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BMC Infectious Diseases Jun 2024Chronic lung disease is a major cause of morbidity in African children with HIV infection; however, the microbial determinants of HIV-associated chronic lung disease...
INTRODUCTION
Chronic lung disease is a major cause of morbidity in African children with HIV infection; however, the microbial determinants of HIV-associated chronic lung disease (HCLD) remain poorly understood. We conducted a case-control study to investigate the prevalence and densities of respiratory microbes among pneumococcal conjugate vaccine (PCV)-naive children with (HCLD +) and without HCLD (HCLD-) established on antiretroviral treatment (ART).
METHODS
Nasopharyngeal swabs collected from HCLD + (defined as forced-expiratory-volume/second < -1.0 without reversibility postbronchodilation) and age-, site-, and duration-of-ART-matched HCLD- participants aged between 6-19 years enrolled in Zimbabwe and Malawi (BREATHE trial-NCT02426112) were tested for 94 pneumococcal serotypes together with twelve bacteria, including Streptococcus pneumoniae (SP), Staphylococcus aureus (SA), Haemophilus influenzae (HI), Moraxella catarrhalis (MC), and eight viruses, including human rhinovirus (HRV), respiratory syncytial virus A or B, and human metapneumovirus, using nanofluidic qPCR (Standard BioTools formerly known as Fluidigm). Fisher's exact test and logistic regression analysis were used for between-group comparisons and risk factors associated with common respiratory microbes, respectively.
RESULTS
A total of 345 participants (287 HCLD + , 58 HCLD-; median age, 15.5 years [IQR = 12.8-18], females, 52%) were included in the final analysis. The prevalence of SP (40%[116/287] vs. 21%[12/58], p = 0.005) and HRV (7%[21/287] vs. 0%[0/58], p = 0.032) were higher in HCLD + participants compared to HCLD- participants. Of the participants positive for SP (116 HCLD + & 12 HCLD-), 66% [85/128] had non-PCV-13 serotypes detected. Overall, PCV-13 serotypes (4, 19A, 19F: 16% [7/43] each) and NVT 13 and 21 (9% [8/85] each) predominated. The densities of HI (2 × 10 genomic equivalents [GE/ml] vs. 3 × 10 GE/ml, p = 0.006) and MC (1 × 10 GE/ml vs. 1 × 10 GE/ml, p = 0.031) were higher in HCLD + compared to HCLD-. Bacterial codetection (≥ any 2 bacteria) was higher in the HCLD + group (36% [114/287] vs. (19% [11/58]), (p = 0.014), with SP and HI codetection (HCLD + : 30% [86/287] vs. HCLD-: 12% [7/58], p = 0.005) predominating. Viruses (predominantly HRV) were detected only in HCLD + participants. Lastly, participants with a history of previous tuberculosis treatment were more likely to carry SP (adjusted odds ratio (aOR): 1.9 [1.1 -3.2], p = 0.021) or HI (aOR: 2.0 [1.2 - 3.3], p = 0.011), while those who used ART for ≥ 2 years were less likely to carry HI (aOR: 0.3 [0.1 - 0.8], p = 0.005) and MC (aOR: 0.4 [0.1 - 0.9], p = 0.039).
CONCLUSION
Children with HCLD + were more likely to be colonized by SP and HRV and had higher HI and MC bacterial loads in their nasopharynx. The role of SP, HI, and HRV in the pathogenesis of CLD, including how they influence the risk of acute exacerbations, should be studied further.
TRIAL REGISTRATION
The BREATHE trial (ClinicalTrials.gov Identifier: NCT02426112 , registered date: 24 April 2015).
