Search

The circadian clock is a cell-autonomous process that regulates daily internal rhythms by interacting with environmental signals. Reports across species show that infection can alter the expression of circadian genes; however, in teleosts, these effects are influenced by light exposure. Currently, no reports analyze the direct effects of bacterial exposure on the zebrafish clock. Using zebrafish Z3 cells, we demonstrate that exposure to heat-killed Streptococcus pneumoniae (HK-Spn) augments the expression of core repressive factors in a light- and time-dependent manner. In constant darkness, HK-Spn highly upregulated cry1a, per3, and per1b expression. In the presence of light, HK-Spn exposure rapidly and strongly upregulated per2 and cry1a, and this was proportionally increased with light intensity. The combinatorial effect of light and HK-Spn on per2 and cry1a was not duplicated with H2O2, a known byproduct of light exposure. However, the ROS inhibitor N-acetyl cysteine was sufficient to block HK-Spn augmentation of per2, cry1a, and per3. These findings demonstrate that exposure to an inactive bacteria influences the expression of zebrafish clock genes under different light conditions.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Most pneumococcal disease occurs among infants and older adults and is thought to be driven by the transmission of Streptococcus pneumoniae from young children to these vulnerable age groups. However, pneumococcal disease outbreaks also affect non-elderly adults living or working in congregate, close-contact settings. Little is known about pneumococcal carriage in such populations. From July to November 2020, we collected saliva from low-income adult farmworkers in Monterey County, California, and tested for pneumococcal carriage following culture enrichment via quantitative PCR assays targeting the pneumococcal lytA and piaB genes. Participants were considered to carry pneumococci if lytA and piaB cycle threshold values were both below 40. Among 1,283 participants enrolled in our study, 117 (9.1%) carried pneumococci. Carriers tended more often than non-carriers to be exposed to children aged 2-4 and >4 persons per bedroom vs ≤2 persons per bedroom]. Household overcrowding remained associated with increased risk of carriage among participants not exposed to children aged 2 vs ≤2 persons per bedroom]. Exposure to children aged

BACKGROUND: Streptococcus pneumoniae is the most common bacterial cause of community acquired pneumonia and the acute respiratory distress syndrome (ARDS). Some clinical trials have demonstrated a beneficial effect of corticosteroid therapy in community acquired pneumonia, COVID-19, and ARDS, but the mechanisms of this benefit remain unclear. The primary objective of this study was to investigate the effects of corticosteroids on the pulmonary biology of pneumococcal pneumonia in a mouse model. A secondary objective was to identify shared transcriptomic features of pneumococcal pneumonia and steroid treatment in the mouse model and clinical samples. METHODS: We carried out comprehensive physiologic, biochemical, and histological analyses in mice to identify the mechanisms of lung injury in Streptococcus pneumoniae with and without adjunctive steroid therapy. We also studied lower respiratory tract gene expression from a cohort of 15 mechanically ventilated patients (10 with Streptococcus pneumoniae and 5 controls) to compare with the transcriptional studies in the mice. RESULTS: In mice with pneumonia, dexamethasone in combination with ceftriaxone reduced (1) pulmonary edema formation, (2) alveolar protein permeability, (3) proinflammatory cytokine release, (4) histopathologic lung injury score, and (5) hypoxemia but did not increase bacterial burden. Transcriptomic analyses identified effects of steroid therapy in mice that were also observed in the clinical samples. CONCLUSIONS: In combination with appropriate antibiotic therapy in mice, treatment of pneumococcal pneumonia with steroid therapy reduced hypoxemia, pulmonary edema, lung permeability, and histologic criteria of lung injury, and also altered inflammatory responses at the protein and gene expression level. The transcriptional studies in patients suggest that the mouse model replicates some of the features of pneumonia in patients with Streptococcus pneumoniae and steroid treatment. Overall, these studies provide evidence for the mechanisms that may explain the beneficial effects of glucocorticoid therapy in patients with community acquired pneumonia from Streptococcus Pneumoniae.

Sensory neurons sense pathogenic infiltration to drive innate immune responses, but their role in humoral immunity is unclear. Here, using mouse models of Streptococcus pneumoniae infection and Alternaria alternata asthma, we show that sensory neurons are required for B cell recruitment and antibody production. In response to S. pneumoniae, sensory neuron depletion increases bacterial burden and reduces B cell numbers, IgG release, and neutrophil stimulation. Meanwhile, during A. alternata-induced airway inflammation, sensory neuron depletion decreases B cell population sizes, IgE levels, and asthmatic characteristics. Mechanistically, during bacterial infection, sensory neurons preferentially release vasoactive intestinal polypeptide (VIP). In response to asthma, sensory neurons release substance P. Administration of VIP into sensory neuron-depleted mice suppresses bacterial burden, while VIPR1 deficiency increases infection. Similarly, exogenous substance P delivery aggravates asthma in sensory neuron-depleted mice, while substance P deficiency ameliorates asthma. Our data, thus demonstrate that sensory neurons release select neuropeptides which target B cells dependent on the immunogen.

Invasive pneumococcal disease (IPD) is a major cause of morbidity and mortality worldwide, particularly in the pediatric population (children and infants), with high rates of hospitalization and death. This study aimed to create and validate a classifier for Streptococcus pneumoniae serotyping using Fourier-transform infrared (FT-IR) spectroscopy as a rapid alternative to the classical serotyping technique. In this study, a database comprising 76 clinical isolates, including 18 serotypes (predominantly serotypes 19A, 6C, and 3) of S. pneumoniae from pediatric patients with IPD, was tested at a tertiary pediatric hospital in southern Brazil during 2016–2023. All isolates were previously serotyped using the Quellung reaction, and 843 FT-IR spectra were obtained to create a classification model using artificial neural network (ANN) machine learning. After the creation of this classifier, internal validation was performed using 384 spectra as the training dataset and 459 as the testing dataset, resulting in a predictive accuracy of 98% for serotypes 19A, 6, 3, 14, 18C, 22F, 23A, 23B, 33F, 35B, and 9N. In this dataset, serotypes 10A/16F, 15ABC, and 7CF could not be differentiated and were, therefore, grouped as labels. FT-IR is a promising, rapid, and low-cost method for the phenotypic classification of S. pneumoniae capsular serotypes. This methodology has significant implications for clinical and epidemiological practice, improving patient management, monitoring infection trends, and developing new vaccines. [ABSTRACT FROM AUTHOR]

Background: Populations affected by humanitarian crises likely experience high burdens of pneumococcal disease. Streptococcus pneumoniae carriage estimates are essential to understand pneumococcal transmission dynamics and the potential impact of pneumococcal conjugate vaccines (PCV). Over 100 million people are forcibly displaced worldwide, yet here we present only the second pneumococcal carriage estimates for a displaced population. Methods: In October 2019, we conducted a cross-sectional survey among internally displaced people (IDP) living in Digaale, a permanent IDP camp in Somaliland where PCV has not been implemented. We collected nasopharyngeal swab samples from 453 residents which were assessed for presence of pneumococci and serotyped using DNA microarray. Results: We found that pneumococcal carriage prevalence was 36% (95%CI 31–40) in all ages, and 70% (95%CI 64–76) in children under 5. The three most common serotypes were vaccine serotypes 6B, 19F, and 23F. We estimated that the serotypes included in the 10-valent PNEUMOSIL vaccine were carried by 41% (95%CI 33–49) of all pneumococcal carriers and extrapolated that they caused 52% (95%CI 35–70) of invasive pneumococcal disease. We found some evidence that pneumococcal carriage was associated with recent respiratory symptoms, the total number of physical contacts made, and with malnutrition in children under 5. Through linking with a nested contact survey we projected that pneumococcal exposure of children under 2 was predominantly due to contact with children aged 2–5 (39%; 95%CI 31–48) and 6–14 (25%; 95%CI 17–34). Conclusions: These findings suggest considerable potential for direct and indirect protection against pneumococcal disease in Digaale through PCV use in children and potentially adolescents. [ABSTRACT FROM AUTHOR]

Antibiotic resistance is considered a widespread problem with global health implications, leading to increased patient morbidity and impacting the selection of effective antibiotics, consequently influencing patient recovery. This study aimed to assess antibiogram resistance patterns of bacterial records at the Islamic Hospital in Jordan using a retrospective study during the period 2020-2022. A total of 9369 samples obtained from different patients were cultured. Data were processed and analyzed with SPSS v.23.0. The results showed that 2841 (30.3%) samples were positive for bacterial infections. Microbial profiles of positive samples indicated the highest proportion for Escherichia coli, 39%, followed by Klebsiella pneumoniae 12% were the most frequent Gram-negative bacterial isolates, whereas Staphylococcus aureus 13% and Streptococcus pneumoniae 4% were the most common Gram-positive bacterial isolates. Interestingly, multidrug-resistant bacteria comprised 61.7% of the isolates. The percentage of multi-drug resistance in isolates of Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae was 68.7%, 73.1%, and 72%, respectively. Escherichia coli was most resistant to ampicillin (89%) and most sensitive to imipenem (100%). Klebsiella pneumoniae showed a 100% sensitivity to meropenem but 49% resistance to ceftriaxone. Pseudomonas aeruginosa was the most sensitive to amikacin and colistin (86% and 100%, respectively). Staphylococcus aureus isolates have resistance rates of 78% for ciprofloxacin, 35.6% for clindamycin and an overall resistance rate of 68.7%. These findings indicate multiple resistance for isolated bacteria. Therefore, antimicrobial resistance should be monitored continuously, and patients should be treated based on anti-microbial susceptibility tests. [ABSTRACT FROM AUTHOR]

