-
Vaccine Mar 2022Patients with inflammatory bowel disease (IBD) have a high risk for infection. Pneumonia related to influenza and pneumococcal infection is one of the most common... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with inflammatory bowel disease (IBD) have a high risk for infection. Pneumonia related to influenza and pneumococcal infection is one of the most common infection-related complications in IBD.
AIMS
To evaluate the immunogenicity of pneumococcal and influenza vaccination in patients with IBD receiving different treatments.
METHODS
We searched four databases for studies evaluating seroprotection and seroconversion rates after influenza or pneumococcal vaccination in IBD on 20th October 2020. In the meta-analysis, odds ratios (OR) were calculated with 95% confidence intervals (CI).
RESULTS
We included twelve studies (1429 patients with IBD) in this meta-analysis. The seroconversion rate after pneumococcal vaccination and the seroprotection rate after influenza vaccination were not significantly lower in patients receiving conventional immunosuppressive treatment compared to the non-immunosuppressed patients. Meanwhile, the seroconversion rate following pneumococcal vaccine was significantly lower in patients with anti-TNF mono- or combination therapy (OR = 0.28, CI: 0.15-0.53, and OR = 0.27, CI: 0.15-0.49, respectively). In the analysis of patients with IBD on conventional immunosuppressive monotherapy versus anti-TNF therapy, the seroprotection rate after influenza immunization did not differ between patients receiving either anti-TNF mono-or combination therapy (OR = 1.45, CI: 0.62-3.38 and OR = 0.91, CI: 0.37-2.22, respectively).
CONCLUSION
Our data suggest that the immunization against Pneumococcus and influenza is safe and immunogenic despite immunosuppression.
Topics: Adult; Humans; Immunity; Immunosuppressive Agents; Inflammatory Bowel Diseases; Influenza Vaccines; Influenza, Human; Pneumococcal Vaccines; Streptococcus pneumoniae; Tumor Necrosis Factor Inhibitors; Vaccination
PubMed: 35227523
DOI: 10.1016/j.vaccine.2022.02.027 -
Vaccine Apr 2024The cross-protection of pneumococcal conjugate vaccines (PCV) against serotype 6C is not clearly documented, although 6C represents a substantial burden of pneumococcal...
BACKGROUND
The cross-protection of pneumococcal conjugate vaccines (PCV) against serotype 6C is not clearly documented, although 6C represents a substantial burden of pneumococcal disease in recent years. A systematic review by the World Health Organization that covered studies through 2016 concluded that available data were insufficient to determine if either PCV10 (which contains serotype 6B but not 6A) or PCV13 (containing serotype 6A and 6B) conferred protection against 6C.
METHODS
We performed a systematic review of randomized controlled trials and observational studies published between January 2010 - August 2022 (Medline/Embase), covering the direct, indirect, and overall effect of PCV10 and PCV13 against 6C invasive pneumococcal disease (IPD), non-IPD, nasopharyngeal carriage (NPC), and antimicrobial resistance (AMR).
RESULTS
Of 2548 publications identified, 112 were included. Direct vaccine effectiveness against 6C IPD in children ranged between 70 and 85 % for ≥ 1 dose PCV13 (n = 3 studies), was 94 % in fully PCV13 vaccinated children (n = 2), and -14 % for ≥ 1 dose of PCV10 (n = 1). Compared to PCV7, PCV13 efficacy against 6C NPC in children was 66 % (n = 1). Serotype 6C IPD rates or NPC prevalence declined post-PCV13 in most studies in children (n = 5/6) and almost half of studies in adults (n = 5/11), while it increased post-PCV10 for IPD and non-IPD in all studies (n = 6/6). Changes in AMR prevalence were inconsistent.
CONCLUSIONS
In contrast to PCV10, PCV13 vaccination consistently protected against 6C IPD and NPC in children, and provided some level of indirect protection to adults, supporting that serotype 6A but not 6B provides cross-protection to 6C. Vaccine policy makers and regulators should consider the effects of serotype 6A-containing PCVs against serotype 6C disease in their decisions.
