Pneumococcal Vaccination In Older Adults Research Articles

EPH268 Effectiveness of Pneumococcal Vaccination in Older Adults in a Real-World Setting: A Systematic Review and Meta-Analysis of Observational Studies Using Test-Negative Designs

EPH268 Effectiveness of Pneumococcal Vaccination in Older Adults in a Real-World Setting: A Systematic Review and Meta-Analysis of Observational Studies Using Test-Negative Designs

Pre-vaccination CD56 dimCD16 +NK cell abundance and T h1/T h17 ratio predict responsiveness to conjugated pneumococcal vaccine in older adults

Abstract Older adults are at high risk of morbidity and mortality from Streptococcus pneumoniae (pneumococcus) infections. There are two available vaccines for pneumococcus: T-cell-independent capsular polysaccharide Pneumovax and T-cell-dependent conjugated Prevnar. However, how older adults respond to these vaccines at the cellular level and whether there are baseline predictors for responsiveness, is not known. To address this, we recruited older adults (60+ yrs), who are vaccinated with Prevnar (n=19) or Pneumovax (n=20). Vaccine responsiveness was quantified using opsonophagocytic assays, which revealed that both vaccines induce strong responses. Interestingly, sex was associated with Prevnar responses, where women mounted stronger responses than men. Pre-vaccination flow cytometry data showed that Th1 cells positively, Th17 cells negatively correlated with Prevnar responses. Furthermore, bulk RNA-seq data from PBMCs showed that baseline expression levels of cytotoxic genes (NCAM1, GNLY, PRF1) are negatively associated with Prevnar responses. scRNA-seq data from top and bottom responders showed that this cytotoxicity signature stems from CD56 dimCD16 +NK cells, where having more of these cells are detrimental to responses. Interestingly, women had significantly higher Th1, lower Th17 and lower CD16+ NK cells compared to men, which explains their stronger Prevnar responses. This is the first study to uncover older adults’ responses to two pneumococcal vaccines; we uncovered an activated immune phenotype of Th and NK cell subsets that impedes responses to Prevnar. Interestingly, this phenotype only affected adjuvanted vaccine responses, providing an opportunity for precision vaccinology for pneumococcus disease. Supported by grants from National Institute of Health (R35 GM124922, R01 AG052608) and JAX cancer center (JAX-CC).

Optimal age targeting for pneumococcal vaccination in older adults; a modelling study

Invasive pneumococcal disease (IPD) risk increases with age for older adults whereas the population size benefiting from pneumococcal vaccines and robustness of immunogenic response to vaccination decline. We estimate how demographics, vaccine efficacy/effectiveness (VE), and waning VE impact on optimal age for a single-dose pneumococcal vaccination. Age- and vaccine-serotype-specific IPD cases from routine surveillance of adults ≥ 55 years old (y), ≥ 4-years after infant-pneumococcal vaccine introduction and before 2020, and VE data from prior studies were used to estimate IPD incidence and waning VE which were then combined in a cohort model of vaccine impact. In Brazil, Malawi, South Africa and England 51, 51, 54 and 39% of adults older than 55 y were younger than 65 years old, with a smaller share of annual IPD cases reported among < 65 years old in England (4,657; 20%) than Brazil (186; 45%), Malawi (4; 63%), or South Africa (134, 48%). Vaccination at 55 years in Brazil, Malawi, and South Africa, and at 70 years in England had the greatest potential for IPD prevention. Here, we show that in low/middle-income countries, pneumococcal vaccines may prevent a substantial proportion of residual IPD burden if administered earlier in adulthood than is typical in high-income countries.

Real-world effectiveness of pneumococcal vaccination in older adults: Cohort study using the UK Clinical Practice Research Datalink.

BackgroundThe 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended for UK older adults, but how age moderates effectiveness is unclear.MethodsThree annual cohorts of primary-care patients aged≥65y from the Clinical Practice Research Datalink selected from 2003–5 created a natural experiment (n = 324,804), reflecting the staged introduction of the vaccine. The outcome was symptoms consistent with community-acquired pneumococcal pneumonia (CAP) requiring antibiotics or hospitalisation. We used the prior event rate ratio (PERR) approach to address bias from unmeasured confounders.ResultsVaccinated patients had higher rates of CAP in the year before vaccination than their controls, indicating the potential for confounding bias. After adjustment for confounding using the prior event rate ratio (PERR) method, PPV23 was estimated to be effective against CAP for two years after vaccination in all age sub-groups with hazard ratios (95% confidence intervals) of 0.86 (0.80 to 0.93), 0.74 (0.65 to 0.85) and 0.65 (0.57 to 0.74) in patients aged 65–74, 75–79 and 80+ respectively in the 2005 cohort. Age moderated the effect of vaccination with predicted risk reductions of 8% at 65y and 29% at 80y.ConclusionsPPV23 is moderately effective at reducing CAP among UK patients aged≥65y, in the two years after vaccination. Vaccine effectiveness is maintained, and may increase, in the oldest age groups in step with increasing susceptibility to CAP.

