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PLoS Pathogens May 2024Infants are highly susceptible to invasive respiratory and gastrointestinal infections. To elucidate the age-dependent mechanism(s) that drive bacterial spread from the...
Infants are highly susceptible to invasive respiratory and gastrointestinal infections. To elucidate the age-dependent mechanism(s) that drive bacterial spread from the mucosa, we developed an infant mouse model using the prevalent pediatric respiratory pathogen, Streptococcus pneumoniae (Spn). Despite similar upper respiratory tract (URT) colonization levels, the survival rate of Spn-infected infant mice was significantly decreased compared to adults and corresponded with Spn dissemination to the bloodstream. An increased rate of pneumococcal bacteremia in early life beyond the newborn period was attributed to increased bacterial translocation across the URT barrier. Bacterial dissemination in infant mice was independent of URT monocyte or neutrophil infiltration, phagocyte-derived ROS or RNS, inflammation mediated by toll-like receptor 2 or interleukin 1 receptor signaling, or the pore-forming toxin pneumolysin. Using molecular barcoding of Spn, we found that only a minority of bacterial clones in the nasopharynx disseminated to the blood in infant mice, indicating the absence of robust URT barrier breakdown. Rather, transcriptional profiling of the URT epithelium revealed a failure of infant mice to upregulate genes involved in the tight junction pathway. Expression of many such genes was also decreased in early life in humans. Infant mice also showed increased URT barrier permeability and delayed mucociliary clearance during the first two weeks of life, which corresponded with tighter attachment of bacteria to the respiratory epithelium. Together, these results demonstrate a window of vulnerability during postnatal development when altered mucosal barrier function facilitates bacterial dissemination.
Topics: Animals; Pneumococcal Infections; Mice; Streptococcus pneumoniae; Humans; Animals, Newborn; Disease Models, Animal; Mice, Inbred C57BL; Respiratory Mucosa; Female; Nasopharynx
PubMed: 38718049
DOI: 10.1371/journal.ppat.1012111 -
Frontiers in Immunology 2024Recovery from respiratory pneumococcal infections generates lung-localized protection against heterotypic bacteria, mediated by resident memory lymphocytes. Optimal...
Recovery from respiratory pneumococcal infections generates lung-localized protection against heterotypic bacteria, mediated by resident memory lymphocytes. Optimal protection in mice requires re-exposure to pneumococcus within days of initial infection. Serial surface marker phenotyping of B cell populations in a model of pneumococcal heterotypic immunity revealed that bacterial re-exposure stimulates the immediate accumulation of dynamic and heterogeneous populations of B cells in the lung, and is essential for the establishment of lung resident memory B (B) cells. The B cells in the early wave were activated, proliferating locally, and associated with both CD4 T cells and CXCL13. Antagonist- and antibody-mediated interventions were implemented during this early timeframe to demonstrate that lymphocyte recirculation, CD4 cells, and CD40 ligand (CD40L) signaling were all needed for lung B cell establishment, whereas CXCL13 signaling was not. While most prominent as aggregates in the loose connective tissue of bronchovascular bundles, morphometry and live lung imaging analyses showed that lung B cells were equally numerous as single cells dispersed throughout the alveolar septae. We propose that CD40L signaling from antigen-stimulated CD4 T cells in the infected lung is critical to establishment of local B cells, which subsequently protect the airways and parenchyma against future potential infections.
Topics: Animals; Mice; CD4-Positive T-Lymphocytes; CD40 Ligand; Chemokine CXCL13; Disease Models, Animal; Immunologic Memory; Lung; Memory B Cells; Mice, Inbred C57BL; Pneumococcal Infections; Signal Transduction; Streptococcus pneumoniae
PubMed: 38715601
DOI: 10.3389/fimmu.2024.1382638 -
Frontiers in Immunology 2024remains a significant global threat, with existing vaccines having important limitations such as restricted serotype coverage and high manufacturing costs. Pneumococcal...
remains a significant global threat, with existing vaccines having important limitations such as restricted serotype coverage and high manufacturing costs. Pneumococcal lipoproteins are emerging as promising vaccine candidates due to their surface exposure and conservation across various serotypes. While prior studies have explored their potential in mice, data in a human context and insights into the impact of the lipid moiety remain limited. In the present study, we examined the immunogenicity of two pneumococcal lipoproteins, DacB and MetQ, both in lipidated and non-lipidated versions, by stimulation of primary human immune cells. Immune responses were assessed by the expression of common surface markers for activation and maturation as well as cytokines released into the supernatant. Our findings indicate that in the case of MetQ lipidation was crucial for activation of human antigen-presenting cells such as dendritic cells and macrophages, while non-lipidated DacB demonstrated an intrinsic potential to induce an innate immune response. Nevertheless, immune responses to both proteins were enhanced by lipidation. Interestingly, following stimulation of dendritic cells with DacB, LipDacB and LipMetQ, cytokine levels of IL-6 and IL-23 were significantly increased, which are implicated in triggering potentially important Th17 cell responses. Furthermore, LipDacB and LipMetQ were able to induce proliferation of CD4+ T cells indicating their potential to induce an adaptive immune response. These findings contribute valuable insights into the immunogenic properties of pneumococcal lipoproteins, emphasizing their potential role in vaccine development against pneumococcal infections.
