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EClinicalMedicine Mar 2024Human Immunodeficiency Virus (HIV)-exposed uninfected (HEU) infants have a higher burden of infectious diseases related morbidity and mortality compared with...
BACKGROUND
Human Immunodeficiency Virus (HIV)-exposed uninfected (HEU) infants have a higher burden of infectious diseases related morbidity and mortality compared with HIV-unexposed uninfected (HUU). Immunization of pregnant women living with HIV (PWLWH) could reduce the severity and burden of infectious diseases for HEU in early infancy.
METHODS
We conducted a systematic review of safety and immunogenicity of vaccines administered to PWLWH and meta-analyses to test the overall effect of immunogenicity comparing pregnant women without HIV (PWWH) to PWLWH. We searched MEDLINE, Embase, Web of Science, Virtual Health Library and Cochrane databases in accordance with PRISMA guidelines for randomized controlled trials and observational studies. Review articles, case series, conference abstracts, and animal studies were excluded. Studies were included from inception to 6th September 2023, with no language restrictions. Random effects meta-analyses were performed for immunogenicity using Review manager (RevMan) analysis software version 5.4.1, Geometric Mean Titer (GMT) values were transformed to obtain the mean and standard deviation within RevMan, the effect size was computed and reported as mean difference with respective 95% confidence intervals. The review was registered with PROSPERO CRD42021289081.
FINDINGS
We included 12 articles, comprising 3744 pregnant women, 1714 were PWLWH given either influenza, pneumococcal or an investigational Group B (GBS) vaccine. Five studies described safety outcomes, and no increase in adverse events was reported in PWLWH compared to PWWH. The GMT increase from baseline to 28-35 weeks post vaccination in HA units ranged from 12.4 (95% CI: 9.84-14.9) to 238.8 (95% CI: 0.35-477.9). Meta-analyses of influenza vaccines showed the pooled geometric mean difference in Hemagglutination Inhibition (HAI) titers post vaccination was 56.01 (95% CI: 45.01-67.01), p < 0.001. The increase was less in PWLWH when compared with PWWH: -141.76 (95% CI: -194.96, -88.55), p < 0.001.
INTERPRETATION
There are limited data on the safety and immunogenicity of vaccines given to PWLWH making policy consideration in this group difficult when new vaccines are introduced. With new vaccines on the horizon, PWLWH need to be included in studies to promote vaccine confidence for this special population.
FUNDING
This work was funded by Medical Research Council Joint Clinical Trials Round 9 [MR/T004983/1].
PubMed: 38333366
DOI: 10.1016/j.eclinm.2024.102448 -
Frontiers in Public Health 2024Invasive pneumococcal disease has declined since pneumococcal conjugate vaccine introduction in Latin America and the Caribbean (LAC). However, serotype distribution and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Invasive pneumococcal disease has declined since pneumococcal conjugate vaccine introduction in Latin America and the Caribbean (LAC). However, serotype distribution and antimicrobial resistance patterns have changed.
METHODS
We conducted a systematic review to evaluate the frequency of antimicrobial resistance of from invasive disease in LAC. Articles published between 1 January 2000, and 27 December 2022, with no language restriction, were searched in major databases and gray literature. Pairs of reviewers independently selected extracted data and assessed the risk of bias in the studies. The quality of antimicrobial resistance (AMR) studies was evaluated according to WHO recommendations (PROSPERO CRD42023392097).
RESULTS
From 8,600 records identified, 103 studies were included, with 49,660 positive samples of for AMR analysis processed. Most studies were from Brazil (29.1%) and Argentina (18.4%), were cross-sectional (57.3%), reported data on AMR from IPD cases (52.4%), and were classified as moderate risk of bias (50.5%). Resistance to penicillin was 21.7% (95%IC 18.7-25.0, I: 95.9), and for ceftriaxone/cefotaxime it was 4.7% (95%IC 3.2-6.9, I: 96.1). The highest resistance for both penicillin and ceftriaxone/cefotaxime was in the age group of 0 to 5 years (32.1% [95%IC 28.2-36.4, I: 87.7], and 9.7% [95%IC 5.9-15.6, I: 96.9] respectively). The most frequent serotypes associated with resistance were 14 for penicillin and 19A for ceftriaxone/cefotaxime.
CONCLUSION
Approximately one-quarter of invasive pneumococcal disease isolates in Latin America and the Caribbean displayed penicillin resistance, with higher rates in young children. Ongoing surveillance is essential to monitor serotype evolution and antimicrobial resistance patterns following pneumococcal conjugate vaccine introduction.
Topics: Child; Humans; Child, Preschool; Infant, Newborn; Infant; Streptococcus pneumoniae; Anti-Bacterial Agents; Latin America; Ceftriaxone; Vaccines, Conjugate; Pneumococcal Vaccines; Drug Resistance, Bacterial; Pneumococcal Infections; Penicillins; Cefotaxime
PubMed: 38317800
DOI: 10.3389/fpubh.2024.1337276 -
BMJ Open Dec 2023To determine the evidence for non-specific effects of the Pneumococcal and Haemophilus influenza vaccine in children aged 5 years and under.