Acceptance of pneumococcal vaccination in older adults: A general population-based survey

BackgroundPneumococcal infection is a leading cause of disability and death globally. The Hong Kong Government has launched two programmes for pneumococcal vaccination - The Vaccination Subsidy Scheme (VSS) and the Government Vaccination Programme (GVP). This study aimed to examine the enabling factors, obstacles and perception of pneumococcal vaccination, and their association with its uptake in a general Chinese population. MethodsWe performed a population-based, telephone survey in the general public aged 65 or above via simple random sampling. A validated survey based on the Health Belief Model (HBM) was used. Their socio-demographic information; history of previous participation in the GVP or VSS; and self-perceived health status were captured. Binary logistic regression models were constructed to examine the factors independently associated with vaccination. ResultsA total of 1,000 respondents were enrolled in the study, with 402 (40.2%) respondents having intention to join the GVP/VSS in 12 months. Respondents with long-term medical consultant and medication (adjusted odds ratios [aOR] = 1.541, 95% confidence interval (CI): 1.008–2.356, p = 0.046); high levels of perceived susceptibility of infections (aOR = 3.624, 95 %CI: 2.318–5.665, p < 0.001); high levels of perceived benefits of vaccine (aOR = 1.699, 95 %CI: 1.153–2.504, p < 0.001); recommendations from government (aOR = 8.025, 95 %CI: 4.771–13.497, p < 0.001) or physicians (aOR = 7.399, 95 %CI: 3.472–15.764, p = 0.008); and high levels of self-efficacy (aOR = 3.045, 95 %CI: 1.458–6.362, p = 0.003) were more likely to have intention to participate in the vaccination programme. ConclusionsThe acceptance rate of pneumococcal vaccination programme remained suboptimal in the population. The government and physicians should be involved in the promotion of pneumococcal vaccination and GVP/VSS by increasing perceived benefits and self-efficacy, and reducing barriers towards vaccination among the target population. More studies are required to confirm our findings in other settings.

Pneumococcal vaccine uptake and vaccine effectiveness in older adults with invasive pneumococcal disease in Germany: A retrospective cohort study.

BackgroundInvasive pneumococcal disease (IPD) in people ≥60 years old is on the rise in Germany. There has been a recommendation for pneumococcal vaccination in this age group since 1998.MethodsWe determined the vaccination status of people ≥60 years old with IPD in Germany. We assessed vaccine effectiveness (VE) of the recommended 23-valent polysaccharide vaccine (PPV23) against IPD using the indirect cohort method.ResultsThe rate of pneumococcal vaccination in older adults with IPD is low, 26%, with only 16% of people receiving a pneumococcal vaccine within five years of the IPD episode. Age- and gender- adjusted vaccine effectiveness (VE) for PPV23 was 37% (95% confidence interval 12% - 55%). For people vaccinated with PPV23 less than two years prior to IPD, VE was -20% (-131% - 34%), between two and four years prior to IPD, VE was 56% (20% - 76%), and 47% (17% - 63%) for those vaccinated ≥5 five years ago. Excluding serotype 3, overall VE for the remaining serotypes in PPV23 was 63% (49% - 74%). For people receiving PPV23 within the past two years, VE against all serotypes except 3 was 49% (12% - 71%); for people vaccinated between two and four years prior to IPD 66% (37% - 82%); for those vaccinated ≥five years ago, 69% (50% - 81%). VE of PPV23 against serotype 3 IPD only was -110% (-198% - -47%).ConclusionsTo reduce IPD in older adults in Germany, we must increase the rate of pneumococcal vaccine uptake. For 22/23 serotypes, PPV23 was effective. Serotype 3 remains a major problem.FundingThis work was supported by an investigator-initiated research grant from Pfizer.

