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EClinicalMedicine Dec 2020The objective of this systematic review and meta-analysis was to summarise the literature regarding the immunogenicity of pneumococcal conjugate vaccines (PCV) and...
BACKGROUND
The objective of this systematic review and meta-analysis was to summarise the literature regarding the immunogenicity of pneumococcal conjugate vaccines (PCV) and pneumococcal polysaccharide vaccines (PPSV) in adult people living with HIV (PLWH) in the era of advanced combination antiretroviral therapy (cART).
METHODS
The systematic review protocol was published online (PROSPERO ID: CRD 42020153137). We searched Medline (Ovid), EMBASE (Ovid), and the Global Health Library for publications from 2000 to June 11, 2020. We included all studies in adult PLWH that reported vaccine immunogenicity outcomes. The primary outcome was seroconversion rate (SCR) after PCV, PPSV and PCV/PPSV combined. For random-effects meta-analysis, we included studies defining SCR as ≥ 2-fold increase in IgG from baseline, and reporting SCR for serotypes 6B, 14, or overall SCR, 1-3 months after vaccination.
FINDINGS
Our search identified 1597 unique studies, of which 115 were eligible for full-text assessment. Of these, 39 met the inclusion criteria (11 RCTs; 28 cohort studies). A high degree of heterogeneity was observed. Nineteen studies were included in the meta-analysis. Pooled overall SCRs were 42% (95% CI 30-56%), 44% (95% CI 33-55%) and 57% (95% CI 50-63%) for PLWH who received PPSV, PCV or a combination of PCV/PPSV, respectively. Compared to PPSV alone, a combination of PCV/PPSV yielded higher SCRs (OR 2.24 95% CI 1.41- 3.58), whereas we did not observe a significant difference in SCR between PCV and PPSV23 alone. There were no statistically significant differences in geometric mean post-vaccination antibody concentrations between vaccination schedules. Vaccination at higher CD4 cell counts improved immunogenicity in 8/21 studies, especially when PCV was administered. No studies assessed the long-term immunogenicity of PCV followed by PPSV23. Quality of evidence ranged from poor ( = 19) to good quality ( = 7). A limited number of pneumococcal serotypes was assessed in the majority of studies.
INTERPRETATION
We show that the recommended immunisation schedule consisting of a combination of PCV13/PPSV23, is immunogenic in PLWH in the era of advanced cART. However, the durability of this vaccination schedule remains unknown and must be addressed in future research. Vaccination with PCV should be delayed until immunological recovery (CD4>200) in recently diagnosed PLWH for optimal immunogenicity. The evidence gathered here supports wide implementation of the combination of PCV/PPSV23 for all PLWH. We recommend reassessment of this strategy once higher-valent PCVs become available.
FUNDING
HMGG is funded by a public research grant of ZonMw (project number 522004005).
PubMed: 33294820
DOI: 10.1016/j.eclinm.2020.100576 -
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 -
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 -
BMC Geriatrics Jan 2023There is low uptake of the pneumococcal vaccination in eligible older adults, even in high-income countries that offer routine and universal vaccination programs.
BACKGROUND
There is low uptake of the pneumococcal vaccination in eligible older adults, even in high-income countries that offer routine and universal vaccination programs.
OBJECTIVE
To systematically characterize interventions aimed at improving pneumococcal vaccine uptake in older adults.
DESIGN
We conducted a scoping review following PRISMA-SCr guidelines of five interdisciplinary databases: Medline-Ovid, Embase, CINAHL, PsychInfo, and Cochrane Library. Databases were searched from January 2015 until April 2020. The interventions were summarized into three pillars according to the European Union Conceptional Framework for Action: information campaigns, prioritization of vaccination schemes, and primary care interventions.
RESULTS
Our scoping review included 39 studies that summarized interventions related to pneumococcal vaccine uptake for older adults, encompassing 2,481,887 study participants (945 healthcare providers and 2,480,942 older adults) across seven countries. Examples of interventions that were associated with increased pneumococcal vaccination rate included periodic health examinations, reminders and decision-making tools built into electronic medical records, inpatient vaccination protocols, preventative health checklists, and multimodal educational interventions. When comparing the three pillars, prioiritization of vaccination schemes had the highest evidence for improved rates of vaccination (n = 14 studies), followed by primary care interventions (n = 8 studies), then information campaigns (n = 5 studies).