The present study evaluates the physicochemical attributes, antibacterial efficacy, and antioxidant capacities of four distinct varieties of honey from the West Bank region of Palestine: Assal Barsem (Medicago sativa) AB, Assal Morar (Centaurea dumulosa Boiss) AM, Assal Horfesh (Silybum) AH, and Assal Sader (Ziziphus spina-christi) AS. The analysis encompassed parameters such as pH, electrical conductivity, Total Flavonoid Content (TFC), and Total Phenolic Content (TPC). Furthermore, the antioxidant potential was gauged through Total Antioxidant Capacity (TAC) determination and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. In addition, the antibacterial effectiveness of the honeys was measured against a spectrum of bacterial strains including Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, Haemophilus influenzae, and Bacillus subtilis, utilizing minimum inhibitory concentration (MIC) and Minimum Bactericidal Concentrations (MBC). The outcomes of the physicochemical analysis adhered to the quality benchmarks outlined by the European Union Commission and the Codex Alimentarius Commission. The MIC and MBC values exhibited notable variance across the tested honey varieties, with MIC values ranging from 0.024% w/w to 1.56% w/w, and MBC values ranging from 0.048% w/w to 3.15% w/w. Particularly, AH demonstrated superior efficacy against all seven bacterial strains, with MIC values spanning from 0.1 to 0.6% w/w, and MBC values ranging from 0.3% w/w to 0.8% w/w. Staphylococcus aureus and Escherichia coli were notably susceptible to all honey samples. Collectively, our findings underscore the therapeutic potential of Palestinian honey varieties, highlighting their multifaceted health-promoting attributes. Further exploration is warranted to elucidate the mechanistic underpinnings of bioactive constituents and explore their potential applications in healthcare. [ABSTRACT FROM AUTHOR]

Background: Healthcare settings may amplify transmission of respiratory pathogens, however empirical evidence is lacking. We aimed to describe the spectrum and distribution of respiratory pathogens among healthcare workers in eastern China. Methods: Healthcare workers were recruited from October 2020 to November 2021 in Jiangsu province. Participants were interviewed regarding demographic and hospital-based protective measures. Thirty-seven common respiratory pathogens were tested using real-time PCR/RT-PCR (Probe qPCR). The role of demographic and hospital-based protective measures on pathogens colonization using multivariable logistic regression models. Results: Among 316 enrolled healthcare workers, a total of 21 pathogens were detected. In total, 212 (67.1%) healthcare workers had at least one respiratory pathogen; 195 (61.7%) and 70 (22.2%) with a bacterial and viral pathogen. The most commonly detected pathogen was streptococcus pneumoniae (47.5%) followed by Haemophilus influenzae (21.2%). One hundred and five (33.2%) healthcare workers with copathogens had at least two respiratory pathogens. Both bacterial and viral colonization were more common in 2020 compared to 2021. A decreased risk of colonization was seen in participants with infection prevention and control training and suitable hand hygiene. Conclusions: Colonization of respiratory pathogens in healthcare workers from eastern China was high. Differential risk was impacted only by hospital-based protective measures and not demographic factors. [ABSTRACT FROM AUTHOR]

Objectives: Due to disease- or therapy-associated immunosuppression, oncological patients suffer from significantly higher morbidity and mortality due to infections transmitted by respiratory pathogens such as Streptococcus pneumoniae and influenza virus. Although the German Standing Committee on Vaccination (STIKO) provides specific recommendations for vaccination against these pathogens, there is no data on vaccination rates in this high-risk population. Methods: Data from the interventional EVO study were analyzed to provide information on vaccination rates against Streptococcus pneumoniae and influenza virus in oncological patients. Numbers presented in this publication summarize baseline and follow-up data of the control group; thus, data were not influenced by the intervention. Results: Data of 370 patients were analyzed; 20.5% of patients were treated for hematological malignancies and 79.5% for solid cancer. 28.1% of patients had received vaccination against influenza and 32.2% against Streptococcus pneumoniae; for the latter only 7.3% according recommendations. While vaccination rates where even lower for patients with thoracic carcinoma (influenza 26.7% and Streptococcus pneumoniae 6.0% according to STIKO recommendations), rates in patients with multiple myeloma were remarkably higher (39.0% and 14.6%). Conclusions: Despite strong recommendations to vaccinate and the clear clinical need to prevent infections in the vulnerable group of oncological patients, only the minority was vaccinated against Streptococcus pneumoniae or influenza, underlining the urgent need for better vaccination strategies in this high-risk population. [ABSTRACT FROM AUTHOR]

Objective This study investigated executive functions (EFs) in young adult survivors of childhood bacterial meningitis (BM). These skills are important for normal development, and their potential vulnerability in early years suggests that childhood BM could affect executive functions in the longer term. Method The adult self-report Behavior Rating Inventory of Executive Function was administered to 474 young adult survivors of childhood BM who participated in the 20|30 Dutch Postmeningitis study. Average scores were compared to population-norm group scores. Subgroup scores were compared according to causative pathogen and age at onset. Results Young adult survivors of childhood BM scored lower on overall metacognition than the age-matched population norm group. Young adult survivors of childhood BM caused by Streptococcus pneumoniae , S. agalactiae , or Escherichia coli had lower scores than cases caused by Neisseria meningitidis. Survivors with age-at-onset below 12 months had a higher (worse) overall EF score than survivors with age-at-onset above 12 months. Conclusions Young adult survivors of childhood BM experience difficulties in EF. However, most of the self-reported EF scores were within the norm. Future studies need to additionally assess EF in adult survivors of childhood BM using performance-based tests. [ABSTRACT FROM AUTHOR]

We report an unusual case of recurrent parotitis caused by Streptococcus pneumoniae in a 23-year-old female university student with poor oral hygiene and vitamin D insufficiency. Despite multiple antibiotic courses, symptoms persisted, highlighting the complexity of diagnosis and management in such cases. Diagnostic workup included blood tests, which showed normal inflammatory markers, and magnetic resonance sialography, revealing two intraductal stones in the right parotid gland. Microbiological culture of purulent discharge from the parotid duct identified S. pneumoniae. The patient was successfully treated with levofloxacin, guided by culture sensitivity, along with parotid massage and hydration. Pneumococcal vaccination was recommended as a preventive measure, with no reported side effects after the first dose. This case underscores the importance of considering S. pneumoniae, an uncommon pathogen in immunocompetent adults, as a potential cause of parotitis. It emphasises the role of comprehensive diagnostics, including imaging and microbiology, in managing recurrent parotitis, especially when typical treatments fail. The case also highlights the potential interplay between oral hygiene, vitamin D status, and susceptibility to unusual pathogens in parotid infections. [ABSTRACT FROM AUTHOR]

Rapid identification of causative bacteria in treatment of acute otitis media (AOM) is of paramount importance for appropriate antibiotic use. This prospective observational study was conducted in 15 hospitals and clinics in Japan between 2018 and 2020. A new rapid antigen test kit (AOS-116), which simultaneously detects antigens for Streptococcus pneumoniae (Sp) and Haemophilus influenzae (Hi), was applied for middle ear fluids (MEFs) and nasopharyngeal secretions (NPSs) in patients with moderate to severe AOM. We investigated relationship between the results of rapid test, severity at initial visit, and clinical course. Regarding performance accuracy based on culture results, AOS-116 showed 1) high (>80%) sensitivity, specificity, and negative predictive value (NPV) in MEFs for both antigens, 2) high sensitivity, specificity, and positive predictive value (PPV) in NPSs for Hi antigen, and 3) high specificity, and PPV in NPSs for Sp antigen. Regarding predictive value of nasopharyngeal culture and antigen detection for causative middle ear pathogens, similar results were observed between AOS-116 and culture, which was characterized with high sensitivity and NPV for both pathogens. MEFs/NPSs positive for Hi antigen were significantly associated with eardrum findings, and severity. MEFs/NPSs positive for pneumococcal antigen were significantly associated with severity of otalgia, fever, and otorrhea. Among patients with prior antimicrobial treatment, improvement tended to be slower in cases positive for Hi than in cases negative. The rapid antigen detection test is useful as a decision-making tool for prescribing antimicrobial agents and may play an important role in promoting appropriate antimicrobial use. [ABSTRACT FROM AUTHOR]

