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BMJ Global Health Oct 2023Maternal vaccination is a promising strategy to reduce the burden of vaccine-preventable diseases for mothers and infants. We aimed to provide an up-to-date overview of... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Maternal vaccination is a promising strategy to reduce the burden of vaccine-preventable diseases for mothers and infants. We aimed to provide an up-to-date overview of the efficacy and safety of all available maternal vaccines.
METHODS
We searched PubMed, Embase, CENTRAL and ClinicalTrials.gov on 1 February 2022, for phase III and IV randomised controlled trials (RCTs) that compared maternal vaccination against any pathogen with placebo or no vaccination. Primary outcomes were laboratory-confirmed or clinically confirmed disease in mothers and infants. Secondary safety outcomes included intrauterine growth restriction, stillbirth, maternal death, preterm birth, congenital malformations and infant death. Random effects meta-analysis were used to calculate pooled risk ratio's (RR). Quality appraisal was performed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE).
RESULTS
Six RCTs on four maternal vaccines, influenza, tetanus, diphtheria and pertussis (Tdap), pneumococcal and respiratory syncytial virus (RSV) were eligible. The overall risk of bias and certainty of evidence varied from low to high. Maternal influenza vaccination significantly reduced the number of laboratory-confirmed influenza cases (RR 0.58, 95% CI 0.42 to 0.79, event rate 57 vs 98, 2 RCTs, n=6003, I=0%), and clinically confirmed influenza cases in mothers (RR 0.88, 95% CI 0.78 to 0.99, event rate 418 vs 472, 2 RCTs, n=6003, I=0%), and laboratory-confirmed influenza in infants (RR 0.66, 95% CI 0.52 to 0.85, event rate 98 vs 148, 2 RCTs, n=5883, I=0%), although this was not significant for clinically confirmed influenza in infants (RR 0.99, 95% CI 0.94 to 1.05, event rate 1371 vs 1378, 2 RCTs, n=5883, I=0%). No efficacy data were available on maternal Tdap vaccination. Maternal pneumococcal vaccination did not reduce laboratory-confirmed and clinically confirmed middle ear disease (RR 0.49, 95% CI 0.24 to 1.02, event rate 9 vs 18, 1 RCT, n=133 and RR 0.88 95% CI 0.69 to 1.12, event rate 42 vs 47, 1 RCT, n=133, respectively), and clinically confirmed lower-respiratory tract infection (LRTI) (RR 1.08, 95% CI 0.82 to 1.43, event rate 18 vs 34, 1 RCT, n=70) in infants. Maternal RSV vaccination did not reduce laboratory-confirmed RSV LRTI in infants (RR 0.75, 95% CI 0.56 to 1.01, event rate 103 vs 71, 1 RCT, n=4527). There was no evidence of a significant effect of any of the maternal vaccines on the reported safety outcomes.
CONCLUSIONS
The few RCTs with low event rates suggest that, depending on the type of maternal vaccine, the vaccine might effectively prevent disease and within its size does not show safety concerns in mothers and infants.
PROSPERO REGISTRATION NUMBER
CRD42021235115.
Topics: Infant, Newborn; Female; Humans; Infant; Influenza, Human; Influenza Vaccines; Mothers; Vaccination; Respiratory Tract Infections; Randomized Controlled Trials as Topic
PubMed: 37899087
DOI: 10.1136/bmjgh-2023-012376 -
Vaccine Oct 2019Serotype 3 pneumococcal disease has not substantially declined at the population level after the routine introduction of 13-valent pneumococcal conjugate vaccine (PCV13)...
BACKGROUND
Serotype 3 pneumococcal disease has not substantially declined at the population level after the routine introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into pediatric immunization programs across the globe. This epidemiological finding has generated debate regarding the effectiveness of PCV13 against serotype 3 disease. Evaluating PCV13 effectiveness against serotype 3 is especially critical in adults, where serotype 3 makes up an important amount of remaining pneumococcal disease.
