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Open Heart 2015Animal models and clinical studies suggest a mechanistic link between the pneumococcal polysaccharide vaccine (PPV) and a cardiovascular protective effect. However,... (Review)
Review
Animal models and clinical studies suggest a mechanistic link between the pneumococcal polysaccharide vaccine (PPV) and a cardiovascular protective effect. However, conflicting results exist from several large observational studies in humans. We set out to systematically review current literature and conduct meta-analyses of studies on PPV and cardiovascular outcomes. Medline, Embase and CENTRAL were searched for randomised controlled trials (RCTs) and observational studies in adults, using PPV as the intervention, up to 30 April 2014. Studies that compared PPV with a control (another vaccine, no vaccine or placebo) and recorded ischaemic events were included in this review. Two investigators extracted data independently on study design, baseline characteristics and summary outcomes. Study quality was examined using the Newcastle-Ottawa Quality Assessment Scale. Pooled estimates using random effects models and their 95% CIs were calculated separately for the outcomes of acute coronary syndrome (ACS) events and stroke. No RCT data were available. A total of 230 426 patients were included in eight observational studies and recorded as ACS events. PPV was associated with significantly lower odds of ACS events in patients 65 years and older (pooled OR=0.83 (95% CI 0.71 to 0.97), I(2)=77.0%). However, there was no significant difference in ACS events when younger people were included (pooled OR=0.86 (95% CI 0.73 to 1.01), I(2)=81.4%). Pooling of four studies, covering a total of 192 210 patients, did not find a significantly reduced risk of stroke in all patients (pooled OR=1.00 (95% CI 0.89 to 1.12), I(2)=55.3%), or when restricted to those 65 years and older (pooled OR=0.96 (95% CI 0.87 to 1.05), I(2)=22.5%). In this meta-analysis of observational studies, the use of PPV was associated with a significantly lower risk of ACS events in the older population, but not stroke. An adequately powered and blinded RCT to confirm these findings is warranted.
PubMed: 26196020
DOI: 10.1136/openhrt-2015-000247 -
Journal of Microbiology, Immunology,... Feb 2022A number of pneumococcal carriage studies in children have been conducted in recent years. However, summary data of carriage prevalence and serotype distribution from... (Meta-Analysis)
Meta-Analysis Review
Carriage of Streptococcus pneumoniae in children under five years of age prior to pneumococcal vaccine introduction in Southeast Asia: A systematic review and meta-analysis (2001-2019).
A number of pneumococcal carriage studies in children have been conducted in recent years. However, summary data of carriage prevalence and serotype distribution from South East Asia Region (SEAR) are limited. This may lead to the misconception that Streptococcus pneumoniae vaccine-types are uncommon in the region. Systematic reviews of pneumococcal carriage and the distribution of serotypes are critically important for evidence-based decision-making. We aimed to summarize published data on the serotype prevalence of S. pneumoniae carried in the nasopharynx of children under 5 years of age in SEAR. We performed a systematic review and meta-analysis for relevant studies on S. pneumoniae carriage conducted prior to PCV program implementation from online journal databases published between January 2001 to December 2019. The pooled prevalence of S. pneumoniae in healthy children under 5 years of age in SEAR was 36.0% (95% CI 34.2%-37.8%), and ranged from 68.0% (95% CI: 61.9%-74.0%) in Cambodia to 7.6% (95% CI: 5.7%-9.6%) in Malaysia. Serotypes 6A/B, 23F and 19F were the most common serotypes in children <5 years, accounting for 12.9% (95% CI: 9.4%-16.3%), 9.3% (95% CI: 5.9%-12.8%) and 10.1% (95% CI: 6.6%-13.5%) of isolates, respectively. Vaccine policy makers should take these results into account when making decisions on pneumococcal conjugate vaccine programs implementation. Given the paucity of data, collection of more extensive and updated information of S. pneumoniae serotype epidemiology in children under five years in SEAR is also very important for future studies.
