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Microorganisms Apr 2024The epidemiology, diagnostic methods and management of infectious complications after solid-organ transplantation (SOT) are evolving. The aim of our study is to describe...
The epidemiology, diagnostic methods and management of infectious complications after solid-organ transplantation (SOT) are evolving. The aim of our study is to describe current infectious complications in the year following SOT and risk factors for their development and outcome. We conducted a retrospective study in adult SOT recipients in a Belgian university hospital between 2018 and 2019. We gathered demographic characteristics, comorbidities leading to transplantation, clinical, microbiological, surgery-specific and therapeutic data concerning infectious episodes, and survival status up to one year post-transplantation. Two-hundred-and-thirty-one SOT recipients were included (90 kidneys, 79 livers, 35 lungs, 19 hearts and 8 multiple organs). We observed 381 infections in 143 (62%) patients, due to bacteria (235 (62%)), viruses (67 (18%)), and fungi (32 (8%)). Patients presented a median of two (1-5) infections, and the first infection occurred during the first six months. Nineteen (8%) patients died, eleven (58%) due to infectious causes. Protective factors identified against developing infection were obesity [OR [IC]: 0.41 [0.19-0.89]; = 0.025] and liver transplantation [OR [IC]: 0.21 [0.07-0.66]; = 0.007]. Risk factors identified for developing an infection were lung transplantation [OR [IC]: 6.80 [1.17-39.36]; = 0.032], CMV mismatch [OR [IC]: 3.53 [1.45-8.64]; = 0.006] and neutropenia [OR [IC]: 2.87 [1.27-6.47]; = 0.011]. Risk factors identified for death were inadequate cytomegalovirus prophylaxis, infection severity and absence of pneumococcal vaccination. Post-transplant infections were common. Addressing modifiable risk factors is crucial, such as pneumococcal vaccination.
PubMed: 38674699
DOI: 10.3390/microorganisms12040755 -
PLoS Computational Biology Apr 2024Multiplex panel tests identify many individual pathogens at once, using a set of component tests. In some panels the number of components can be large. If the panel is...
Multiplex panel tests identify many individual pathogens at once, using a set of component tests. In some panels the number of components can be large. If the panel is detecting causative pathogens for a single syndrome or disease then we might estimate the burden of that disease by combining the results of the panel, for example determining the prevalence of pneumococcal pneumonia as caused by many individual pneumococcal serotypes. When we are dealing with multiplex test panels with many components, test error in the individual components of a panel, even when present at very low levels, can cause significant overall error. Uncertainty in the sensitivity and specificity of the individual tests, and statistical fluctuations in the numbers of false positives and false negatives, will cause large uncertainty in the combined estimates of disease prevalence. In many cases this can be a source of significant bias. In this paper we develop a mathematical framework to characterise this issue, we determine expressions for the sensitivity and specificity of panel tests. In this we identify a counter-intuitive relationship between panel test sensitivity and disease prevalence that means panel tests become more sensitive as prevalence increases. We present novel statistical methods that adjust for bias and quantify uncertainty in prevalence estimates from panel tests, and use simulations to test these methods. As multiplex testing becomes more commonly used for screening in routine clinical practice, accumulation of test error due to the combination of large numbers of test results needs to be identified and corrected for.
Topics: Humans; Prevalence; Sensitivity and Specificity; Computer Simulation; Computational Biology; Streptococcus pneumoniae; Models, Statistical; Pneumonia, Pneumococcal
PubMed: 38669293
DOI: 10.1371/journal.pcbi.1012062 -
Diseases (Basel, Switzerland) Apr 2024Globally, sepsis and pneumonia account for significant mortality and morbidity. A complex interplay of immune-molecular pathways underlies both sepsis and pneumonia,... (Review)
Review
Globally, sepsis and pneumonia account for significant mortality and morbidity. A complex interplay of immune-molecular pathways underlies both sepsis and pneumonia, resulting in similar and overlapping disease characteristics. Sepsis could result from unmanaged pneumonia. Similarly, sepsis patients have pneumonia as a common complication in the intensive care unit. A significant percentage of pneumonia is misdiagnosed as septic shock. Therefore, our knowledge of the clinical relationship between pneumonia and sepsis is imperative to the proper management of these syndromes. Regarding pathogenesis and etiology, pneumococcus is one of the leading pathogens implicated in both pneumonia and sepsis syndromes. Growing evidence suggests that pneumococcal pneumonia can potentially disseminate and consequently induce systemic inflammation and severe sepsis. Streptococcus pneumoniae could potentially exploit the function of dendritic cells (DCs) to facilitate bacterial dissemination. This highlights the importance of pathogen-immune cell crosstalk in the pathophysiology of sepsis and pneumonia. The role of DCs in pneumococcal infections and sepsis is not well understood. Therefore, studying the immunologic crosstalk between pneumococcus and host immune mediators is crucial to elucidating the pathophysiology of pneumonia-induced lung injury and sepsis. This knowledge would help mitigate clinical diagnosis and management challenges.
