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Human Vaccines & Immunotherapeutics Dec 2016The purpose of this study was to perform a meta-analysis comparing the effectiveness of influenza vaccination alone versus influenza plus pneumococcal dual vaccination... (Comparative Study)
Comparative Study Meta-Analysis Review
Comparison of dual influenza and pneumococcal polysaccharide vaccination with influenza vaccination alone for preventing pneumonia and reducing mortality among the elderly: A meta-analysis.
The purpose of this study was to perform a meta-analysis comparing the effectiveness of influenza vaccination alone versus influenza plus pneumococcal dual vaccination for the prevention of pneumonia and mortality in adults ≥ 65 years of age. Medline, Cochrane, CENTRAL, EMBASE, and Google Scholar databases were searched. Inclusion criteria were: 1) Randomized controlled trials (RCTs), 2-arm prospective studies, or retrospective cohort studies; 2) Patients were ≥ 65 years of age with or without chronic respiratory disease; 3) Patients received the influenza vaccine alone or dual pneumococcal and influenza vaccination; 4) Results included incidence of recurrent respiratory tract infections, length of hospital stay, and overall mortality rate. The outcomes were pneumonia and all-cause mortality rates. Of 142 studies identified in the database searches, 6 were ultimately included in the systematic review, and 5 were included in meta-analysis. The number of patients that received the influenza vaccination alone ranged from 211 to 29,346 (total = 53,107), and the number that received influenza+pneumococcal vaccination ranged from 246 to 72,107 (total = 102,068). Influenza+pneumococcal vaccination was associated with a significantly lower pneumonia rate than influenza vaccination alone (relative risk [RR] = 0.835, 95% confidence interval [CI]: 0.718-0.971, P = 0.019), and with a significantly lower all-cause mortality rate than influenza vaccination alone (relative risk [RR] = 0.771, 95% confidence interval [CI]: 0.707-0.842, P = 0.001). In conclusion, the results of this study support concomitant pneumococcal and influenza vaccination of the elderly as a dual vaccination strategy is associated with lower pneumonia and all-cause mortality rates.
Topics: Aged; Aged, 80 and over; Humans; Influenza Vaccines; Influenza, Human; Length of Stay; Pneumococcal Vaccines; Pneumonia, Pneumococcal; Survival Analysis; Treatment Outcome; Vaccination
PubMed: 27629584
DOI: 10.1080/21645515.2016.1221552 -
Clinical Microbiology and Infection :... Oct 2012Streptococcus pneumoniae causes different types of acute, invasive and non-invasive clinical infections, being the most frequently detected pathogen responsible for... (Review)
Review
Streptococcus pneumoniae causes different types of acute, invasive and non-invasive clinical infections, being the most frequently detected pathogen responsible for community-acquired pneumonia. Pneumococcal pneumonia is accompanied by bacteraemia in 10-30% of cases. Streptococcus pneumoniae is gaining resistance to the in vitro activity of several antimicrobial agents and, even if questions remain regarding the clinical impact of this phenomenon, more and more reports indicate that antibiotic resistance can lead to more treatment failures if not higher mortality. Use of the 23-valent anti-pneumococcal vaccine appears to offer subpotimal protection against pneumococcal disease, particularly among high-risk adult populations. Vaccination against S. pneumoniae with new conjugate vaccines seems to be the most promising field for real improvement in the management of pneumococcal infections in adults.