CONCLUSION
Several promising interventions were associated with improved outcomes related to vaccine uptake, although controlled study designs are needed to determine which interventions are most effective.
Topics: Aged; Humans; Developed Countries; Electronic Health Records; Immunization Programs; Pneumococcal Vaccines; Vaccination
PubMed: 36593474
DOI: 10.1186/s12877-022-03653-9 -
Journal of the American Pharmacists... 2022The underutilization of immunization services remains a big public health concern. Pharmacists can address this concern by playing an active role in immunization... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The underutilization of immunization services remains a big public health concern. Pharmacists can address this concern by playing an active role in immunization administration.
OBJECTIVE
We performed a systematic review and meta-analysis to assess the impact of pharmacist-involved interventions on immunization rates and other outcomes indirectly related to vaccine uptake.
METHODS
A systematic literature search was conducted using MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases from inception to February 2022 to identify randomized controlled trials (RCTs) and observational studies in which pharmacists were involved in the immunization process. Studies were excluded if no comparator was reported. Two reviewers independently completed data extraction and bias assessments using standardized forms. Meta-analyses were performed using a random-effects model.
RESULTS
A total of 14 RCTs and 79 observational studies were included. Several types of immunizations were provided, including influenza, pneumococcal, herpes zoster, Tdap, and others in a variety of settings (community pharmacy, hospital, clinic, others). Pooled analyses from RCTs indicated that a pharmacist as immunizer (risk ratio 1.14 [95% CI 1.12-1.15]), advocator (1.31 [1.17-1.48]), or both (1.14 [1.12-1.15]) significantly increased immunization rates compared with usual care or non-pharmacist-involved interventions. The quality of evidence was assessed as moderate or low for those meta-analyses. Evidence from observational studies was consistent with the results found in the analysis of the RCTs.
CONCLUSION
Pharmacist involvement as immunizer, advocator, or both roles has favorable effects on immunization uptake, especially with influenza vaccines in the United States and some high-income countries. As the practice of pharmacists in immunization has been expanded globally, further research on investigating the impact of pharmacist involvement in immunization in other countries, especially developing ones, is warranted.
Topics: Humans; Immunization; Influenza Vaccines; Influenza, Human; Pharmacists; United States; Vaccination
PubMed: 35961937
DOI: 10.1016/j.japh.2022.06.008 -
Value in Health Regional Issues Mar 2022In 2017, the Argentine Ministry of Health incorporated a sequential 13-valent pneumococcal conjugate vaccine (PCV13)-23-valent pneumococcal polysaccharide vaccine...
OBJECTIVES
In 2017, the Argentine Ministry of Health incorporated a sequential 13-valent pneumococcal conjugate vaccine (PCV13)-23-valent pneumococcal polysaccharide vaccine (PPSV23) regimen for adults aged ≥65 years to reduce pneumococcal disease burden. Cost-effectiveness analysis of PCV13-PPSV23 schedule for adults aged ≥65 years in Argentina was performed compared with PPSV23 only.
METHODS
Markov model was developed. Local data were incorporated for costs and disease burden analysis. Vaccine efficacy or effectiveness was obtained from a systematic review adjusted to current local vaccine serotype circulation and vaccines coverage. A total of 3 scenarios were evaluated: main scenario according to published literature of pneumonia incidence, epidemiologic surveillance scenario based on Argentine Ministry of Health data, and an alternative scenario assuming a 50% hypothetical pneumonia incidence reduction resulting from herd immunity induced by childhood vaccination. Sensitivity analyses were done.
RESULTS
Sequential PCV13-PPSV23 schedule showed cost-savings results in the main scenario with -$1 667 742.23 saved and 716 life-years gained (LYG). The epidemiologic surveillance scenario showed an incremental cost-effectiveness ratio of $2141.92 per LYG and an alternative scenario with $3740.30 per LYG. Tornado diagram shows widest bars related to adjustment for vaccine-type pneumococcal pneumonia (urine analysis) pneumonia at risk cost and pneumonia incidence rate. Monte Carlo simulation shows that >98% of simulations were cost-saving for the main scenario.