PubMed: 38667530
DOI: 10.3390/diseases12040072 -
Diagnostics (Basel, Switzerland) Apr 2024Currently, there are more than 500 million people suffering from diabetes around the world. People aged 65 years or older are the most affected by this disease, and it... (Review)
Review
Currently, there are more than 500 million people suffering from diabetes around the world. People aged 65 years or older are the most affected by this disease, and it is estimated that approximately 96% of diabetes cases worldwide are type 2 diabetes. People with diabetes mellitus are at an increased risk of infections such as pneumonia, due to a series of factors that may contribute to immune dysfunction, including hyperglycemia, inhibition of neutrophil chemotaxis, impaired cytokine production, phagocytic cell dysfunction, altered T cell-mediated immune responses and the co-existence of chronic comorbidities. Rates of infection, hospitalization and mortality in diabetic patients are reported to be higher than in the general population. Research into the risk of infectious diseases such as pneumonia in these patients is very important because it will help improve their management and treatment.
PubMed: 38667504
DOI: 10.3390/diagnostics14080859 -
Clinical Immunology (Orlando, Fla.) Jun 2024Antibiotic resistance and the surge of infectious diseases during the pandemic present significant threats to human health. Trained immunity emerges as a promising and...
Antibiotic resistance and the surge of infectious diseases during the pandemic present significant threats to human health. Trained immunity emerges as a promising and innovative approach to address these infections. Synthetic or natural fungal, parasitic and viral components have been reported to induce trained immunity. However, it is not clear whether bacterial virulence proteins can induce protective trained immunity. Our research demonstrates Streptococcus pneumoniae virulence protein PepO, is a highly potent trained immunity inducer for combating broad-spectrum infection. Our findings showcase that rPepO training confers robust protection to mice against various pathogenic infections by enhancing macrophage functionality. rPepO effectively re-programs macrophages, re-configures their epigenetic modifications and bolsters their immunological responses, which is independent of T or B lymphocytes. In vivo and in vitro experiments confirm that trained macrophage-secreted complement C3 activates peritoneal B lymphocyte and enhances its bactericidal capacity. In addition, we provide the first evidence that granulocyte colony-stimulating factor (G-CSF) derived from trained macrophages plays a pivotal role in shaping central-trained immunity. In summation, our research demonstrates the capability of rPepO to induce both peripheral and central trained immunity in mice, underscoring its potential application in broad-spectrum anti-infection therapy. Our research provides a new molecule and some new target options for infectious disease prevention.
Topics: Animals; Streptococcus pneumoniae; Mice; Macrophages; Mice, Inbred C57BL; Pneumococcal Infections; Bacterial Proteins; B-Lymphocytes; Female; Trained Immunity
PubMed: 38663493
DOI: 10.1016/j.clim.2024.110226 -
Mucosal adjuvanticity and mucosal booster effect of colibactin-depleted probiotic membrane vesicles.Human Vaccines & Immunotherapeutics Dec 2024There is a growing interest in development of novel vaccines against respiratory tract infections, due to COVID-19 pandemic. Here, we examined mucosal adjuvanticity and...
There is a growing interest in development of novel vaccines against respiratory tract infections, due to COVID-19 pandemic. Here, we examined mucosal adjuvanticity and the mucosal booster effect of membrane vesicles (MVs) of a novel probiotic derivative lacking both flagella and potentially carcinogenic colibactin (ΔΔ). ΔΔ-derived MVs showed rather strong mucosal adjuvanticity as compared to those of a single flagellar mutant strain (Δ-MVs). In addition, glycoengineered ΔΔ-MVs displaying serotype-14 pneumococcal capsular polysaccharide (CPS14MVs) were well-characterized based on biological and physicochemical parameters. Subcutaneous (SC) and intranasal (IN) booster effects of CPS14MVs on systemic and mucosal immunity were evaluated in mice that have already been subcutaneously prime-immunized with the same MVs. With a two-dose regimen, an IN boost (SC-IN) elicited stronger IgA responses than homologous prime-boost immunization (SC-SC). With a three-dose regimen, serum IgG levels were comparable among all tested regimens. Homologous immunization (SC-SC-SC) elicited the highest IgM responses among all regimens tested, whereas SC-SC-SC failed to elicit IgA responses in blood and saliva. Furthermore, serum IgA and salivary SIgA levels were increased with an increased number of IN doses administrated. Notably, SC-IN-IN induced not only robust IgG response, but also the highest IgA response in both serum and saliva among the groups. The present findings suggest the potential of a heterologous three-dose administration for building both systemic and mucosal immunity, . an SC-IN-IN vaccine regimen could be beneficial. Another important observation was abundant packaging of colibactin in MVs, suggesting increased applicability of ΔΔ-MVs in the context of vaccine safety.