Purpose: The COVID-19 pandemic has altered the infection dynamics of numerous pathogens. This study aimed to elucidate its impact on Streptococcus pneumoniae (S. pneumoniae) infections in children with community acquired pneumonia (CAP). Methods: A retrospective analysis was conducted in pediatric CAP patients admitted before (2018–2019) and during (2020–2022) the COVID-19 pandemic. The epidemiology and antimicrobial resistance (AMR) patterns of S. pneumoniae were compared to reveal the impact of the pandemic. Results: A total of 968 S. pneumoniae-associated pediatric CAP patients were enrolled. Although the positivity rate and gender of patients were stable across both periods, the age notably increased in 2021 and 2022. Additionally, significant changes were observed in the co-infections with several pathogens and the resistance rates to certain antibiotics during the COVID-19 pandemic. The resistance rate to clindamycin and quinupristin-dalfopristin increased, whereas the resistance rate to tetracycline, trimethoprim-sulfamethoxazole, telithromycin, and proportion of multi-drug resistant isolates decreased. The number of S. pneumoniae strains and resistant isolates exhibited similar seasonal patterns in 2018 and 2019, peaking in November or December with another minor peak in March or April. During the COVID-19 pandemic, there was a sharp decrease in February 2020 and no resurgence was observed at the end of 2022. Additionally, the minor peak was absent in 2020 and shifted to other months in 2021 and 2022. Conclusions: The COVID-19 pandemic has markedly altered the infection spectrum of S. pneumoniae in pediatric CAP patients, as evidenced by shifts in the age of patients, respiratory co-infections, AMR patterns, and seasonal trends. [ABSTRACT FROM AUTHOR]

The pulmonary epithelial glycocalyx is rich in glycosaminoglycans such as hyaluronan and heparan sulfate. Despite their presence, the importance of these glycosaminoglycans in bacterial lung infections remains elusive. To address this, we intranasally inoculated mice with Streptococcus pneumoniae in the presence or absence of enzymes targeting pulmonary hyaluronan and heparan sulfate, followed by characterization of subsequent disease pathology, pulmonary inflammation, and lung barrier dysfunction. Enzymatic degradation of hyaluronan and heparan sulfate exacerbated pneumonia in mice, as evidenced by increased disease scores and alveolar neutrophil recruitment. However, targeting epithelial hyaluronan in combination with S. pneumoniae infection further exacerbated systemic disease, indicated by elevated splenic bacterial load and plasma concentrations of proinflammatory cytokines. In contrast, enzymatic cleavage of heparan sulfate resulted in increased bronchoalveolar bacterial burden, lung damage, and pulmonary inflammation in mice infected with S. pneumoniae. Accordingly, heparinase-treated mice also exhibited disrupted lung barrier integrity as evidenced by higher alveolar edema scores and vascular protein leakage into the airways. This finding was corroborated in a human alveolus-on-a-chip platform, confirming that heparinase treatment also disrupts the human lung barrier during S. pneumoniae infection. Notably, enzymatic pretreatment with either hyaluronidase or heparinase also rendered human epithelial cells more sensitive to pneumococci-induced barrier disruption, as determined by transepithelial electrical resistance measurements, consistent with our findings in murine pneumonia. Taken together, these findings demonstrate the importance of intact hyaluronan and heparan sulfate in limiting pneumococci-induced damage, pulmonary inflammation, and epithelial barrier function and integrity. [ABSTRACT FROM AUTHOR]

Bacterial drug resistance is becoming increasingly serious, this study aims to investigate the relationship between the resistance rate of erythromycin-resistant Streptococcus pneumoniae (SP) and reasons for the epidemic under complex geographical and climatic factors in China. Data spanning from 2014 to 2021, including drug resistance rates, isolate rates, meteorological variables, and demographic statistics, were collected from the China Antimicrobial Resistance Monitoring System, the China Statistical Yearbook and China Meteorological Website. Our analysis involved nonparametric tests and the construction of multifaceted regression models for rigorous multivariate analysis. Single-factor analysis revealed significant differences in the resistance rate and isolate rate of erythromycin-resistant SP across different regions characterized by Hu Huanyong lines or different climate types. Multivariate regression analysis indicated positive correlations between the drug resistance rate and temperature, Subtropical climate, Gross Domestic Product (GDP), Hu Huanyong line, and the highest temperature in the past period (Tm); the isolate rate showed a positive correlation with regional GDP and a negative correlation with monsoon climate. The model developed in this study provides valuable insights into the resistance rate and potential relationships of erythromycin-resistant SP under complex meteorological conditions in China. [ABSTRACT FROM AUTHOR]

Nucleic acid amplification tests (NAATs) greatly enhance the capacity to identify the etiology of pediatric complicated pneumonia. However, the use of pneumococcal conjugate vaccines could reduce the importance of Streptococcus pneumoniae in pediatric complicated pneumonia with the potential emergence of other bacterial agents. Using an expanded NAAT in culture negative pleural fluid or empyema samples collected in 2010–2024 (n = 554) in Portugal, we show that S. pneumoniae remains the most frequent agent despite decades of pneumococcal conjugate vaccine use and the COVID-19 pandemic. A rebound in pediatric complicated pneumonia occurred post-pandemic, including a rise in cases by Streptococcus pyogenes and Haemophilus influenzae. Empiric therapy of pediatric complicated pneumonia should still consider S. pneumoniae as the most likely cause, even in countries where the pneumococcal conjugate vaccine is in the national immunization program with a high uptake. [ABSTRACT FROM AUTHOR]

BackgroundMethodsResultsConclusionPneumococcal diseases pose a significant public health concern globally, particularly among young children and the elderly. Vaccination plays a crucial role in their prevention. This study evaluated the functional immune responses to Pneumococcal polysaccharide vaccine serotypes in healthy Indian adults before and after administering a single dose of PPSV23 immunization.A total of 125 healthy participants aged 18–65 received the PPSV23 vaccine, and their pre- and post-immunization sera were analyzed by MOPA. Opsonic Index, Geometric mean OPA titers and fold increase for each serotype was calculated.The highest baseline OPA GMTs were observed for serotypes 33F,17F,9N,20, and 6B. The lowest OPA GMTs were noted against types 1 and 12F. OPA GMTs post-vaccination increased significantly for all serotypes, with geometric mean fold rise (GMFR) ranging from 4.3 to 267.5. Participants with low pre-immunization OPA titers (<8 & <64) showed significant increases in OI fold raise across all tested serotypes post-vaccination. This robust immune response was consistent across serotypes, indicating highly effective seroconversion in individuals with low baseline antibody levels.The PPSV23 vaccine elicits a strong immunogenic response in individuals with low pre-immunization OPA titers, achieving substantial increases in opsonic index fold raise across various serotypes. [ABSTRACT FROM AUTHOR]

Background Pneumococcal carriage is associated with increased acquisition and duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among adults. While pneumococcal conjugate vaccines (PCVs) prevent carriage of vaccine-serotype pneumococci, their potential impact on coronavirus disease 2019 (COVID-19)–related outcomes remains poorly understood in populations with prevalent immunity against SARS-CoV-2. Methods We undertook a retrospective cohort study of adults aged ≥65 years in the Kaiser Permanente Southern California healthcare system who had received ≥2 COVID-19 vaccine doses, comparing risk of SARS-CoV-2 infection between 1 January 2021 and 31 December 2022 among recipients and nonrecipients of 13-valent PCV (PCV13) employing multiple strategies to mitigate bias from differential test-seeking behavior. Results The ajusted hazard ratio of confirmed SARS-CoV-2 infection comparing PCV13 recipients to nonrecipients was 0.92 (95% confidence interval [CI],.90–.95), corresponding to prevention of 3.9 (95% CI, 2.6–5.3) infections per 100 person-years. Following receipt of 2, 3, and ≥4 COVID-19 vaccine doses, aHRs (95% CI) were 0.85 (.81–.89), 0.94 (.90–.97), and 0.99 (.93–1.04), respectively. The aHR (95% CI) for persons who had not received COVID-19 vaccination in the preceding 6 months was 0.90 (.86–.93), versus 0.94 (.91–.98) within 6 months after COVID-19 vaccination. Similarly, aHRs (95% CI) were 0.92 (.89–.94) for persons without history of documented SARS-CoV-2 infection, versus 1.00 (.90–1.12) for persons with documented prior infection. Conclusions Among older adults who had received ≥2 COVID-19 vaccine doses, PCV13 was associated with modest protection against SARS-CoV-2 infection. Protective effects of PCV13 were greater among individuals expected to have weaker immune protection against SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Toll-like receptor 5 (TLR5) signaling plays a key role in antibacterial defenses. We previously showed that respiratory administration of flagellin, a potent TLR5 agonist, in combination with amoxicillin (AMX) improves the treatment of primary pneumonia or superinfection caused by AMX-sensitive or AMX-resistant Streptococcus pneumoniae. Here, the impact of adjunct flagellin therapy on antibiotic dose/regimen and the selection of antibiotic-resistant S. pneumoniae was investigated using superinfection with isogenic antibiotic-sensitive and antibiotic-resistant bacteria and population dynamics analysis. Our findings demonstrate that flagellin allows for a 200-fold reduction in the antibiotic dose, achieving the same therapeutic effect observed with antibiotic alone. Adjunct treatment also reduced the selection of antibiotic-resistant bacteria in contrast to the antibiotic monotherapy. A mathematical model was developed that captured the population dynamics and estimated a 20-fold enhancement immune-modulatory factor on bacterial clearance. This work paves the way for the development of host-directed therapy and refinement of treatment by modeling. [ABSTRACT FROM AUTHOR]