Topics: Humans; Streptococcus pneumoniae; Adaptive Immunity; Cytokines; Bacterial Proteins; Lipoproteins; Dendritic Cells; Antigen-Presenting Cells; Pneumococcal Vaccines; Pneumococcal Infections; Macrophages; Cells, Cultured
PubMed: 38711516
DOI: 10.3389/fimmu.2024.1392316 -
Vaccine Jun 2024A U.S. case-control study (2010-2014) demonstrated vaccine effectiveness (VE) for ≥ 1 dose of the thirteen-valent pneumococcal conjugate vaccine (PCV13) against...
Effectiveness of 13-valent pneumococcal conjugate vaccine for prevention of invasive pneumococcal disease among children in the United States between 2010 and 2019: An indirect cohort study.
BACKGROUND
A U.S. case-control study (2010-2014) demonstrated vaccine effectiveness (VE) for ≥ 1 dose of the thirteen-valent pneumococcal conjugate vaccine (PCV13) against vaccine-type (VT) invasive pneumococcal disease (IPD) at 86 %; however, it lacked statistical power to examine VE by number of doses and against individual serotypes.
METHODS
We used the indirect cohort method to estimate PCV13 VE against VT-IPD among children aged < 5 years in the United States from May 1, 2010 through December 31, 2019 using cases from CDC's Active Bacterial Core surveillance, including cases enrolled in a matched case-control study (2010-2014). Cases and controls were defined as individuals with VT-IPD and non-PCV13-type-IPD (NVT-IPD), respectively. We estimated absolute VE using the adjusted odds ratio of prior PCV13 receipt (1-aOR x 100 %).
RESULTS
Among 1,161 IPD cases, 223 (19.2 %) were VT cases and 938 (80.8 %) were NVT controls. Of those, 108 cases (48.4 %; 108/223) and 600 controls (64.0 %; 600/938) had received > 3 PCV13 doses; 23 cases (17.6 %) and 15 controls (2.4 %) had received no PCV doses. VE ≥ 3 PCV13 doses against VT-IPD was 90.2 % (95 % Confidence Interval75.4-96.1 %), respectively. Among the most commonly circulating VT-IPD serotypes, VE of ≥ 3 PCV13 doses was 86.8 % (73.7-93.3 %), 50.2 % (28.4-80.5 %), and 93.8 % (69.8-98.8 %) against serotypes 19A, 3, and 19F, respectively.
CONCLUSIONS
At least three doses of PCV13 continue to be effective in preventing VT-IPD among children aged < 5 years in the US. PCV13 was protective against serotypes 19A and 19F IPD; protection against serotype 3 IPD did not reach statistical significance.
Topics: Humans; Pneumococcal Vaccines; Pneumococcal Infections; United States; Child, Preschool; Infant; Female; Male; Streptococcus pneumoniae; Case-Control Studies; Serogroup; Vaccines, Conjugate; Vaccine Efficacy; Cohort Studies; Infant, Newborn; Vaccination
PubMed: 38704263
DOI: 10.1016/j.vaccine.2024.04.061 -
Vaccine May 2024Globally, cardiovascular disease (CVD) is the leading cause of death and illness. Vaccine-preventable infections may increase acute coronary vascular disease events and...
BACKGROUND
Globally, cardiovascular disease (CVD) is the leading cause of death and illness. Vaccine-preventable infections may increase acute coronary vascular disease events and the risk of complications. Low vaccine coverage has been reported among adults at high risk of complications from vaccine-preventable infections. There is a gap in research evidence around determinants of uptake of vaccines among adults with CVD. This study examined the uptake of influenza, pneumococcal and zoster vaccines and the determinants of uptake of the vaccines among cardiac patients.
METHOD
A prospective cross-sectional study was carried out among hospitalised cardiac patients through an interviewer-administered questionnaire. Descriptive statistics were used to investigate self-reported uptake of influenza, pneumococcal and zoster vaccines. Univariate and multivariate analyses of participants' social demographic and clinical characteristics were conducted to identify factors for receiving influenza vaccine.
RESULTS
Low vaccination rates among 104 participants were found for influenza (45.2%), pneumococcal (13.5%) and zoster (5.8%) vaccines. The most common reason for not receiving influenza vaccine was concern about side effects. Lack of awareness about the pneumococcal and zoster vaccines was the main reason for the poor uptake of these vaccines. Australia-born participants were more likely to receive influenza vaccine than overseas-born participants. Working-age participants and, interestingly, people living with a current smoker were less likely to receive influenza vaccine.