Topics: Cambodia; Carrier State; Child; Child, Preschool; Humans; Infant; Nasopharynx; Pneumococcal Infections; Pneumococcal Vaccines; Prevalence; Serogroup; Streptococcus pneumoniae; Vaccines, Conjugate
PubMed: 34511388
DOI: 10.1016/j.jmii.2021.08.002 -
BMC Infectious Diseases Nov 2016In many industrialized countries routine vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPSV-23) is recommended to prevent pneumococcal disease in... (Review)
Review
BACKGROUND
In many industrialized countries routine vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPSV-23) is recommended to prevent pneumococcal disease in the elderly. However, vaccine-induced immunity wanes after a few years, and there are controversies around revaccination with PPSV-23. Here, we systematically assessed the effectiveness and safety of PPSV-23 revaccination.
METHOD
We conducted a systematic literature review in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from inception to June 2015. We included all study types that compared effectiveness, immunogenicity and/or safety of PPSV-23 as a primary vs. a revaccination dose in persons aged 50 years and older. With respect to immunogenicity, we calculated the ratio of geometric mean antibody concentrations and opsonophagocytic indexes at identical time-points after primary and revaccination. Additionally, we compared rates and severity of adverse events (AEs) after primary and revaccination.
RESULTS
We included 14 observational studies. 10 studies had a prospective design and analysed data on (i) the same individuals after a first and a second dose of PPSV-23 given 1 to 10 years later (n = 5) or (ii) two groups consisting of participants receiving PPSV-23 who were either vaccine-naïve or had received a first PPSV-23 dose 3 to 13 years earlier (n = 5). Three studies used electronic data bases to compare AEs after primary vs. revaccination doses of PPSV-23 after 1 to 10 years and one study had a cross-sectional design. Number of participants in the non-register-based and register-based studies ranged from 29 to 1414 and 360 to 316,000, respectively. 11 out of 14 included studies were at high risk of bias, three studies had an unclear risk of bias. None of the studies reported data on clinical effectiveness. Immunogenicity studies revealed that during the first two months antibody levels tended to be lower after revaccination as compared to primary vaccination. Thereafter, no obvious differences in antibody levels were observed. Compared to primary vaccination, revaccination was associated with an increased risk of local and systemic AEs, which, however, were usually mild and self-limiting. The risk and severity of AEs appeared to decrease with longer intervals between primary and revaccination.
CONCLUSION
Data comparing the effectiveness of primary vs. revaccination with PPSV-23 are still lacking, because there are no studies with clinical endpoints. Data from observational studies indicates that revaccination with PPSV-23 is likely to induce long-term antibody levels that are comparable to those after primary vaccination. Given the high disease burden and the waning of vaccine-induced immunity, revaccination with PPSV-23 could be considered in the elderly. The increased risk of local and systemic AEs can likely be mitigated when giving revaccination at least five years after the primary dose. Adequately powered randomized controlled trials using clinical endpoints are urgently needed.
Topics: Age Factors; Aged; Aged, 80 and over; Antibodies, Bacterial; Biomarkers; Humans; Immunization, Secondary; Middle Aged; Pneumococcal Infections; Pneumococcal Vaccines
PubMed: 27887596
DOI: 10.1186/s12879-016-2040-y -
Clinical Infectious Diseases : An... Apr 2022Vaccine regulatory decision making is based on vaccine efficacy against etiologically confirmed outcomes, which may underestimate the preventable disease burden. To...
Vaccine-Preventable Disease Incidence Based on Clinically, Radiologically, and Etiologically Confirmed Outcomes: Systematic Literature Review and Re-analysis of Pneumococcal Conjugate Vaccine Efficacy Trials.
BACKGROUND
Vaccine regulatory decision making is based on vaccine efficacy against etiologically confirmed outcomes, which may underestimate the preventable disease burden. To quantify this underestimation, we compared vaccine-preventable disease incidence (VPDI) of clinically defined outcomes with radiologically/etiologically confirmed outcomes.