Background Characterizing strains causing noninvasive and invasive pneumococcal disease (IPD) may inform the impact of new pneumococcal conjugate vaccines (PCVs). Methods During 2011–2019, among children aged 6–36 months, pneumococcal serotype distribution and antibiotic nonsusceptibility of nasopharyngeal and middle ear fluid (MEF) isolates collected at onset of acute otitis media (AOM) in Rochester, New York, were compared with IPD isolates from the Active Bacterial Core surveillance (ABCs) system across 10 US sites. Results From Rochester, 400 (nasopharyngeal) and 156 (MEF) pneumococcal isolates were collected from 259 children. From ABCs, 907 sterile-site isolates were collected from 896 children. Non-PCV serotypes 35B and 21 were more frequent among the Rochester AOM cases, while serotypes 3, 19A, 22F, 33F, 10A, and 12F contained in PCVs were more frequent among ABCs IPD cases. The proportion of antibiotic-nonsusceptible pneumococcal isolates was generally more common among IPD cases. In 2015–2019, serotype 35B emerged as the most common serotype associated with multiclass antibiotic nonsusceptibility for both the Rochester AOM and ABCs IPD cases. Conclusions Pneumococcal isolates from children in Rochester with AOM differ in serotype distribution and antibiotic susceptibility compared to IPD cases identified through US surveillance. Non-PCV serotype 35B emerged as a common cause of AOM and IPD. [ABSTRACT FROM AUTHOR]

In respiratory pathogens such as Streptococcus pneumoniae , biofilm formation is associated with the colonization of the nasopharynx and chronic respiratory infection. Previous data have shown that pneumococcal conjugate vaccines (PCVs) had an impact on S. pneumoniae colonization and a potential replacement by other respiratory pathogens such as Staphylococcus aureus. The objective of this work was to evaluate the evasion of the immune system by monospecific biofilms and by S. aureus-S. pneumoniae mixed biofilms. We performed opsonophagocytosis assays (OPA) using human HL-60 against previously disaggregated monospecific biofilms of MSSA, MRSA and S. aureus-S. pneumoniae mixed biofilms. We used pre-immune and post-immune serum from immunocompetent adult patients vaccinated with PCV13. Immune sera had a clear effect in reducing pneumococcal biofilms of serotypes 3, 14, 18C, 19F and 19A, whereas had no effect in non-PCV13 serotypes such as 8, 11A and 24F. Our study confirmed that serum from vaccinated patients with PCV13 did not have any effect in reducing S. aureus population in monospecific biofilms, regardless the methicillin resistance phenotype. Moreover, immunized sera from vaccinated patients with PCV13 did not have any effect in S. aureus population in the mixed biofilm, whereas significantly reduced the population of pneumococcal serotype 19A strain in the mixed biofilm which is of great interest because this serotype is included in PCV13, and it is associated with vaccine failures. [ABSTRACT FROM AUTHOR]

Background: Streptococcus pneumoniae is the most frequent causative pathogen of bacterial pneumonia in children worldwide. Bangladesh introduced the 10-valent pneumococcal conjugate vaccine (PCV10) in their national immunization program for infants in 2015. We assessed its potential coverage in under-fives with community-acquired pneumonia (CAP) in the years before PCV10 was introduced. Methods: A total of 1502 childhood pneumonia cases (< 5 year olds living in the urban section Kamalapur, Dhaka) were enrolled between 2011 and 2013. Acute phase and late (convalescent) serum samples were collected from 1380 cases. Serotype-specific pneumococcal antibody concentrations were measured using a 25-plex immunoassay panel. Pneumococcal CAP was diagnosed based on a serotype-specific pneumococcal antibody response. Results: S. pneumoniae was serologically identified as causative pathogen in 406/1380 (29%) cases. The five most prevalent serotypes were (in descending order) 11A, 22F, 3, 2 and 19F. Based on the percentage of pneumonia cases associated with PCV10 vaccine types, the potential PCV10 coverage was 29% (116/406). Conclusions: In almost a third of the studied cases S. pneumoniae was identified as a causative pathogen. Because of the characteristics of the immunoassay, this might well be a gross underestimation. Nevertheless, the potential PCV10-coverage was low. Given the high serotype diversity, the region might benefit greatly from a higher-coverage PCV or recombinant protein vaccine. [ABSTRACT FROM AUTHOR]

Introduction. In light of the global desire to prevent the onset of diseases more than treating them, vaccines have become the main players on the medical stage. Ensuring a high level of immunization, with the goal of achieving herd immunity, requires broadening the accessibility for as many beneficiaries as possible. Subsidized vaccination programs provide the means to reach a significant number of the population. It is important to analyze these programs from the perspective of medical professionals, in order to optimize and eliminate any potential obstacles. Materials and method. The study was based on a questionnaire completed by 64 general practitioners from Mureș County, reunited for a symposium on a different topic than that of the questionnaire. However, the data were collected before the lectures began. Results. Following the centralization of the information from the questionnaire, the practitioners reported an increase in vaccination rates due to the compensation, an increase that could be more significant with greater attention to raising awareness about the program and eliminating the patient’s fear of side effects. It was also highlighted that the groups that are the most at risk and the ones who most frequently accessed the immunization are patients with chronic lung diseases and the elderly. Conclusions. The success of the vaccination campaign and ensuring better immunization rates require more detailed and comprehensive awareness programs for the population. This aspect could significantly influence the patient’s decision to access the immunization program. [ABSTRACT FROM AUTHOR]

Introduction: Allergic fungal rhinosinusitis (AFRS) is a severe phenotype of chronic rhinosinusitis with nasal polyposis (CRSwNP), characterised by localised and exaggerated type 2 inflammation. While fungal antigenic stimulation of unregulated Th2‐mediated inflammation is the core pathophysiological mechanism, the direct and synergistic role of bacteria in disease modification is a pervasive hypothesis. We set out to define the microenvironment of AFRS to elucidate virulent organisms that may be implicated in the pathophysiology of AFRS. Methodology: We undertook a cross‐sectional study of AFRS patients and non‐fungal CRSwNP patients. Demographics, disease severity, culture and microbiome sequences were analysed. Multimodality microbiome sequencing included short‐read next‐generation sequencing (NGS) on the Illumina Miseq (16S rRNA and ITS) and full‐length 16S rRNA sequencing on the Oxford Nanopore Technologies GridION (ONT). Results: Thirty‐two AFRS and 29 non‐fungal CRSwNP patients (NF) were included in this study. Staphylococcus aureus was the dominant organism cultured and sequenced in both AFRS and NF groups (AFRS 27.54%; NF 18.04%; p =.07). Streptococcus pneumoniae (AFRS 12.31%; NF 0.98%; p =.03) and Haemophilus influenzae (AFRS 15.03%; NF 0.24%; p =.005) were significantly more abundant in AFRS. Bacterial diversity (Shannon's index) was considerably lower in AFRS relative to NF (AFRS 0.6; NF 1.0, p =.008). Aspergillus was the most cultured fungus in AFRS (10/32, 31.3%). The AFRS sequenced mycobiome was predominantly represented by Malassezia (43.6%), Curvularia (18.5%) and Aspergillus (16.8%), while the NF mycobiome was nearly exclusively Malassezia (84.2%) with an absence of Aspergillus or dematiaceous fungi. Conclusion: A low diversity, dysbiotic microenvironment dominated by Staphylococcus aureus, Streptococcus pneumoniae and Haemophilus influenzae characterised the bacterial microbiome of AFRS, with a mycobiome abundant in Malassezia, Aspergillus and Curvularia. While Staphylococcus aureus has been previously implicated in AFRS through enterotoxin superantigen potential, Streptococcus pneumoniae and Haemophilus influenzae are novel findings that may represent alternate cross‐kingdom pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

Objective This retrospective study evaluates the demographic characteristics, clinical symptoms, laboratory results, treatment approaches, and outcomes of children with complications arising from bacterial sinusitis. Methods Fifty-four pediatric inpatients with sinusitis complications admitted between September 2013 and October 2022 were included in the study. These patients were categorized into two groups: those with preseptal cellulitis (group 1) and those with orbital–intracranial complications (group 2). Results The median age of the patients was 10.8 years, and 61.1% were males. Maxillary sinusitis (n = 40.74%) was the most common type of sinus involvement. Half of the patients exhibited preseptal cellulitis. The median age of our patients with intracranial complications was 13.7 years, while the median age of patients with orbital complications was 8 years. The predominant orbital–intracranial complication was meningitis, which accounted for 41% of the cases. All patients with a subdural abscess (n = 6) presented with frontal sinusitis, while all cases of cavernous sinus thrombosis (n = 3) involved the sphenoidal sinus. Surgical intervention was undertaken in 37% of cases. Streptococcus pneumoniae was the most frequently isolated microorganism. The median duration of hospital stay was 14 days, with a total median treatment duration of 21 days. There were no fatalities, although neurological sequelae were observed in 7.4% of patients (n = 4). Conclusion Preseptal cellulitis and meningitis remain the most common complications of sinusitis in children. Adolescents with sinusitis should be monitored closely for intracranial complications. The prevalence of S. pneumoniae as the most frequently detected pathogen underscores the importance of vaccination. [ABSTRACT FROM AUTHOR]

