years was 46%. The long-term immunogenicity of PCV13 in pneumococcal vaccine-naive older adults was investigated as part of CAPiTA. We determined the immune responses to PCV13 before and at 1, 12, and 24 months after vaccination in 1006 PCV13 recipients and 1005 controls with 3 age-stratified study participant cohorts. PCV13 serotype-specific opsonophagocytic activity (OPA) titers and immunoglobulin G (IgG) concentrations were determined. Sample collection completeness was at least 93.4% at each time point. In all 3 age categories, a single dose of PCV13 elicited OPA titers and IgG concentrations for all 13 serotypes that were significantly higher than baseline and the corresponding responses in the placebo group at all time points. In the eldest subjects (≥80 years of age at vaccination), OPA titers and IgG concentrations remained above baseline and there was no apparent difference in OPA titers and IgG concentrations between those with self-reported comorbidities and healthy older adults. However, the study was not powered to determine statistical significance between different age and comorbidity groups, and thus these results are exploratory. In immunocompetent adults ≥65 years of age, PCV13 elicits significant increases in OPA titers and IgG concentrations that persist 2 years postvaccination for all 13 serotypes, regardless of age and comorbidity. NCT00744263.

Exploratory efficacy endpoints in the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA)

BackgroundThe Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) assessed vaccine-type community-acquired pneumonia (VT-CAP) and vaccine-type invasive pneumococcal disease (VT-IPD) prevention with 13-valent pneumococcal conjugate vaccine (PCV13) in adults aged ⩾65years. We report vaccine efficacy (VE) of PCV13 for the remaining 23 exploratory endpoints and serotype distributions for pneumococcal CAP and IPD. MethodsThis was a parallel-group, randomised, placebo-controlled, double-blind trial comparing single-dose PCV13 with placebo. Exploratory CAP endpoints included first episode of confirmed non-VT (NVT) pneumococcal CAP; all confirmed episodes of NVT pneumococcal CAP, pneumococcal CAP, nonbacteraemic/noninvasive (NB/NI) VT pneumococcal CAP, and NB/NI pneumococcal CAP; and first and all episodes of culture-confirmed VT pneumococcal CAP, culture-confirmed pneumococcal CAP, culture-confirmed NVT pneumococcal CAP, probable VT pneumococcal CAP, probable NVT pneumococcal CAP, and probable and possible pneumococcal CAP. Exploratory IPD endpoints included all episodes of VT-IPD and IPD, and first and all episodes of NVT-IPD. The per-protocol and modified intent-to-treat (mITT) populations were evaluated. ResultsIn total, 84,496 participants were enrolled. Eight of 23 exploratory CAP and IPD endpoints were statistically significant in both populations. In the per-protocol population, these included VE of 29% for all episodes of confirmed pneumococcal CAP, 43% for all NB/NI episodes of VT pneumococcal CAP, 52% for all episodes of culture-confirmed pneumococcal CAP, and 53% for all episodes of IPD. Comparable VE estimates were observed in the mITT population. The most common VT serotypes were 1 (10 first episodes of confirmed pneumococcal CAP; 2 first episodes of IPD) and 7F (22; 7) among PCV13 and placebo recipients, respectively. ConclusionsThe results of this analysis yielded statistically significant PCV13 VE for all episodes of confirmed pneumococcal CAP (including NB/NI and culture-confirmed episodes) and for all episodes of IPD in adults aged ⩾65years. These findings are consistent with the primary efficacy analysis. ClinicalTrials.gov identifier: NCT00744263.

Hospitalization costs for community-acquired pneumonia in Dutch elderly: an observational study.

BackgroundCommunity-acquired pneumonia (CAP) is one of the most common infections, especially in the elderly (≥65 years). The aim of this study was to quantify hospitalization costs for CAP in different age groups and in patients with different CAP risk profiles. Secondary objectives were to assess disease severity differences between placebo and vaccine receiving participants and identify cost driving factors of CAP in hospitalized elderly in the Netherlands.MethodsThis prospective cohort study of hospitalized CAP patients was executed in parallel to the Community Acquired Pneumonia Immunization Trial in Adults (CAPiTA). Within the CAPiTA, a cohort of 84,496 subjects aged ≥65, all suspected CAP-episodes presenting in one of the 58 participating hospitals between September 2008 and August 2013 were included. CAP was diagnosed on clinical and radiographical criteria. Invasive pneumococcal disease (IPD) and non-IPD-CAP episodes, regardless of the causing pathogen, were evaluated separately. Costs were calculated by multiplying recorded healthcare resources with Dutch unit cost prices for the year 2012. Multivariate regression analysis was performed to identify cost drivers.ResultsIn the sentinel hospitals 3225 suspected CAP and IPD episodes were included, of which 1933 were radiographically confirmed by chest X-ray. Analyses were conducted on confirmed CAP episodes only. Overall mean length of hospital stay was 12.1 days, the in-hospital mortality rate was 11.26 %, and mean costs were €8301 (95 % CI: €7760–€8999). When stratified in age-categories 65–74, 75–84 and ≥85, mean hospitalization costs were €8674, €8770 and €6197, respectively (p = 0.649). IPD-CAP and non-IPD-CAP mean hospitalization costs were €13,611 and €8081, respectively. Higher CURB-65 score and individuals at medium risk for developing pneumococcal disease were significantly associated with higher costs. Being male, lower age, previous admissions, lower risk, lower urbanity and higher socio-economic status were associated with lower costs.ConclusionsMean hospitalization costs of a CAP subject were €8301 and higher for IPD-CAP compared to non-IPD-CAP cases. Medium risk patients and higher CURB-65 scores were identified as cost driving factors.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1783-9) contains supplementary material, which is available to authorized users.