Topics: Humans; Case-Control Studies; Adolescent; Child; Male; Female; HIV Infections; Zimbabwe; Malawi; Lung Diseases; Young Adult; Chronic Disease; Bacteria; Viruses; Respiratory Tract Infections; Streptococcus pneumoniae; Respiratory System
PubMed: 38926682
DOI: 10.1186/s12879-024-09540-5 -
PloS One 2024Pleural empyema is a serious complication of pneumonia in children. Negative bacterial cultures commonly impede optimal antibiotic therapy. To improve bacterial... (Observational Study)
Observational Study
Pleural empyema is a serious complication of pneumonia in children. Negative bacterial cultures commonly impede optimal antibiotic therapy. To improve bacterial identification, we developed a molecular assay and evaluated its performance compared with bacterial culture. Our multiplex-quantitative PCR to detect Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus and Haemophilus influenzae was assessed using bacterial genomic DNA and laboratory-prepared samples (n = 267). To evaluate clinical performance, we conducted the Molecular Assessment of Thoracic Empyema (MATE) observational study, enrolling children hospitalised with empyema. Pleural fluids were tested by bacterial culture and multiplex-qPCR, and performance determined using a study gold standard. We determined clinical sensitivity and time-to-organism-identification to assess the potential of the multiplex-qPCR to reduce the duration of empiric untargeted antibiotic therapy. Using spiked samples, the multiplex-qPCR demonstrated 213/215 (99.1%) sensitivity and 52/52 (100%) specificity for all organisms. During May 2019-March 2023, 100 children were enrolled in the MATE study; median age was 3.9 years (IQR 2-5.6). A bacterial pathogen was identified in 90/100 (90%) specimens by multiplex-qPCR, and 24/100 (24%) by bacterial culture (P <0.001). Multiplex-qPCR identified a bacterial cause in 68/76 (90%) culture-negative specimens. S. pneumoniae was the most common pathogen, identified in 67/100 (67%) specimens. We estimate our multiplex-qPCR would have reduced the duration of untargeted antibiotic therapy in 61% of cases by a median 20 days (IQR 17.5-23, range 1-55). Multiplex-qPCR significantly increased pathogen detection compared with culture and may allow for reducing the duration of untargeted antibiotic therapy.
Topics: Humans; Child, Preschool; Empyema, Pleural; Male; Female; Multiplex Polymerase Chain Reaction; Child; Haemophilus influenzae; Staphylococcus aureus; Streptococcus pneumoniae; Streptococcus pyogenes; Infant; Hospitalization; Anti-Bacterial Agents; Sensitivity and Specificity; DNA, Bacterial
PubMed: 38917227
DOI: 10.1371/journal.pone.0304861 -
The Pediatric Infectious Disease Journal Jun 2024Vaccination can effectively prevent hepatitis B virus (HBV) infection. Vaccination with 3 doses of hexavalent HBV-containing vaccines led to a higher Hepatitis B surface...
Comparison of Hepatitis B Surface Antibody Levels After Vaccination With Combined One Dose of Hexavalent Vaccine and Two Doses of Pentavalent Vaccine Versus Three Doses of Pentavalent Vaccine.
BACKGROUND
Vaccination can effectively prevent hepatitis B virus (HBV) infection. Vaccination with 3 doses of hexavalent HBV-containing vaccines led to a higher Hepatitis B surface antibody (anti-HBs) antibody level than vaccination with 3 doses of pentavalent HBV-containing vaccines. Whether the substitution of one dose of hexavalent HBV-containing vaccine in the pentavalent regimen could lead to a higher anti-HBs antibody level remains unknown.
METHODS
A randomized, open-label controlled trial was conducted. Infants aged 30-120 days were randomly assigned to either a combined hexavalent/pentavalent regimen (hexavalent HBV-containing vaccine at 2 months of age and pentavalent HBV-containing vaccine at 4 and 6 months of age) or a 3-dose pentavalent regimen (pentavalent HBV-containing vaccine at 2, 4, and 6 months of age). Anti-HBs antibody levels were measured 3-6 months after the last vaccination.