Streptococcus pneumoniae (S. pneumoniae) is a major cause of community-acquired pneumonia. Current standard clinical therapies mainly focus on combating S. pneumoniae through antibiotics. However, the limited delivery of antibiotics and the undetoxified hydrogen peroxide (H 2 O 2) virulence factor secreted by S. pneumoniae impede the therapeutic outcomes. Here we report an inhalable catalase (CAT)-tannic acid (TA) nanoassembly for local antibiotic (levofloxacin) delivery and simultaneously neutralizing the secreted H 2 O 2 virulence factors to treat pneumococcal pneumonia. After aerosol inhalation, the inhalable formulation (denoted as CT@LVX) effectively accumulates in lung tissues through TA-mediated mucoadhesion. CAT can reduce alveolar epithelial cells apoptosis by catalyzing the decomposition of accumulated H 2 O 2 in the infected lung tissues. In synergy with antibiotic LVX-mediated S. pneumoniae elimination, CT@LVX significantly decreases lung injury companied with reduced inflammatory, resulting in 100 % survival of mice with pneumonia. In a clinically isolated S. pneumoniae strain-induced pneumonia mouse model, CT@LVX also shows superior outcomes compared to the traditional antibiotic treatment, highlighting its potential clinical application prospects. An inhalable LVX-loaded CAT-tannic acid (TA) nanoassembly (denoted as CT@LVX) was designed for the treatment of pneumococcal pneumonia, aiming neutralizing H 2 O 2 virulence factors and effectively delivering antibiotics. This nanoassembly has demonstrated strong tissue retention and protection capabilities, showing significant therapeutic potential in both standard and clinically isolated Streptococcus pneumoniae -induced pneumonia mouse models. [Display omitted] • An inhalable levofloxacin (LVX)-loaded catalase (CAT)-tannic acid (TA) nanoassembly (denoted as CT@LVX) was developed. • The inhalable CT@LVX formulation effectively accumulates in lung tissues via TA-mediated mucoadhesion. • CAT efficiently catalyzes H 2 O 2 secreted by Streptococcus pneumoniae , reducing alveolar epithelial cell apoptosis. • Combination of CAT neutralizing H 2 O 2 and LVX eliminating bacteria offers a promising treatment for pneumococcal pneumonia. [ABSTRACT FROM AUTHOR]

Streptococcus pneumoniae , a commensal in the nasopharynx, can cause invasive pneumococcal diseases (IPDs). To prevent the aggravation of IPDs, it is important to enhance host immune defense against S. pneumoniae. Hochuekkito (HET) is expected to have an immunostimulatory effect against infections. HET was administrated by gavage to adult BALB/cA mice before and after intranasal inoculation of S. pneumoniae. We evaluated the effect of HET on pneumococcal nasal colonization and subsequent development of lethal pneumococcal infections. No effect on nasal colonization was observed, but HET significantly reduced bacterial count in the blood, decreased the incidence of bacteremia, and improved survival. HET also reduced nasal tissue damage 3 days after intranasal infection. Neutrophils from HET-treated mice showed significantly higher bactericidal activity against S. pneumoniae in the presence of the serum from the HET group compared with from the control group. The non-specific immunostimulatory effect of HET is suggested by this study to be effective in preventing the progression in IPDs and provided insights into novel strategy in the post-pneumococcal vaccine era. [ABSTRACT FROM AUTHOR]

Lower respiratory tract infections, commonly caused by respiratory syncytial virus (RSV) or Streptococcus pneumoniae (pneumococcus), pose a substantial global health burden, especially in children younger than 5 years of age. A deeper understanding of the relationship between RSV and pneumococcus would aid the development of health-care approaches to disease prevention and management. We completed a systematic review to identify and assess evidence pertaining to the relationship between RSV and pneumococcus in the pathogenesis of childhood respiratory infections. We found mechanistic evidence for direct pathogen–pathogen interactions and for indirect interactions involving host modulation. We found a strong seasonal epidemiological association between these two pathogens, which was recently confirmed by a parallel decrease and a subsequent resurgence of both RSV and pneumococcus-associated disease during the COVID-19 pandemic. Importantly, we found that pneumococcal vaccination was associated with reduced RSV hospitalisations in infants, further supporting the relevance of their interaction in modulating severe disease. Overall evidence supports a broad biological and clinical interaction between pneumococcus and RSV in the pathogenesis of childhood respiratory infections. We hypothesise that the implementation of next-generation pneumococcal and RSV vaccines and monoclonal antibodies targeting RSV will act synergistically to reduce global morbidity and mortality related to childhood respiratory infections. [ABSTRACT FROM AUTHOR]

Background: Vaccination against Streptococcus pneumoniae is advised for transplant recipients to reduce morbidity and mortality associated with invasive pneumococcal disease. However, data on alloantibodies after sequential vaccination (with a pneumococcal conjugate vaccine followed by a polysaccharide vaccine) are still lacking. Methods: In the current study, we determined HLA class I and II and major histocompatibility class I-related chain A (MICA) antibodies in 41 clinically stable kidney transplant recipients. These antibodies were measured prior to and post sequential pneumococcal vaccination over a period of 12 months. Alloantibodies were measured by Luminex bead-based assays, and pneumococcal IgG antibodies were measured by ELISA. Results: Over a 12-month period, the sequential analysis revealed no significant change in alloantibodies. One patient developed de novo donor-specific antibodies (DSA) 1.5 months after the first vaccination, with mean fluorescence intensities of up to 2300. These DSA became undetectable in the follow-up, and the patient showed no signs of allograft rejection. Another patient experienced a biopsy-proven borderline rejection 7 months after the first vaccination but did not develop de novo DSA. Both maintained stable kidney function. As expected, the pneumococcal antibodies increased significantly after vaccination (p < 0.0001). Conclusions: Given the overall risk of alloimmune responses in transplant recipients, we would not attribute the two noticeable patient courses to vaccination. Thus, we consider sequential vaccination immunologically safe. [ABSTRACT FROM AUTHOR]

Background: Elderly individuals over 65, along with children under 5, are the most affected by invasive pneumococcal diseases (IPDs). Monitoring vaccination coverage and conducting surveillance are essential for guiding evidence-based prevention campaigns and public health measures. Methods: Since 2007, the Veneto Region has relied on three sources for surveillance of invasive bacterial infections, contributing to an increase in reported IPD cases. This study analyzed notifications related to individuals aged ≥65 years from 2007 to 2023. Results: A total of 1527 cases of IPDs in elderly individuals were reported between 2007 and 2023. The notification rate significantly increased from 5.61 to 14.63 per 100,000 inhabitants, despite underreporting during the COVID-19 pandemic. Cases associated with sepsis increased from 3.89 to 9.58 per 100,000, while notifications of meningitis and case fatality rates remained stable at 1.5 per 100,000 and 11.8%, respectively. Serotyping was not performed in 52% of the notifications. The most common serotypes were 3 (21.6%), 8 (11.1%), and 19A (5.0%), with fluctuations over time. There was a significant decline in serotypes covered by PCV7 and PCV13 and an increase in non-vaccine serotypes. Conclusions: The regional surveillance system allows for an increasingly comprehensive profile of the epidemiological landscape of IPDs in Veneto. However, the surveillance of pneumococcal infections still presents challenges. The currently available data are likely to be underestimated, mainly referring to the most severe cases, and the serotyping necessary to identify the etiological agent is still not often performed. [ABSTRACT FROM AUTHOR]

Copyright of Innere Medizin (2731-7080) is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Streptococcus pneumoniae is an important cause of community-acquired pneumonia (CAP) in Japan. Here, we report the serotype distribution and antimicrobial susceptibility of cultured pneumococcal isolates from Japanese adults aged ≥18 years with CAP. This was a prospective, population-based, active surveillance study conducted in Goto City, Japan from December 2015 to November 2020. Pneumococcal isolates from sterile sites (blood and pleural fluid) and non-sterile sites (sputum and bronchoalveolar lavage) were cultured as part of the standard of care. S. pneumoniae were serotyped using the Quellung reaction. Antimicrobial susceptibility was tested using microdilution and interpreted according to the Clinical and Laboratory Standards Institute criteria. Isolates resistant to erythromycin were phenotyped using the triple-risk test and genotyped by polymerase chain reaction. A total of 156 pneumococcal isolates were collected (138 from sputum, 15 from blood, and 3 from bronchoalveolar lavage) from 1992 patients. Of these, 142 were non-duplicate isolates from unique patients and were included in the analyses. Serotypes contained within the 13-valent pneumococcal conjugate vaccine (PCV13) (including 6C), PCV15 (including 6C), and PCV20 (including 6C and 15C) were detected in 39 (27%), 45 (32%), and 80 (56%) of 142 isolates, respectively. The most common serotypes were 35B (12%), 11A (11%), and 3 (11%). Multidrug resistance (MDR) was detected in 96/142 (68%) isolates. Of the 96 MDR isolates, 31, 32, and 59% were PCV13, PCV15, and PCV20 serotypes, respectively; the most common MDR serotypes were 35B (16%), 6C, 10A, and 15A (9% each), and 3 and 11A (8% each). A total of 119 isolates were resistant to macrolides; 41 (35%) had an M phenotype, 53 (45%) had an iMcLS phenotype, and 25 (21%) had a cMLS phenotype. In conclusion, pneumococcal serotypes 35B, 11A and 3 were most frequently associated with pneumonia and antimicrobial resistance was common among pneumococcal isolates from adults with CAP in Goto City, Japan. Implementing higher-valency PCVs May help reduce vaccine-type CAP among Japanese adults. [ABSTRACT FROM AUTHOR]

