Pneumococcal Respiratory Infections Research Articles

B cells in the pneumococcus-infected lung are heterogeneous and require CD4+ T cell help including CD40L to become resident memory B cells.

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 (BRM) 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 BRM 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 BRM 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 BRM cells, which subsequently protect the airways and parenchyma against future potential infections.

Outpatient Visits and Antibiotic Use Due to Higher-Valency Pneumococcal Vaccine Serotypes.

In 2022-2023, 15- and 20-valent pneumococcal conjugate vaccines (PCV15/PCV20) were recommended for infants. We aimed to estimate the incidence of outpatient visits and antibiotic prescriptions in US children (≤17 years) from 2016-2019 for acute otitis media, pneumonia, and sinusitis associated with PCV15- and PCV20-additional (non-PCV13) serotypes to quantify PCV15/20 potential impacts. We estimated the incidence of PCV15/20-additional serotype-attributable visits and antibiotic prescriptions as the product of all-cause incidence rates, derived from national health care surveys and MarketScan databases, and PCV15/20-additional serotype-attributable fractions. We estimated serotype-specific attributable fractions using modified vaccine-probe approaches incorporating incidence changes post-PCV13 and ratios of PCV13 versus PCV15/20 serotype frequencies, estimated through meta-analyses. Per 1000 children annually, PCV15-additional serotypes accounted for an estimated 2.7 (95% confidence interval, 1.8-3.9) visits and 2.4 (95% CI, 1.6-3.4) antibiotic prescriptions. PCV20-additional serotypes resulted in 15.0 (95% CI, 11.2-20.4) visits and 13.2 (95% CI, 9.9-18.0) antibiotic prescriptions annually per 1000 children. PCV15/20-additional serotypes account for 0.4% (95% CI, 0.2%-0.6%) and 2.1% (95% CI, 1.5%-3.0%) of pediatric outpatient antibiotic use. Compared with PCV15-additional serotypes, PCV20-additional serotypes account for > 5 times the burden of visits and antibiotic prescriptions. Higher-valency PCVs, especially PCV20, may contribute to preventing pediatric pneumococcal respiratory infections and antibiotic use.

Airport smoking zones: a prospective public health hazard.

Airport smoking zones: a prospective public health hazard.

Pneumococcal Vaccination in Adults: What Can We Learn From Observational Studies That Evaluated PCV13 and PPV23 Effectiveness in the Same Population?

IntroductionFifteen and 20-valent pneumococcal conjugate vaccines (PCV15; PCV20) were recently licensed to prevent pneumococcal disease in adults. In the absence of efficacy or effectiveness data for these new vaccines, studies comparing 23-valent pneumococcal polysaccharide vaccine (PPV23) and PCV13 might help inform decision-making on how to best implement expanded-valency PCVs. Comparing PPV23 and PCV13 is problematic, as no head-to-head clinical trials evaluated efficacy. Comparing effectiveness results across observational studies that vary by population, design, and outcomes is difficult. To address these limitations, we undertook a narrative review of studies that assessed PPV23 and PCV13 vaccine effectiveness (VE) in the same adult populations. MethodsWe conducted a literature search in PubMed and Google Scholar and screened 525 studies using a standardized evaluation framework. ResultsNine studies met inclusion criteria, all from high-income countries. None evaluated invasive pneumococcal disease (IPD) alone. VE against vaccine-type pneumococcal pneumonia ranged from 2 to 6% for PPV23 and 41 to 71% for PCV13. VE against pneumococcal pneumonia or severe pneumococcal disease (IPD or pneumococcal pneumonia) ranged from −10 to 11% for PPV23, 40 to 79% for PCV13, and 39 to 83% for sequential PCV13/PPV23. VE against all-cause pneumonia or lower respiratory tract infection ranged from −8 to 3% for PPV23 and 9 to 12% for PCV13. ConclusionsOverall, PCV13 demonstrated better protection than PPV23 against pneumococcal disease and all-cause respiratory outcomes in the included studies. Where evaluated, sequential PCV13/PPV23 vaccination showed little benefit over PCV13 alone. Results support the use of PCVs to protect against pneumococcal disease and respiratory infections in adults.