Pneumococcal vaccination in older adults: An initial analysis of social determinants of health and vaccine uptake

ObjectivesTo examine the potential influence of social determinants of health on pneumococcal vaccination in older American adults. MethodsThis study used nationwide, US Medicare claims data from 2013 to 2016 to assess uptake of pneumococcal vaccination among adults in the first year after turning age 65. Patients were followed from the point of being 65 years of age and initially enrolled in traditional fee-for-service Medicare or a Medicare Advantage plan through the subsequent year and observed for pneumococcal vaccination in outpatient clinics and pharmacies. Publicly-available data on select social determinants of health were incorporated and guided by the World Health Organization vaccine hesitancy matrix. Logistic regression determined predictors of vaccination while controlling clinical and demographic characteristics. ResultsA total of 307,488 and 74,995 adults aged 65 years were identified from Medicare Advantage and Medicare fee-for-service claims, respectively, and 21.1% of Medicare Advantage and 38.2% of Medicare fee-for-service patients received a pneumococcal vaccine in the first year after turning 65. Those residing in urban areas had a higher likelihood of pneumococcal vaccination in both the Medicare Advantage (OR: 1.31; 95% CI: 1.267–1.344) and Medicare fee-for-service (OR: 1.53; 95% CI: 1.450–1.615) cohorts. Additionally, residing in areas of higher health literacy or communities with more democratic voters were consistently associated with a higher odds of pneumococcal vaccination regardless of Medicare type. Results also pointed to a synergistic relationship between receiving the influenza vaccine and also being vaccinated against pneumococcal disease. ConclusionSocial determinants of health, including local health literacy, poverty, residing in more liberal areas, and access to information, may be influencing the pneumococcal vaccine-related decisions of older adults. However, additional factors associated with the vaccine hesitancy matrix and more granular data (e.g., zip code-level) are needed to fully determine the impact in this and other vaccines recommended in older adults.

Round table: Using evidence for action – the story on life-course vaccination

Abstract Vaccination represents a cost-effective public health intervention that saves millions of lives globally each year as well as increasing health and wellbeing of the population. Approximately 20 vaccines are currently in use in routine schedules, with several new or improved in the research pipeline. While immunisation programmes have traditionally targeted children, in recent strategic thinking around vaccination has shifted from an infancy focus to a life course approach that considers the benefits of vaccination at all ages. There are many benefits to targeting different age groups for vaccination, such as targeting individuals at an age that maximises protection (HPV among teenagers, shingles among older adults); boosting waning immunity (Td/IPV among teenagers); protecting at-risk individuals when they are most vulnerable (influenza in pregnancy, pneumococcal vaccine in older adults at clinical risk); protecting newborns in utero before they have the chance to be vaccinated (pertussis in pregnancy); or targeting an older age group to indirectly protect younger infants (MenACWY vaccination of teenagers). Even though the public health benefits of the life-course approach are evident, delivering vaccination programmes spanning such disparate groups represent constant challenges. These challenges can be grouped into: a) limited access to services b) communication challenges influencing attitudes and knowledge of vaccination and c) logistical challenges associated with the use of a wide range of settings for vaccination. This session will explore, at country and regional levels, experiences and reflections on delivering vaccination across the life course, and evidence-based policy and operational actions taken to deliver an optimal programme at all ages. Key messages Life course vaccination presents opportunities to better protect the population but also brings unique challenges, both from the patient side and from the health systems side. Evidence-based tools and strategies to improve vaccine programmes across the life-course are increasingly available. Country and European level action is needed to achieve optimal results.

Effectiveness and safety of dual influenza and pneumococcal vaccination versus separate administration or no vaccination in older adults: a meta-analysis

ABSTRACTBackground: The advantages of dual pneumococcal and influenza vaccination in older adults have not been clarified and controversy remains regarding their optimal use.Methods: This meta-analysis was conducted on 25 January 2018 using PubMed, the Cochrane Library, and Embase databases. Seventeen studies were selected ultimately for meta-analysis using a multi-step approach by two separate authors. Primary outcomes were pneumonia, pneumococcal pneumonia, influenza, hospitalization, and all-cause mortality rates, and the secondary outcome was adverse effects (AEs).Results: The additive preventive effects of dual influenza and pneumococcal vaccination versus influenza vaccination alone for pneumonia and death were 15% (95% confidence interval [CI]: 4-24%) and 19% (95% CI: 6-30%), respectively. Compared with pneumococcal vaccination alone, dual influenza and pneumococcal vaccination resulted in a 24% (95% CI: 16-31%) reduction in pneumonia and a 28% (95% CI: 13-40%) reduction in death. Compared with placebo or no vaccination, the effectiveness of dual vaccination was 29% (95% CI: 14-42%) for pneumonia, 38% (95% CI: 25-49%) for death, 35% (95% CI: 22-46%) for influenza, and 18% (95% CI: 6-29%) for hospitalization. Both vaccines showed acceptable safety profiles and AEs were mild or moderate.Conclusion: Our findings highlight the importance of concomitant influenza and pneumococcal vaccination in older adults.