This study investigates the potential of energy‐coupling factor (ECF) transporters as promising anti‐infective targets to combat antimicrobial resistance (AMR). ECF transporters, a subclass of ATP‐binding cassette (ABC) transporters, facilitate the uptake of B‐vitamins across bacterial membranes by utilizing ATP as an energy source. Vitamins are essential cofactors for bacterial metabolism and growth, and they can either be synthesized de novo or absorbed from the environment. These transporters are considered promising drug targets, underscoring the need for further research to harness their medicinal potential and develop selective inhibitors that block vitamin uptake in bacteria. Herein, we focused on the ECF transporter for pantothenate (vitamin B5) from Streptococcus pneumoniae and the ECF transporter for folate (vitamin B9) from Lactobacillus delbrueckii as a reference protein. We also included the energizing module for pantothenate along with both full transporter complexes. Initially, we transformed and purified the transporters, followed by an assessment of their thermal stability under various buffer composition, pH, and salt concentrations. Additionally, we monitored the melting temperature over six days to confirm their stability for further assays. We then measured the binding affinities of six ECF inhibitors using surface plasmon resonance (SPR) and evaluated their inhibitory effects through in vitro assays, including bacterial growth assay, whole‐cell uptake, and transport‐activity assays. After determining cytotoxicity in two human cell lines, we established an in vivo infection model using Galleria mellonella larvae to further validate our findings. [ABSTRACT FROM AUTHOR]

The immunization of mice with the sterile culture medium supernatants of Mycobacterium tuberculosis (Mtb) H37Rv permitted the production of several monoclonal antibodies (mAbs) specific for secreted and/or released antigens. Two mAbs bound and immunoprecipitated an 80-kDa protein that was identified by mass spectrometry as Rv1133c, the methionine synthase MetE. The protein MetE is ubiquitous among prokaryota and shows a significant sequence homology in many bacteria. We produced both the full-length recombinant MetE and its N-terminal fragment, whose sequence is more conserved among mycobacteria, to select mAbs recognizing an Mtb-specific region of MetE. Finally, we produced and selected eight mAbs that specifically detect the MetE protein in the supernatant and cell lysate of Mtb and BCG, but not other bacteria such as non-tuberculous mycobacteria (NTM), Streptococcus pneumoniae, Staphylococcus aureus, Acinetobacter baumanii, or Escherichia coli. Taking advantage of our mAbs, we studied (i) the vitamin B12 dependence for the synthesis of MetE in Mtb and NTM and (ii) the kinetics of MetE production and secretion in supernatants during the in vitro reproduced replicative, dormant, and resuscitation cycle of Mtb. Our data demonstrate that dormant Mtb, which are assumed to be prevalent in latent infections, as well as NTM do not produce and secrete MetE. Results indicate an unexpected specificity for Mtb of our anti-MetE mAbs and encourage the use of rMetE and our mAbs as tools for the immunodiagnosis of TB and its stages. [ABSTRACT FROM AUTHOR]

Background: Netherton syndrome (NS) is a rare, severe genetic skin disorder, currently classified as an inborn error of immunity (IEI) due to previously reported immune dysregulation. We recently reported the results of an immunological evaluation showing no evidence for a relevant B- and/or T-cell mediated immunodeficiency, but immune responses after vaccination were not evaluated in that study. Therefore, we evaluated immune responses to three vaccine platforms in adult NS patients to further investigate the presence of a clinically relevant B- and/or T-cell immunodeficiency. Methods: Vaccination responses in eight adult NS patients were assessed in a cross-sectional study performed between January and August 2022. Clinical patient data were retrospectively retrieved from electronic patient files. Immune responses to a polysaccharide Streptococcus pneumoniae vaccine (PPV23) and conjugate Haemophilus influenzae type b vaccine (ActHiB) were measured. SARS-CoV-2-specific (functional) antibody and T-cell responses following booster vaccination with an mRNA-based COVID-19 vaccine were compared to controls. Results: None of the included patients suffered from recurrent and/or severe infections that could be attributed to a B- and/or T-cell immunodeficiency. ActHiB induced immune responses were normal in 7/7 NS patients. PPV23 induced responses were absent in 1/7, diminished in 2/7, and normal in 4/7 patients. Levels of SARS-CoV-2-specific binding and neutralizing antibodies after mRNA-based COVID-19 booster vaccination in NS patients were comparable to controls. SARS-CoV-2-specific CD4 + T-cell responses were detectable in all NS patients. In contrast, SARS-CoV-2-specific CD8 + T-cell responses were detectable in only 2/6 NS patients. T-cell responses to a positive control antigen pool were comparable to controls. Conclusions: Vaccine-induced immune responses were detectable after polysaccharide, conjugate and mRNA-based vaccination in our cohort of NS patients. A spectrum of responsiveness to vaccine challenges was found, with the ranges of vaccine responses overlapping those demonstrated in healthy control populations. [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal carriage of S. pneumoniae is a global health problem that has been associated with the emergence of severe disease and pathogen dissemination in the community. However, summary data on the carriage rate, antimicrobial susceptibility profile, and determinant factors is lacking. Method: Articles were extensively searched in bibliographic databases and gray literature using entry terms or phrases. Studies meeting eligibility criteria were extracted in MS Excel and exported to STATA version 17 software for statistical analysis. A random-effects model was used to compute the pooled magnitude of the nasal carriage of S. pneumoniae and its multidrug resistance. The heterogeneity was quantified by using the I2 value. Publication bias was assessed using a funnel plot and Egger's test. Sensitivity analysis was done to assess the impact of a single study on the pooled effect size. Result: Of the 146 studies identified, 8 studies containing a total of 3223 children were selected for meta-analysis of the magnitude of the nasal carriage of S. pneumoniae and its multidrug resistance. The overall pooled prevalence of nasal carriage of S. pneumoniae and its MDR status in Ethiopian children was 32.77% (95%CI: 25.1, 40.44). and 31.22% (95%CI: 15.06, 46.84), respectively. The highest resistant pattern of S. pneumoniae was against tetracycline, which was 46.27% (95%CI: 37.75, 54.79), followed by 45.68% (95%CI: 34.43, 57.28) trimethoprim-sulfamethoxazole, while the least pooled prevalence was against chloramphenicol, which was 16.2% (95%CI: 9.44, 22.95). The pooled effect of age less than 5 years old (pooled OR = 1.97; 95% CI: 1.35, 2.88, P < 0.001), co-sleeping habit with others (pooled OR = 2.36; 95% CI: 1.77, 3.66; P < 0.001), sibling (pooled OR = 1.82; 95% CI: 1.14, 2.91, P = 0.01), history of hospitalization (pooled OR = 4.39; 95% CI: 1.86, 10.34, P = 0.001), and malnutrition (pooled OR = 2.18; 95% CI: 1.49, 3.19; P < 0.001) showed a statistical association with S. pneumoniae nasal carriage rate by using the random effect Sidik-Jonkman model. Conclusion: The magnitude of the nasopharyngeal carriage rate and multi-drug resistance status of S. pneumoniae alarms the need for immediate interventions such as strengthening antimicrobial stewardship programs, undertaking national antimicrobial surveillance, one-health initiatives, and national immunization programs. [ABSTRACT FROM AUTHOR]

Background: Streptococcus pneumoniae is a major cause of mortality globally. The introduction of pneumococcal conjugate vaccines (PCVs) has reduced the incidence of the targeted serotypes significantly, but expansion of non-targeted serotypes, serotype replacement, and incomplete vaccine-targeting contribute to pneumococcal disease in the vaccine era. Here, we characterize the changing population genetic landscape of S. pneumoniae in Norway over a 41-year period (1982–2022). Methods: Since 2018, all cases of invasive pneumococcal disease have undergone whole-genome sequencing (WGS) at the Norwegian Institute of Public Health. In order to characterize the changing population over time, historical isolates were re-cultured and sequenced, resulting in a historical WGS dataset. Isolates were assigned to global pneumococcal sequence clusters (GPSCs) using PathogenWatch and assigned to serotypes using in silico (SeroBA) and in vitro methods (Quellung reaction). Temporal phylogenetic analyses were performed on GPSCs of particular interest. Results: The availability of WGS data allowed us to study capsular variation at the level of individual lineages. We detect highly divergent fates for different GPSCs following the introduction of PCVs. For two out of eight major GPSCs, we identified multiple instances of serotype switching from vaccine types to non-vaccine types. Dating analyses suggest that most instances of serotype switching predated the introduction of PCVs, but expansion occurred after their introduction. Furthermore, selection for penicillin non-susceptibility was not a driving force for the changing serotype distribution within the GPSCs over time. Conclusions: PCVs have been major shapers of the Norwegian disease-causing pneumococcal population, both at the level of serotype distributions and the underlying lineage dynamics. Overall, the introduction of PCVs has reduced the incidence of invasive disease. However, some GPSCs initially dominated by vaccine types escaped the effect of vaccination through expansion of non-vaccine serotypes. Close monitoring of circulating lineages and serotypes will be key for ensuring optimal vaccination coverage going forward. [ABSTRACT FROM AUTHOR]