OBJECTIVE
To determine the evidence for non-specific effects of the Pneumococcal and Haemophilus influenza vaccine in children aged 5 years and under.
DATA SOURCES
A key word literature search of MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, the European Union Clinical Trials Register and ClinicalTrials.gov up to June 2023.
STUDY ELIGIBILITY CRITERIA
Randomised controlled trials (RCTs), quasi-RCT or cohort studies.
PARTICIPANTS
Children aged 5 or under.
STUDY APPRAISAL AND SYNTHESIS METHODS
Studies were independently screened by two reviewers, with a third where disagreement arose. Risk of bias assessment was performed by one reviewer and confirmed by a second. Results were tabulated and a narrative description performed.
RESULTS
Four articles were identified and included in this review. We found a reduction in hospitalisations from influenza A (44%), pulmonary tuberculosis (42%), metapneumovirus (45%), parainfluenza virus type 1-3 (44%), along with reductions in mortality associated with pneumococcal vaccine. No data on the Haemophilus vaccine was found.
CONCLUSIONS AND IMPLICATIONS
In this systematic review, we demonstrate that there is a reduction in particular viral infections in children aged 5 years and under who received the 9-valent pneumococcal conjugate vaccine which differ from those for which the vaccine was designed to protect against. While limited studies have demonstrated a reduction in infections other than those which the vaccine was designed to protect against, substantial clinical trials are required to solidify these findings.
PROSPERO REGISTRATION NUMBER
CRD42020146640.
Topics: Child; Humans; Haemophilus Vaccines; Pneumococcal Vaccines; Influenza, Human; Streptococcus pneumoniae; Cohort Studies
PubMed: 38101831
DOI: 10.1136/bmjopen-2023-077717 -
Human Vaccines & Immunotherapeutics Dec 2023Despite widespread use of pneumococcal vaccines throughout Europe, the burden of pneumococcal disease (PD) in adults is considerable. To mitigate this burden, National...
Recent changes to adult national immunization programs for pneumococcal vaccination in Europe and how they impact coverage: A systematic review of published and grey literature.
Despite widespread use of pneumococcal vaccines throughout Europe, the burden of pneumococcal disease (PD) in adults is considerable. To mitigate this burden, National Immunization Technical Advisory Groups (NITAGs) and Health Technology Assessment (HTA) agencies assess the value of different vaccine schedules for protecting against PD. The aim of this review was to assess the evidence and rationales used by NITAGs/HTA agencies, when considering recent changes to National Immunization Programs (NIPs) for adults, and how identified changes affected vaccine coverage rates (VCRs). A systematic review was conducted of published literature from PubMed® and Embase®, and gray literature from HTA/NITAG websites from the last 5 y, covering 31 European countries. Evidence related to NIP recommendations, epidemiology (invasive PD, pneumonia), health economic assessments and VCRs were collected and synthesized. Eighty-four records providing data for 26 countries were identified. Of these, eight described explicit changes to NIPs for adults in seven countries. Despite data gaps, some trends were observed; first, there appears to be a convergence of NIP recommendations in many countries toward sequential vaccination, with a pneumococcal conjugate vaccine (PCV), followed by pneumococcal polysaccharide vaccine 23. Second, reducing economic or healthcare burden were common rationales for implementing changes. Third, most health economic analyses assessing higher-valency PCVs for adults found its inclusion in NIPs cost-effective. Finally, higher coverage rates were seen in most cases where countries had expanded their NIPs to cover at-risk populations. The findings can encourage agencies to improve surveillance systems and work to reach the NIP's target populations more effectively.
Topics: Adult; Humans; Gray Literature; Vaccination; Pneumococcal Vaccines; Pneumococcal Infections; Vaccines, Conjugate; Europe; Immunization Programs
PubMed: 38014651
DOI: 10.1080/21645515.2023.2279394 -
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 -
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 -
Vaccines Sep 2023Workers occupationally exposed to welding dusts and fumes have been suspected to be at increased risk of invasive pneumococcal disease (IPD). Since the 2010s, the United... (Review)
Review
Workers occupationally exposed to welding dusts and fumes have been suspected to be at increased risk of invasive pneumococcal disease (IPD). Since the 2010s, the United Kingdom Department of Health and the German Ständige Impfkommission (STIKO) actively recommend welders undergo immunization with the 23-valent polysaccharide (PPV23) pneumococcal vaccine, but this recommendation has not been extensively shared by international health authorities. The present meta-analysis was therefore designed to collect available evidence on the occurrence of pneumococcal infection and IPD among welders and workers exposed to welding fumes, in order to ascertain the effective base of evidence for this recommendation. PubMed, Embase and MedRxiv databases were searched without a timeframe restriction for the occurrence of pneumococcal infections and IPD among welders and workers exposed to metal dusts, and articles meeting the inclusion criteria were included in a random-effect meta-analysis model. From 854 entries, 14 articles (1.6%) underwent quantitative analysis, including eight retrospective studies (publication range: 1980-2010), and six reports of professional clusters in shipbuilding (range: 2017-2020). Welders had an increased likelihood of developing IPD compared with non-welders (odds ratio 2.59, 95% CI 2.00-3.35, I = 0%, = 0.58), and an increased likelihood of dying from IPD (standardized mortality ratio (SMR) 2.42, 95% CI 1.96-2.99, I = 0%, = 0.58). Serotype typing was available for 72 cases, 60.3% of which were represented by serotype 4, followed by 12F (19.2%) and serotype 8 (8.2%). Although the available data derive from a limited number of studies, available results suggest that pneumococcal vaccination should be recommended for workers exposed to welding fumes, and vaccination strategies should consider the delivery of recombinant formulates in order to combine the direct protection against serotypes of occupational interest with the mucosal immunization, reducing the circulation of the pathogen in occupational settings characterized by close interpersonal contact.