Influenza and pneumococcal vaccination in older adults living in nursing home: a survival analysis on the shelter study.

Influenza and pneumococcal vaccines have been proved to be effective and safe in preventing and controlling infection among elderly, reducing morbidity and mortality. However, some evidences raised health concerns related to these vaccinations. This study aims to identify prevalence and outcomes related to influenza and pneumococcal vaccinations in a large European population of frail old people living in nursing homes (NHs). We conducted a survival analysis of NH residents participating to the Services and Health for Elderly in Long-TERm project, a prospective cohort study collecting information on residents admitted to 57 NH in eight countries (Czech Republic, England, Finland, France, Germany, Italy, The Netherlands and Israel). Clinical and demographical data were collected using the international resident assessement instrument for long-term care facilities. Incident mortality was recorded during 1-year follow-up. A shared-frailty Cox regression model was used to assess the impact of vaccination status on mortality. Mean age of 3510 participants was 84.6 years (SD = 7.7). In total, 81.7 and 27.0% received influenza and pneumococcal vaccination, respectively. Overall, 727 (20.7%) residents died during the follow-up period. After adjusting for potential confounders, which included age, sex, number of diseases, depression, cognitive and functional status, influenza (HR = 0.80; 95% CI 0.66-0.97) and the combination of influenza and pneumococcal vaccination (HR = 0.72; 95% CI 0.57-0.91), but not pneumococcal vaccination alone (HR = 0.52; 95% CI 0.25-1.06), were associated with a statistically significant reduction in mortality in respect of no vaccinations. In a population of older adult living in NH influenza and the combination of influenza and pneumococcal vaccination were associated with a reduction in all-cause mortality respect to no vaccination.

Economic studies applied to vaccines against invasive diseases: An updated budget impact analysis of age-based pneumococcal vaccination strategies in the elderly in Italy

ABSTRACTMany evaluations have been performed on the economic impact of pneumococcal vaccination in older adults (>64 y of age) in several countries, including Italy. However, these studies did not include the new data on the effectiveness of 13-valent conjugate pneumococcal vaccine (PCV13) in the elderly reported by the CAPiTA Study. The aim of the present study was to update our previous budget impact analysis of multi-cohort PCV13 vaccination in adults in Italy by including new scientific evidence. We also compared single-cohort vaccination strategies per year, in order to identify the cohort with the most favorable economic profile, in the event of the multi-cohort approach not being economically sustainable for the National Health System (NHS).The new impact analysis highlights that the vaccination of one, two or three adult cohorts per year in Italy would lead to a considerable reduction in pneumococcal disease and its related costs over 5 y. The strategies proved cost-effective (ICERs ranging from €14,605 to €15,412/QALY), i.e. well below the threshold of €50,000/QALY. The ICERs were slightly lower than those calculated in the first published analysis and vaccination continued to be economically favorable. In the case of a mono-cohort strategy, the vaccination of 65-year-old subjects, albeit more expensive, proved to be more favorable than the vaccination of 70- or 75-year-old cohorts.Finally, after the inclusion of the recent clinical evidence, the age-based PCV13 vaccination of the elderly in Italy continued to be economically justified from the NHS perspective in the short period. Vaccination of the elderly should therefore be strongly recommended nationwide in Italy.

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].

Pneumococcal vaccination in older adults in the era of childhood vaccination: Public health insights from a Norwegian statistical prediction study