CONCLUSION
Influenza, pneumococcal and zoster vaccine uptake among cardiac patients was low. Encouraging physician recommendations for vaccination for cardiac patients under 65 years of age and addressing vaccination challenges among people from culturally and linguistically diverse backgrounds and pharmacy, workplace, and hospital vaccination may help increase vaccination uptake among cardiac patients.
Topics: Humans; Male; Female; Influenza Vaccines; Middle Aged; Cross-Sectional Studies; Pneumococcal Vaccines; Aged; Prospective Studies; Influenza, Human; Cardiovascular Diseases; Herpes Zoster Vaccine; Vaccination; Adult; Pneumococcal Infections; Surveys and Questionnaires; Vaccination Coverage; Australia; Aged, 80 and over
PubMed: 38704255
DOI: 10.1016/j.vaccine.2024.04.031 -
Expert Review of Vaccines 2024The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is used in the Japanese National Immunization Program for older adults and adults with increased risk for...
BACKGROUND
The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is used in the Japanese National Immunization Program for older adults and adults with increased risk for pneumococcal disease, however, disease incidence and associated burden remain high. We evaluated the cost-effectiveness of pneumococcal conjugate vaccines (PCVs) for adults aged 65 years and high-risk adults aged 60-64 years in Japan.
RESEARCH DESIGN AND METHODS
Using a Markov model, we evaluated lifetime costs using societal and healthcare payer perspectives and estimated quality-adjusted life-years (QALYs), and number of prevented cases and deaths caused by invasive pneumococcal disease (IPD) and non-IPD. The base case analysis used a societal perspective.
RESULTS
In comparison with PPSV23, the 20-valent PCV (PCV20) prevented 127 IPD cases 10,813 non-IPD cases (inpatients: 2,461, outpatients: 8,352) and 226 deaths, and gained more QALYs (+0.0015 per person) with less cost (-JPY22,513 per person). All sensitivity and scenario analyses including a payer perspective analysis indicated that the incremental cost-effectiveness ratios (ICERs) were below the cost-effectiveness threshold value in Japan (JPY5 million/QALY).
CONCLUSIONS
PCV20 is both cost saving and more effective than PPSV23 for adults aged 65 years and high-risk adults aged 60-64 years in Japan.
Topics: Humans; Cost-Benefit Analysis; Pneumococcal Vaccines; Japan; Pneumococcal Infections; Middle Aged; Aged; Vaccines, Conjugate; Male; Female; Quality-Adjusted Life Years; Markov Chains; Cost-Effectiveness Analysis
PubMed: 38703180
DOI: 10.1080/14760584.2024.2350246 -
IDCases 2024Given the high mortality rate of invasive pneumococcal disease (IPD) in hematopoietic stem cell transplant (HSCT) recipients, vaccination is recommended. These...
Given the high mortality rate of invasive pneumococcal disease (IPD) in hematopoietic stem cell transplant (HSCT) recipients, vaccination is recommended. These recipients respond to most vaccines; however, their immune response is typically weaker during the first months or years after transplantation, compared with that of healthy individuals. Here, we report a case of IPD with serotype 3 pneumonia and empyema in an HSCT recipient who had received three doses of the 13-valent pneumococcal conjugate vaccine (PCV) and one dose of the 23-valent pneumococcal polysaccharide vaccine; furthermore, the recipient had no relapse, graft-versus-host disease, or use of immunosuppressive agents after allogeneic HSCT for acute myeloid leukemia. Moreover, we discussed the characteristics of serotype 3 , a case series of breakthrough infections with in HSCT recipients who received pneumococcal vaccines, and the potential implications for the upcoming PCV15 and PCV20 vaccines for serotype 3.
PubMed: 38699526
DOI: 10.1016/j.idcr.2024.e01936 -
Expert Review of Vaccines 2024Lower respiratory tract infection is one of the leading causes of morbidity and mortality all over the world, with a substantial impact on healthcare costs. In Egypt,... (Review)
Review
INTRODUCTION
Lower respiratory tract infection is one of the leading causes of morbidity and mortality all over the world, with a substantial impact on healthcare costs. In Egypt, local consensus on its burden, diagnosis, and vaccination is scarce. This expert opinion is the first to address the local recommendations for vaccinating adults against respiratory infection. It sheds light on the growing need to understand the barriers and underpublicized concept of adult vaccination in Egypt.
AREAS COVERED
A collaborative multidisciplinary panel from Egypt developed an expert opinion-based suggestions/points, including epidemiology, microbiology, and highlights on vaccination in Egypt, as well as challenges and recommendations regarding adult vaccination.