Detection of pneumococcus during hospitalization for SARS-CoV-2.

Infections with respiratory viruses [e.g. influenza and respiratory syncytial virus (RSV)] can increase the risk of severe pneumococcal infections. Likewise, pneumococcal coinfection is associated with poorer outcomes in viral respiratory infection. However, there are limited data describing the frequency of pneumococcus and SARS-CoV-2 coinfection and the role of coinfection in influencing COVID-19 severity. We, therefore, investigated the detection of pneumococcus in COVID-19 inpatients during the early pandemic period. The study included patients aged 18 years and older, admitted to the Yale-New Haven Hospital who were symptomatic for respiratory infection and tested positive for SARS-CoV-2 during March-August 2020. Patients were tested for pneumococcus through culture-enrichment of saliva followed by RT-qPCR (to identify carriage) and serotype-specific urine antigen detection (UAD) assays (to identify presumed lower respiratory tract pneumococcal disease). Among 148 subjects, the median age was 65 years; 54.7% were male; 50.7% had an ICU stay; 64.9% received antibiotics; and 14.9% died while admitted. Pneumococcal carriage was detected in 3/96 (3.1%) individuals tested by saliva RT-qPCR. Additionally, pneumococcus was detected in 14/127 (11.0%) individuals tested by UAD, and more commonly in severe than moderate COVID-19 [OR: 2.20; 95% CI: (0.72, 7.48)]; however, the numbers were small with a high degree of uncertainty. None of the UAD-positive individuals died. Pneumococcal lower respiratory tract infection (LRTI), as detected by positive UAD, occurred in patients hospitalized with COVID-19. Moreover, pneumococcal LRTI was more common in those with more serious COVID-19 outcomes. Future studies should assess how pneumococcus and SARS-CoV-2 interact to influence COVID-19 severity in hospitalized patients.

Laboratory diagnostics and pathogenetic therapy of pneumococcal respiratory tract infections

The article presents the results of diagnostic measures and pathogenetic therapy of pneumococcal infections of the respiratory tract. All patients included in the examination underwent X-ray examination or computed magnetic resonance imaging of the paranasal sinuses. 100 % of the subjects were examined for the presence of antibodies to Human gamma herpesvirus 4 (enzyme immunoassay method), the study of blood serum for IgM and IgG and the test for determining the avidity of Ig G antibodies to γ-herpesviruses. The data obtained indicate the effectiveness of pathogenetic therapy in the treatment of pneumococcal infections of the upper respiratory tract.

Association of Nonpharmaceutical Interventions During the COVID-19 Pandemic With Invasive Pneumococcal Disease, Pneumococcal Carriage, and Respiratory Viral Infections Among Children in France