METHODS
We performed a systematic review of the published literature to assess the direct effectiveness of PCV13 against serotype 3 community-acquired pneumonia (CAP) among adults. We then estimated overall vaccine effectiveness (VE) using a pooled analysis of the individual-level, raw data.
RESULTS
Two published studies met inclusion criteria. One was a randomized controlled trial conducted in the Netherlands and published in 2014. The other was a recently-published case-control study conducted in Louisville, Kentucky that used a test-negative design (TND). We also identified a third TND study conducted in Argentina that was recently presented as a conference abstract but is not yet published. All three studies were conducted in adults aged ≥65 years. PCV13 VE against serotype 3 hospitalized CAP was 52.5% (95%CI: 6.2-75.9%) from the pooled analysis of individual-level data from all three studies. Results were similar if the unpublished estimate was excluded (serotype 3 VE = 53.6% [95%CI: 6.7-76.9%]). No heterogeneity was observed.
CONCLUSIONS
Currently-available evidence, although limited to three studies, suggests that PCV13 provides direct protection against serotype 3 hospitalized CAP in adults aged ≥65 years.
Topics: Adult; Argentina; Case-Control Studies; Humans; Kentucky; Netherlands; Pneumococcal Infections; Pneumococcal Vaccines; Pneumonia, Pneumococcal; Randomized Controlled Trials as Topic; Research Design; Serogroup; Streptococcus pneumoniae; Vaccine Potency; Vaccines, Conjugate
PubMed: 31522807
DOI: 10.1016/j.vaccine.2019.08.059 -
Expert Review of Vaccines 2023Diabetic patients are at a higher risk of getting pneumococcal disease and are therefore recommended to get vaccinated. The aim of our systematic review is the retrieval... (Review)
Review
INTRODUCTION
Diabetic patients are at a higher risk of getting pneumococcal disease and are therefore recommended to get vaccinated. The aim of our systematic review is the retrieval and analysis of all available evidence on the effect of pneumococcal vaccination on the risk of hospitalization and death in adult patients with diabetes.
RESEARCH DESIGN AND METHODS
MEDLINEand EMBASE were searched from inception until January 2023. We included all studies investigating whether pneumococcal vaccination reduces the risk of dying or being hospitalized in diabetic patients. The Newcastle-Ottawa scale was used to assess risk of bias.
RESULTS
Only two studies, encompassing a total of 68,246 subjects, were considered eligible for inclusion and of high quality. In both studies polysaccharide pneumococcal vaccination was associated with a reduction of the risk of hospitalization or death in adult diabetic patients (aHR: 0.76 in one study, aOR: 0.97 in the other one). However, in neither of the two included studies the lower risk was statistically significant.
CONCLUSIONS
Further research is needed due to the potentially major clinical implications for diabetic patients. The results of this systematic review can serve as a foundation for future studies, indicating the importance of continuing research in this area to improve patient outcomes.
Topics: Humans; Aged; Pneumococcal Infections; Hospitalization; Streptococcus pneumoniae; Diabetes Mellitus; Vaccination; Pneumococcal Vaccines
PubMed: 37990793
DOI: 10.1080/14760584.2023.2286374 -
The Cochrane Database of Systematic... 2001Infection with Streptococcus pneumoniae is an important cause of pneumonia and other serious illnesses, particularly amongst those with certain high-risk medical... (Review)
Review
BACKGROUND
Infection with Streptococcus pneumoniae is an important cause of pneumonia and other serious illnesses, particularly amongst those with certain high-risk medical conditions such as asthma. Although pneumococcal vaccine is routinely advocated for people with asthma, there is uncertainty about the evidence base that underpins this recommendation.
OBJECTIVES
To determine the efficacy of pneumococcal vaccine in reducing mortality or morbidity from pneumococcal disease in asthmatics.
