-
Vaccine May 2023In January 2020 the UK changed from a 2 + 1 schedule for 13-valent pneumococcal conjugate vaccine (PCV13) to a 1 + 1 schedule (doses at 3 and 12 months) based on a... (Randomized Controlled Trial)
Randomized Controlled Trial
In January 2020 the UK changed from a 2 + 1 schedule for 13-valent pneumococcal conjugate vaccine (PCV13) to a 1 + 1 schedule (doses at 3 and 12 months) based on a randomized immunogenicity trial comparing the two schedules. Carriage prevalence measured at the time of booster and 6 months later in 191 of the 213 study infants was 57 % (109/191) and 60 % (114/190) respectively. There were eight episodes of vaccine-type (VT) or vaccine-related 6C carriage in the 2 + 1 and six in the 1 + 1 group; ≥4-fold rises in serotype-specific IgG in 71 children with paired post-booster and follow up blood samples at 21-33 months of age were found in 20 % (7/35) of the 2 + 1 and 15 % (6/41) of the 1 + 1 group. VTs identified in carriage and inferred from serology were similar comprising 3, 19A and 19F. Dropping a priming dose from the 2 + 1 PCV 13 schedule did not increase VT carriage in the study cohort. Ongoing population level carriage studies will be important to confirm this.
Topics: Child; Humans; Infant; Antibodies, Bacterial; Immunization Schedule; Nasopharynx; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae; United Kingdom; Vaccines, Conjugate
PubMed: 37045683
DOI: 10.1016/j.vaccine.2023.04.017 -
The Journal of Clinical Investigation Feb 2010Sickle cell disease (SCD) is characterized by intravascular hemolysis and inflammation coupled to a 400-fold greater incidence of invasive pneumococcal infection...
Sickle cell disease (SCD) is characterized by intravascular hemolysis and inflammation coupled to a 400-fold greater incidence of invasive pneumococcal infection resulting in fulminant, lethal pneumococcal sepsis. Mechanistically, invasive infection is facilitated by a proinflammatory state that enhances receptor-mediated endocytosis of pneumococci into epithelial and endothelial cells. As statins reduce chronic inflammation, in addition to their serum cholesterol-lowering effects, we hypothesized that statin therapy might improve the outcome of pneumococcal infection in SCD. In this study, we tested this hypothesis in an experimental SCD mouse model and found that statin therapy prolonged survival following pneumococcal challenge. The protective effect resulted in part from decreased platelet-activating factor receptor expression on endothelia and epithelia, which led to reduced bacterial invasion. An additional protective effect resulted from inhibition of host cell lysis by pneumococcal cholesterol-dependent cytotoxins (CDCs), including pneumolysin. We conclude therefore that statins may be of prophylactic benefit against invasive pneumococcal disease in patients with SCD and, more broadly, in settings of bacterial pathogenesis driven by receptor-mediated endocytosis and the CDC class of toxins produced by Gram-positive invasive bacteria.
Topics: Anemia, Sickle Cell; Animals; Anti-Inflammatory Agents; Bacterial Proteins; Cytotoxins; Disease Models, Animal; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lung; Mice; Mice, Knockout; Mice, Transgenic; Platelet Membrane Glycoproteins; Pneumococcal Infections; Receptors, G-Protein-Coupled; Streptolysins
PubMed: 20093777
DOI: 10.1172/JCI39843 -
Tuberkuloz Ve Toraks Sep 2020Pneumococcal infections are an important cause of mortality and morbidity in Chronic Lung Diseases. However, exacerbations, which make the treatment of diseases very... (Review)
Review
Pneumococcal infections are an important cause of mortality and morbidity in Chronic Lung Diseases. However, exacerbations, which make the treatment of diseases very difficult, and corticosteroids used during treatment carry a great risk of pneumococcal infection and adversely affect the treatment. The most rational way to reduce the negative impact of pneumococcal infections on the clinical and economic burden of Chronic Lung Diseases is vaccination of the risky population. Although, vaccination recommendations are well defined, recommended by national and international guidelines and are paid by health authorities, in Turkey, vaccination rates in adults with chronic lung disease is far below the expected. Since physicians are considered to be the most important and reliable resource that can guide their patients in vaccination, applying pneumococcal vaccination routinely in all patients with chronic lung diagnosis and making it a part of daily practice will greatly contribute to reducing the clinical and economic burden of pneumococcal infections in these patients. In this review, the effects of pneumococcal diseases on chronic lung diseases, the risk and clinical burden of pneumococcal diseases in chronic lung diseases are discussed in the light of guidelines and current literature, and the importance of protection from pneumonia in these patients is emphasized. In addition to general information and efficacy data about pneumococcal vaccines available in our country, application methods and access routes to vaccines are also described.
