Clinical effectiveness of 13-valent and 23-valent pneumococcal vaccination in middle-aged and older adults: The EPIVAC cohort study, 2015-2016.

BACKGROUND: Clinical benefits using the 23-valent pneumococcal polysaccharide vaccine (PPsV23) or the 13-valent pneumococcal conjugate vaccine (PCV13) in adults are controversial. This study investigated clinical effectiveness for both PPsV23 and PCV13 in preventing pneumonia among middle-aged and older adults. METHODS: Population-based cohort study involving 2,025,730 persons ≥50 years in Catalonia, Spain, who were prospectively followed between 01/01/2015 and 31/12/2016. Primary outcomes were hospitalisation from pneumococcal or all-cause pneumonia and main explanatory variable was PCV13/PPsV23 vaccination status. Multivariable Cox regression models were used to estimate vaccination effectiveness adjusted for age and baseline-risk conditions. RESULTS: Cohort members were followed for 3,897,151 person-years (17,496 PCV13 vaccinated and 1,551,502 PPsV23 vaccinated), observing 3259 pneumococcal pneumonias (63 in PCV13 vaccinated, 2243 in PPsV23 vaccinated) and 24,079 all-cause pneumonias (566 in PCV13 vaccinated, 17,508 in PPsV23 vaccinated). Global incidence rates (per 100,000 person-years) were 83.6 for pneumococcal pneumonia (360.1 in PCV13 vaccinated, 144.6 in PPsV23 vaccinated) and 617.9 for all-cause pneumonia (3235.0 in PCV13 vaccinated, 1128.5 in PPsV23 vaccinated). In the multivariable analyses, the PCV13 appeared significantly associated with an increased risk of pneumococcal pneumonia (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.17-1.97; p = 0.002) and all-cause pneumonia (HR: 1.76; 95% CI: 1.61-1.92; p < 0.001) whereas the PPsV23 did not alter the risk of pneumococcal pneumonia (HR: 1.08; 95% CI: 0.98-1.19; p = 0.132) and slightly increased the risk of all-cause pneumonia (HR: 1.17; 95% CI: 1.13-1.21; p < 0.001). In stratified analyses focused on specific target population subgroups (i.e., elderly people, at-risk and high-risk individuals), protective effects of vaccination did not emerge either. CONCLUSION: Data does not support clinical benefits from pneumococcal vaccination (nor PCV13 neither PPsV23) against pneumonia among Catalonian adults in the current era of universal PCV's childhood immunisation.

Evaluating clinical effectiveness of 13-valent pneumococcal conjugate vaccination against pneumonia among middle-aged and older adults in Catalonia: results from the EPIVAC cohort study.

BACKGROUND: Benefits using the 13-valent pneumococcal conjugate vaccine (PCV13) in adults are controversial. This study investigated clinical effectiveness of PCV13 vaccination in preventing hospitalisation from pneumonia among middle-aged and older adults. METHODS: Population-based cohort study involving 2,025,730 individuals ≥50 years in Catalonia, Spain, who were prospectively followed from 01/01/2015 to 31/12/2015. Primary outcomes were hospitalisation for pneumococcal or all-cause pneumonia and death from any cause. Cox regression models were used to evaluate the association between PCV13 vaccination and the risk of each outcome, adjusting for age, sex and major comorbidities/underlying risk conditions. RESULTS: Cohort members were observed for a total of 1,990,701 person-years, of which 6912 person-years were PCV13 vaccinated. Overall, crude incidence rates (per 100,000 person-years) were 82.8 (95% confidence interval [CI]: 77.7-88.1) for pneumococcal pneumonia, 637.9 (95% CI: 599.0-678.7) for all-cause pneumonia and 2367.2 (95% CI: 2222.8-2518.7) for all-cause death. After multivariable adjustments we found that the PCV13 vaccination did not alter significantly the risk of pneumococcal pneumonia (multivariable-adjusted hazard ratio [mHR]: 1.17; 95% CI: 0.75-1.83; p = 0.493) and all-cause death (mHR: 1.07; 95% CI: 0.97-1.18; p = 0.190), although it remained significantly associated with an increased risk of all-cause pneumonia (mHR: 1.69; 95% CI: 1.48-1.94; p < 0.001). In stratified analyses focused on middle-aged or elderly persons and immunocompromised or immunocompetent subjects, PCV13 vaccination did not appear effective either. CONCLUSION: Our data does not support clinical benefits of PCV13 vaccination against pneumonia among adults in Catalonia. It must be closely monitored in future studies involving more vaccinated person-time at-observation.

Influence of chronic illnesses and underlying risk conditions on the incidence of pneumococcal pneumonia in older adults.