Topics: Anti-Bacterial Agents; Bacteremia; Community-Acquired Infections; Drug Resistance, Bacterial; Humans; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae; Treatment Failure
PubMed: 22882668
DOI: 10.1111/j.1469-0691.2012.03937.x -
Human Vaccines & Immunotherapeutics 2016Pneumococcal conjugate vaccines (PCVs) have been successful in preventing invasive pneumococcal disease but effectiveness has been challenged by replacement of vaccine... (Randomized Controlled Trial)
Randomized Controlled Trial
Pneumococcal conjugate vaccines (PCVs) have been successful in preventing invasive pneumococcal disease but effectiveness has been challenged by replacement of vaccine serotypes with non-vaccine serotypes. Vaccines targeting common pneumococcal protein(s) found in most/all pneumococci may overcome this limitation. This phase II study assessed safety and immunogenicity of a new protein-based pneumococcal vaccine containing polysaccharide conjugates of 10 pneumococcal serotypes combined with pneumolysin toxoid(dPly) and pneumococcal histidine triad protein D(PhtD) (PHiD-CV/dPly/PhtD-30) in African children. 120 Gambian children (2-4 years, not previously vaccinated against Streptococcus pneumoniae) randomized (1:1) received a single dose of PHiD-CV/dPly/PhtD-30 or PCV13. Adverse events occurring over 4 d post-vaccination were reported, and blood samples obtained pre- and 1-month post-vaccination. Serious adverse events were reported for 6 months post-vaccination. Solicited local and systemic adverse events were reported at similar frequency in each group. One child (PHiD-CV/dPly/PhtD-30 group) reported a grade 3 local reaction to vaccination. Haematological and biochemical parameters seemed similar pre- and 1-month post-vaccination in each group. High pre-vaccination Ply and PhtD antibody concentrations were observed in each group, but only increased in PHiD-CV/dPly/PhtD-30 vaccinees one month post-vaccination. One month post-vaccination, for each vaccine serotype ≥96.2% of PHiD-CV/dPly/PhtD-30 vaccinees had serotype-specific polysaccharide antibody concentrations ≥0.20µg/mL except serotypes 6B (80.8%) and 23F (65.4%), and ≥94.1% had OPA titres of ≥8 except serotypes 1 (51.9%), 5 (38.5%) and 6B (78.0%), within ranges seen in PCV13-vaccinated children. A single dose of PHiD-CV/dPly/PhtD-30 vaccine, administered to Gambian children aged 2-4 y not previously vaccinated with a pneumococcal vaccine, was well-tolerated and immunogenic.
Topics: Antibodies, Bacterial; Bacterial Proteins; Child, Preschool; Female; Gambia; Humans; Hydrolases; Male; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae; Streptolysins; Vaccination; Vaccines, Conjugate
PubMed: 26618243
DOI: 10.1080/21645515.2015.1111496 -
Clinical Microbiology and Infection :... Oct 2012Pneumococcal conjugated vaccines have been recommended in children for over a decade in many countries worldwide. Here we review the development of pneumococcal vaccines... (Review)
Review
Pneumococcal conjugated vaccines have been recommended in children for over a decade in many countries worldwide. Here we review the development of pneumococcal vaccines with a focus on the two types currently available for children and their safety record. We discuss also the effect of vaccines, including the 13-valent pneumococcal conjugate vaccine, on invasive pneumococcal diseases in children, particularly bacteraemia, pneumonia and meningitis, as well as on mucosal disease and carriage. In regions where immunization was implemented in young children, the number of invasive pneumococcal diseases decreased significantly, not only in the target age group, but also in younger and much older subjects. Challenges and future perspectives regarding the development of new 'universal' vaccines, which could bypass the current problem of serotype-specific protection in a context of serotype replacement, are also discussed.
Topics: Carrier State; Child, Preschool; History, 20th Century; History, 21st Century; Humans; Incidence; Infant; Pneumococcal Infections; Pneumococcal Vaccines; Prevalence; Vaccines, Conjugate
PubMed: 22862432
DOI: 10.1111/j.1469-0691.2012.03938.x -
The Pediatric Infectious Disease Journal Aug 2020Pneumococcal disease remains a public health priority worldwide. This phase 2 study (V114-008; NCT02987972; EudraCT 2016-001117-25) compared safety and immunogenicity of... (Comparative Study)
Comparative Study Randomized Controlled Trial
A Phase II Trial of Safety, Tolerability and Immunogenicity of V114, a 15-Valent Pneumococcal Conjugate Vaccine, Compared With 13-Valent Pneumococcal Conjugate Vaccine in Healthy Infants.