Topics: Adult; Humans; Immunization Programs; Physicians, Primary Care; Pneumococcal Infections; Pneumococcal Vaccines; Pulmonary Disease, Chronic Obstructive; Risk Factors; Turkey; Vaccination
PubMed: 33295729
DOI: 10.5578/tt.70012 -
Nature Communications Feb 2023Invasive pneumococcal disease (IPD) risk increases with age for older adults whereas the population size benefiting from pneumococcal vaccines and robustness of...
Invasive pneumococcal disease (IPD) risk increases with age for older adults whereas the population size benefiting from pneumococcal vaccines and robustness of immunogenic response to vaccination decline. We estimate how demographics, vaccine efficacy/effectiveness (VE), and waning VE impact on optimal age for a single-dose pneumococcal vaccination. Age- and vaccine-serotype-specific IPD cases from routine surveillance of adults ≥ 55 years old (y), ≥ 4-years after infant-pneumococcal vaccine introduction and before 2020, and VE data from prior studies were used to estimate IPD incidence and waning VE which were then combined in a cohort model of vaccine impact. In Brazil, Malawi, South Africa and England 51, 51, 54 and 39% of adults older than 55 y were younger than 65 years old, with a smaller share of annual IPD cases reported among < 65 years old in England (4,657; 20%) than Brazil (186; 45%), Malawi (4; 63%), or South Africa (134, 48%). Vaccination at 55 years in Brazil, Malawi, and South Africa, and at 70 years in England had the greatest potential for IPD prevention. Here, we show that in low/middle-income countries, pneumococcal vaccines may prevent a substantial proportion of residual IPD burden if administered earlier in adulthood than is typical in high-income countries.
Topics: Infant; Humans; Aged; Middle Aged; Pneumococcal Infections; Pneumococcal Vaccines; Vaccination; Serogroup; Incidence
PubMed: 36797259
DOI: 10.1038/s41467-023-36624-8 -
Clinical Microbiology Reviews Apr 2003As individuals advance in age, the risk of infection, bacteremia, and mortality caused by Streptococcus pneumoniae rises. Retrospective data demonstrate that the... (Review)
Review
As individuals advance in age, the risk of infection, bacteremia, and mortality caused by Streptococcus pneumoniae rises. Retrospective data demonstrate that the licensed penumococcal polysaccharide vaccine (PPV) is effective in older persons in reducing serotype-specific invasive disease. PPV demonstrates good immunogenicity in older adults, generally comparable to that in younger subjects, although certain cohorts respond less well. The response to PPV is T cell independent, however, and does not elicit immunologic memory. The duration of the anti-capsular polysaccharide antibody response appears to wane as early as 3 years after vaccination. In older persons, revaccination induces an antibody response, although it may not be as strong as that from the initial vaccine. While revaccination of older adults has been recommended, clinical efficacy has not yet been proven. Measures of antibody function may be at least as important in determining protection as are quantitative antibody levels. Additional studies of immunogenicity, particularly regarding revaccination, will facilitate the design of an optimal pneumococcal vaccination policy. Research into conjugate- and protein-based pneumococcal vaccines, which elicit T-cell-dependent responses and induce immunologic memory, is needed in older persons. In the meantime, administering to PPV to recommended groups should be a public health priority.
Topics: Adult; Aged; Antibodies, Bacterial; Humans; Immunization, Secondary; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae
PubMed: 12692100
DOI: 10.1128/CMR.16.2.308-318.2003 -
Frontiers in Cellular and Infection... 2022is a major cause of invasive diseases such as pneumonia, meningitis, and sepsis, with high associated mortality. Our previous molecular evolutionary analysis revealed...
is a major cause of invasive diseases such as pneumonia, meningitis, and sepsis, with high associated mortality. Our previous molecular evolutionary analysis revealed that the gene , encoding the enzyme β-galactosidase (BgaA), had a high proportion of codons under negative selection among the examined pneumococcal genes and that deletion of significantly reduced host mortality in a mouse intravenous infection assay. BgaA is a multifunctional protein that plays a role in cleaving terminal galactose in -linked glycans, resistance to human neutrophil-mediated opsonophagocytic killing, and bacterial adherence to human epithelial cells. In this study, we performed and assays to evaluate the precise role of as a virulence factor in sepsis. Our assays showed that the deletion of significantly reduced the bacterial association with human lung epithelial and vascular endothelial cells. The deletion of also reduced pneumococcal survival in human blood by promoting neutrophil-mediated killing, but did not affect pneumococcal survival in mouse blood. In a mouse sepsis model, mice infected with an -deleted mutant strain exhibited upregulated host innate immunity pathways, suppressed tissue damage, and blood coagulation compared with mice infected with the wild-type strain. These results suggest that BgaA functions as a multifunctional virulence factor whereby it induces host tissue damage and blood coagulation. Taken together, our results suggest that BgaA could be an attractive target for drug design and vaccine development to control pneumococcal infection.