Immunization update: A look back at 2015

Immunization update: A look back at 2015

A post hoc assessment of duration of protection in CAPiTA (Community Acquired Pneumonia immunization Trial in Adults)

BackgroundThe 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 ⩾65years. 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. MethodsThis 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. ResultsA 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. ConclusionsThe results of this post hoc analysis of the persistence of PCV13 VE in adults ⩾65years, indicate that PCV13 was protective over the 5-year duration of the study, with no waning of efficacy observed. ClinicalTrials.gov identifierNCT00744263

Economic Evidence of Pneumococcal Vaccination in Older Adults: Uncertain Modelling or Competitive Tendering?

Diseases caused by Streptococcus pneumonia contribute considerably to morbidity and mortality worldwide [1]. The main types of illness are grouped as bacteremic pneumococcal pneumonia (BPP) and non-bacteremic pneumococcal pneumonia (NBPP), the latter causing less serious manifestations [1, 2]. Pneumococcal vaccination for infants has been widely debated in the last decade following the launch of the new and expensive conjugate vaccines (PCVs); unlike the old and cheap 23-valent polysaccharide vaccine (PPV23), PCV vaccines are immunogenic in children under 2 years of age [3]. Lately, the debate has shifted to the extension of PCV13 (the only PCV approved for adults) to at-risk and older adults instead of PPV23, which is still adopted in many European countries for campaigning on this population target. This hot debate [4, 5] is fuelled by two crucial issues that are still uncertain. First, although PPV23 has been shown to be effective in older adults, the extent and especially the duration of its protection are still doubtful [6, 7]. Second, vaccination of infants with PCVs (unlike with PPV23) provides herd immunity that has an impact on serotype replacement [8] and thus prevents disease in all ages [9], elderly included. Against this background, economic evaluations (EEs) of pneumococcal vaccines for adults published so far have had to rely on many assumptions [4, 10]. Very recently, the CAPiTA (Community-Acquired Pneumonia Immunization Trial in Adults) study (a Dutch clinical trial supported by the manufacturer) [11] showed that PCV13 is efficacious in preventing two thirds of BPP (75 %) and around half the NBPP (45 %) cases in older adults. The Spanish CAPAMIS (Community-Acquired Pneumonia, Acute Myocardial Infarction and Stroke) cohort study [12] (funded by public authorities) confirmed that PPV23 is effective against both BPP (62 %) and NBPP (48 %) in adults C60 years [5], although only for up to 5 years after vaccination. Here we critically review the most recent EEs published in the EU focussed on the elderly, to assess their potential contribution to public decision making and examine whether sponsorship by manufacturers influenced the results, as happened for studies focussed on infants [13].

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

ObjectivesTo 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 SettingStudy 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. ResultsOf 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). ConclusionWith 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.

Cost-effectiveness of adult pneumococcal conjugate vaccination in the Netherlands.

The Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) demonstrated the efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) in preventing vaccine-type community-acquired pneumonia and vaccine-type invasive pneumococcal disease in elderly subjects. We examined the cost-effectiveness of PCV13 vaccination in the Netherlands.Using a Markov-type model, incremental cost-effectiveness ratios (ICER) of PCV13 vaccination in different age- and risk-groups for pneumococcal disease were evaluated using a societal perspective. Estimates of quality-adjusted life-years (QALYs), costs, vaccine efficacy and epidemiological data were based on the CAPiTA study and other prospective studies. The base-case was PCV13 vaccination of adults aged 65–74 years compared to no vaccination, assuming no net indirect effects in base-case due to paediatric 10-valent pneumococcal conjugate vaccine use. Analyses for age- and risk-group specific vaccination strategies and for different levels of hypothetical herd effects from a paediatric PCV programme were also conducted.The ICER for base-case was €8650 per QALY (95% CI 5750–17 100). Vaccination of high-risk individuals aged 65–74 years was cost-saving and extension to medium-risk individuals aged 65–74 years yielded an ICER of €2900. Further extension to include medium- and high-risk individuals aged ≥18 years yielded an ICER of €3100.PCV13 vaccination is highly cost-effective in the Netherlands. The transferability of our results to other countries depends upon vaccination strategies already implemented in those countries.

110413-Valent Pneumococcal Conjugate Vaccine (PCV13) Immunogenicity in the Community Acquired Pneumonia Immunization Trial In Adults (CAPiTA)

110413-Valent Pneumococcal Conjugate Vaccine (PCV13) Immunogenicity in the Community Acquired Pneumonia Immunization Trial In Adults (CAPiTA)

1091Serotype Distribution of S. pneumoniae Community Acquired Pneumonia (CAP) in Adults in the Netherlands in the CAPiTA (Community-Acquired Pneumonia Immunization Trial In Adults) Study Period

1091Serotype Distribution of S. pneumoniae Community Acquired Pneumonia (CAP) in Adults in the Netherlands in the CAPiTA (Community-Acquired Pneumonia Immunization Trial In Adults) Study Period

LB-7A Post-Hoc Assessment of Duration of Protection in CAPiTA (Community Acquired Pneumonia Immunization Trial in Adults)

LB-7A Post-Hoc Assessment of Duration of Protection in CAPiTA (Community Acquired Pneumonia Immunization Trial in Adults)