Two different vaccines, a 23-valent polysaccharide vaccine (PPV23) and a 13-valent conjugate vaccine (PCV13), are available for prevention of invasive pneumococcal disease (IPD) in the population aged 65 years and older (65+). The IPD epidemiology in the 65+ is undergoing change due to indirect effects of childhood immunisation. Vaccine recommendations for the 65+ must take into account these trends in epidemiology. We therefore explored the preventive potential of vaccination strategies to prevent IPD in the 65+, including PPV23, PCV13 or PCV13+PPV23 in 2014–2019. Quasi-Poisson regression models were fitted to 2004–2014 population-wide surveillance data and used to predict incidences for vaccine-type and non-vaccine type IPD. We determined the number of people needed to be vaccinated to prevent one case per season (NNV) for each strategy and estimated the public health impact on the IPD case counts from increasing the vaccine uptake to 28–45%. Our results indicate that PCV13-IPD will decrease by 71% from 58 (95% prediction interval 55–61) cases in 2014/15 to 17 (6–52) in 2018/19 and PPV23-IPD by 32% from 168 (162–175) to 115 (49–313) cases. The NNV will increase over time for all strategies because of a decreasing vaccine-type IPD incidence. In 2018/19, the PCV13-NNV will be 5.3 times higher than the PPV23-NNV. Increasing the vaccine uptake will lead to a larger public health impact for all scenarios. Combining PCV13 and PPV23 is most effective, but the additional effect of PCV13 will decrease and is only marginal in 2018/19. Our study demonstrates the importance of increasing PPV23 uptake and of developing vaccines that confer broader immunity.

Is there a potential role for protein‐conjugate pneumococcal vaccine in older adults?

Longstanding controversy over the efficacy of 23-valent pneumococcal polysaccharide vaccine (PPV23) led to a recommendation by the Joint Committee on Vaccination and Immunisation (JCVI) of the United Kingdom in March 2011, to discontinue routine use of PPV23 in older adults.(1) Following careful review of the evidence and feedback from stakeholders, the JCVI decided to retain the original policy of uniform vaccination of adults >65 years of age, while keeping the subject under continued review. In the United States, the Advisory Committee on Immunization Practices (ACIP) which is also concerned about the efficacy of PPV23 is currently considering a different strategy, i.e. adding 13-valent pneumococcal protein-conjugate vaccine (PCV13) for recommended use in adults, following recent Food and Drug Administration (FDA) approval for this purpose in adults over 50 years of age. It is therefore timely to review the options for prevention of pneumococcal disease in adults.

Strategies to Overcome Barriers to Pneumococcal Vaccination in Older Adults: An Integrative Review

Health care systems and policy changes have been critical in increasing pneumococcal vaccination rates to current levels. Still, numerous barriers to immunization persist. To assist clinicians caring for older adults, an integrative review of the literature was performed to examine interventions demonstrating efficacy in office settings. Within the 11 studies reviewed, immunization rates increased consistently when health care systems supported organizational changes in clinical procedures and staffing. Data supporting the use of provider reminders were inconsistent, but the availability of information technology to generate reminders and access clinical guidelines modestly increased vaccination rates. Patient reminders (telephone or mail) demonstrated efficacy in multiple studies. Not surprisingly, the literature also supported the nurse's role in enhancing vaccination rates. Findings of this review support the need for sustained organizational change; implications for clinical practice are apparent. Advanced practice nurses can assume leadership roles within change processes as the nation transitions to electronic medical records.

EDITORIAL WHAT ROLE FOR PROTEIN‐CONJUGATE PNEUMOCOCCAL VACCINE IN OLDER ADULTS? Invasive pneumococcal disease is a significant cause of morbidity and mortality among persons aged 65 years and older. Pneumococcal disease burden also remains high among adults over 50 years of age. In this editorial the authors discuss the priority of continued 23‐valent pneumococcal polysaccharide vaccine use in older adults, whilst

EDITORIAL WHAT ROLE FOR PROTEIN‐CONJUGATE PNEUMOCOCCAL VACCINE IN OLDER ADULTS? Invasive pneumococcal disease is a significant cause of morbidity and mortality among persons aged 65 years and older. Pneumococcal disease burden also remains high among adults over 50 years of age. In this editorial the authors discuss the priority of continued 23‐valent pneumococcal polysaccharide vaccine use in older adults, whilst

Pneumococcal vaccination in older adults induces antibodies with low opsonic capacity and reduced antibody potency

The primary mode of prevention of adult disease from Streptococcus pneumoniae is vaccination with anti-capsular polysaccharide vaccine; however, its effects are less in the targeted older population than in young persons. Few studies have examined the mechanism behind this limited effectiveness. We have measured antibody concentrations and opsonization titers for multiple serotypes amongst both old adults and young, healthy controls. To avoid specificity problems associated with pneumococcal antibody ELISA, we absorbed the serum samples with c-polysaccharide and capsular polysaccharide of 22F type. Antibody concentrations were found to be similar for six out of the seven tested serotypes, while opsonization titers were significantly higher in six out of seven serotypes in the younger population. Antibody potency, as measured by the ratio of opsonization titer to antibody concentration, was found to be significantly higher for the younger subjects for all serotypes. We conclude that, while all ages of adults make similar concentrations of antibodies in response to pneumococcal vaccine, the effectiveness of those antibodies is significantly reduced in the older adult population.