METHODS
We performed a systematic review of efficacy trials for several vaccines (1997-2019) and report results for pneumococcal conjugate vaccines. Data were extracted for outcomes within a clinical syndrome, organized from most sensitive to most specific. VPDI was determined for each outcome, and VPDI ratios were calculated, with a clinically defined outcome (numerator) and a radiologically/etiologically confirmed outcome (denominator).
RESULTS
Among 9 studies, we calculated 27 VPDI ratios; 24 had a value >1. Among children, VPDI ratios for clinically defined versus vaccine serotype otitis media were 0.6 (95% CI not calculable), 2.1 (1.5-3.0), and 3.7 (1.0-10.2); the VPDI ratios comparing clinically defined with radiologically confirmed pneumonia ranged from not calculable to 2.7 (1.2-10.4); the VPDI ratio comparing clinically suspected invasive pneumococcal disease (IPD) with laboratory-confirmed IPD was 3.8 (95% CI not calculable). Among adults, the ratio comparing clinically defined with radiologically confirmed pneumonia was 1.9 (-6.0 to 9.1) and with vaccine serotype-confirmed pneumonia was 2.9 (.5-7.8).
CONCLUSIONS
While there is substantial uncertainty around individual point estimates, there is a consistent trend in VPDI ratios, most commonly showing under-ascertainment of 1.5- to 4-fold, indicating that use of clinically defined outcomes is likely to provide a more accurate estimate of a pneumococcal conjugate vaccine's public health value.
Topics: Adult; Child; Humans; Incidence; Infant; Pneumococcal Infections; Pneumococcal Vaccines; Randomized Controlled Trials as Topic; Vaccine Efficacy; Vaccine-Preventable Diseases; Vaccines, Conjugate
PubMed: 34313721
DOI: 10.1093/cid/ciab649 -
Microorganisms Jul 2023Higher valency pneumococcal conjugate vaccines (PCV15 and PCV20) have been developed to address the disease burden of current non-vaccine serotypes. This review... (Review)
Review
Systematic Literature Review of the Epidemiological Characteristics of Pneumococcal Disease Caused by the Additional Serotypes Covered by the 20-Valent Pneumococcal Conjugate Vaccine.
Higher valency pneumococcal conjugate vaccines (PCV15 and PCV20) have been developed to address the disease burden of current non-vaccine serotypes. This review describes the epidemiological characteristics of serotypes beyond PCV13 (serotypes 8, 10A, 11A, 12F, 15B/C, 22F, and 33F; PCV20nonPCV13 serotypes). Peer-reviewed studies published between 1 January 2010 (the year PCV13 became available) and 18 August 2020 were systematically reviewed (PROSPERO number: CRD42021212875). Data describing serotype-specific outcomes on disease proportions, incidence, severity, and antimicrobial non-susceptibility were summarized for individual and aggregate PCV20nonPCV13 serotypes by age group and by type and duration of pediatric PCV immunization program. Of 1168 studies, 127 (11%) were included in the analysis. PCV20nonPCV13 serotypes accounted for 28% of invasive pneumococcal disease (IPD), although the most frequent serotypes differed between children (10A, 15B/C) and adults (8, 12F, 22F). In children, serotype 15B/C tended to be more frequently associated with pneumococcal meningitis and acute otitis media; in adults, serotype 8 was more frequently associated with pneumonia and serotype 12F with meningitis. Serotypes 10A and 15B/C in children and 11A and 15B/C in adults were often associated with severe IPD. Serotype 15B/C was also among the most frequently identified penicillin/macrolide non-susceptible PCV20nonPCV13 serotypes. These results could inform decision making about higher valency PCV choice and use.