RESULTS
Seventy-six infants were enrolled, 38 in each group. The geometric mean of anti-HBs antibody levels in the combined hexavalent/pentavalent group was significantly higher than that of the 3-dose pentavalent group [316.2 mIU/mL (95% CI: 173.8-575.4 mIU/mL) versus 81.3 mIU/mL (95% CI: 38.9-169.8 mIU/mL), P = 0.006]. By multivariate analysis, the combined hexavalent/pentavalent regimen (coefficient 0.57; P = 0.003) was associated with higher anti-HBs antibody levels, while body weight <10th percentile (coefficient -0.85; P = 0.006) and receiving concomitant pneumococcal conjugated vaccines (coefficient -0.65; P = 0.001) were associated with lower anti-HBs antibody levels.
CONCLUSION
Substituting the first dose with a hexavalent HBV-containing vaccine in the pentavalent regimen for HBV vaccination led to higher anti-HBs antibody levels in infants. Concomitant pneumococcal conjugated vaccine administration may have an adverse impact on anti-HBs antibody level.
PubMed: 38916932
DOI: 10.1097/INF.0000000000004449 -
Future Microbiology Jun 2024The value of preventive medicine is superior to treatment with vaccinations occupying high priority. Nevertheless, heavy pressure has started to form in regard to... (Review)
Review
The value of preventive medicine is superior to treatment with vaccinations occupying high priority. Nevertheless, heavy pressure has started to form in regard to strains not included in vaccines contributing to the changing epidemiology of pathogen subtypes leading to 'vaccine-induced strain replacement'. Among other mechanisms, increasing fitness of nonvaccine strains and metabolic shifts in the subtypes have been described. Classical examples include pneumococcal infections and viral diseases, such as the human papilloma virus. Recently, it has been described in SARS-CoV-2, leading to the emergence of new subtypes, such as Omicron and Delta variants. The phenomenon has also been reported in , and rotavirus. This study addresses the concepts, examples and implications of this phenomenon.
PubMed: 38913745
DOI: 10.1080/17460913.2024.2345003 -
Microbial Genomics Jun 2024Understanding how pathogens spread across geographical space is fundamental for control measures such as vaccination. (the pneumococcus) is a respiratory bacterium...
Understanding how pathogens spread across geographical space is fundamental for control measures such as vaccination. (the pneumococcus) is a respiratory bacterium responsible for a large proportion of infectious disease morbidity and mortality globally. Even in the post-vaccination era, the rates of invasive pneumococcal disease (IPD) remain stable in most countries, including Israel. To understand the geographical spread of the pneumococcus in Israel, we analysed 1174 pneumococcal genomes from patients with IPD across multiple regions. We included the evolutionary distance between pairs of isolates inferred using whole-genome data within a relative risk (RR) ratio framework to capture the geographical structure of . While we could not find geographical structure at the overall lineage level, the extra granularity provided by whole-genome sequence data showed that it takes approximately 5 years for invasive pneumococcal isolates to become fully mixed across the country.This article contains data hosted by Microreact.
Topics: Streptococcus pneumoniae; Israel; Humans; Pneumococcal Infections; Genome, Bacterial; Whole Genome Sequencing; Phylogeny; Genomics
PubMed: 38913413
DOI: 10.1099/mgen.0.001262 -
Medicina 2024Despite improvements in health care, pneumonia-associated mortality remains high. The objective of this study was to analyze the factors associated with mortality in...
INTRODUCTION
Despite improvements in health care, pneumonia-associated mortality remains high. The objective of this study was to analyze the factors associated with mortality in bacteremic pneumonia caused by pneumococcus.
METHODS
Retrospective cohort study in adult patients with pneumonia diagnosis and isolation of pneumococcus in blood cultures, between January 2012 and May 2021, was carried out. Clinical and laboratory variables, radiological involvement, evolution and mortality during hospitalization were analyzed. The group of deceased patients was compared with that of survivors.