Effectiveness of pneumococcal vaccination in older adults with chronic respiratory diseases: Results of the EVAN-65 study

A prospective cohort study evaluating the clinical effectiveness of the 23-valent pneumococcal polysaccharide vaccine was conducted among 1298 Spanish older adults with chronic respiratory diseases (bronchitis, emphysema or asthma) who were followed between 2002 and 2005. Main outcomes were all-cause community-acquired pneumonia (CAP) and 30 days mortality from CAP. The association between vaccination and the risk of each outcome was evaluated by multivariable Cox proportional-hazard models adjusted for age and comorbidity pneumococcal vaccination did not alter significantly the risk of overall CAP (hazard ratio [HR]: 0.77; 95% confidence interval [CI]: 0.56-1.07) and 30 days mortality from CAP (HR: 0.87; 95% CI: 0.33-2.28). However, a borderline significant reduction of 30% in the risk of all-cause hospitalisation for CAP was observed among vaccinated subjects (HR: 0.70; 95% CI: 0.48-1.00; p=0.052). The effectiveness of the vaccine on the combined endpoint of pneumococcal and unknown organism infections reached 34% (HR: 0.66; 95% CI: 0.43-1.01; p=0.059). Although our findings suggest moderate benefits from the vaccination, the evidence of clinical effectiveness appears limited.

Pneumococcal Immunization in Older Adults: Implications for the Long-Term–Care Setting

To compare the efficacy of the polysaccharide pneumococcal vaccine in older adults between clinical trial and observational studies and to discuss the implications for long-term-care facilities (LTCFs). A Medline search (to April 2003). All meta-analyses of randomized and quasi-randomized trials of pneumococcal vaccines with placebo or no treatment were sought. All cohort or case-control studies were sought. Of the 16 individual randomized clinical trials included in the reviews, 8 compared pneumococcal vaccine in individuals 55 years and older individuals. Only one study specifically addressed LTCF residents. Although no significant protective effect of the vaccine in elderly subpopulations was found, on the basis of wide confidence intervals and small subpopulation sample sizes, beneficial effects, particularly for pneumococcal bacteremia, could not be ruled out. Of the individual observational studies, 11 specifically evaluated vaccine efficacy in older adults. Vaccine efficacy was demonstrated in 9 of the 11 studies with no protective effect was shown in 2 studies. Although the pooling of clinical trial data does not demonstrate significant efficacy of the pneumococcal polysaccharide vaccine in subgroups of older adults, these subgroup studies lacked power to show significant differences. Observational studies repeatedly demonstrate efficacy in older adults, and the vaccine has been demonstrated to be cost-effective and safe. It is strongly promoted by U.S. and Canadian advisory committees. On the basis of this available evidence, the pneumococcal polysaccharide vaccine should currently be recommended for older adults, especially those who are residents of LTCFs.

Low baseline antibody level to diphtheria is associated with poor response to conjugated pneumococcal vaccine in adults.

Joining polysaccharide antigens to protein increases immunogenicity in infants. In older adults, using conjugation to protein carriers to improve the immune response to pneumococcal polysaccharide vaccine has thus far proved disappointing. Low immunity to the carrier protein in the elderly may explain the failure of conjugated vaccines to elicit a T-cell-dependent response. We immunized 49 older adults (ages 60-78) and 50 younger adults (ages 18-45) with either 23-valent pneumococcal polysaccharide (PS) vaccine or 5-valent CRM197-conjugated pneumococcal oligosaccharide. Sera obtained before and after vaccination were analyzed for antibody to pneumococcal serotypes 14 and 6B and diphtheria toxin by ELISA. Baseline diphtheria toxin antibody level was lower in older adults than in younger adults (0.31 and 0.88 IU/ml, respectively; p < 0.0001). Adults with higher diphtheria antibody level had a higher antibody level to PS type 6B after vaccination than those with lower diphtheria antibody level (9.9 vs. 3.5 microg/ml, respectively; p = 0.01). Antibody level to PS type 14 was higher, but differed by baseline anti-diphtheria antibody level only when the older group was evaluated alone. Low levels of antibody to diphtheria protein may explain some of the lower responses to conjugate pneumococcal vaccine in older adults.