SEARCH STRATEGY
Randomised controlled trials were identified using the Cochrane Airways Group's register derived from MEDLINE, EMBASE, and CINAHL electronic databases and hand searched respiratory journals and meeting abstracts.
SELECTION CRITERIA
Randomised controlled trials, with or without blinding, in which pneumococcal vaccine has been compared with placebo or no treatment in people with clinician diagnosed asthma.
DATA COLLECTION AND ANALYSIS
Two reviewers independently reviewed all abstracts and full papers of all articles of potential relevance were retrieved. Methodological quality was rated using the Cochrane approach and the Jadad rating scale. Data extraction was performed by one reviewer and checked independently by a second. We planned to perform quantitative analyses of outcomes on an intention-to-treat basis, where possible.
MAIN RESULTS
Of the three papers retrieved, only one satisfied the inclusion criteria and the methodological quality of this study was low (unblinded and inadequate allocation concealment). None of the data could be aggregated in a meta-analysis. Comparisons in a sub-set of 30 asthmatic children prone to recurrent episodes of otitis media, showed that pneumococcal vaccination decreased the incidence of acute asthma exacerbations from 10 to 7 (per child per year).
REVIEWER'S CONCLUSIONS
This review found very limited evidence to support the routine use of pneumococcal vaccine in people with asthma. A randomised trial of vaccine efficacy in children and adults with asthma is needed.
Topics: Asthma; Humans; Pneumococcal Vaccines; Pneumonia, Pneumococcal
PubMed: 11687018
DOI: 10.1002/14651858.CD002165 -
Journal of Global Health Feb 2023There is an ongoing need to assess the impact of pneumococcal conjugate vaccines (PCVs) to guide the use of these potentially valuable but under-utilized vaccines...
Systematic review on the impact of the pneumococcal conjugate vaccine ten valent (PCV10) or thirteen valent (PCV13) on all-cause, radiologically confirmed and severe pneumonia hospitalisation rates and pneumonia mortality in children 0-9 years old.
BACKGROUND
There is an ongoing need to assess the impact of pneumococcal conjugate vaccines (PCVs) to guide the use of these potentially valuable but under-utilized vaccines against pneumonia, which is one of the most common causes of post-neonatal mortality.
METHODS
We conducted a systematic review of the literature on PCV10 and PCV13 impact on all-cause, radiologically confirmed and severe pneumonia hospitalisation rates as well as all-cause and pneumonia-specific mortality rates. We included studies that were published from 2003 onwards, had a post-licensure observational study design, and reported on any of our defined outcomes in children aged between 0-9 years. We derived incidence rates (IRs), incidence rate ratios (IRRs) or percent differences (%). We assessed all studies for risk of bias using the Effective Public Health Practice Project (EPHPP) quality assessment tool.
RESULTS
We identified a total of 1885 studies and included 43 comparing one or more of the following hospitalised outcomes of interest: all-cause pneumonia (n = 27), severe pneumonia (n = 6), all-cause empyema (n = 8), radiologically confirmed pneumonia (n = 8), pneumococcal pneumonia (n = 7), and pneumonia mortality (n = 10). No studies evaluated all-cause mortality. Studies were conducted in all WHO regions except South East Asia Region (SEAR) and low- or middle-income countries (LMICs) in the Western Pacific Region (WPR). Among children <5 years old, PCV impact ranged from 7% to 60% for all-cause pneumonia hospitalisation, 8% to 90% for severe pneumonia hospitalisation, 12% to 79% for radiologically confirmed pneumonia, and 45% to 85% for pneumococcal confirmed pneumonia. For pneumonia-related mortality, impact was found in three studies and ranged from 10% to 78%. No obvious differences were found in vaccine impact between PCV10 and PCV13. One study found a 17% reduction in all-cause pneumonia among children aged 5-9 years, while another found a reduction of 81% among those aged 5-17 years. A third study found a 57% reduction in all-cause empyema among children 5-14 years of age.