An association between pneumococcal nasopharyngeal carriage and invasive pneumococcal disease (IPD) has been previously established. However, it is unclear whether the decrease in IPD incidence observed after implementation of nonpharmaceutical interventions (NPIs) during the COVID-19 pandemic was associated with concomitant changes in pneumococcal carriage and respiratory viral infections. To assess changes in IPD incidence after the implementation of NPIs during the COVID-19 pandemic and examine their temporal association with changes in pneumococcal carriage rate and respiratory viral infections (specifically respiratory syncytial virus [RSV] and influenza cases) among children in France. This cohort study used interrupted time series analysis of data from ambulatory and hospital-based national continuous surveillance systems of pneumococcal carriage, RSV and influenza-related diseases, and IPD between January 1, 2007, and March 31, 2021. Participants included 11 944 children younger than 15 years in France. Implementation of NPIs during the COVID-19 pandemic. The estimated fraction of IPD change after implementation of NPIs and the association of this change with concomitant changes in pneumococcal carriage rate and RSV and influenza cases among children younger than 15 years. The estimated fraction of change was analyzed using a quasi-Poisson regression model. During the study period, 5113 children (median [IQR] age, 1.0 [0.6-4.0] years; 2959 boys [57.9%]) had IPD, and 6831 healthy children (median [IQR] age, 1.5 [0.9-3.9] years; 3534 boys [51.7%]) received a swab test. Data on race and ethnicity were not collected. After NPI implementation, IPD incidence decreased by 63% (95% CI, -82% to -43%; P < .001) and was similar for non-13-valent pneumococcal conjugate vaccine serotypes with both high disease potential (-63%; 95% CI, -77% to -48%; P < .001) and low disease potential (-53%; 95% CI, -70% to -35%; P < .001). The overall pneumococcal carriage rate did not significantly change after NPI implementation (-12%; 95% CI, -37% to 12%; P = .32), nor did the carriage rate for non-PCV13 serotypes with high disease potential (-26%; 95% CI, -100% to 52%; P = .50) or low disease potential (-7%; 95% CI, -34% to 20%; P = .61). After NPI implementation, the estimated number of influenza cases decreased by 91% (95% CI, -74% to -97%; P < .001), and the estimated number of RSV cases decreased by 74% (95% CI, -55% to -85%; P < .001). Overall, the decrease in influenza and RSV cases accounted for 53% (95% CI, -28% to -78%; P < .001) and 40% (95% CI, -15% to -65%; P = .002) of the decrease in IPD incidence during the NPI period, respectively. The decrease in IPD incidence was not associated with pneumococcal carriage, with carriage accounting for only 4% (95% CI, -7% to 15%; P = .49) of the decrease. In this cohort study of data from multiple national continuous surveillance systems, a decrease in pediatric IPD incidence occurred after the implementation of NPIs in France; this decrease was associated with a decrease in viral infection cases rather than pneumococcal carriage rate. The association between pneumococcal carriage and IPD was potentially modified by changes in the number of RSV and influenza cases, suggesting that interventions targeting respiratory viruses, such as immunoprophylaxis or vaccines for RSV and influenza, may be able to prevent a large proportion of pediatric IPD cases.

WCK 1152, WCK 1153: Discovery and structure activity relationship for the treatment of resistant pneumococcal and staphylococcal respiratory infections

Novel antibacterial agents needed constantly to counter the ever emergent resistance development to commercially available drugs; one of the effective synthetic antibacterial classes is fluoroquinolone (FQ). This study includes structure activity relationship based design and synthesis of novel fluoroquinolone molecules active against resistant pathogens bearing mutations of DNA gyrase and/or topoisomerase IV which also express efflux pumps. Here, series of compounds were prepared by treating 1-cyclopropyl-6,7-difluoro-8-methoxy-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid as a core with various 4-substituted-3,3-dialkyl piperidines as side chains, through conventional synthetic approaches. Subsequently, antibacterial activities of these fluoroquinolones were examined against Streptococcus pneumoniae, SPN 5844 (Moxi resistant DNA gyrase and topo IV mutant) and SPN 706 (FQ efflux positive). The current manuscript covers >50 examples of fluoroquinolone NCEs, amongst 20 NCEs have shown MIC in the range of (0.4 to >6.25 μg/ml) for SPN 5844 and (0.1–12.5 μg/ml) for SPN 706 strains. During the course of this study; WCK 919, comprising two chiral isomers; WCK 1152 and WCK 1153 were emerged as lead among the different series synthesized. Advance studies suggested either WCK 1152 or WCK 1153 are the worthy candidates for further clinical developments for respiratory infections caused by resistant pneumococci and staphylococci. However, on the basis of in house preclinical work, WCK 1152 had been selected for phase-1 domestic clinical trials.

