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Nature Communications Nov 2023Surface antigenic variation is crucial for major pathogens that infect humans. To escape the immune system, they exploit various mechanisms. Understanding these...
Surface antigenic variation is crucial for major pathogens that infect humans. To escape the immune system, they exploit various mechanisms. Understanding these mechanisms is important to better prevent and fight the deadly diseases caused. Those used by the fungus Pneumocystis jirovecii that causes life-threatening pneumonia in immunocompromised individuals remain poorly understood. Here, though this fungus is currently not cultivable, our detailed analysis of the subtelomeric sequence motifs and genes encoding surface proteins suggests that the system involves the reassortment of the repertoire of ca. 80 non-expressed genes present in each strain, from which single genes are retrieved for mutually exclusive expression. Dispersion of the new repertoires, supposedly by healthy carrier individuals, appears very efficient because identical alleles are observed in patients from different countries. Our observations reveal a unique strategy of antigenic variation. They also highlight the possible role in genome rearrangements of small imperfect mirror sequences forming DNA triplexes.
Topics: Humans; Mosaicism; Pneumocystis carinii; Antigenic Variation; DNA, Fungal
PubMed: 37919276
DOI: 10.1038/s41467-023-42685-6 -
BMJ Open Oct 2023We aimed to identify exercise tests that have been validated to support a safe discharge to home in patients with or without COVID-19. (Review)
Review
OBJECTIVES
We aimed to identify exercise tests that have been validated to support a safe discharge to home in patients with or without COVID-19.
STUDY DESIGN
Scoping review, using PRISMA-ScR reporting standards. Medline, PubMed, AMED, Embase, CINAHL and LitCovid databases were searched between 16 and 22 February 2021, with studies included from any publication date up to and including the search date.
INTERVENTION
Short exercise tests.
PRIMARY OUTCOME MEASURES
Safe discharge from hospital, readmission rate, length of hospital stay, mortality. Secondary outcomes measures: safety, feasibility and reliability.
RESULTS
Of 1612 original records screened, 19 studies were included in the analysis. These used a variety of exercise tests in patients with chronic obstructive pulmonary disease, suspected pulmonary embolism and pneumocystis carinii pneumonia, heart failure or critical illness. Only six studies had examined patients with COVID-19, of these two were still recruiting to evaluate the 1 min sit-to-stand test and the 40-steps test. There was heterogeneity in patient populations, tests used and outcome measures. Few exercise tests have been validated to support discharge decisions. There is currently no support for short exercise tests for triage of care in patients with COVID-19.
CONCLUSIONS
Further research is needed to aid clinical decision-making at discharge from hospital.
Topics: Humans; COVID-19; Patient Discharge; Exercise Test; Reproducibility of Results; Hospitals
PubMed: 37907292
DOI: 10.1136/bmjopen-2022-068169 -
Epidemiology and Infection Oct 2023Secondary pneumonia occurs in 8-24% of patients with Coronavirus 2019 (COVID-19) infection and is associated with increased morbidity and mortality. Diagnosis of...
Secondary pneumonia occurs in 8-24% of patients with Coronavirus 2019 (COVID-19) infection and is associated with increased morbidity and mortality. Diagnosis of secondary pneumonia can be challenging. The purpose of this study was to evaluate the use of plasma microbial cell free DNA sequencing (mcfNGS) in the evaluation of secondary pneumonia after COVID-19. We performed a single-center case series of patients with COVID-19 who underwent mcfNGS to evaluate secondary pneumonia and reported the organisms identified, concordance with available tests, clinical utility, and outcomes. In 8/13 (61%) cases, mcfNGS detected 1-6 organisms, with clinically significant organisms identified in 4 cases, including , and spp. Management was changed in 85% (11/13) of patients based on results, including initiation of targeted therapy, de-escalation of empiric antimicrobials, and avoiding contingent escalation of antifungals. mcfNGS may be helpful to identify pathogens causing secondary pneumonia, including opportunistic pathogens in immunocompromised patients with COVID-19. However, providers need to carefully interpret this test within the clinical context.
Topics: Humans; Pneumonia, Pneumocystis; COVID-19; Pneumocystis carinii; Anti-Infective Agents; High-Throughput Nucleotide Sequencing
PubMed: 37886888
DOI: 10.1017/S0950268823001711 -
Journal of Clinical Microbiology Nov 2023Bronchoalveolar lavage is usually employed for molecular diagnosis of but requires a specialized procedure. By contrast, nasopharyngeal (NP) specimens are easily...
Bronchoalveolar lavage is usually employed for molecular diagnosis of but requires a specialized procedure. By contrast, nasopharyngeal (NP) specimens are easily obtained. In this retrospective study of 35 patients with paired NP and bronchoscopy specimens, NP specimens had a 100% negative percent agreement (95% CI 80.5-100) but only 72.2% positive percent agreement (95% CI 46.5-90.3).