BACKGROUND
Pneumococcal disease remains a public health priority worldwide. This phase 2 study (V114-008; NCT02987972; EudraCT 2016-001117-25) compared safety and immunogenicity of 2 clinical lots of V114 (investigational 15-valent pneumococcal vaccine: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19F, 19A, 22F*, 23F, 33F*) to 13-valent pneumococcal conjugate vaccine (PCV13) in healthy infants (*serotypes unique to V114).
METHODS
Healthy infants 6-12 weeks old were randomized to receive a 4-dose regimen of V114 Lot 1, V114 Lot 2 or PCV13 at 2, 4, 6 and 12-15 months old. Adverse events were evaluated after each dose. Primary immunogenicity endpoint was to demonstrate noninferiority of V114 Lot 1 and V114 Lot 2 relative to PCV13 based on proportion of infants achieving serotype-specific IgG concentration ≥0.35 µg/mL for 13 serotypes shared with PCV13 at 1 month postdose 3 (PD3). Serotype-specific IgG geometric mean concentrations (GMCs) for all 15 V114 serotypes were measured at PD3, predose 4 and 1 month postdose 4 (PD4).
RESULTS
Overall, 1044 of 1051 randomized infants received ≥1 dose of vaccine (V114 Lot 1 [n = 350], V114 Lot 2 [n = 347] or PCV13 [n = 347]). Adverse events were generally comparable across groups. At PD3, both V114 lots met noninferiority criteria for all 13 serotypes shared with PCV13. IgG GMCs were comparable among V114 and PCV13 recipients at PD3 and PD4. Serotype 3 responses were higher following receipt of V114 than PCV13. Both V114 lots induced higher GMCs than PCV13 to the 2 unique V114 serotypes.
CONCLUSIONS
Immunogenicity of both V114 lots was noninferior to PCV13 for all 13 shared serotypes between the 2 vaccines and displayed comparable safety and tolerability profiles to PCV13.
Topics: Antibodies, Bacterial; Double-Blind Method; Drug Administration Schedule; Female; Humans; Immunogenicity, Vaccine; Immunoglobulin G; Infant; Male; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae; Vaccines, Conjugate
PubMed: 32639460
DOI: 10.1097/INF.0000000000002765 -
Vaccine Sep 2015Post-licensure real world evaluation of vaccine implementation is important for establishing evidence of vaccine effectiveness (VE) and programme impact, including... (Review)
Review
Post-licensure real world evaluation of vaccine implementation is important for establishing evidence of vaccine effectiveness (VE) and programme impact, including indirect effects. Large cohort studies offer an important epidemiological approach for evaluating VE, but have inherent methodological challenges. Since March 2012, we have conducted an open prospective cohort study in two sites in rural Malawi to evaluate the post-introduction effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) against all-cause post-neonatal infant mortality and monovalent rotavirus vaccine (RV1) against diarrhoea-related post-neonatal infant mortality. Our study sites cover a population of 500,000, with a baseline post-neonatal infant mortality of 25 per 1000 live births. We conducted a methodological review of cohort studies for vaccine effectiveness in a developing country setting, applied to our study context. Based on published literature, we outline key considerations when defining the denominator (study population), exposure (vaccination status) and outcome ascertainment (mortality and cause of death) of such studies. We assess various definitions in these three domains, in terms of their impact on power, effect size and potential biases and their direction, using our cohort study for illustration. Based on this iterative process, we discuss the pros and cons of our final per-protocol analysis plan. Since no single set of definitions or analytical approach accounts for all possible biases, we propose sensitivity analyses to interrogate our assumptions and methodological decisions. In the poorest regions of the world where routine vital birth and death surveillance are frequently unavailable and the burden of disease and death is greatest We conclude that provided the balance between definitions and their overall assumed impact on estimated VE are acknowledged, such large scale real-world cohort studies can provide crucial information to policymakers by providing robust and compelling evidence of total benefits of newly introduced vaccines on reducing child mortality.