Children with Pneumonia Caused by &amp;lt;i&amp;gt;Streptococcus pneumoniae&amp;lt;/i&amp;gt; Resistance Analysis and Clinical Features

Objective: To analyze the causes of childhood pneumonia Streptococcus pneumoniae resistance and clinical characteristics, and provide a basis for better and timely clinical therapy, and medication to reduce blindness. Methods: MIC method in our hospital 114 under 2020 pediatric pneumococcal respiratory infection in children with lower respiratory tract specimens were isolated antimicrobial susceptibility testing, and analyzed retrospectively. Results: 84 male children, 30 female children, the largest of which 9 years old, the youngest two months, infants less than 1 year old, 90 people; suffering from bronchial pneumonia, 90 cases, 21 cases of pneumonia, wheezing, 3 cases of bronchitis, the average length of stay for about a week; improved in 79 cases, 33 cases were cured, 2 cases transferred to higher level hospitals. All children with throat congestion, swollen tonsils, lung breath sounds rough, smell and moist rales. 114 penicillin-resistant streptococcus pneumoniae was 64.9%, erythromycin 97.4%, clindamycin 86.8%, tetracycline 87.7%, trimethoprim-sulfamethoxazole 82.5%, amoxicillin 21.9%, cefotaxime 49.1%, chloramphenicol 10.5%, was not found to levofloxacin and vancomycin. Conclusion: Penicillin, erythromycin, and clindamycin are not as pneumococcal pneumonia in children experience preferred medication in children less than one year old child could easily cause lung chain streptococcus pneumonia. Therefore, the antimicrobial resistance of Streptococcus pneumoniae analysis provides a reference for experienced clinicians to adjust medication.

PHARMACOECONOMIC EVALUATION OF ANTI-PNEUMOCOCCAL VACCINATION IN RISK GROUPS FOR THE PREVENTION OF COMMUNITY-ACQUIRED PNEUMONIA AMONG ADULTS IN THE ASTRAKHAN REGION

The aim. To evaluate the economic efficiency and the choice of the vaccination strategy in the respiratory pneumococcal infection risk groups among the adult population of the Astrakhan region.Materials and methods. The data for the period of 2015 - 2018 were analyzed on the number of registered diseases in the patients living in the service area of the medical organizations (Form No. 12, Federal State Statistics Service Orders No. 591, dated 27 November, 2015; No. 679, dated 22 November, 2019). The following working directives were studied: the base medical examination documentation submitted by medical institutions (Form No. 030/y “Dispensary Monitoring Checklist”; lists of the persons subjected to medical observation in the reporting year; Orders of the Ministry of Health of the Russian Federation: No. 1344, dated 12 December, 2012; No. 173n, dated 29 March, 2019). Statistical materials of the territorial fund for compulsory medical insurance of the Astrakhan region on the payment of medical care to 12,970 patients who had had pneumonia in 2015-2018, were analyzed. The financial support of vaccination based on the results of tenders for the procurement of pneumococcal vaccines organized by the regional Ministry of Health, was considered. The calculations were carried out in accordance with the guidelines of “Cost-effectiveness of vaccine prophylaxis” (Methodological guidelines 3.3.1878-04, dated 04.03.2004).Results. The prospective calculation of the vaccination cost showed that the benefits of vaccination with pneumococcal conjugate vaccine Prevenar13 (PCV13) and pneumococcal polyvalent vaccine Pneumovax 23 (PPV23) with a 95% vaccination coverage, are recorded after 2 years. The economic benefit of vaccination by reducing the possible number of pneumonias at the end of 2028 will be 968.2 million rubles.Conclusion. The economic feasibility of vaccine prophylaxis of the adult contingent with an increased risk of developing pneumococcal infection has been established. The sequential strategy of PCV13 and PPV23 application provides the most effective localization of pneumococcal infection. The research results should be widely introduced into the long-term plans for vaccination and healthcare practice in the Astrakhan region.

Lactobacillus casei CRL431 modulates hemostatic activation induced by protein malnourishment and pneumococcal respiratory infection.