Topics: Animals; Mice; Immunity, Mucosal; Probiotics; Escherichia coli; Immunization, Secondary; Female; Adjuvants, Immunologic; Polyketides; Mice, Inbred BALB C; Immunoglobulin A; Peptides; Administration, Intranasal; Immunoglobulin G; Immunoglobulin M; COVID-19 Vaccines
PubMed: 38658133
DOI: 10.1080/21645515.2024.2337987 -
Cell Reports May 2024Atg8 paralogs, consisting of LC3A/B/C and GBRP/GBRPL1/GATE16, function in canonical autophagy; however, their function is controversial because of functional redundancy....
Atg8 paralogs, consisting of LC3A/B/C and GBRP/GBRPL1/GATE16, function in canonical autophagy; however, their function is controversial because of functional redundancy. In innate immunity, xenophagy and non-canonical single membranous autophagy called "conjugation of Atg8s to single membranes" (CASM) eliminate bacteria in various cells. Previously, we reported that intracellular Streptococcus pneumoniae can induce unique hierarchical autophagy comprised of CASM induction, shedding, and subsequent xenophagy. However, the molecular mechanisms underlying these processes and the biological significance of transient CASM induction remain unknown. Herein, we profile the relationship between Atg8s, autophagy receptors, poly-ubiquitin, and Atg4 paralogs during pneumococcal infection to understand the driving principles of hierarchical autophagy and find that GATE16 and GBRP sequentially play a pivotal role in CASM shedding and subsequent xenophagy induction, respectively, and LC3A and GBRPL1 are involved in CASM/xenophagy induction. Moreover, we reveal ingenious bacterial tactics to gain intracellular survival niches by manipulating CASM-xenophagy progression by generating intracellular pneumococci-derived HO.
Topics: Animals; Mice; Autophagy; Autophagy-Related Protein 8 Family; Autophagy-Related Proteins; Macroautophagy; Microtubule-Associated Proteins; Pneumococcal Infections; Streptococcus pneumoniae
PubMed: 38656870
DOI: 10.1016/j.celrep.2024.114131 -
Microbiology Spectrum Jun 2024The International Circumpolar Surveillance (ICS) program is a population-based surveillance network for invasive bacterial diseases throughout Arctic countries and...
UNLABELLED
The International Circumpolar Surveillance (ICS) program is a population-based surveillance network for invasive bacterial diseases throughout Arctic countries and territories. The ICS quality control program for serotyping and antimicrobial susceptibility testing has been ongoing since 1999. Current participating laboratories include the Provincial Laboratory for Public Health in Edmonton, Alberta; Laboratoire de santé publique du Québec in Sainte-Anne-de-Bellevue, Québec; the Centers for Disease Control's Arctic Investigations Program in Anchorage, Alaska; the Neisseria and Streptococcus Reference Laboratory at Statens Serum Institut in Copenhagen, Denmark; the Department of Clinical Microbiology, Landspitali in Reykjavik, Iceland; and Public Health Agency of Canada's National Microbiology Laboratory in Winnipeg, Manitoba. From 2009 to 2020, 140 isolates of were distributed among the six laboratories as part of the quality control program. Overall serotype concordance was 96.9%, with 99.3% concordance to pool level. All participating laboratories had individual concordance rates >92% for serotype and >97% for pool. Overall concordance by modal minimum inhibitory concentration (MIC) for testing done by broth microdilution or Etest was 99.1%, and >98% for all antimicrobials tested. Categorical concordance was >98% by both CLSI and EUCAST criteria. For two laboratories performing disc diffusion, rates of concordance by modal MIC were >97% for most antimicrobials, except chloramphenicol (>93%) and trimethoprim/sulfamethoxazole (>88%). Data collected from 12 years of the ICS quality control program for demonstrate excellent (≥95%) overall concordance for serotype and antimicrobial susceptibility testing results across six laboratories.