Topics: Child; Adult; Humans; Infant; Anti-Bacterial Agents; Serogroup; Drug Resistance, Bacterial; Streptococcus pneumoniae; Pneumococcal Vaccines; Pneumococcal Infections; Vaccines, Conjugate
PubMed: 38553292
DOI: 10.1016/j.vaccine.2024.03.065 -
Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease.The Cochrane Database of Systematic... Mar 2021Sickle cell disease (SCD) is a group of inherited disorders that result in haemoglobin abnormalities and other complications. Injury to the spleen, among other factors,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sickle cell disease (SCD) is a group of inherited disorders that result in haemoglobin abnormalities and other complications. Injury to the spleen, among other factors, contribute to persons with SCD being particularly susceptible to infection. Infants and very young children are especially vulnerable. The 'Co-operative Study of Sickle Cell Disease' observed an incidence rate for pneumococcal septicaemia of 10 per 100 person-years in children under the age of three years. Vaccines, including customary pneumococcal vaccines, may be of limited use in this age group. Therefore, prophylactic penicillin regimens may be advisable for this population. This is an update of a Cochrane Review which was first published in 2002, and previously updated, most recently in 2017. OBJECTIVES: To compare the effects of antibiotic prophylaxis against pneumococcus in children with SCD receiving antibiotic prophylaxis compared to those without in relation to: 1. incidence of Streptococcus pneumoniae infection; 2. mortality (as reported in the included studies); 3. drug-related adverse events (as reported in the included studies) to the individual and the community; 4. the impact of discontinuing at various ages on incidence of infection and mortality.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which is comprised of references identified from comprehensive electronic database searches and also two clinical trials registries: ClinicalTrials.gov and the WHO International Registry Platform (not in 2020 given access issues relating to Covid-19 pandemic). Additionally, we carried out hand searching of relevant journals and abstract books of conference proceedings. Date of the most recent search: 25 January 2021.
SELECTION CRITERIA
All randomised or quasi-randomised controlled trials comparing prophylactic antibiotics to prevent pneumococcal infection in children with SCD with placebo, no treatment or a comparator drug.
DATA COLLECTION AND ANALYSIS
The standard methodological procedures expected by Cochrane were used. Both authors independently extracted data and assessed trial quality. The authors used the GRADE criteria to assess the certainty of the evidence.
MAIN RESULTS
Six trials were identified by the searches, of which three trials were eligible for inclusion. A total of 880 children, who were between three months to five years of age at randomization were included. The included studies were conducted in centres in the USA and in Kingston, Jamaica. In trials that investigated initiation of penicillin on risk of pneumococcal infection, the odds ratio was 0.37 (95% confidence interval 0.16 to 0.86) (two trials, 457 children) (low-certainty evidence), while for withdrawal the odds ratio was 0.49 (95% confidence interval 0.09 to 2.71) (one trial, 400 children) (low-certainty evidence). Adverse drug effects were rare and minor. Rates of pneumococcal infection were found to be relatively low in children over the age of five years. Overall, the certainty of the evidence for all outcomes was judged to be low. The results from the risk of bias assessment undertaken identified two domains in which the risk of bias was considered to be high, these were incomplete outcome data (attrition bias) (two trials) and allocation concealment (selection bias) (one trial). Domains considered to have a low risk of bias for all three trials were selective reporting (reporting bias) and blinding (performance and detection bias).
AUTHORS' CONCLUSIONS
The evidence examined was determined to be of low certainty and suggests that prophylactic penicillin significantly reduces risk of pneumococcal infection in children with homozygous SCD, and is associated with minimal adverse reactions. Further research may help to determine the ideal age to safely withdraw penicillin.
Topics: Age Factors; Anemia, Sickle Cell; Antibiotic Prophylaxis; Bias; Child, Preschool; Hemoglobin SC Disease; Homozygote; Humans; Incidence; Infant; Medication Adherence; Penicillins; Pneumococcal Infections; Randomized Controlled Trials as Topic; Streptococcus pneumoniae; beta-Thalassemia
PubMed: 33724440
DOI: 10.1002/14651858.CD003427.pub5 -
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 -
Human Vaccines & Immunotherapeutics Oct 2021The aim was to summarize pneumococcal disease burden data among adults in Southern Europe and the potential impact of vaccines on epidemiology. Of 4779 identified... (Meta-Analysis)
Meta-Analysis
The aim was to summarize pneumococcal disease burden data among adults in Southern Europe and the potential impact of vaccines on epidemiology. Of 4779 identified studies, 272 were selected. Invasive pneumococcal disease (IPD) incidence was 15.08 (95% CI 11.01-20.65) in Spain versus 2.56 (95% CI 1.54-4.24) per 100,000 population in Italy. Pneumococcal pneumonia incidence was 19.59 (95% CI 10.74-35.74) in Spain versus 2.19 (95% CI 1.36-3.54) per 100,000 population in Italy. Analysis of IPD incidence in Spain comparing pre-and post- PCV7 and PCV13 periods unveiled a declining trend in vaccine-type IPD incidence (larger and statistically significant for the elderly), suggesting indirect effects of childhood vaccination programme. Data from Portugal, Greece and, to a lesser extent, Italy were sparse, thus improved surveillance is needed. Pneumococcal vaccination uptake, particularly among the elderly and adults with chronic and immunosuppressing conditions, should be improved, including shift to a higher-valency pneumococcal conjugate vaccine when available.