Previously, we demonstrated that Lactobacillus casei CRL431, a well-known immunomodulatory bacterium, beneficially regulates coagulation activation, fibrin formation in lung, and the pro-inflammatory state induced by protein malnourishment and pneumococcal infection. In this study, we deepen in the understanding of the mechanisms involved in the immunoregulatory activity of L. casei CRL431 during a nutritional repletion process by evaluating (a) platelet and endothelial activation, (b) tissue factor (TF) expression, and (c) protease-activated receptor (PAR) activation in an experimental bacterial respiratory infection model in malnourished mice. Our findings demonstrate for the first time that the repletion diet supplemented with L. casei CRL431 was effective to normalize platelet counts in blood, modulate platelet activation and their recruitment into the lung, and regulate local and systemic TF expression and endothelial activation, which were affected by malnourishment. Streptococcus pneumoniae challenge induced local and systemic increase of platelet counts, PARs activation, P-selectin and TF expression, as well as endothelial activation in both well-nourished and malnourished mice. Malnourished animals evidenced the highest alterations of the parameters evaluated while the mice fed with the probiotic bacterium had similar behavior to normal controls but with lower PAR activation in lung. These results demonstrate that supplementation of repletion diet with L. casei CRL431 is effective to modulate alterations induced by malnourishment and pneumococcal infection, restraining coagulation activation, the inflammatory process, and lung damage. These observations contribute to set the basis for the application of probiotic functional foods to modulate the inflammation-hemostasis interactions altered by malnourishment or bacterial respiratory infections. KEY POINTS: • Pneumococcal infection increases pro-coagulant state induced by protein malnourishment. • Repletion with L. casei CRL431 modulates platelet, TF, and endothelial activation. • L. casei CRL431 improves immune-coagulative response in protein malnourishment.

Strategy using a new antigenic test for rapid diagnosis of Streptococcus pneumoniae infection in respiratory samples from children consulting at hospital

BackgroundDespite vaccination programs, Streptococcus pneumoniae remains among the main microorganisms involved in bacterial pneumonia, notably in terms of severity. The prognosis of pneumococcal infections is conditioned in part by the precocity of the diagnosis. The aim of this study was to evaluate the impact of a Rapid Diagnostic Test (RDT) targeting cell wall polysaccharide of Streptococcus pneumoniae and performed directly in respiratory samples, on the strategy of diagnosis of respiratory pneumococcal infections in children.ResultsUpper-respiratory tract samples from 196 children consulting at hospital for respiratory infection were tested for detecting S. pneumoniae using a newly-designed RDT (PneumoResp, Biospeedia), a semi-quantitative culture and two PCR assays. If positive on fluidized undiluted specimen, the RDT was repeated on 1:100-diluted sample. The RDT was found highly specific when tested on non-S. pneumoniae strains. By comparison to culture and PCR assays, the RDT on undiluted secretions exhibited a sensitivity (Se) and negative predictive value (NPV) of more than 98%. By comparison to criteria of S. pneumoniae pneumonia combining typical symptoms, X-ray image, and culture ≥107 CFU/ml, the Se and NPV of RDT on diluted specimens were 100% in both cases.ConclusionsIn case of negative result, the excellent NPV of RDT on undiluted secretions allows excluding S. pneumoniae pneumonia. In case of positive result, the excellent sensitivity of RDT on diluted secretions for the diagnosis of S. pneumoniae pneumonia allows proposing a suitable antimicrobial treatment at day 0.

G-CSFR antagonism reduces neutrophilic inflammation during pneumococcal and influenza respiratory infections without compromising clearance