Background: Pneumococcal meningitis, a vaccine-preventable disease caused by Streptococcus pneumoniae (Spn) is the leading bacterial meningitis in under five children. In April 2014, Uganda introduced routine immunization with 10-valent Pneumococcal Conjugate Vaccine (PCV10) for infants. The target coverage for herd immunity is ≥ 90% with three doses (PCV10-dose 3). We assessed the effect of PCV10 introduction and coverage on the trends of pneumococcal meningitis in under five children. Methods: We analyzed laboratory-confirmed pediatric bacterial meningitis (PBM) data at two high-volume WHO-accredited sentinel surveillance hospitals in Kampala City and Gulu District, from 2003 to 2022. We used confirmed cases to estimate the minimum incidence of pneumococcal meningitis in the host districts and calculated annual incidence of pneumococcal meningitis per one million populations, and the proportion of confirmed PBM attributable to Spn. We divided the study period into 2003–2013 (pre-PCV10) and 2014–2022 (post-PCV10), and conducted interrupted time series analysis using autoregressive integrated moving average models for the effect of PCV10 on trends of pneumococcal meningitis and PBM attributable to Spn. We analyzed reported PCV10 data in DHIS2 from 2014 to 2022 for annual PCV10-dose 3 coverage. Results: Among the 534 confirmed PBM cases, 331(62%) were pneumococcal meningitis; 227(69%) from Gulu District and 104(31%) from Kampala City. The majority (95%) of the isolates were not serotyped. The majority (57%) were male and unimmunized (98%); median age = 14(IQR = 6–27) months with most (55%) aged ≥ 12 months. The case-fatality rate was 9%. During Pre-PCV10 period, the overall incidence of pneumococcal meningitis in the host districts increased; slope change = 1.0 (95%CI = 0.99999, 1.00001) but declined in post-PCV10 period (2014–2022) by 92% from 86 cases /1,000,000 in 2014 to 7/1,000,000 in 2022, slope change= -1.00006 (95%CI=-1.00033, -0.99979). Whereas there was an immediate decline in the proportion of confirmed PBM attributable to Spn in the host districts, level change=-1.84611(95%CI=-1.98365,-1.70856), an upward trend was recorded from 2016 to 2022, slope change = 1.0 (95%CI = 0.99997, 1.00003). During 2015–2022, PCV10-dose 3 coverage was largely > 90% for Gulu District and 52–72% for Kampala City. Conclusion: The PCV10 routine immunization program reduced the incidence of pneumococcal meningitis in Kampala City and Gulu District. There was no effect on the confirmed PBM proportionately attributable to Spn. Kampala City persistently recorded PCV10-dose3 coverage < 90%. We recommend enhancing serotyping and periodic nasopharyngeal carriage surveys to ascertain the maximum vaccine effectiveness and monitor Spn serotypes, and strengthening routine immunization in Kampala City. [ABSTRACT FROM AUTHOR]

Background: Immunosuppressive therapies are associated with a risk of infections. Nevertheless, their incidence in this population remains unclear. This study aims to determine the incidence of serious respiratory tract infections (SRI) in a population exposed to immunosuppressive therapies. Methods: Data from a representative sample of the French healthcare claims from 01/01/2014 to 12/31/2019 were analyzed. Exposure to immunosuppressive therapy was defined by the dispensation of drugs through community pharmacies or in hospitals. SRI diagnosis was based on ICD-10 codes from hospitalization records. A cohort analysis was performed to estimate standardized SRI incidence rates. A nested case-control analysis within this cohort was used to study the characteristics associated with SRI. Results: We identified 24,122 individuals exposed to immunosuppressive therapies, among which 1,559 developed SRI, resulting in a standardized incidence rate of 1,398 per 100,000 person-years. In this population, the risk of SRI was associated with a history of cancer (OR 2.68, 95% Confidence Intervals (CI) 2.24–3.21; p < 0.001), chronic respiratory disease (2.62, 95%CI 2.17–3.16; p < 0.001), end-stage renal failure (2.38, 95%CI 1.37–4.13; p = 0.003), neurodegenerative diseases (1.52, 95%CI 1.07–2.17; p = 0.026), diabetes (1.44, 95%CI 1.14–1.82; p < 0.001), psychiatric diseases (1.27, 95%CI 1.06–1.52; p < 0.001), and cardiovascular diseases (1.26, 95%CI 1.04–1.52; p = 0.002). Compared to corticosteroids alone, the risk of SRI was lower in individuals treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) only (0.44, 95%CI 0.25–0.78; p < 0.001). Conclusion: In the population exposed to immunosuppressive therapies, a history of chronic disease is associated with an increased risk of SRI. This risk is lower in those receiving csDMARD alone than corticosteroids alone. [ABSTRACT FROM AUTHOR]

Background: Streptococcus pneumoniae (S. pneumoniae), Haemophilus influenzae (H. influenzae), and Neisseria meningitidis (N. meningitidis) are leading causes of childhood bacterial meningitis and preventable by vaccines. The aim of this hospital-based sentinel surveillance is to describe the epidemiological characteristics of pneumococcal meningitis, including disease burden, and to provide baseline data on pneumococcal serotype distribution to support decision making for pneumococcal conjugate vaccine (PCV) introduction in Vietnam. Methods: Surveillance for probable bacterial meningitis in children 1–59 months of age is conducted in three tertiary level pediatric hospitals: one in Hanoi and two in Ho Chi Minh City. Cerebrospinal fluid (CSF) specimens were collected via lumbar puncture from children with suspected meningitis. Specimens were transferred immediately to the laboratory department of the respective hospital for cytology, biochemistry, and microbiology testing, including culture. PCR testing was conducted on CSF specimens for bacterial detection (S. pneumoniae, H. influenzae, and N. meningitidis) and pneumococcal serotyping. Results: During 2015–2018, a total of 1,803 children with probable bacterial meningitis were detected; 1,780 had CSF specimens available for testing. Of 245 laboratory-confirmed positive cases, the majority were caused by S. pneumoniae (229,93.5%). Of those with S. pneumoniae detected, over 70% were caused by serotypes included in currently available PCV products; serotypes 6 A/6B (27.1%), 14 (19.7%), and 23 F (16.2%) were the most common serotypes. Children with laboratory-confirmed pneumococcal meningitis were more likely to live in Hanoi (p < 0.0001) and children 12–23 months of age were at greater odds (OR = 1.65, 95% CI: 1.11, 2.43; p = 0.006) of having confirmed pneumococcal meningitis compared to children < 12 months of age when compared to those without laboratory-confirmed bacterial meningitis. Additionally, children with confirmed pneumococcal meningitis were more likely to exhibit signs and symptoms consistent with clinical meningitis compared to negative laboratory-confirmed meningitis cases (p < 0.0001) and had a greater odds of death (OR = 6.18, 95% CI: 2.98, 12.86; p < 0.0001). Conclusions: Pneumococcal meningitis contributes to a large burden of bacterial meningitis in Vietnamese children. A large proportion are caused by serotypes covered by PCVs currently available. Introduction of PCV into the routine immunization program could reduce the burden of pneumococcal meningitis in Viet Nam. [ABSTRACT FROM AUTHOR]

Introduction Understanding the pneumococcal serotypes causing community-acquired pneumonia (CAP) is essential for evaluating the impact of pneumococcal vaccines. Methods We conducted a prospective surveillance study of adults aged ≥18 years hospitalized with CAP at 3 hospitals in Tennessee and Georgia between 1 September 2018 and 31 October 2022. We assessed for pneumococcal etiology with cultures, the BinaxNOW urinary antigen detection test, and serotype-specific urinary antigen detection assays that detect 30 pneumococcal serotypes contained in the investigational pneumococcal conjugate vaccine V116, as well as licensed vaccines PCV15 and PCV20 (except serotype 15B). The distribution of pneumococcal serotypes was calculated based on serotype-specific urinary antigen detection results. Results Among 2917 hospitalized adults enrolled with CAP, 352 (12.1%) patients had Streptococcus pneumoniae detected, including 51 (1.7%) patients with invasive pneumococcal pneumonia. The 8 most commonly detected serotypes were: 3, 22F, 19A, 35B, 9N, 19F, 23A, and 11A. Among 2917 adults with CAP, 272 (9.3%) had a serotype detected that is contained in V116, compared to 196 (6.7%) patients with a serotype contained in PCV20 (P <.001), and 168 (5.8%) patients with a serotype contained in PCV15 (P <.001). A serotype contained in V116 but not PCV15 or PCV20 was detected in 120 (4.1%) patients, representing 38.0% of serotype detections. Conclusions Approximately 12% of adults hospitalized with CAP had S. pneumoniae detected, and approximately one-third of the detected pneumococcal serotypes were not contained in PCV15 or PCV20. Development of new pneumococcal vaccines with expanded serotype coverage has the potential to prevent a substantial burden of disease. [ABSTRACT FROM AUTHOR]