Topics: Animals; Bacterial Proteins; Blood Coagulation; Disease Models, Animal; Endothelial Cells; Humans; Mice; Pneumococcal Infections; Pneumococcal Vaccines; Pneumonia, Pneumococcal; Sepsis; Streptococcus pneumoniae; Virulence Factors
PubMed: 35846740
DOI: 10.3389/fcimb.2022.844000 -
PloS One 2020This study describes predictors of pneumococcal nasopharyngeal carriage and density in Fiji. We used data from four annual (2012-2015) cross-sectional surveys, pre- and...
This study describes predictors of pneumococcal nasopharyngeal carriage and density in Fiji. We used data from four annual (2012-2015) cross-sectional surveys, pre- and post-introduction of ten-valent pneumococcal conjugate vaccine (PCV10) in October 2012. Infants (5-8 weeks), toddlers (12-23 months), children (2-6 years), and their caregivers participated. Pneumococci were detected and quantified using lytA qPCR, with molecular serotyping by microarray. Logistic and quantile regression were used to determine predictors of pneumococcal carriage and density, respectively. There were 8,109 participants. Pneumococcal carriage was negatively associated with years post-PCV10 introduction (global P<0.001), and positively associated with indigenous iTaukei ethnicity (aOR 2.74 [95% CI 2.17-3.45] P<0.001); young age (infant, toddler, and child compared with caregiver participant groups) (global P<0.001); urban residence (aOR 1.45 [95% CI 1.30-2.57] P<0.001); living with ≥2 children <5 years of age (aOR 1.42 [95% CI 1.27-1.59] P<0.001); low family income (aOR 1.44 [95% CI 1.28-1.62] P<0.001); and upper respiratory tract infection (URTI) symptoms (aOR 1.77 [95% CI 1.57-2.01] P<0.001). Predictors were similar for PCV10 and non-PCV10 carriage, except PCV10 carriage was negatively associated with PCV10 vaccination (0.58 [95% CI 0.41-0.82] P = 0.002) and positively associated with exposure to household cigarette smoke (aOR 1.21 [95% CI 1.02-1.43] P = 0.031), while there was no association between years post-PCV10 introduction and non-PCV10 carriage. Pneumococcal density was positively associated with URTI symptoms (adjusted median difference 0.28 [95% CI 0.16, 0.40] P<0.001) and toddler and child, compared with caregiver, participant groups (global P = 0.008). Predictors were similar for PCV10 and non-PCV10 density, except infant, toddler, and child participant groups were not associated with PCV10 density. PCV10 introduction was associated with reduced the odds of overall and PCV10 pneumococcal carriage in Fiji. However, after adjustment iTaukei ethnicity was positively associated with pneumococcal carriage compared with Fijians of Indian Descent, despite similar PCV10 coverage rates.
Topics: Adolescent; Adult; Age Factors; Carrier State; Child; Child, Preschool; Cross-Sectional Studies; Female; Fiji; Humans; Infant; Logistic Models; Male; Pneumococcal Infections; Pneumococcal Vaccines; Risk Factors; Young Adult
PubMed: 32236150
DOI: 10.1371/journal.pone.0231041 -
Frontiers in Public Health 2023To analyze the impact of pneumococcal conjugate vaccines (PCVs) on the incidence of invasive pneumococcal diseases (IPDs) and pneumococcal antibiotic resistance in...
Impact of the progressive uptake of pneumococcal conjugate vaccines on the epidemiology and antimicrobial resistance of invasive pneumococcal disease in Gipuzkoa, northern Spain, 1998-2022.
OBJECTIVES
To analyze the impact of pneumococcal conjugate vaccines (PCVs) on the incidence of invasive pneumococcal diseases (IPDs) and pneumococcal antibiotic resistance in Gipuzkoa, northern Spain for a 25 years period.
METHODS
All cases of IPD confirmed by culture between 1998 and 2022 in a population of around 427,416 people were included. Pneumococci were serotyped and antimicrobial susceptibility was assessed by the EUCAST guidelines.
RESULTS
Overall, 1,516 isolates were collected. Annual IPD incidence rates (per 100,000 people) declined from 19.9 in 1998-2001 to 11.5 in 2017-19 (42.2% reduction), especially in vaccinated children (from 46.7 to 24.9) and non-vaccinated older adult individuals (from 48.0 to 23.6). After PCV13 introduction, the decrease in the incidence of infections caused by PCV13 serotypes was balanced by the increase in the incidence of non-PCV13 serotypes. In the pandemic year of 2020, IPD incidence was the lowest: 2.81. The annual incidence rates of penicillin-resistant isolates also decreased, from 4.91 in 1998-2001 to 1.49 in 2017-19 and 0.70 in 2020. Since 2017, serotypes 14, 19A, and 11A have been the most common penicillin-resistant types. The incidence of erythromycin-resistant strains declined, from 3.65 to 1.73 and 0.70 in the same years.