Excessive neutrophilic inflammation can contribute to the pathogenesis of pneumonia. Whilst anti-inflammatory therapies such as corticosteroids are used to treat excessive inflammation, they do not selectively target neutrophils and may compromise antimicrobial or antiviral defences. In this study, neutrophil trafficking was targeted with a granulocyte-colony stimulating factor receptor monoclonal antibody (G-CSFR mAb) during Streptococcus pneumoniae (serotype 19F) or influenza A virus (IAV, strain HKx31) lung infection in mice. Firstly, we demonstrated that neutrophils are indispensable for the clearance of S. pneumoniae from the airways using an anti-Ly6G monoclonal antibody (1A8 mAb), as the complete inhibition of neutrophil recruitment markedly compromised bacterial clearance. Secondly, we demonstrated that G-CSF transcript lung levels were significantly increased during pneumococcal infection. Prophylactic or therapeutic administration of G-CSFR mAb significantly reduced blood and airway neutrophil numbers by 30–60% without affecting bacterial clearance. Total protein levels in the bronchoalveolar lavage (BAL) fluid (marker for oedema) was also significantly reduced. G-CSF transcript levels were also increased during IAV lung infection. G-CSFR mAb treatment significantly reduced neutrophil trafficking into BAL compartment by 60% and reduced blood neutrophil numbers to control levels in IAV-infected mice. Peak lung viral levels at day 3 were not altered by G-CSFR therapy, however there was a significant reduction in the detection of IAV in the lungs at the day 7 post-infection phase. In summary, G-CSFR signalling contributes to neutrophil trafficking in response to two common respiratory pathogens. Blocking G-CSFR reduced neutrophil trafficking and oedema without compromising clearance of two pathogens that can cause pneumonia.

Therapeutic Synergy Between Antibiotics and Pulmonary Toll-Like Receptor 5 Stimulation in Antibiotic-Sensitive or -Resistant Pneumonia.

Bacterial infections of the respiratory tract constitute a major cause of death worldwide. Given the constant rise in bacterial resistance to antibiotics, treatment failure is increasingly frequent. In this context, innovative therapeutic strategies are urgently needed. Stimulation of innate immune cells in the respiratory tract [via activation of Toll-like receptors (TLRs)] is an attractive approach for rapidly activating the body's immune defenses against a broad spectrum of microorganisms. Previous studies of the TLR5 agonist flagellin in animal models showed that standalone TLR stimulation does not result in the effective treatment of pneumococcal respiratory infection but does significantly improve the therapeutic outcome of concomitant antibiotic treatment. Here, we investigated the antibacterial interaction between antibiotic and intranasal flagellin in a mouse model of pneumococcal respiratory infection. Using various doses of orally administered amoxicillin or systemically administered cotrimoxazole, we found that the intranasal instillation of flagellin (a dose that promotes maximal lung pro-inflammatory responses) induces synergistic rather than additive antibacterial effects against antibiotic–susceptible pneumococcus. We next set up a model of infection with pneumococcus that is resistant to multiple antibiotics in the context of influenza superinfection. Remarkably, the combination of amoxicillin and flagellin effectively treated superinfection with the amoxicillin-resistant pneumococcus since the bacterial clearance was increased by more than 100-fold compared to standalone treatments. Our results also showed that, in response to flagellin, the lung tissue generated an innate immune response even though it had been damaged by the influenza virus and pneumococcal infections. In conclusion, we demonstrated that the selective boosting of lung innate immunity is a conceptually advantageous approach for improving the effectiveness of antibiotic treatment and fighting antibiotic-resistant bacteria.

Lactobacillus casei CRL 431 improves endothelial and platelet functionality in a pneumococcal infection model.

Streptococcus pneumoniae is able to activate coagulation and induce platelet aggregation, both of which are typical responses to systemic inflammation. The interactions between inflammation and coagulation and between soluble adhesion molecules and endothelial cells are important in the pathogenesis of an unbalanced haemostatic system. Therefore, an exaggerated and/or insufficiently controlled haemostatic activity may appreciably contribute to the severity of the disease. The aim of the present study was to evaluate the effect of the oral administration of Lactobacillus casei CRL 431 on platelet and endothelial activation mechanisms in a respiratory pneumococcal infection model in mice. S. pneumoniae induced an increase in platelet counts and enhanced the expression of P-selectin in control group, with higher endothelial activation in lung shown by the increase in von Willebrand factor (vWF) and vascular cell adhesion molecule 1 (VCAM-1) expression. Also, infection induced a decrease in CXCR-4 leukocytes, increased expression in annexinV and cell death at the pulmonary level and decreased antithrombin levels in bronchoalveolar lavage. In contrast, L. casei mice restored platelet counts, favoured faster P-selectin expression, lower vWF levels and VCAM-1 expression than control group. Also, L. casei induced higher levels of annexinV expression and lower cell death in the lung. Moreover, it was able to modulate antithrombin levels within the normal range, which would indicate lower coagulation activation and a protective effect locally exerted by L. casei. In this work, the ability of L. casei to favourably modulate platelet and endothelial functionality during a pulmonary infection with S. pneumoniae was demonstrated. Our findings offer a promising perspective for the use of this probiotic strain in the prevention of thrombotic complications associated with pneumococcal pneumonia, especially in at-risk patients. In addition, the use of L. casei would provide novel alternatives for the prevention and treatment of thrombosis associated with various diseases.