Topics: Adult; Aged; Europe; Greece; Humans; Incidence; Infant; Italy; Pneumococcal Infections; Pneumococcal Vaccines; Pneumonia, Pneumococcal; Portugal; Spain; Vaccines, Conjugate
PubMed: 34106040
DOI: 10.1080/21645515.2021.1923348 -
PloS One 2023This systematic review evaluates pneumolysin (PLY) as a target for new treatments against pneumococcal infections. Pneumolysin is one of the main virulence factors... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review evaluates pneumolysin (PLY) as a target for new treatments against pneumococcal infections. Pneumolysin is one of the main virulence factors produced by all types of pneumococci. This toxin (53 kDa) is a highly conserved protein that binds to cholesterol in eukaryotic cells, forming pores that lead to cell destruction.
METHODS
The databases consulted were MEDLINE, Web of Science, and Scopus. Articles were independently screened by title, abstract, and full text by two researchers, and using consensus to resolve any disagreements that occurred. Articles in other languages different from English, patents, cases report, notes, chapter books and reviews were excluded. Searches were restricted to the years 2000 to 2021. Methodological quality was evaluated using OHAT framework.
RESULTS
Forty-one articles describing the effects of different molecules that inhibit PLY were reviewed. Briefly, the inhibitory molecules found were classified into three main groups: those exerting a direct effect by binding and/or blocking PLY, those acting indirectly by preventing its effects on host cells, and those whose mechanisms are unknown. Although many molecules are proposed as toxin blockers, only some of them, such as antibiotics, peptides, sterols, and statins, have the probability of being implemented as clinical treatment. In contrast, for other molecules, there are limited studies that demonstrate efficacy in animal models with sufficient reliability.
DISCUSSION
Most of the studies reviewed has a good level of confidence. However, one of the limitations of this systematic review is the lack of homogeneity of the studies, what prevented to carry out a statistical comparison of the results or meta-analysis.
CONCLUSION
A panel of molecules blocking PLY activity are associated with the improvement of the inflammatory process triggered by the pneumococcal infection. Some molecules have already been used in humans for other purposes, so they could be safe for use in patients with pneumococcal infections. These patients might benefit from a second line treatment during the initial stages of the infection preventing acute respiratory distress syndrome and invasive pneumococcal diseases. Additional research using the presented set of compounds might further improve the clinical management of these patients.
Topics: Animals; Humans; Reproducibility of Results; Pneumococcal Infections; Streptococcus pneumoniae; Streptolysins; Bacterial Proteins
PubMed: 36947540
DOI: 10.1371/journal.pone.0282970 -
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 -
The Lancet. Microbe Sep 2021Pneumococcal diseases are a leading cause of morbidity and mortality among children globally, and the burden of these diseases might be worsened by antimicrobial...
BACKGROUND
Pneumococcal diseases are a leading cause of morbidity and mortality among children globally, and the burden of these diseases might be worsened by antimicrobial resistance. To understand the effect of pneumococcal conjugate vaccine (PCV) deployment on antimicrobial resistance in pneumococci, we assessed the susceptibility of paediatric pneumococcal isolates to various antimicrobial drugs before and after PCV implementation.
METHODS
We did a systematic review of studies reporting antimicrobial susceptibility profiles of paediatric pneumococcal isolates between 2000 and 2020 using PubMed and the Antimicrobial Testing Leadership and Surveillance database (ATLAS; Pfizer). Population-based studies of invasive pneumococcal disease or nasopharyngeal colonisation were eligible for inclusion. As primary outcome measures, we extracted the proportions of isolates that were non-susceptible or resistant to penicillin, macrolides, sulfamethoxazole-trimethoprim, third-generation cephalosporins, and tetracycline from each study. Where available, we also extracted data on pneumococcal serotypes. We estimated changes in the proportion of isolates with reduced susceptibility or resistance to each antibiotic class using random-effects meta-regression models, adjusting for study-level and region-level heterogeneity, as well as secular trends, invasive or colonising isolate source, and countries' per-capita gross domestic product.
FINDINGS
From 4910 studies screened for inclusion, we extracted data from 559 studies on 312 783 paediatric isolates. Susceptibility of isolates varied substantially across regions both before and after implementation of any PCV product. On average across all regions, we estimated significant absolute reductions in the proportions of pneumococci showing non-susceptibility to penicillin (11·5%, 95% CI 8·6-14·4), sulfamethoxazole-trimethoprim (9·7%, 4·3-15·2), and third-generation cephalosporins (7·5%, 3·1-11·9), over the 10 years after implementation of any PCV product, and absolute reductions in the proportions of pneumococci resistant to penicillin (7·3%, 5·3-9·4), sulfamethoxazole-trimethoprim (16·0%, 11·0-21·2), third-generation cephalosporins (4·5%, 0·3-8·7), macrolides (3·6%, 0·7-6·6) and tetracycline (2·0%, 0·3-3·7). We did not find evidence of changes in the proportion of isolates non-susceptible to macrolides or tetracycline after PCV implementation. Observed changes in penicillin non-susceptibility were driven, in part, by replacement of vaccine-targeted serotypes with non-vaccine serotypes that were less likely to be non-susceptible.