OBJECTIVE: To investigate hospitalizations from pneumococcal pneumonia in older adults with specific underlying chronic conditions, evaluating the influence of these conditions in developing pneumonia. METHODS: Population-based cohort study involving 27,204 individuals ≥ 60 years old in Southern Catalonia, Spain. All cases of hospitalization from pneumococcal pneumonia (bacteremic and nonbacteremic) were collected since 01/12/2008 until 30/11/2011. Cox regression was used to calculate hazards ratio (HR) and estimate the association between baseline conditions and the risk of developing pneumococcal pneumonia. RESULTS: Maximum incidences (per 1000 person-years) appeared among patients with history of prior pneumonia (14.6), nursing home residents (12.8), persons with immunodeficiency/asplenia (7.7) and patients with chronic pulmonary disease (7.6). In multivariable analysis, age (HR: 1.05), nursing home residence (HR: 4.59), history of prior pneumonia (HR: 3.58), stroke (HR: 2.50), chronic heart disease (HR: 1.53), chronic pulmonary disease (HR: 4.09), diabetes mellitus (HR: 1.66), smoking (HR: 1.69) and immunosuppressive medication (HR: 1.87) appeared significantly associated with an increased risk of pneumococcal pneumonia. CONCLUSION: Our data support that nursing home residence, chronic pulmonary disease and immunocompromising conditions are the underlying conditions most strongly associated with an increasing risk of pneumococcal pneumonia in older adults. This data underline the need for better prevention strategies among these persons.

[Prevalence of serotypes causing invasive pneumococcal disease in the region of Tarragona, Spain, 2006-2009: vaccine-serotype coverage for the distinct antipneumococcal vaccine formulations]. / Prevalencia de serotipos causantes de enfermedad neumocócica invasiva en el área de Tarragona, 2006-2009: cobertura de serotipos para las distintas formulaciones de vacuna antineumocócica.

BACKGROUND: Pneumococcal infections remain a major health problem worldwide. This study analysed the distribution of distinct Streptococcus pneumoniae serotypes causing invasive pneumococcal disease (IPD) among all-age population in the region of Tarragona (Spain) throughout 2006-2009. METHODS: An amount of 237 strains were evaluated, of which 203 (85.7%) were isolated from blood cultures, 14 (5.9%) from pleural fluids, 13 (5.5%) from CSF samples and 7 (3%) from other sterile sites. Forty-seven cases (19.8%) were children ≤ 14 years, 94 (39.7%) were patients 15-64 years and 96 (40.5%) were patients ≥ 65 years. RESULTS: Seven serotypes (1, 3, 6A, 7F, 12F, 14 and 19A) caused almost two thirds (63.3%) of cases among all-age patients. Serotype 1 was the most common serotype among children (44.7%) and among people 15-64 years (21.3%), whereas serotype 19A was the most common among people ≥ 65 years (12.5%).Among all-age population, serotype-vaccine coverage for the distinct pneumococcal polysaccharide vaccine (PPV) and conjugate vaccines (PCVs) were 17.3% for the PCV7, 49.8% for the PCV10, 73% for the PCV13 and 80.2% for the PPV23 (p < 0.001). Among children, vaccine-serotype coverage was 23.4% for the PCV7, 72.3% for the PCV10 and 83% for the PCV13. Among people ≥ 65 years, vaccine-serotype coverage was 62.5% for the PCV13 and 68.8% for the PPV23. CONCLUSION: A considerable proportion of IPD cases among our population would not be covered by the current pneumococcal vaccines.

Clinical effectiveness of pneumococcal vaccination against acute myocardial infarction and stroke in people over 60 years: the CAPAMIS study, one-year follow-up.

BACKGROUND: Conflicting results have been recently reported evaluating the relationship between pneumococcal vaccination and the risk of thrombotic vascular events. This study assessed the clinical effectiveness of the 23-valent polysaccharide pneumococcal vaccine (PPV23) against acute myocardial infarction and ischaemic stroke in older adults. METHODS: Population-based prospective cohort study conducted from December 1, 2008 until November 30, 2009, including all individuals ≥ 60 years-old assigned to nine Primary Care Centres in Tarragona, Spain (N = 27,204 individuals). Primary outcomes were hospitalisation for acute myocardial infarction and/or ischaemic stroke. All cases were validated by checking clinical records. The association between pneumococcal vaccination and the risk of each outcome was evaluated by Multivariable Cox proportional-hazard models (adjusted by age, sex, influenza vaccine status, presence of comorbidities and cardiovascular risk factors). RESULTS: Cohort members were followed for a total of 26,444 person-years, of which 34% were for vaccinated subjects. Overall incidence rates (per 1000 person-years) were 4.9 for myocardial infarction and 4.6 for ischaemic stroke. In the multivariable analysis, vaccination was associated with a marginally significant 35% lower risk of stroke (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.42-0.99; p = 0.046). We found no evidence for an association between pneumococcal vaccination and reduced risk of myocardial infarction (HR: 0.83; 95% CI: 0.56-1.22; p = 0.347). CONCLUSIONS: Our data supports a benefit of PPV23 against ischaemic stroke among the general population over 60 years, suggesting a possible protective role of pneumococcal vaccination against some acute thrombotic events.