Topics: Developing Countries; Epidemiologic Methods; Humans; Malawi; Pneumococcal Vaccines; Prospective Studies; Rotavirus Vaccines; Survival Analysis; Treatment Outcome; Vaccines, Attenuated
PubMed: 26235370
DOI: 10.1016/j.vaccine.2015.07.062 -
PloS One 2011Although the substantial burdens of rotavirus and pneumococcal disease have motivated many countries to consider introducing the rotavirus vaccine (RV) and heptavalent...
Although the substantial burdens of rotavirus and pneumococcal disease have motivated many countries to consider introducing the rotavirus vaccine (RV) and heptavalent pneumococcal conjugate vaccine (PCV-7) to their National Immunization Programs (EPIs), these new vaccines could affect the countries' vaccine supply chains (i.e., the series of steps required to get a vaccine from their manufacturers to patients). We developed detailed computational models of the Trang Province, Thailand, vaccine supply chain to simulate introducing various RV and PCV-7 vaccine presentations and their combinations. Our results showed that the volumes of these new vaccines in addition to current routine vaccines could meet and even exceed (1) the refrigerator space at the provincial district and sub-district levels and (2) the transport cold space at district and sub-district levels preventing other vaccines from being available to patients who arrive to be immunized. Besides the smallest RV presentation (17.1 cm³/dose), all other vaccine introduction scenarios required added storage capacity at the provincial level (range: 20 L-1151 L per month) for the three largest formulations, and district level (range: 1 L-124 L per month) across all introduction scenarios. Similarly, with the exception of the two smallest RV presentation (17.1 cm³/dose), added transport capacity was required at both district and sub-district levels. Added transport capacity required across introduction scenarios from the provincial to district levels ranged from 1 L-187 L, and district to sub-district levels ranged from 1 L-13 L per shipment. Finally, only the smallest RV vaccine presentation (17.1 cm³/dose) had no appreciable effect on vaccine availability at sub-districts. All other RV and PCV-7 vaccines were too large for the current supply chain to handle without modifications such as increasing storage or transport capacity. Introducing these new vaccines to Thailand could have dynamic effects on the availability of all vaccines that may not be initially apparent to decision-makers.
Topics: Child; Child, Preschool; Female; Heptavalent Pneumococcal Conjugate Vaccine; Humans; Infant; Infant, Newborn; Male; Pneumococcal Vaccines; Pregnancy; Rotavirus; Thailand
PubMed: 21931805
DOI: 10.1371/journal.pone.0024673 -
MEDICC Review Jan 2019The process of research and evaluation of new products and technologies requires a combination of transdisciplinary theoretical and methodological approaches for...
The process of research and evaluation of new products and technologies requires a combination of transdisciplinary theoretical and methodological approaches for managing and achieving objectives. The research, development and evaluation strategy of the new Cuban pneumococcal vaccine combines the approaches of team science and accelerated vaccine introduction. These frameworks are proposed for discussions regarding biotech product evaluation, using their application to the Pneumococcus Project as an example. Emphasis is on the use of team science to eliminate obstacles to obtaining a product of great scientific and technological complexity while establishing robust scientific evidence to support its use and marketing. All of this is in support of opportune and efficient decisions for accelerated introduction of new vaccines in Cuba.