CONCLUSION
We found clear evidence of declines in hospitalisation rates due to all-cause, severe, radiologically confirmed, and bacteraemic pneumococcal pneumonia in children aged <5 years, supporting ongoing use of PCV10 and PCV13. However, there were few studies from countries with the highest <5-year mortality and no studies from SEAR and LMICs in the WPR. Standardising methods of future PCV impact studies is recommended.
Topics: Infant, Newborn; Child; Humans; Infant; Child, Preschool; Adolescent; Pneumonia, Pneumococcal; Vaccines, Conjugate; Pneumococcal Infections; Pneumococcal Vaccines; Hospitalization; Observational Studies as Topic
PubMed: 36734192
DOI: 10.7189/jogh.13.05002 -
Travel Medicine and Infectious Disease 2018Invasive pneumococcal disease (IPD) is associated with high morbidity and mortality, with immunocompromised patients (ICPs) at particular risk. Therefore, guidelines... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Invasive pneumococcal disease (IPD) is associated with high morbidity and mortality, with immunocompromised patients (ICPs) at particular risk. Therefore, guidelines recommend pneumococcal vaccination for these patients. However, guidelines are scarcely underpinned with references to incidence studies of IPD in this population. This, potentially results in unawareness of the importance of vaccination and low vaccination rates. The objective of this systematic review and meta-analysis was to assess the incidence of IPD in ICPs.
METHODS
We systematically searched PubMed and Embase to identify studies in English published before December 6th, 2017 that included terms related to 'incidence', 'rate', 'pneumococcal', 'pneumoniae', 'meningitis', 'septicemia', or 'bacteremia'. We focused on patients with HIV, transplantation and chronic inflammatory diseases.
RESULTS
We included 45 studies in the systematic review reporting an incidence or rate of IPD, defined as isolation of Streptococcus pneumoniae from a normally sterile site. Random effects meta-analysis of 38 studies showed a pooled IPD incidence of 331/100,000 person years in patients with HIV in the late-antiretroviral treatment era in non-African countries, and 318/100,000 in African countries; 696 and 812/100,000 in patients who underwent an autologous or allogeneic stem cell transplantation, respectively; 465/100,000 in patients with a solid organ transplantation; and 65/100,000 in patients with chronic inflammatory diseases. In healthy control cohorts, the pooled incidence was 10/100,000.
DISCUSSION
ICPs are at increased risk of contracting IPD, especially those with HIV, and those who underwent transplantation. Based on our findings, we recommend pneumococcal vaccination in immunocompromised patients.
PROSPERO REGISTRATION
ID: CRD42016048438.
Topics: Adult; Africa; Child; Cohort Studies; Female; HIV Infections; Humans; Immunocompromised Host; Incidence; Male; Pneumococcal Infections; Pneumococcal Vaccines; Risk Factors; Streptococcus pneumoniae; Transplantation; Vaccination
PubMed: 29860151
DOI: 10.1016/j.tmaid.2018.05.016 -
The Pediatric Infectious Disease Journal Jan 2014Pneumococcal conjugate vaccines (PCV) reduce nasopharyngeal carriage of vaccine type (VT) pneumococci, an important driver of vaccine programs' overall benefits. The... (Review)
Review
BACKGROUND
Pneumococcal conjugate vaccines (PCV) reduce nasopharyngeal carriage of vaccine type (VT) pneumococci, an important driver of vaccine programs' overall benefits. The dosing schedule that best reduces carriage is unclear.
METHODS
We performed a systematic review of English language publications from 1994 to 2010 (supplemented post hoc with studies from 2011) reporting PCV effects on VT carriage to assess variability in effect by dosing schedule.