Serotypes and clones causing invasive pneumococcal disease before the use of new conjugate vaccines in Catalonia, Spain.

OBJECTIVES: The objective of this study was to learn the serotype distribution and clonal composition of pneumococci causing invasive pneumococcal disease (IPD) in children and adults in Spain before the introduction of new 10-valent (PCV10) and 13-valent (PCV13) conjugate vaccines. METHODS: This is a 1-year prospective study including all patients with culture-proved IPD admitted to 30 medical centers in Catalonia, Spain, during the year 2009. RESULTS: A total of 614 episodes of IPD occurred in 612 patients. The rates of IPD were highest in children aged <24 months and adults >64 years (64.5 and 44.7 per 100,000 population). The burden of disease was mainly due to pneumonia in all age ranges. 609 of 614 strains were serotyped and 47 different serotypes were found. Among the 609 IPD cases with known serotype, 12.2% were caused by PCV7 serotypes, 51% by PCV10 serotypes, and 71.7% by PCV13 serotypes. 608 of 614 isolates were characterized by MLST. The main clonal types detected were ST306, CC191 and CC230. CONCLUSIONS: PCV13 conjugate vaccine offers good coverage against IPD in Catalonia, Spain. However, the high genetic diversity of pneumococci highlights the importance of molecular surveillance systems for monitoring IPD during the vaccination period. SUMMARY: This study shows that 13-valent conjugate vaccine offers good coverage against invasive pneumococcal disease in children and adults in Spain. However, the high genetic diversity of pneumococci highlights the importance of molecular surveillance systems for monitoring IPD during the vaccination period.

Rationale and design of the CAPAMIS study: effectiveness of pneumococcal vaccination against community-acquired pneumonia, acute myocardial infarction and stroke.

BACKGROUND: The 23-valent polysaccharide pneumococcal vaccine (PPV-23) is recommended for elderly and high-risk people, although its effectiveness is controversial. Some studies have reported an increasing risk of acute vascular events among patients with pneumonia, and a recent case-control study has reported a reduction in the risk of myocardial infarction among patients vaccinated with PPV-23. Given that animal experiments have shown that pneumococcal vaccination reduces the extent of atherosclerotic lesions, it has been hypothesized that PPV-23 could protect against acute vascular events by an indirect effect preventing pneumonia or by a direct effect on oxidized low-density lipoproteins. The main objective of this study is to evaluate the clinical effectiveness of PPV-23 in reducing the risk of pneumonia and acute vascular events (related or nonrelated with prior pneumonia) in the general population over 60 years. METHODS/DESIGN: Cohort study including 27,000 individuals 60 years or older assigned to nine Primary Care Centers in the region of Tarragona, Spain. According to the reception of PPV-23 before the start of the study, the study population will be divided into vaccinated and nonvaccinated groups, which will be followed during a consecutive 30-month period. Primary Care and Hospitals discharge databases will initially be used to identify study events (community-acquired pneumonia, hospitalisation for acute myocardial infarction and stroke), but all cases will be further validated by checking clinical records. Multivariable Cox regression analyses estimating hazard ratios (adjusted for age, sex and comorbidities) will be used to estimate vaccine effectiveness. DISCUSSION: The results of the study will contribute to clarify the controversial effect of the PPV-23 in preventing community-acquired pneumonia and they will be critical in determining the possible role of pneumococcal vaccination in cardiovascular prevention.

Clinical effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumonia in middle-aged and older adults: a matched case-control study.

The 23-valent polysaccharide pneumococcal vaccine is currently recommended in elderly and high-risk adults. Its efficacy against invasive pneumococcal disease has been demonstrated, but its effectiveness in preventing pneumonia remains uncertain. This study assessed the clinical effectiveness of vaccination against pneumonia among middle-aged and older adults. We conducted a population-based case-control study including 304 case patients over 50 years old with radiographically confirmed pneumococcal pneumonia (94 bacteremic and 210 nonbacteremic cases) and 608 outpatient control subjects (matched by primary care centre, age, sex and risk stratum). Adjusted odds ratios (ORs) for vaccination were calculated using conditional logistic regression, controlling for underlying conditions. Vaccine effectiveness against all pneumococcal pneumonia was 48% (OR: 0.52; 95% confidence interval [CI]: 0.37-0.73). Vaccination was effective against bacteremic cases (OR: 0.34; 95% CI: 0.27-0.66) as well as nonbacteremic cases (OR: 0.58; 95% CI: 0.39-0.86). Vaccine effectiveness was highest against bacteremic infections caused by vaccine types (OR: 0.24; 95% CI: 0.09-0.66). These findings confirm the effectiveness of the vaccine against invasive disease, but they also support the benefit of vaccination in preventing nonbacteremic pneumococcal pneumonia.

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.