PubMed: 37512988
DOI: 10.3390/microorganisms11071816 -
The Pediatric Infectious Disease Journal Jan 2014To aid decision making for pneumococcal conjugate vaccine (PCV) use in infant national immunization programs, we summarized the indirect effects of PCV on clinical... (Review)
Review
BACKGROUND
To aid decision making for pneumococcal conjugate vaccine (PCV) use in infant national immunization programs, we summarized the indirect effects of PCV on clinical outcomes among nontargeted age groups.
METHODS
We systematically reviewed the English literature on infant PCV dosing schedules published from 1994 to 2010 (with ad hoc addition of 2011 articles) for outcomes on children >5 years of age and adults including vaccine-type nasopharyngeal carriage (VT-NP), vaccine-type invasive pneumococcal disease (VT-IPD) and syndromic pneumonia.
RESULTS
Of 12,980 citations reviewed, we identified 21 VT-IPD, 6 VT-NP and 9 pneumonia studies. Of these 36, 21 (58%) included 3 primary doses plus PCV or pneumococcal polysaccharide vaccine (PPV23) booster schedule (3+1 or 3+PPV23), 5 (14%) 3+0, 9 (25%) 2+1 and 1 (3%) 2+0. Most (95%) were PCV7 studies. Among observational VT-IPD studies, all schedules (2+1, 3+0 and 3+1) demonstrated reductions in incidence among young adult groups. Among syndromic pneumonia observational studies (2+1, 3+0 and 3+1), only 3+1 schedules showed significant indirect impact. Of 2 VT-NP controlled trials (3+0 and 3+1) and 3 VT-NP observational studies (2+1, 3+1 and 3+PPV23), 3+1 and 3+PPV23 schedules showed significant indirect effect. The 1 study to directly compare between schedules was a VT-NP study (2+0 vs. 2+1), which found no indirect effect on older siblings and parents of vaccinated children with either schedule.
CONCLUSIONS
Indirect benefit of a 3+1 infant PCV dosing schedule has been demonstrated for VT-IPD, VT-NP and syndromic pneumonia; 2+1 and 3+0 schedules have demonstrated indirect effect only for VT-IPD. The choice of optimal infant PCV schedule is limited by data paucity on indirect effects, especially a lack of head-to-head studies and studies of PCV10 and PCV13.
Topics: Adolescent; Adult; Aged; Carrier State; Child; Child, Preschool; Humans; Immunization Schedule; Infant; Middle Aged; Nasopharynx; Observational Studies as Topic; Pneumococcal Infections; Pneumococcal Vaccines; Randomized Controlled Trials as Topic; Vaccines, Conjugate; Young Adult
PubMed: 24336058
DOI: 10.1097/INF.0000000000000084 -
Clinical Infectious Diseases : An... Jun 2019A notable reduction of the pneumococcal disease burden among adults was observed after the introduction of a 7-valent pneumococcal conjugate vaccine (PCV7) in childhood... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A notable reduction of the pneumococcal disease burden among adults was observed after the introduction of a 7-valent pneumococcal conjugate vaccine (PCV7) in childhood immunization programs. In 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in many jurisdictions; a comparative assessment of PCV13's impact was missing. Our objective was to summarize the available data and assess the change in the incidence of invasive pneumococcal disease (IPD) in adults after the introduction of PCV13 in childhood immunization programs.
METHODS
We conducted a systematic literature search from January 1946 to May 2017 of randomized, controlled trials and observational studies OBS reporting the incidence of IPD, non-invasive pneumococcal disease, hospitalizations, and mortality in adults for the periods before and after the introduction of PCV13. Incidence rate ratios (IRRs) were pooled across studies using restricted, maximum-likelihood, random-effects models.
RESULTS
From 3306 records,we included 29 OBS studies and 2033961 cases. Significantly lower IPD rates were seen after PCV13 introduction in adults aged <65 years (IRR 0.78, 95% confidence interval [CI] 0.72-0.85) and those aged ≥65 years (IRR 0.86, 95% CI 0.81-0.91). Lower rates of IPD were seen with PCV7 (IRR 0.45, 95% CI 0.38-0.54) and PCV13 serotypes (IRR 0.60, 95% CI 0.54-0.68). A significantly higher IRR of 1.10 (95% CI 1.04-1.17) for non-vaccine serotypes was observed, especially among those aged 65 years and older (IRR 1.20, 95% CI 1.11-1.29).