RESULTS
We identified 32 relevant studies (36 citations) from 12,980 citations reviewed. Twenty-one (66%) evaluated PCV7; none used PCV10 or PCV13. Five studies evaluated 2 primary doses and 13 three primary doses. After the first year of life, 14 evaluated 3-dose primary series with PCV booster (3+1), seven 3 doses plus 23-valent polysaccharide booster "3+1PPV23," five "3+0," four "2+1," three "2+1PPV23" and two "2+0." Four studies directly compared schedules. From these, 3 primary doses reduced VT carriage more than 2 doses at 1-7 months following the series (1 study significant; 2 borderline). In a study, the 2+1 schedule reduced VT carriage more than 2+0 at 18, but not at 24 months of age. One study of a 23-valent pneumococcal polysaccharide vaccine booster showed no effect. All 16 clinical trials with unvaccinated controls and 11 observational studies with before-after designs showed reduction in VT carriage.
CONCLUSIONS
The available literature demonstrates VT-carriage reduction for 2+0, 2+1, 3+0 and 3+1 PCV schedules, but not for 23-valent pneumococcal polysaccharide vaccine booster. Comparisons between schedules show that 3 primary doses and a 2+1 schedule may reduce carriage more than 2 primary doses and a 2+0 schedule, respectively.
Topics: Carrier State; Heptavalent Pneumococcal Conjugate Vaccine; Humans; Immunization Schedule; Infant; Nasopharynx; Pneumococcal Infections; Pneumococcal Vaccines; Vaccines, Conjugate
PubMed: 24336057
DOI: 10.1097/INF.0000000000000083 -
Pneumonia (Nathan Qld.) 2018is capable of causing multiple infectious syndromes and occasionally causes outbreaks. The objective of this review is to update prior outbreak reviews, identify... (Review)
Review
BACKGROUND
is capable of causing multiple infectious syndromes and occasionally causes outbreaks. The objective of this review is to update prior outbreak reviews, identify control measures, and comment on transmission.
METHODS
We conducted a review of published outbreaks, defined as at least two linked cases of .
RESULTS
A total of 98 articles (86 respiratory; 8 conjunctivitis; 2 otitis media; 1 surgical site; 1 multiple), detailing 94 unique outbreaks occurring between 1916 to 2017 were identified. Reported serotypes included 1, 2, 3, 4, 5, 7F, 8, 12F, 14, 20, and 23F, and serogroups 6, 9, 15, 19, 22. The median attack rate for pneumococcal outbreaks was 7.0% (Interquartile range: 2.4%, 13%). The median case-fatality ratio was 12.9% (interquartile range: 0%, 29.2%). Age groups most affected by outbreaks were older adults (60.3%) and young adults (34.2%). Outbreaks occurred in crowded settings, such as universities/schools/daycares, military barracks, hospital wards, and long-term care facilities. Of outbreaks that assessed vaccination coverage, low initial vaccination or revaccination coverage was common. Most (73.1%) of reported outbreaks reported non-susceptibility to at least one antibiotic, with non-susceptibility to penicillin (56.0%) and erythromycin (52.6%) being common. Evidence suggests transmission in outbreaks can occur through multiple modes, including carriers, infected individuals, or medical devices. Several cases developed disease shortly after exposure (< 72 h). Respiratory outbreaks used infection prevention (55.6%), prophylactic vaccination (63.5%), and prophylactic antibiotics (50.5%) to prevent future cases. PPSV23 covered all reported outbreak serotypes. PCV13 covered 10 of 16 serotypes. For conjunctival outbreaks, only infection prevention strategies were used.
CONCLUSIONS
To prevent the initial occurrence of respiratory outbreaks, vaccination and revaccination is likely the best preventive measure. Once an outbreak occurs, vaccination and infection-prevention strategies should be utilized. Antibiotic prophylaxis may be considered for high-risk exposed individuals, but development of antibiotic resistance during outbreaks has been reported. The short period between initial exposure and development of disease indicates that pneumococcal colonization is not a prerequisite for pneumococcal respiratory infection.
PubMed: 30410854
DOI: 10.1186/s41479-018-0055-4 -
EClinicalMedicine Jul 2023Vaccination of infants with pneumococcal conjugate vaccines (PCV) is recommended by the World Health Organization. Evidence is mixed regarding the differences in...