CONCLUSIONS
In the main scenario, cost-saving results were obtained considering only reduction of vaccine serotype coverage after the introduction of childhood PCV13 vaccination. In the epidemiologic surveillance and alternative scenarios, assuming a hypothetical incidence reduction, highly cost-effective results were observed.
Topics: Adult; Aged; Argentina; Cost-Benefit Analysis; Humans; Pneumococcal Vaccines; Vaccination; Vaccines, Conjugate
PubMed: 34801962
DOI: 10.1016/j.vhri.2021.08.003 -
Value in Health : the Journal of the... Nov 2019Pneumococcal diseases cause substantial mortality, morbidity, and economic burden. Evidence on data inputs for economic evaluations of interventions targeting...
BACKGROUND
Pneumococcal diseases cause substantial mortality, morbidity, and economic burden. Evidence on data inputs for economic evaluations of interventions targeting pneumococcal disease is critical.
OBJECTIVES
To summarize evidence on resource use, costs, health utilities, and cost-effectiveness for pneumococcal disease and associated interventions to inform future economic analyses.
METHODS
We searched MEDLINE, Embase, Web of Science, CINAHL, PsycINFO, EconLit, and Cochrane databases for peer-reviewed studies in English on pneumococcal disease that reported health utilities using direct or indirect valuation methods, resource use, costs, or cost-effectiveness of intervention programs, and summarized the evidence descriptively.
RESULTS
We included 383 studies: 9 reporting health utilities, 131 resource use, 160 economic costs of pneumococcal disease, 95 both resource use and costs, and 178 economic evaluations of pneumococcal intervention programs. Health state utility values ranged from 0 to 1 for both meningitis and otitis media and from 0.3 to 0.7 for both pneumonia and sepsis. Hospitalization was shortest for otitis media (range: 0.1-5 days) and longest for sepsis/septicemia (6-48). The main categories of costs reported were drugs, hospitalization, and household or employer costs. Resource use was reported in hospital length of stay and number of contacts with general practitioners. Costs and resource use significantly varied among population ages, disease conditions, and settings. Current vaccination programs for both adults and children, antibiotic use and outreach programs to promote vaccination, early disease detection, and educational programs are cost-effective in most countries.
CONCLUSION
This study has generated a comprehensive repository of health economic evidence on pneumococcal disease that can be used to inform future economic evaluations of pneumococcal disease intervention programs.
Topics: Anti-Bacterial Agents; Cost-Benefit Analysis; Costs and Cost Analysis; Health Expenditures; Health Resources; Humans; Pneumococcal Infections; Pneumococcal Vaccines; Quality of Life; Vaccination
PubMed: 31708071
DOI: 10.1016/j.jval.2019.06.011 -
Vaccines Dec 2019The growing number of available vaccines that can be potentially co-administered makes the assessment of the safety of vaccine co-administration increasingly relevant... (Review)
Review
The growing number of available vaccines that can be potentially co-administered makes the assessment of the safety of vaccine co-administration increasingly relevant but complex. We aimed to synthesize the available scientific evidence on the safety of vaccine co-administrations in children by performing a systematic literature review of studies assessing the safety of vaccine co-administrations in children between 1999 and 2019, in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Fifty studies compared co-administered vaccines versus the same vaccines administered separately. The most frequently studied vaccines included quadrivalent meningococcal conjugate (MenACWY) vaccine, diphtheria and tetanus toxoids and acellular pertussis (DTaP) or tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccines, diphtheria and tetanus toxoids and acellular pertussis adsorbed, hepatitis B, inactivated poliovirus and type b conjugate (DTaP-HepB-IPV/Hib) vaccine, measles, mumps, and rubella (MMR) vaccine, and pneumococcal conjugate 7-valent (PCV7) or 13-valent (PCV13) vaccines. Of this, 16% (n = 8) of the studies reported significantly more adverse events following immunization (AEFI) while in 10% (n = 5) significantly fewer adverse events were found in the co-administration groups. Statistically significant differences between co-administration and separate administration were found for 16 adverse events, for 11 different vaccine co-administrations. In general, studies briefly described safety and one-third of studies lacked any statistical assessment of AEFI. Overall, the evidence on the safety of vaccine co-administrations compared to separate vaccine administrations is inconclusive and there is a paucity of large post-licensure studies addressing this issue.
PubMed: 31906218
DOI: 10.3390/vaccines8010012 -
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 -
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