RESULTS
152 patients were included. Median age: 58 years; men: 58.9%; 33% presented a CURB-65 > than 2 at admission. Overall mortality: 34% (n=52). Deceased patients were more tachypneic on admission (respiratory rate 26 vs. 22; p=0.003), presented sensory alteration more frequently (58% vs. 14%; p< 0.001), PaO2/fraction of inspired oxygen ratio < 250 (58% vs. 22%; p<0.001), bilateral radiological compromise (50% vs. 32%; p=0.03), needed mechanical ventilation (50% vs 12%; p< 0.001), higher blood creatinine values (1.6 vs. 1.15; p=0.01), lower white blood cell count (10 900 vs 17 400; p=0.002), a lower glucose dosage (111 vs. 120; p=0.01), and fewer days of hospital stay (6 vs. 9; p=0.015). In logistic regression model, significant differences were maintained in the following factors associated with mortality: mechanical ventilation (OR=3.54), altered mental status (OR=5.95), chest X-ray with bilateral compromise (OR 3.20) and PAFI less than 250 (OR=3.62).
CONCLUSION
In our series, the factors related to mortality, despite the presence of bacteremia, do not differ from those published in the literature and which are part of the different prognostic scores used in routine practice.
Topics: Humans; Male; Retrospective Studies; Middle Aged; Female; Aged; Pneumonia, Pneumococcal; Risk Factors; Adult; Streptococcus pneumoniae; Hospital Mortality; Bacteremia
PubMed: 38907962
DOI: No ID Found -
Frontiers in Immunology 2024Protein kinases are indispensable reversible molecular switches that adapt and control protein functions during cellular processes requiring rapid responses to internal...
INTRODUCTION
Protein kinases are indispensable reversible molecular switches that adapt and control protein functions during cellular processes requiring rapid responses to internal and external events. Bacterial infections can affect kinase-mediated phosphorylation events, with consequences for both innate and adaptive immunity, through regulation of antigen presentation, pathogen recognition, cell invasiveness and phagocytosis. (), a human respiratory tract pathogen and a major cause of community-acquired pneumoniae, affects phosphorylation-based signalling of several kinases, but the pneumococcal mediator(s) involved in this process remain elusive. In this study, we investigated the influence of pneumococcal HO on the protein kinase activity of the human lung epithelial H441 cell line, a generally accepted model of alveolar epithelial cells.
METHODS
We performed kinome analysis using PamGene microarray chips and protein analysis in Western blotting in H441 lung cells infected with wild type () or with -a deletion mutant strongly attenuated in HO production- to assess the impact of pneumococcal hydrogen peroxide (HO) on global protein kinase activity profiles.
RESULTS
Our kinome analysis provides direct evidence that kinase activity profiles in infected H441 cells significantly vary according to the levels of pneumococcal HO. A large number of kinases in H441 cells infected with are significantly downregulated, whereas this no longer occurs in cells infected with the mutant strain, which lacks HO In particular, we describe for the first time HO-mediated downregulation of Protein kinase B (Akt1) and activation of lymphocyte-specific tyrosine protein kinase (Lck) via HO-mediated phosphorylation.
Topics: Streptococcus pneumoniae; Hydrogen Peroxide; Humans; Phosphorylation; Host-Pathogen Interactions; Cell Line; Protein Kinases; Pneumococcal Infections; Signal Transduction
PubMed: 38903521
DOI: 10.3389/fimmu.2024.1414195 -
Cureus May 2024Meningitis, an infection of the meninges of the central nervous system (CNS), can advance quickly and carries a mortality rate reaching 30% among affected patients. It...
Meningitis, an infection of the meninges of the central nervous system (CNS), can advance quickly and carries a mortality rate reaching 30% among affected patients. It may become complicated by conditions such as hydrocephalus, ventriculitis, and cerebral abscess. Here, we describe a case of meningitis that was complicated by pyogenic ventriculitis and hydrocephalus in a patient with diffuse large B-cell lymphoma (DLBCL) who underwent chemotherapy and radiotherapy. The patient presented with acute change in mental status and high-grade fever, with few episodes of non-bloody vomiting. Blood culture and cerebrospinal fluid (CSF) culture grew which was sensitive to ceftriaxone. CT scan of the head showed ventriculomegaly, pansinusitis, and a large left mastoid effusion. MRI of the brain showed layering in ventricles, hydrocephalus, and dural enhancement consistent with pachymeningitis. She was treated with ceftriaxone for 21 days with a meaningful outcome. She was discharged home with near-baseline mental capacity for further physical therapy.