BACKGROUND
Vaccination of infants with pneumococcal conjugate vaccines (PCV) is recommended by the World Health Organization. Evidence is mixed regarding the differences in immunogenicity and efficacy of the different pneumococcal vaccines.
METHODS
In this systematic-review and network meta-analysis, we searched the Cochrane Library, Embase, Global Health, Medline, clinicaltrials.gov and trialsearch.who.int up to February 17, 2023 with no language restrictions. Studies were eligible if they presented data comparing the immunogenicity of either PCV7, PCV10 or PCV13 in head-to-head randomised trials of young children under 2 years of age, and provided immunogenicity data for at least one time point after the primary vaccination series or the booster dose. Publication bias was assessed via Cochrane's Risk Of Bias due to Missing Evidence tool and comparison-adjusted funnel plots with Egger's test. Individual participant level data were requested from publication authors and/or relevant vaccine manufacturers. Outcomes included the geometric mean ratio (GMR) of serotype-specific IgG and the relative risk (RR) of seroinfection. Seroinfection was defined for each individual as a rise in antibody between the post-primary vaccination series time point and the booster dose, evidence of presumed subclinical infection. Seroefficacy was defined as the RR of seroinfection. We also estimated the relationship between the GMR of IgG one month after priming and the RR of seroinfection by the time of the booster dose. The protocol is registered with PROSPERO, ID CRD42019124580.
FINDINGS
47 studies were eligible from 38 countries across six continents. 28 and 12 studies with data available were included in immunogenicity and seroefficacy analyses, respectively. GMRs comparing PCV13 vs PCV10 favoured PCV13 for serotypes 4, 9V, and 23F at 1 month after primary vaccination series, with 1.14- to 1.54- fold significantly higher IgG responses with PCV13. Risk of seroinfection prior to the time of booster dose was lower for PCV13 for serotype 4, 6B, 9V, 18C and 23F than for PCV10. Significant heterogeneity and inconsistency were present for most serotypes and for both outcomes. Two-fold higher antibody after primary vaccination was associated with a 54% decrease in risk of seroinfection (RR 0.46, 95% CI 0.23-0.96).
INTERPRETATION
Serotype-specific differences were found in immunogenicity and seroefficacy between PCV13 and PCV10. Higher antibody response after vaccination was associated with a lower risk of subsequent infection. These findings could be used to compare PCVs and optimise vaccination strategies.
FUNDING
The NIHR Health Technology Assessment Programme.
PubMed: 37425373
DOI: 10.1016/j.eclinm.2023.102073 -
Human Vaccines & Immunotherapeutics Dec 2022Otitis media (OM) is a common disease of childhood and available pneumococcal conjugate vaccines (PCVs), with different compositions, could have different impact on OM...
Otitis media (OM) is a common disease of childhood and available pneumococcal conjugate vaccines (PCVs), with different compositions, could have different impact on OM reduction. This systematic literature review evaluated available data describing the efficacy, effectiveness, and impact of 10-valent pneumococcal protein D conjugate vaccine (PHiD-CV) and 13-valent PCV (PCV13) on OM outcomes. Statistically significant reductions in all-cause and complicated OM, tympanostomy tube placement and OM-related hospitalizations were consistently observed after the introduction of PHiD-CV and PCV13. Impact studies with data in children <2 years of age using PCV13 report 47-51% and PHiD-CV 34-43% reduction of all-cause OM (primary care, outpatient, ambulatory, emergency department visits) compared to periods before PCV introduction. When the impact of both vaccines is assessed in comparable settings, some studies suggest PHiD-CV may offer better protection against some OM outcomes. Well-designed, head-to-head comparisons are needed to better understand the differences and guide vaccination policies.
Topics: Child; Humans; Otitis Media; Pneumococcal Infections; Vaccination; Vaccines, Conjugate
PubMed: 35020530
DOI: 10.1080/21645515.2021.2013693