Topics: Humans; Pneumonia, Pneumocystis; Retrospective Studies; Bronchoalveolar Lavage Fluid; Sensitivity and Specificity; Canada; Polymerase Chain Reaction; Pneumocystis carinii
PubMed: 37877691
DOI: 10.1128/jcm.00913-23 -
Gut and Liver May 2024: pneumonia (PJP) is a rare but potentially fatal infection. This study was conducted to investigate the risk factors for PJP in inflammatory bowel disease (IBD)...
BACKGROUND/AIMS
: pneumonia (PJP) is a rare but potentially fatal infection. This study was conducted to investigate the risk factors for PJP in inflammatory bowel disease (IBD) patients.
METHODS
: This nationwide, population-based study was conducted in Korea using claims data. Cases of PJP were identified in patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) between 2010 and 2017, and the clinical data of each patient was analyzed. Dual and triple therapy was defined as the simultaneous prescription of two or three of the following drugs: steroids, calcineurin inhibitors, immunomodulators, and biologics.
RESULTS
: During the mean follow-up period (4.6±2.3 years), 84 cases of PJP were identified in 39,462 IBD patients (31 CD and 53 UC). For CD patients, only age at diagnosis >40 years (hazard ratio [HR], 6.12; 95% confidence interval [CI], 1.58 to 23.80) was significantly associated with the risk of PJP, whereas in UC patients, diagnoses of diabetes (HR, 2.51; 95% CI, 1.19 to 5.31) and chronic obstructive pulmonary disease (HR, 3.41; 95% CI, 1.78 to 6.52) showed significant associations with PJP risk. Triple therapy increased PJP risk in both UC (HR, 3.90; 95% CI, 1.54 to 9.88) and CD patients (HR, 5.69; 95% CI, 2.32 to 14.48). However, dual therapy increased PJP risk only in UC patients (HR, 2.53; 95% CI, 1.36 to 4.70). Additionally, 23 patients (27%) received intensive care treatment, and 10 (12%) died within 30 days.
CONCLUSIONS
: PJP risk factors differ in CD and UC patients. Considering the potential fatality of PJP, prophylaxis should be considered for at-risk IBD patients.
Topics: Humans; Male; Female; Pneumonia, Pneumocystis; Risk Factors; Adult; Republic of Korea; Middle Aged; Pneumocystis carinii; Colitis, Ulcerative; Crohn Disease; Inflammatory Bowel Diseases; Aged; Young Adult; Retrospective Studies
PubMed: 37867439
DOI: 10.5009/gnl230152 -
BMC Infectious Diseases Oct 2023Pneumocystis jirovecii pneumonia (PCP) and SARS-CoV2 share some similarities in their effects on the respiratory system, clinical presentation, and management. The... (Observational Study)
Observational Study
BACKGROUND
Pneumocystis jirovecii pneumonia (PCP) and SARS-CoV2 share some similarities in their effects on the respiratory system, clinical presentation, and management. The COVID-19 pandemic required rapid action to curb transmission and mitigate its lethiferous impact. Non-pharmaceutical interventions (NPIs) were globally adopted. We hypothesized that these measures reduced the transmission and acquisition of P. jirovecii in both hospital and community settings.
METHODS
We conducted a retrospective observational study on 2950 respiratory specimens from patients with suspected pulmonary infection, analyzed at the Laboratory of Parasitology Unit of the Policlinico Tor Vergata of Rome, Italy, from January 2014 to December 2022.
RESULTS
We show a significant reduction in the frequency of PCP in the COVID-19 pandemic era compared to the previous period. Among the four sequence types of P. jirovecii identified, genotype 1 was the most prevalent (37%). We observed a non-significant trend of decreasing cases with genotype 1 and increasing cases with genotype 3 over the study period.
CONCLUSIONS
The nationwide implementation of NPIs against COVID-19 may have changed the microbiological landscape of exposure, thereby decreasing the exposure to P. jirovecii and consequently reducing the incidence of PCP.
Topics: Humans; Pneumonia, Pneumocystis; Retrospective Studies; Pneumocystis carinii; Pandemics; RNA, Viral; COVID-19; SARS-CoV-2
PubMed: 37848811
DOI: 10.1186/s12879-023-08545-w -
Emerging Microbes & Infections Dec 2023AIDS: acquired immune deficiency syndrome; CI: confidence interval; EPHI: Ethiopian Public Health Institute; HAART: highly active antiretroviral therapy; HIV: human...
AIDS: acquired immune deficiency syndrome; CI: confidence interval; EPHI: Ethiopian Public Health Institute; HAART: highly active antiretroviral therapy; HIV: human immunodeficiency virus; HR: hazard ratio; Mg/dl: milligram per deciliter; TB: tuberculosis; PCP: pneumocystis carinii pneumonia; ZJU: Zhejiang University.