Efficacy of 13-valent pneumococcal conjugate vaccine in healthcare workers

Aim. To establish the efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) for healthcare workers protection from occupational acquired infection and impact of healthcare staff vaccination on the risk of transmission to patients. Materials and methods. Healthcare personnel (n=157 of whom 105 critical care department staff) and 1770 patients of that critical care department observed. Healthcare workers received PCV13. Infections caused by Str. pneumoniae, respiratory infections regardless of etiology, work absenteeism in healthcare workers during 12 month before and after vaccination assessed. In the same time monitoring of hospital-acquired infections in patients of critical care department performed. Statistical analysis was done using SPSS 24, relationships were assessed by rate ratio, Cox regression, logistic regression and Kaplan-Meier estimator. Results. Healthcare workers' vaccine coverage in critical care department was 97.2%. In healthcare personnel the rate of all pneumococcal infections, asymptomatic carriage of Str. pneumoniae and respiratory pneumococcal infections were decreased after vaccination by 2.1, 2.2 and 2.1 times accordingly. The rate of respiratory infections regardless of etiology was decreased by 30%, р

An Adjuvant That Increases Protective Antibody Responses to Polysaccharide Antigens and Enables Recall Responses.

Protection against encapsulated bacteria can be elicited using polysaccharide vaccines. These antigens often behave as T-cell-independent type 2 antigens (TI-2 Ags). However, TI-2 Ags, including pneumococcal polysaccharides, often elicit weak immunoglobulin G (IgG) responses and are refractive to boosting. Conjugate vaccines have not completely overcome this challenge and hence, alternative strategies are required to enhance polysaccharide vaccine responses. Herein, we describe an adjuvant consisting of a Toll-like receptor and C-type lectin receptor agonist pairing that significantly increases primary immunoglobulin M and IgG responses to TI-2 Ags as well as enables significant boosting when coadministered with polysaccharide vaccines. Consistent with this, the adjuvant significantly increased the generation of both TI-2 memory B cells and long-lived antibody secreting cells. Adjuvant effects were highly dependent on B-cell-intrinsic MyD88, but not Trif expression. Importantly, coadministration of the adjuvant with the Pneumovax vaccine significantly increased the protective efficacy of vaccination in a lethal challenge mouse model of pneumococcal respiratory infection. Collectively, these data provide evidence that B-cell-directed adjuvants have promise in significantly improving the quality and quantity of serologic and B-cell memory responses to clinically relevant polysaccharide vaccines.

Toll-Interleukin 1 Receptor Domain-Containing Adaptor Protein 180L Single-Nucleotide Polymorphism Is Associated With Susceptibility to Recurrent Pneumococcal Lower Respiratory Tract Infections in Children.