IMPORTANCE
Arctic populations experience several social and physical challenges that lead to the increased spread and incidence of invasive diseases. The International Circumpolar Surveillance (ICS) program was developed to monitor five invasive bacterial diseases in Arctic countries and territories. Each ICS organism has a corresponding interlaboratory quality control (QC) program for laboratory-based typing, to ensure the technical precision and accuracy of reference testing services for these regions, and identify and correct potential problems. Here, we describe the results of the ICS QC program, from 2009 to 2020. Excellent overall concordance was achieved for serotype and antimicrobial susceptibility testing results across six laboratories. Ongoing participation in these QC programs ensures the continuation of quality surveillance systems within Arctic populations that experience health disparities.
Topics: Streptococcus pneumoniae; Quality Control; Humans; Microbial Sensitivity Tests; Pneumococcal Infections; Arctic Regions; Anti-Bacterial Agents; Laboratories; Serotyping; Alaska; Serogroup; Epidemiological Monitoring
PubMed: 38651880
DOI: 10.1128/spectrum.04245-23 -
Clinical Medicine (London, England) May 2024The objective of this review was to gain new insight into the rare condition, Austrian syndrome: the triad of endocarditis, meningitis and pneumonia caused by...
OBJECTIVE
The objective of this review was to gain new insight into the rare condition, Austrian syndrome: the triad of endocarditis, meningitis and pneumonia caused by Streptococcus pneumoniae.
METHODS
A systematic review of case reports was conducted using the PRISMA guideline. Cases were rigorously screened to meet a set of well-defined inclusion criteria. Relevant data was aggregated and reported using descriptive statistics.
RESULTS
Seventy-one cases from 69 case reports were included in the final review. The mean age was 56.5 years with a male-to-female ratio of 2.4:1. Alcoholism was reported in 41% of patients. Altered mental state (69%) and fever (65%) (mean temperature on admission = 38.9°C) were the commonest presenting symptoms. The mean duration of symptoms before presentation to the hospital was 8 days. The aortic valve was most commonly affected (56%). The mean duration of antibiotic therapy was 5.6 weeks. Seventy percent of patients were admitted to the intensive care unit (ICU). Fifty-six percent of patients had valvular surgery. The average length of stay in the hospital was 36.9 days. Mortality was recorded in 28% of patients.
CONCLUSION
Austrian syndrome is rare but deadly. The true incidence is unknown but is commoner in middle-aged men and in alcoholics. Affected patients are usually critically unwell, often requiring ICU admission and prolonged hospital stays. Treatment is aggressive including prolonged courses of antibiotics and often, surgery. Despite these, the case fatality rate is high, with death occurring in over a quarter of patients. Surgery appears to be associated with better prognosis.
Topics: Aged; Female; Humans; Male; Middle Aged; Endocarditis, Bacterial; Meningitis, Pneumococcal; Pneumonia, Pneumococcal; Streptococcus pneumoniae; Syndrome
PubMed: 38649138
DOI: 10.1016/j.clinme.2024.100205 -
JCI Insight Apr 2024Sepsis is a leading cause of mortality worldwide, and pneumonia is the most common cause of sepsis in humans. Low levels of high-density lipoprotein cholesterol (HDL-C)...
Sepsis is a leading cause of mortality worldwide, and pneumonia is the most common cause of sepsis in humans. Low levels of high-density lipoprotein cholesterol (HDL-C) levels are associated with an increased risk of death from sepsis, and increasing levels of HDL-C by inhibition of cholesteryl ester transfer protein (CETP) decreases mortality from intraabdominal polymicrobial sepsis in APOE*3-Leiden.CETP mice. Here, we show that treatment with the CETP inhibitor (CETPi) anacetrapib reduced mortality from Streptococcus pneumoniae-induced sepsis in APOE*3-Leiden.CETP and APOA1.CETP mice. Mechanistically, CETP inhibition reduced the host proinflammatory response via attenuation of proinflammatory cytokine transcription and release. This effect was dependent on the presence of HDL, leading to attenuation of immune-mediated organ damage. In addition, CETP inhibition promoted monocyte activation in the blood prior to the onset of sepsis, resulting in accelerated macrophage recruitment to the lung and liver. In vitro experiments demonstrated that CETP inhibition significantly promoted the activation of proinflammatory signaling in peripheral blood mononuclear cells and THP1 cells in the absence of HDL; this may represent a mechanism responsible for improved bacterial clearance during sepsis. These findings provide evidence that CETP inhibition represents a potential approach to reduce mortality from pneumosepsis.
Topics: Animals; Female; Humans; Mice; Apolipoprotein E3; Cholesterol Ester Transfer Proteins; Cholesterol, HDL; Disease Models, Animal; Macrophages; Monocytes; Pneumonia, Pneumococcal; Sepsis; Streptococcus pneumoniae; THP-1 Cells
PubMed: 38646937
DOI: 10.1172/jci.insight.173205