Topics: Humans; Female; Ethiopia; AIDS-Related Opportunistic Infections; HIV Infections; Acquired Immunodeficiency Syndrome; Neoplasms; Antiretroviral Therapy, Highly Active
PubMed: 37824698
DOI: 10.1080/22221751.2023.2271065 -
BioRxiv : the Preprint Server For... Sep 2023spp. are host obligate fungal pathogens that can cause severe pneumonia in mammals and rely heavily on their host for essential nutrients. The lack of a sustainable...
spp. are host obligate fungal pathogens that can cause severe pneumonia in mammals and rely heavily on their host for essential nutrients. The lack of a sustainable culture system poses challenges in understanding their metabolism and the acquisition of essential nutrients from host lungs remains unexplored. Transmission electron micrographs show Extracellular Vesicles (EVs) are found near spp. within the lung. We hypothesized that EVs transport essential nutrients to the fungi during infection. To investigate this, EVs from and infected rodents were biochemically and functionally characterized. These EVs contained host proteins involved in cellular, metabolic, and immune processes as well as proteins with homologs found in other fungal EV proteomes, indicating may release EVs. Notably, EV uptake by indicated their potential involvement in nutrient acquisition and indicate a possibility for using engineered EVs for efficient therapeutic delivery. However, EVs added to , did not show increased growth or viability, implying that additional nutrients or factors are necessary to support their metabolic requirements. Exposure of macrophages to EVs increased proinflammatory cytokine levels, but did not affect macrophages' ability to kill or phagocytose . These findings provide vital insights into and host EV interactions, yet the mechanisms underlying 's survival in the lung remain uncertain. These studies are the first to isolate, characterize, and functionally assess EVs from -infected rodents, promising to enhance our understanding of host-pathogen dynamics and therapeutic potential.
PubMed: 37786700
DOI: 10.1101/2023.09.19.558454 -
Biomedica : Revista Del Instituto... Aug 2023Pneumocystis jirovecii is an opportunistic fungus that affects mainly people living with HIV (CD4 cell count lower than 200 cells/ml) and other immunosuppressed...
INTRODUCTION
Pneumocystis jirovecii is an opportunistic fungus that affects mainly people living with HIV (CD4 cell count lower than 200 cells/ml) and other immunosuppressed patients. Since P. jirovecii does not grow on routine mycological media, diagnosis of P. jirovecii pneumonia relies on indirect evidence of its presence in respiratory samples.
OBJECTIVES
To associate the results of direct immunofluorescence and two molecular methods with a score to predict P. jirovecii pneumonia in patients with AIDS.
MATERIALS AND METHODS
A prospective study was conducted with 40 patients. A respiratory sample collected before treatment was subjected to direct immunofluorescence using the Merifluor kit, to nested PCR targeting the mitochondrial large subunit ribosomal RNA, and to the VIASURE real-time PCR kit.
RESULTS
These three techniques revealed P. jirovecii in 6, 12, and 15 samples, respectively. All positive samples by direct immunofluorescence were positive by nested PCR, and all positive samples by nested PCR amplified by real-time PCR. There was a statistically significant association between the P. jirovecii pneumonia score and the molecular methods. Two patients were early diagnosed and responded well to treatment.
CONCLUSION
Molecular methods, especially real-time PCR, are recommended for early diagnosis of P. jirovecii pneumonia in AIDS patients.
Topics: Humans; Real-Time Polymerase Chain Reaction; Pneumonia, Pneumocystis; Acquired Immunodeficiency Syndrome; Prospective Studies; Pneumocystis carinii
PubMed: 37721900
DOI: 10.7705/biomedica.7020 -
Diagnostics (Basel, Switzerland) Aug 2023The objective of this study was to formulate and validate a prognostic model for postoperative severe pneumonia (SPCP) in kidney transplant recipients utilizing machine...
BACKGROUND
The objective of this study was to formulate and validate a prognostic model for postoperative severe pneumonia (SPCP) in kidney transplant recipients utilizing machine learning algorithms, and to compare the performance of various models.
METHODS
Clinical manifestations and laboratory test results upon admission were gathered as variables for 88 patients who experienced PCP following kidney transplantation. The most discriminative variables were identified, and subsequently, Support Vector Machine (SVM), Logistic Regression (LR), Random Forest (RF), K-Nearest Neighbor (KNN), Light Gradient Boosting Machine (LGBM), and eXtreme Gradient Boosting (XGB) models were constructed. Finally, the models' predictive capabilities were assessed through ROC curves, sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and F1-scores. The Shapley additive explanations (SHAP) algorithm was employed to elucidate the contributions of the most effective model's variables.
RESULTS
Through lasso regression, five features-hemoglobin (Hb), Procalcitonin (PCT), C-reactive protein (CRP), progressive dyspnea, and Albumin (ALB)-were identified, and six machine learning models were developed using these variables after evaluating their correlation and multicollinearity. In the validation cohort, the RF model demonstrated the highest AUC (0.920 (0.810-1.000), F1-Score (0.8), accuracy (0.885), sensitivity (0.818), PPV (0.667), and NPV (0.913) among the six models, while the XGB and KNN models exhibited the highest specificity (0.909) among the six models. Notably, CRP exerted a significant influence on the models, as revealed by SHAP and feature importance rankings.
CONCLUSIONS
Machine learning algorithms offer a viable approach for constructing prognostic models to predict the development of severe disease following PCP in kidney transplant recipients, with potential practical applications.
PubMed: 37685276
DOI: 10.3390/diagnostics13172735