CONCLUSION
PCV use was associated with declines in the incidence of IPD and the spread of non-vaccine serotypes, that balanced the beneficial effect off PCV13, some of them showing high rates of antibiotic resistance.
Topics: Child; Humans; Aged; Anti-Bacterial Agents; Vaccines, Conjugate; Spain; Drug Resistance, Bacterial; Pneumococcal Infections; Penicillins
PubMed: 37719737
DOI: 10.3389/fpubh.2023.1238502 -
Journal of the Formosan Medical... May 2022Influenza is frequently complicated with bacterial co-infection. This study aimed to disclose the significance of Streptococcus pneumoniae co-infection in children with...
BACKGROUND/PURPOSE
Influenza is frequently complicated with bacterial co-infection. This study aimed to disclose the significance of Streptococcus pneumoniae co-infection in children with influenza.
METHODS
We retrospectively reviewed medical records of pediatric patients hospitalized for influenza with or without pneumococcal co-infection at the National Taiwan University Hospital from 2007 to 2019. Clinical characteristics and outcomes were compared between patients with and without S. pneumoniae co-infection.
RESULTS
There were 558 children hospitalized for influenza: 494 had influenza alone whereas 64 had S. pneumoniae co-infection. Patients with S. pneumoniae co-infection had older ages, lower SpO, higher C-Reactive Protein (CRP), lower serum sodium, lower platelet counts, more chest radiograph findings of patch and consolidation on admission, longer hospitalization, more intensive care, longer intensive care unit (ICU) stay, more mechanical ventilation, more inotropes/vasopressors use, more surgical interventions including video-assisted thoracoscopic surgery (VATS) and extracorporeal membrane oxygenation (ECMO), and higher case-fatality rate.
CONCLUSION
Compared to influenza alone, patients with S. pneumoniae co-infection had more morbidities and mortalities. Pneumococcal co-infection is considered when influenza patients have lower SpO, lower platelet counts, higher CRP, lower serum sodium, and more radiographic patches and consolidations on admission.
Topics: Bacterial Infections; C-Reactive Protein; Child; Coinfection; Humans; Influenza, Human; Pneumococcal Infections; Retrospective Studies; Sodium; Streptococcus pneumoniae
PubMed: 34332830
DOI: 10.1016/j.jfma.2021.07.012 -
Infection and Immunity Apr 2021remains a leading cause of bacterial pneumonia despite the widespread use of vaccines. While vaccines are effective at reducing the incidence of most serotypes included...
remains a leading cause of bacterial pneumonia despite the widespread use of vaccines. While vaccines are effective at reducing the incidence of most serotypes included in vaccines, a rise in infection due to nonvaccine serotypes and moderate efficacy against some vaccine serotypes have contributed to high disease incidence. Additionally, numerous isolates of are antibiotic or multidrug resistant. Several conserved pneumococcal proteins prevalent in the majority of serotypes have been examined for their potential as vaccines in preclinical and clinical trials. An additional, yet-unexplored tool for disease prevention and treatment is the use of human monoclonal antibodies (MAbs) targeting conserved pneumococcal proteins. Here, we isolated the first human MAbs (PhtD3, PhtD6, PhtD7, PhtD8, and PspA16) against the pneumococcal histidine triad protein (PhtD) and the pneumococcal surface protein A (PspA), two conserved and protective antigens. MAbs to PhtD target diverse epitopes on PhtD, and MAb PspA16 targets the N-terminal segment of PspA. The PhtD-specific MAbs bind to multiple serotypes, while MAb PspA16 serotype breadth is limited. MAbs PhtD3 and PhtD8 prolong the survival of mice infected with pneumococcal serotype 3. Furthermore, MAb PhtD3 prolongs the survival of mice in intranasal and intravenous infection models with pneumococcal serotype 4 and in mice infected with pneumococcal serotype 3 when administered 24 h after pneumococcal infection. All PhtD and PspA MAbs demonstrate opsonophagocytic activity, suggesting a potential mechanism of protection. Our results identify new human MAbs for pneumococcal disease prevention and treatment and identify epitopes on PhtD and PspA recognized by human B cells.
Topics: Antibodies, Monoclonal; Antibody Specificity; Dose-Response Relationship, Immunologic; Epitopes; Host-Pathogen Interactions; Humans; Hydrolases; Pneumococcal Infections; Protein Binding; Serogroup; Streptococcus pneumoniae
PubMed: 33649050
DOI: 10.1128/IAI.00747-20