PubMed: 37766171
DOI: 10.3390/vaccines11091495 -
Antimicrobial Resistance and Infection... Jul 2023Vaccination can prevent bacterial and viral infections that could otherwise increase the chances of receiving (unnecessary) antibiotic treatment(s). As a result,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vaccination can prevent bacterial and viral infections that could otherwise increase the chances of receiving (unnecessary) antibiotic treatment(s). As a result, vaccination may provide an important public health intervention to control antimicrobial resistance (AMR).
OBJECTIVES
Perform a systematic literature review to better understand the impact of influenza, pneumococcal and COVID-19 vaccination on antibiotic use, and to identify differences in effect between world regions and study designs.
METHODS
We performed a systematic literature review and meta-analysis which updated previous literature reviews with new data from 1 October 2018 to 1 December 2021. The study focuses on randomised controlled trials (RCTs) and observational studies. Results from the meta-analysis of RCTs were stratified by WHO region and age group. Vote counting based on the direction of effect was applied to synthesize the results of the observational studies.
RESULTS
Most studies are performed in the WHO European Region and the Region of the Americas in high-income countries. RCTs show that the effect of influenza vaccination on the number of antibiotic prescriptions or days of antibiotic use (Ratio of Means (RoM) 0.71, 95% CI 0.62-0.83) is stronger compared to the effect of pneumococcal vaccination (RoM 0.92, 95% CI 0.85-1.00). These studies also confirm a reduction in the proportion of people receiving antibiotics after influenza vaccination (Risk Ratio (RR) 0.63, 95% CI 0.51-0.79). The effect of influenza vaccination in the European and American regions ranged from RoM 0.63 and 0.87 to RR 0.70 and 0.66, respectively. The evidence from observational studies supports these findings but presents a less consistent picture. No COVID-19 studies were identified.
CONCLUSION
We find that both RCTs and observational studies show that influenza vaccination significantly reduces antibiotic use, while the effect of pneumococcal vaccination is less pronounced. We were unable to study the effect of COVID-19 vaccination and no clear regional patterns were found due to the high heterogeneity between studies. Overall, our data supports the use of influenza vaccination as an important public health intervention to reduce antibiotic use and possibly control AMR.
Topics: Humans; Influenza, Human; Anti-Bacterial Agents; COVID-19; Virus Diseases; Vaccination
PubMed: 37452389
DOI: 10.1186/s13756-023-01272-6 -
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 -
Microorganisms May 2023Pneumococcal disease is a major cause of morbidity/mortality worldwide, and vaccination is an important measure in its prevention. Despite European children being... (Review)
Review
Pneumococcal disease is a major cause of morbidity/mortality worldwide, and vaccination is an important measure in its prevention. Despite European children being vaccinated with pneumococcal conjugate vaccines (PCVs), pneumococcal infections are still a major cause of morbidity/mortality in adults with risk conditions and their vaccination might be an important prevention strategy. New PCVs have been approved, but information is lacking on their potential impact in European adults. In our review, we searched PubMed, MEDLINE, and Embase for studies on the additional PCV20 serotypes (concerning incidence, prevalence, disease severity, lethality, and antimicrobial resistance) in European adults, between January 2010 and April 2022, having included 118 articles and data from 33 countries. We found that these serotypes have become more prevalent in both invasive and non-invasive pneumococcal disease (IPD and NIPD), representing a significant proportion of cases (serotypes 8, 12F, 22F) and more serious disease and/or lethality (10A, 11A, 15B, 22F), showing antimicrobial resistance (11A, 15B, 33F), and/or affecting more vulnerable individuals such as the elderly, immunocompromised patients, and those with comorbidities (8, 10A, 11A, 15B, 22F). The relevance of pneumococcal adult carriers (11A, 15B, 22F, and 8) was also identified. Altogether, our data showed an increase in the additional PCV20 serotypes' prevalence, accounting for a proportion of approximately 60% of all pneumococcal isolates in IPD in European adults since 2018/2019. Data suggest that adults, as older and/or more vulnerable patients, would benefit from vaccination with higher-coverage PCVs, and that PCV20 may address an unmet medical need.
PubMed: 37374878
DOI: 10.3390/microorganisms11061376