Lower respiratory tract infections (LRTI) are often caused by Streptococcus pneumoniae (Spn) and can be recurrent in 8% of children older than 2 years of age. Spn is recognized by pattern-recognition receptors (PRRs) of the innate immune system, in particular toll-like receptors (TLRs) 2 and 4. To assess whether a defect somewhere along this TLR signaling pathway increases susceptibility to recurrent pneumococcal LRTI, we conducted a prospective case–control study with 88 healthy individuals and 45 children with recurrent LRTI aged 2–5 years old. We examined cell surface expression of TLR2 and TLR4, as well as eight genetic variants of these receptors or associated co-receptors TLR1 and TLR6. Interleukin-6 production was measured after whole blood stimulation assays with specific agonists and heat-killed Spn. Our findings reveal that single-nucleotide polymorphisms within toll-interleukin 1 receptor domain-containing adaptor protein (TIRAP) alone or in combination with TLR1 N248S, TLR1 I602S, or TLR6 S249P polymorphisms contributes to various degree of susceptibility to recurrent pneumococcal LRTI in children by modulating the inflammatory response. In that respect, carriage of the TIRAP S180L heterozygous trait increases the likelihood to protect against pneumococcal LRTI, whereas children carrying the mutant homozygous TIRAP 180L polymorphism might be more likely susceptible to recurrent pneumococcal LRTI.

Evaluation of the Role of stat3 in Antibody and TH17-Mediated Responses to Pneumococcal Immunization and Infection by Use of a Mouse Model of Autosomal Dominant Hyper-IgE Syndrome.

Loss-of-function mutations in the signal transducer and activator of transcription 3 gene (stat3) result in autosomal dominant hyper-IgE syndrome (AD-HIES), a condition in which patients have recurrent debilitating infections, including frequent pneumococcal and staphylococcal pneumonias. stat3 mutations cause defective adaptive TH17 cellular responses, an immune mechanism believed to be critical for clearance of pneumococcal colonization and diminished antibody responses. Here we wished to evaluate the role of stat3 in the clearance of pneumococcal carriage and immunity using mice with a stat3 mutation recapitulating AD-HIES. We show here that naive AD-HIES mice have prolonged nasal carriage of pneumococcus compared to WT mice. Mutant and wild-type mice were then immunized with a pneumococcal whole-cell vaccine (WCV) that provides TH17-mediated protection against pneumococcal colonization and antibody-mediated protection against pneumonia and sepsis. WCV-immunized AD-HIES mice made significantly less pneumococcus-specific interleukin-17A (IL-17A) and antibody than WT mice. The WCV-elicited protection against colonization was abrogated in AD-HIES mice, but immunization with WCV still protected AD-HIES mice against aspiration pneumonia/sepsis. Taken together, our results suggest that impaired clearance of nasopharyngeal carriage due to poor adaptive IL-17A responses may contribute to the increased rates of pneumococcal respiratory infection in AD-HIES patients.

Efficacy of 13-valent pneumococcal conjugate vaccine in healthcare workers.

To establish the efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) for healthcare workers protection from occupational acquired infection and impact of healthcare staff vaccination on the risk of transmission to patients. Healthcare personnel (n=157 of whom 105 critical care department staff) and 1770 patients of that critical care department observed. Healthcare workers received PCV13. Infections caused by Str. pneumoniae, respiratory infections regardless of etiology, work absenteeism in healthcare workers during 12 month before and after vaccination assessed. In the same time monitoring of hospital-acquired infections in patients of critical care department performed. Statistical analysis was done using SPSS 24, relationships were assessed by rate ratio, Cox regression, logistic regression and Kaplan-Meier estimator. Healthcare workers' vaccine coverage in critical care department was 97.2%. In healthcare personnel the rate of all pneumococcal infections, asymptomatic carriage of Str. pneumoniae and respiratory pneumococcal infections were decreased after vaccination by 2.1, 2.2 and 2.1 times accordingly. The rate of respiratory infections regardless of etiology was decreased by 30%, р&lt;0.05. Cumulative percent of subjects without pneumococcal respiratory infections during 12 month was 87.9 before and 94.3 after vaccination, р=0.015. Work absenteeism due to respiratory infections was reduced. In patients of critical care department decreasing of all respiratory infections by 58%, pneumococcal respiratory infections by 66%, hospital acquired pneumonias by 46% were seen, р&lt;0.05. Healthcare personnel vaccination with PCV 13 is effective in protection from occupational acquired pneumococcal respiratory infections and asymptomatic carriage and promotes decreasing of hospital acquired infections among patients.