Topics: Biomedical Research; Cuba; Humans; Interdisciplinary Research; Pneumococcal Infections; Pneumococcal Vaccines
PubMed: 31242151
DOI: 10.37757/MR2019.V21.N1.8 -
Clinical Interventions in Aging 2012Vaccination remains the primary preventive strategy in the elderly against Streptococcus pneumoniae and influenza infections. The effectiveness of this strategy in... (Review)
Review
Vaccination remains the primary preventive strategy in the elderly against Streptococcus pneumoniae and influenza infections. The effectiveness of this strategy in preventing pneumonia has been in doubt despite the increase in vaccination coverage among older adults. Randomized controlled trials (RCTs) and observational studies aimed at determining clinical outcomes and immune response following pneumococcal vaccination have yielded conflicting results. The protective efficacy of pneumococcal vaccination against pneumonia in older adults has not been firmly established due to a lack of RCTs specifically examining patients ≥ 65 years of age. Similarly, the reported benefits of influenza vaccination have been derived from observational data. The assessment of clinical benefit from influenza vaccination in the elderly population is complicated by varying cohorts, virulence of the influenza strain, and matching of vaccine and circulating viral strains. The presence of selection bias and use of nonspecific end points in these studies make the current evidence inconclusive in terms of overall benefit. The development of more immunogenic vaccines through new formulations or addition of adjuvants holds the promise of revolutionizing delivery and improving efficacy. Dismantling existing barriers through education, providing technology assistance predominantly to developing countries, and establishing clear regulatory guidance on pathways for approval are necessary to ensure timely production and equitable distribution.
Topics: Age Factors; Aged; Aged, 80 and over; Humans; Influenza Vaccines; Middle Aged; Pneumococcal Vaccines; Pneumonia; Vaccines, Conjugate; Vaccines, Inactivated
PubMed: 23152675
DOI: 10.2147/CIA.S29675 -
AIDS (London, England) Jul 2015Immunocompromised individuals are at an increased risk of pneumococcal disease. Vaccination is recommended as an important strategy to reduce risk of pneumococcal...
OBJECTIVE
Immunocompromised individuals are at an increased risk of pneumococcal disease. Vaccination is recommended as an important strategy to reduce risk of pneumococcal disease in HIV-infected individuals. This study evaluated the safety and immunogenicity of three 13-valent pneumococcal conjugate vaccine (PCV13) doses followed by one dose of 23-valent pneumococcal polysaccharide vaccine (PPSV23) at 1-month intervals in pneumococcal vaccine-naive, HIV-infected individuals.
DESIGN
This was a phase 3, open-label, single-arm study.
METHODS
Pneumococcal vaccine-naive, HIV-infected individuals at least 6 years of age with CD4 T-cell count at least 200 cells/μl and viral load less than 50 000 copies/ml received three doses of PCV13 followed by one dose of PPSV23 at 1-month intervals. Serotype-specific antipneumococcal immune responses were assessed by IgG geometric mean concentrations (GMCs) and opsonophagocytic activity (OPA) assay geometric mean titres (GMTs) after each dose. Local reactions at the PCV13 injection site, systemic and other adverse events were collected.
RESULTS
Three hundred and one individuals were enrolled and vaccinated; 279 completed the study. Statistically significant increases in IgG GMCs and OPA GMTs were observed for all serotypes after dose 1 of PCV13 compared with prevaccine levels. GMCs and GMTs were comparable or only modestly increased for all serotypes after PCV13 doses 2 and 3 and after PPSV23. The majority of local reactions and systemic events were mild to moderate in severity.
CONCLUSION
A three-dose regimen of PCV13 was well tolerated in pneumococcal vaccine-naive, HIV-infected individuals. Significant immune responses to all serotypes were observed following the first dose of PCV13, with only modest increases in antibody titres following subsequent PCV13 or PPSV23 administration.
Topics: Adolescent; Adult; Antibodies, Bacterial; CD4 Lymphocyte Count; Child; Female; HIV Infections; Humans; Immunization Schedule; Immunization, Secondary; Male; Middle Aged; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae; Viral Load
PubMed: 25888646
DOI: 10.1097/QAD.0000000000000689