CONCLUSIONS
PCV13 use in children had a moderate impact on reducing the overall and vaccine-type IPDs, but there was a significant increase in non-vaccine type IPDs among adults, especially in those over 65 years.
Topics: Adult; Age Factors; Hospitalization; Humans; Immunization; Immunization Programs; Incidence; Observational Studies as Topic; Pneumococcal Infections; Pneumococcal Vaccines; Randomized Controlled Trials as Topic; Serogroup
PubMed: 30312379
DOI: 10.1093/cid/ciy872 -
PloS One 2017Routine vaccination of elderly people against pneumococcal diseases is recommended in many countries. National guidelines differ, recommending either the 23-valent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Routine vaccination of elderly people against pneumococcal diseases is recommended in many countries. National guidelines differ, recommending either the 23-valent polysaccharide vaccine (PPV23), the 13-valent conjugate vaccine (PCV13) or both. Considering the ongoing debate on the effectiveness of PPV23, we performed a systematic literature review and meta-analysis of the vaccine efficacy/effectiveness (VE) of PPV23 against invasive pneumococcal disease (IPD) and pneumococcal pneumonia in adults aged ≥60 years living in industrialized countries.
METHODS
We searched for pertinent clinical trials and observational studies in databases MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. We assessed the risk of bias of individual studies using the Cochrane Risk of Bias tool for randomized controlled trials and the Newcastle-Ottawa Scale for observational studies. We rated the overall quality of the evidence by GRADE criteria. We performed meta-analyses of studies grouped by outcome and study design using random-effects models. We applied a sensitivity analysis excluding studies with high risk of bias.
RESULTS
We identified 17 eligible studies. Pooled VE against IPD (by any serotype) was 73% (95%CI: 10-92%) in four clinical trials, 45% (95%CI: 15-65%) in three cohort studies, and 59% (95%CI: 35-74%) in three case-control studies. After excluding studies with high risk of bias, pooled VE against pneumococcal pneumonia (by any serotype) was 64% (95%CI: 35-80%) in two clinical trials and 48% (95%CI: 25-63%) in two cohort studies. Higher VE estimates in trials (follow-up ~2.5 years) than in observational studies (follow-up ~5 years) may indicate waning protection. Unlike previous meta-analyses, we excluded two trials with high risk of bias regarding the outcome pneumococcal pneumonia, because diagnosis was based on serologic methods with insufficient specificity.
CONCLUSIONS
Our meta-analysis revealed significant VE of PPV23 against both IPD and pneumococcal pneumonia by any serotype in the elderly, comparable to the efficacy of PCV13 against vaccine-serotype disease in a recent clinical trial in elderly people. Due to its broader serotype coverage and the decrease of PCV13 serotypes among adults resulting from routine infant immunization with PCV13, PPV23 continues to play an important role for protecting adults against IPD and pneumococcal pneumonia.
Topics: Age Factors; Aged; Aged, 80 and over; Clinical Trials as Topic; Female; Humans; Male; Odds Ratio; Outcome Assessment, Health Care; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae
PubMed: 28061505
DOI: 10.1371/journal.pone.0169368 -
Atencion Primaria Sep 2002Estimate pneumococcal vaccine effectiveness in preventing Streptococcus pneumoniae illness in the elderly. (Comparative Study)
Comparative Study Meta-Analysis Review
AIM
Estimate pneumococcal vaccine effectiveness in preventing Streptococcus pneumoniae illness in the elderly.
DESIGN
Systematic review and meta-analysis. DATA SOURCE. MEDLINE, years 1964 to the 2000; EMBASE, from 1988 to the 2000; Cochrane Library, identified studies and previously published systematic reviews citations peruse, and contacts with field experts.