PubMed: 38903366
DOI: 10.7759/cureus.60800 -
BMC Infectious Diseases Jun 2024Pneumococcal pneumonia (PP) is a serious infection caused by Streptococcus pneumoniae (pneumococcus), with a wide spectrum of clinical manifestations. The aim of this...
BACKGROUND
Pneumococcal pneumonia (PP) is a serious infection caused by Streptococcus pneumoniae (pneumococcus), with a wide spectrum of clinical manifestations. The aim of this study was to analyze the comorbidity factors that influenced the mortality in patients with asplenia according to PP.
METHODS
Discharge reports from the Spanish Minimum Basic Data Set (MBDS) was used to retrospectively analyze patients with asplenia and PP, from 1997 to 2021. Elixhauser Comorbidity Index (ECI) was calculated to predict in-hospital mortality (IHM).
RESULTS
97,922 patients with asplenia were included and 381 cases of PP were identified. The average age for men was 63.87 years and for women 65.99 years. In all years, ECI was larger for splenectomized than for non-splenectomized patients, with men having a higher mean ECI than women. An association was found between risk factors ECI, splenectomy, age group, sex, pneumococcal pneumonia, and increased mortality (OR = 0.98; 95% CI: 0.97-0.99; p < 0.001). The IHM increased steadily with the number of comorbidities and index scores in 1997-2021.
CONCLUSIONS
Asplenia remain a relevant cause of hospitalization in Spain. Comorbidities reflected a great impact in patients with asplenia and PP, which would mean higher risk of mortality.
Topics: Humans; Male; Female; Middle Aged; Pneumonia, Pneumococcal; Spain; Aged; Retrospective Studies; Comorbidity; Hospital Mortality; Risk Factors; Splenectomy; Streptococcus pneumoniae; Adult; Aged, 80 and over; Inpatients; Hospitalization
PubMed: 38902621
DOI: 10.1186/s12879-024-09517-4 -
Journal of Innate Immunity Jun 2024The hydrophilic, polymeric chain of the lipoteichoic acid (LTA) of the Gram-positive pathobiont Streptococcus pneumoniae is covalently linked to the glycosylglycerolipid...
INTRODUCTION
The hydrophilic, polymeric chain of the lipoteichoic acid (LTA) of the Gram-positive pathobiont Streptococcus pneumoniae is covalently linked to the glycosylglycerolipid -D-glucopyranosyl-(1,3)-diacylglycerol by the lipoteichoic acid ligase TacL, leading to its fixation in the cytoplasmic membrane. Pneumococcal LTA, sharing identical repeating units with the wall teichoic acids, are dispensable for normal growth but required for full-virulence in invasive infections.
METHODS
Mutants deficient in TacL and complemented strains constructed were tested for their growth, resistance against oxidative stress and susceptibility against antimicrobial peptides. Further, the membrane fluidity of pneumococci, their capability to adhere to lung epithelial cells and virulence in a Galleria mellonella as well as intranasal mouse infection model were assessed.
RESULTS
In the present study, we indicate that LTA is already indispensable for pneumococcal adherence to human nasopharyngeal cells and colonization in an intranasal mouse infection model. Mutants deficient for TacL did not show morphological defects. However, our analysis of pneumococcal membranes in different serotypes showed an altered membrane fluidity and surface protein abundance of lipoproteins in mutants deficient for LTA but not WTA. These mutants had a decreased membrane fluidity, exhibited higher amounts of lipoproteins, and showed an increased susceptibility to antimicrobial peptides. In complemented mutant strains this defect was fully restored.
CONCLUSION
Taken together, LTA is crucial for colonization and required to effectively protect pneumococci from innate immune defence mechanisms by maintaining the membrane integrity.
PubMed: 38901409
DOI: 10.1159/000539934