EXPERT OPINION
Adult vaccinations against respiratory infections are now recommended for high-risk people by all healthcare regulatory bodies. However, it was acknowledged that there may be hesitancy and concerns among patients; in addition, healthcare professionals' awareness about vaccination guidelines and benefits needs improvement. There are several strategies that could be implemented to enhance vaccine adherence in Egypt. These approaches encompass conducting community education programs, addressing the concerns of patients, and enhancing awareness among healthcare professionals through education, policy changes, and periodical reminders in each healthcare setting.
Topics: Humans; Egypt; Respiratory Tract Infections; Vaccination; Adult; Vaccination Hesitancy; Expert Testimony; Health Personnel; Vaccines
PubMed: 38695193
DOI: 10.1080/14760584.2024.2348608 -
The Malaysian Journal of Medical... Apr 2024is one of the leading causes of mortality and morbidity worldwide. The dramatic increase in in-vitro resistance of antimicrobial agents, particularly beta-lactams and...
BACKGROUND
is one of the leading causes of mortality and morbidity worldwide. The dramatic increase in in-vitro resistance of antimicrobial agents, particularly beta-lactams and macrolides, makes pneumococcal infections difficult to treat. The aim of this study was to describe the drug resistance rate, assess the prevalence of macrolide-resistant genes and review the clinical complications of pneumococcal infections among patients presented to Hospital Universiti Sains Malaysia (HUSM), Kelantan, Malaysia.
METHODS
This is a descriptive cross-sectional study. All isolates collected from clinical specimens within a 1-year period were subjected to selected antimicrobial susceptibility testing using E-test strips. Polymerase chain reaction (PCR) analysis was conducted to detect macrolide-resistant determinants. The patient's clinical data were obtained from clinical notes.
RESULTS
A total of 113 patients with a positive growth of were included in the study. The most common predisposing factors among them were bronchopulmonary diseases (15.9%). The penicillin-resistant rate was 7.1%, with minimal inhibitory concentration (MIC) ranging between 0.012 μg/mL and >32 μg/mL, and the erythromycin-resistant rate was 26.5%, with a MIC range of 0.03 μg/mL-> 256 μg/mL. Most of the erythromycin-resistant isolates were found to have the (A) gene (50.4%) and the (B) gene (20%); 16.7% had a combination of genes (A) and (B), and 13.3% had none of the two genes. Community-acquired pneumonia is the predominant type of pneumococcal infection. There was no significant association between the presence of macrolide resistance determinants and mortality ( = 0.837) or complications ( > 0.999 for empyema and cardiac complication; = 0.135 for subdural abscess).
CONCLUSION
The majority of erythromycin-resistant isolates were found to have the (A) gene, followed by the (B) gene and a combination of genes (A) and (B).
PubMed: 38694572
DOI: 10.21315/mjms2024.31.2.17 -
Expert Review of Vaccines 2024The Japanese National Immunization Program currently includes the pediatric 13 valent pneumococcal conjugate vaccine (PCV13) to prevent pneumococcal infections. We aimed... (Comparative Study)
Comparative Study
BACKGROUND
The Japanese National Immunization Program currently includes the pediatric 13 valent pneumococcal conjugate vaccine (PCV13) to prevent pneumococcal infections. We aimed to evaluate the cost-effectiveness of 20-valent PCV (PCV20) as a pediatric vaccine versus PCV13.
METHODS
A decision-analytic Markov model was used to estimate expected costs, quality-adjusted life-years (QALYs), and prevented cases and deaths caused by invasive pneumococcal disease, pneumonia, and acute otitis media over a ten-year time horizon from the societal and healthcare payer perspectives.
RESULTS
PCV20 was dominant, i.e. less costly and more effective, over PCV13 (gained 294,599 QALYs and reduced Japanese yen [JPY] 352.6 billion [2.6 billion United States dollars, USD] from the societal perspective and JPY 178.9 billion [USD 1.4 billion] from the payer perspective). Sensitivity and scenario analyses validated the robustness of the base scenario results. When comparing PCV20 with PCV13, the threshold analysis revealed an incremental cost-effectiveness ratio that was within the threshold value (JPY 5 million/QALY) at a maximum acquisition cost of JPY 74,033 [USD 563] (societal perspective) and JPY 67,758 [USD 515] (payer perspective).
CONCLUSIONS
As a pediatric vaccine, PCV20 was dominant over PCV13 regardless of the study perspective.
Topics: Pneumococcal Vaccines; Humans; Cost-Benefit Analysis; Japan; Pneumococcal Infections; Infant; Child, Preschool; Immunization Programs; Vaccines, Conjugate; Quality-Adjusted Life Years; Child; Vaccination; Male; Markov Chains; Female; Otitis Media; Adolescent; Cost-Effectiveness Analysis
PubMed: 38682661
DOI: 10.1080/14760584.2024.2345670