Many human pathogens, including malaria, dengue, influenza, Streptococcus pneumoniae, and cytomegalovirus, coexist as multiple genetically distinct strains. Understanding how these multistrain pathogens evolve is of critical importance for forecasting epidemics and predicting the consequences of vaccination. One factor believed to play an important role is naturally acquired immunity. Consequently, a large body of research has sought to predict how acquired immunity molds the genomics of pathogen populations (i.e., what shapes pathogen strain structure). The diversity of existing models has resulted in conflicting evolutionary predictions and has sparked an ongoing debate about which predictions are most broadly applicable. Here, we adopt a multilocus population genetics perspective that unifies the predictions of existing models. We identify three key factors that determine the role of naturally acquired immunity in the evolution of pathogen strain structure: i) the strength and specificity of immune protections, ii) the dynamic immunological landscape, and iii) the number of loci coding for the antigens of the pathogen. Isolating and discussing these three factors clarifies the relationship among previous models of multistrain dynamics, and establishes a solid theoretical foundation for the study of the evolutionary epidemiology of multistrain pathogens. [ABSTRACT FROM AUTHOR]

Pneumococcal surface protein A (PspA) is an important virulence factor in Streptococcus pneumoniae that binds to lactoferrin and protects the bacterium from the bactericidal action of lactoferricins—cationic peptides released upon lactoferrin proteolysis. The present study investigated if PspA can prevent killing by another cationic peptide, indolicidin. PspA-negative pneumococci were more sensitive to indolicidin-induced killing than bacteria expressing PspA, suggesting that PspA prevents the bactericidal action of indolicidin. Similarly, chemical removal of choline-binding proteins increased sensitivity to indolicidin. The absence of capsule and PspA had an additive effect on pneumococcal killing by the AMP. Furthermore, anti-PspA antibodies enhanced the bactericidal effect of indolicidin on pneumococci, while addition of soluble PspA fragments competitively inhibited indolicidin action. Previous in silico analysis suggests a possible interaction between PspA and indolicidin. Thus, we hypothesize that PspA acts by sequestering indolicidin and preventing it from reaching the bacterial membrane. A specific interaction between PspA and indolicidin was demonstrated by mass spectrometry, confirming that PspA can actively bind to the AMP. These results reinforce the vaccine potential of PspA and suggest a possible mechanism of innate immune evasion employed by pneumococci, which involves binding to cationic peptides and hindering their ability to damage the bacterial membranes. [ABSTRACT FROM AUTHOR]

Streptococcus pneumoniae is a major cause of meningitis in under developed countries with low vaccination rates and high antibiotic resistance. This study aimed to analyze 83 suspected meningitis patients in Karachi for the detection of S. pneumoniae followed by its whole genome sequencing and Pan Genome analysis. Out of the 83 samples collected, 33 samples with altered physical (turbidity), cytological (white blood cell count) and biochemical (total protein and total glucose concentrations) parameters indicated potential meningitis cases, while these parameters were within normal healthy ranges in remaining 50 samples. Latex particle agglutination (LPA) was performed on the 33 samples, revealing 20 positive cases of bacterial meningitis. The PCR and culturing methods revealed 5 S. pneumoniae isolates. Antibiotic susceptibility tests showed that one S.pneumoniae strain was resistant to erythromycin, levofloxacin, and tetracycline. Whole-genome sequencing of this resistant strain was performed and S. pneumoniae was confirmed with MLST analysis, while it had > 2.3 Mb genome and a single repUS43 plasmid. In CARD analysis, the strain had tet(M), ermB, RlmA(II), patB, pmrA, and patA ARGs, which could provide resistance against tetracycline, macrolide, fluoroquinolone, and glycopeptide antibiotics. Phylogenetic analysis revealed that the isolate was closely related to strains from Hungary and the USA. Pan-genome analysis with 144 genome assemblies from NCBI database showed that 1101 non-redundant core genes were shared between all strains. This study gives valuable understanding into the prevalence and characterization of meningitis-causing bacteria in Karachi, Pakistan with prime focus on multi-drug resistant S. pneumoniae. [ABSTRACT FROM AUTHOR]

Metal ions have important roles in supporting the catalytic activity of DNA-regulating enzymes such as topoisomerases (topos). Bacterial type II topos, gyrases and topo IV, are primary drug targets for fluoroquinolones, a class of clinically relevant antibacterials requiring metal ions for efficient drug binding. While the presence of metal ions in topos has been elucidated in biochemical studies, accurate location and assignment of metal ions in structural studies have historically posed significant challenges. Recent advances in X-ray crystallography address these limitations by extending the experimental capabilities into the long-wavelength range, exploiting the anomalous contrast from light elements of biological relevance. This breakthrough enables us to confirm experimentally the locations of Mg2+ in the fluoroquinolone-stabilized Streptococcus pneumoniae topo IV complex. Moreover, we can unambiguously identify the presence of K+ and Cl-ions in the complex with one pair of K+ ions functioning as an additional intersubunit bridge. Overall, our data extend current knowledge on the functional and structural roles of metal ions in type II topos. [ABSTRACT FROM AUTHOR]

Background: Streptococcus pneumoniae (S. pneumoniae) is a major cause of morbidity and mortality in children worldwide, and its evolving serotype distribution and antibiotic resistance patterns are of global health concern. This meta-analysis aims to investigate the serotype distribution and antimicrobial resistance of S. pneumoniae after the introduction of pneumococcal conjugate vaccine 13-valent (PCV13) as a self-funded vaccine in Chinese pediatric populations. Methods: We systematically reviewed studies published between 2017 and 2024 that focused on S. pneumoniae serotypes isolated from children under 14 years old in mainland China. Data sources included PubMed, Embase, Web of Science, CNKI, Wanfang, and SinoMed. The findings were synthesized using either a fixed-effects or random-effects model. Results: Our meta-analysis included 12 studies, identifying the most common serotypes of S. pneumoniae were 19 F, 19 A, 23 F, 14, 6B and 6 A. Vaccine serotype coverage rates were 52.17% (95%CI: 44.91-59.42%) for PCV10, 74.77% (95%CI: 71.53-78.01%) for PCV13, 76.72% (95%CI: 75.37-78.07%) for PCV15 and 92.90% (95%CI: 92.09-93.71%) for PPSV23. Antimicrobial resistance was most pronounced for erythromycin at 93.73% (95%CI: 90.58-96.88%), followed by azithromycin, tetracycline, clindamycin, and sulfamethoxazole. Serotype prevalence and vaccine coverage varied regionally and by strain type. Conclusion: The distribution of S. pneumoniae serotypes and their antibiotic resistance profiles in children under 14 years in mainland China have remained relatively stable post-PCV13 introduction as a self-funded vaccine. The results support continued use and possible expansion of PCV13 immunization and highlight the importance of ongoing surveillance and vaccine development to cover all prevalent serotypes in China. [ABSTRACT FROM AUTHOR]

Background: The 13-valent pneumococcal conjugate vaccine (PCV-13) was introduced in Malawi in 2011 with an expected impact of reducing pneumococcal pneumonia in children. We aimed to describe clinical characteristics and nasopharyngeal (NP) carriage of pneumococcus by serotype in children hospitalized with primary end-point pneumonia (PEP) between 2013 and 19 after the introduction of PCV-13. Methods: We conducted a secondary analysis of children aged under-5-years hospitalized with acute respiratory illness (ARI) in Malawi. Chest radiographs conducted at admission were read by two independent clinicians according to WHO criteria for PEP, and a third reviewer resolved discordant diagnoses. NP swab specimens were processed and Streptococcus pneumoniae growth was serotyped. Multivariable regression analysis was conducted to assess the association between clinical characteristics, NP serotypes, and PEP. Results: We had complete radiographic and NP serotype data for 500 children, of which 54 isolates were vaccine-type (VT) (10.8%), 165 were non-VT (NVT; 33.0%), and 281 had no pneumococcal growth (56.2%). Among these, 176 (35.2%) had PEP on chest x-ray. Among those with PEP, pneumococcal carriage was documented in 43.8% of cases, and VT serotypes accounted for 10.8%. For children with PEP, we found no association between clinical characteristics and carrying either VT, NVT, or no pneumococcus. Conclusion: Carriage of S. pneumoniae remains high among children hospitalized with ARI in Malawi, but children with VT carriage were no more likely to have PEP than children carrying no pneumococcus or those with NVT carriage. There were no differences in clinical characteristics between those carrying VT, NVT, or no pneumococcus. [ABSTRACT FROM AUTHOR]