STUDY SELECTION
Clinical trials, cohort and case-control studies, published in Spanish, English or French, that estimated pneumococcal disease rates in vaccinated or not vaccinated elderly.
DATA EXTRACTION
The studies were valued independently by four investigators with predefined criteria of validity, such as results comparing rates of disease caused by serotypes included in the vaccine, random allocation, double blind design, included subjects pertaining to the same study base, and losses of less than 10% in clinical trials and 20% in observational studies.
RESULTS
Eight clinical trials considered the relative risk (RR) of pneumococcal pneumonia, three did not make estimations on pneumonia originated by serotypes included in the vaccine and only one study fulfilled all the inclusion criteria. Vaccinated versus not vaccinated pneumococcal pneumonia RR was 0.86 (95%CI, 0.24 to 2.99). Vaccine effectiveness was 14% (95%CI, -199 to 76%). Ten studies performed estimations on the effectiveness of the vaccine on invasive disease by vaccine serotypes. Of these, two clinical trials and two observational studies fulfilled the required quality criteria. RR of invasive disease was of 0.68 (95%CI, 0.39-1.18); vaccine effectiveness was 32% (95%CI, 18-61%).
CONCLUSIONS
No evidence was found supporting pneumococcal vaccine effectiveness to reduce or avoid S. pneumoniae disease in the elderly.
Topics: Adult; Age Factors; Aged; Aged, 80 and over; Case-Control Studies; Clinical Trials as Topic; Cohort Studies; Double-Blind Method; Humans; Middle Aged; Pneumococcal Vaccines; Pneumonia, Pneumococcal; Random Allocation; Risk
PubMed: 12372207
DOI: 10.1016/s0212-6567(02)79027-6 -
Vaccine Dec 2011Pneumococcal conjugate vaccines (PCV) were first licensed for use with 3 primary doses in infancy and a booster dose. The evidence for the effects of different schedules... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pneumococcal conjugate vaccines (PCV) were first licensed for use with 3 primary doses in infancy and a booster dose. The evidence for the effects of different schedules was examined in this systematic review and meta-analysis.
METHODS
We searched 12 databases and trial registers up to March 2010. We selected randomised controlled trials (RCTs), cohort and case-control studies making direct comparisons between PCV schedules with (2p) or (3p) primary doses, with (+1) or without (+0) a booster dose. We extracted data on clinical, nasopharyngeal carriage and immunological outcomes and used meta-analysis to combine results where appropriate.
RESULTS
Seropositivity levels (antibody concentration ≥0.35 μg/ml) following 3p and 2p PCV schedules were high for most serotypes (5 RCTs). Differences between schedules were generally small and tended to favour 3p schedules, particularly for serotypes 6B and 23F; between-study heterogeneity was high. Seropositivity levels following 3p+1 and 2p+1 schedules were similar but small differences favouring 3p+1 schedules were seen for serotypes 6B and 23F. We did not identify any RCTs reporting clinical outcomes for these comparisons. In 2 RCTs there was weak evidence of a reduction in carriage of S. pneumoniae serotypes included in the vaccine when 3p+0 schedules were compared to 2p+0 at 6 months of age.
CONCLUSIONS
Most data about the relative effects of different PCV schedules relate to immunological outcomes. Both 3p and 2p schedules result in high levels of seropositivity. The clinical relevance of differences in immunological outcomes between schedules is not known. There is an absence of clinical outcome data from RCTs with direct comparisons of any 2p with any 3p PCV schedule.
Topics: Antibodies, Bacterial; Carrier State; Humans; Immunization Schedule; Immunization, Secondary; Infant; Pneumococcal Infections; Pneumococcal Vaccines; Prevalence; Vaccination; Vaccines, Conjugate
PubMed: 21821080
DOI: 10.1016/j.vaccine.2011.07.042