INTERPRETATION
Implementation of PCVs has reduced the proportion of circulating pneumococci resistant to first-line antibiotic treatments for pneumonia. This effect merits consideration in assessments of vaccine impact and investments in coverage improvements.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Cephalosporins; Child; Drug Resistance, Bacterial; Humans; Macrolides; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Regression Analysis; Streptococcus pneumoniae; Sulfamethoxazole; Tetracycline; Trimethoprim; Vaccines, Conjugate
PubMed: 34485957
DOI: 10.1016/S2666-5247(21)00064-1 -
BMJ Open Aug 2022Urinary antigen tests have been used for the rapid identification of infection in patients with pneumonia, thereby leading to earlier targeted therapy than when using... (Meta-Analysis)
Meta-Analysis
Diagnostic accuracy of urinary antigen tests for pneumococcal pneumonia among patients with acute respiratory failure suspected pneumonia: a systematic review and meta-analysis.
BACKGROUND/OBJECTIVES
Urinary antigen tests have been used for the rapid identification of infection in patients with pneumonia, thereby leading to earlier targeted therapy than when using conventional diagnostic culture methods. This study aimed to update the knowledge on the diagnostic accuracy of urinary antigen tests for among patients with acute respiratory failure suspected of pneumonia based on a systematic review and meta-analysis.
METHODS
A systematic search was performed using MEDLINE and the Cochrane Central Register of Controlled Trials for studies published up to 3 June 2020. Prospective and retrospective cohort studies (in English) that reported on the diagnostic performance of urinary antigen tests versus culture or smear diagnostic methods in adult patients with clinically diagnosed pneumonia were selected and analysed. The QUADAS-2 tool was used to assess the risk of bias, and a bivariate random effects model was applied to perform a meta-analysis of the selected studies.
RESULTS
A total of 2179 studies were screened, of which 30 met the eligibility criteria for quality assessment and meta-analysis. Overall, data from 12 366 patients, including 1548 patients (12.5%) with the target condition and suspected pneumococcal pneumonia, were included in the analysis. The overall quality of the included studies was determined to be serious. The calculated pooled sensitivity and specificity were of 0.66 (95% CI 0.62 to 0.69) and 0.90 (95% CI 0.85 to 0.93), respectively.
CONCLUSIONS
The urinary antigen test is useful for achieving a definitive diagnosis of infection in patients with pneumonia.
Topics: Adult; Humans; Pneumonia, Pneumococcal; Prospective Studies; Respiratory Distress Syndrome; Respiratory Insufficiency; Retrospective Studies; Sensitivity and Specificity; Streptococcus pneumoniae
PubMed: 35953247
DOI: 10.1136/bmjopen-2021-057216 -
Human Vaccines & Immunotherapeutics Nov 2022National Immunization Technical Advisory Groups (NITAGs) and Health Technology Assessment (HTA) agencies evaluate the value of vaccines and provide decision-making...
National Immunization Technical Advisory Groups (NITAGs) and Health Technology Assessment (HTA) agencies evaluate the value of vaccines and provide decision-making authorities with recommendations. The availability of information on disease-burden evidence considered or required for the assessment of vaccines included in national immunization programs (NIPs) is limited. The aim of this review is to summarize the epidemiologic and health economic (HE) evidence considered by NITAGs/HTA agencies when evaluating pediatric pneumococcal conjugate vaccine (PCV) NIPs. A systematic literature review of national recommendation reports for PCV NIPs in children in 31 European countries, published since 2001, was performed using NITAG/HTA agency websites, Google, MEDLINE, and EMBASE. The presence of epidemiological data was mapped, HE data was extracted, and findings were summarized. A total of 46 records for 19 countries were identified. Fifteen countries' records included a recommendation concerning implementation of PCV NIP, switching from one PCV to another or a change in vaccination schedule within an existing NIP. All of these included epidemiological invasive pneumococcal disease data, and to varying degree epidemiological data on acute otitis media and pneumonia. HE data was referenced in 13 countries' records, with 8 countries providing in-depth details on cost-effectiveness analyses. Pediatric PCV NIP recommendations were published by 61% of European countries, with varying degree of details and decision rationale. Some countries only publish the HE aspect of their rationale. The identified material can provide insight and support local policymakers and clinicians how data influenced the decision-making process in their countries.
Topics: Child; Europe; Humans; Immunization Programs; Pneumococcal Infections; Pneumococcal Vaccines; Technology Assessment, Biomedical; Vaccination; Vaccines, Conjugate
PubMed: 35438039
DOI: 10.1080/21645515.2022.2060017