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European Journal of Clinical... Jan 2014Invasive fungal diseases (IFDs) have been widely studied in recent years, largely because of the increasing population at risk. Aspergillus and Candida species remain... (Review)
Review
Invasive fungal diseases (IFDs) have been widely studied in recent years, largely because of the increasing population at risk. Aspergillus and Candida species remain the most common causes of IFDs, but other fungi are emerging. The early and accurate diagnosis of IFD is critical to outcome and the optimisation of treatment. Rapid diagnostic methods and new antifungal therapies have advanced disease management in recent years. Strategies for the prevention and treatment of IFDs include prophylaxis, and empirical and pre-emptive therapy. Here, we review the available primary literature on the clinical and economic burden of IFDs in Europe from 2000 to early 2011, with a focus on the value and outcomes of different approaches.
Topics: Antifungal Agents; Aspergillosis; Candidiasis; Clinical Laboratory Techniques; Early Diagnosis; Europe; Humans
PubMed: 24026863
DOI: 10.1007/s10096-013-1944-3 -
Frontiers in Immunology 2022Aspergillosis is a fungal infection caused mainly by that often results in respiratory disease in birds. Aspergillosis is a major cause of morbidity and mortality in...
Aspergillosis is a fungal infection caused mainly by that often results in respiratory disease in birds. Aspergillosis is a major cause of morbidity and mortality in captive-bred penguin species. Currently, there is no registered vaccine to prevent aspergillosis. Recent research demonstrated that oral administration of gram-negative bacteria expressing high levels of galactose-α-1,3-galactose (α-Gal) modulates anti-α-Gal immunity and protects turkeys from clinical aspergillosis caused by experimental infection. The role of anti-α-Gal immunity in penguins has not been studied. Here, we tested the distribution of α-1,3-galactosyltransferase (α1,3GT) genes in the fecal microbiome of Humboldt penguins (). The occurrence of natural anti-α-Gal antibodies (Abs) in sera and eggs of healthy Humboldt penguins was also assessed. A trial was then conducted to test whether oral administration of Nissle, expressing high α-Gal levels, modulates anti-α-Gal immunity in a colony of Humboldt penguins. Animals in the vaccination and placebo groups were evaluated before the trial and followed for one year for aspergillosis detection using a diagnostic panel including computed tomography scans, capillary zone electrophoresis, 3-hydroxybutyrate levels, and anti- Abs. Anti-α-Gal Abs were detected in sera (IgM and IgY) and eggs (IgY) of healthy penguins. Microbiota analysis and functional predictions revealed the presence of α1,3GT genes in the microbiota of Humboldt penguins and other penguin species. A strong decrease in anti-α-Gal IgM levels was observed in all animals in the placebo group three months after vaccination protocol. This decrease was not observed in Nissle-treated penguins. After the vaccination protocol, we found a positive correlation between anti- IgY and anti-α-Gal IgY in the Nissle group, suggesting a correlation between the presence of the bacteria and these Abs. During the study period, three penguins exhibited respiratory signs consistent with aspergillosis. Two were from the placebo group whose symptoms resolved with specific treatments, while a single vaccinated individual developed fatal respiratory aspergillosis eight months after the trial. We conclude that Nissle represents a safe potential probiotic with a protective effect against aspergillosis in Humboldt penguins that deserves to be further explored for therapeutic uses in these animals.
Topics: Animals; Aspergillosis; Escherichia coli; Galactose; Immunoglobulin M; Probiotics; Spheniscidae; Vaccines
PubMed: 35634323
DOI: 10.3389/fimmu.2022.897223 -
BMC Infectious Diseases Feb 2024Invasive Aspergillosis (IA) is a life-threatening fungal disease with significant mortality rates. Timely diagnosis and treatment greatly enhance patient outcomes. This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Invasive Aspergillosis (IA) is a life-threatening fungal disease with significant mortality rates. Timely diagnosis and treatment greatly enhance patient outcomes. This study aimed to explore the association between patient age and the development of IA, as well as the potential implications for risk stratification strategies.
METHODS
We searched National Center for Biotechnology Information (NCBI) databases for publications until October 2023 containing age characteristics of patients with and without IA. A random-effects model with the application of inverse-variance weighting was used to pool reported estimates from each study, and meta-regression and subgroup analyses were utilized to assess sources of heterogeneity.
RESULTS
A systematic review was conducted, resulting in the inclusion of 55 retrospective observational studies with a total of 13,983 patients. Meta-analysis revealed that, on average, patients with IA were approximately two and a half years older (95% Confidence Interval [CI] 1.84-3.31 years; I = 26.1%) than those without the disease (p < 0.0001). No significant moderators could explain the observed heterogeneity in age difference. However, subgroup analysis revealed that age differences were more pronounced within particular patient groups compared to others. For example, patients with and without IA who had primary severe lung infections exhibited a greater difference in mean age than other patient cohorts.
CONCLUSIONS
Further research, such as individual patient data meta-analysis, is necessary to better understand the potential relationship between increasing age and the likelihood of IA. Improved risk stratification strategies based on patient age could potentially enhance the early detection and treatment of IA, ultimately improving patient outcomes.
Topics: Humans; Retrospective Studies; Aspergillosis; Invasive Fungal Infections; Databases, Factual; Probability
PubMed: 38373908
DOI: 10.1186/s12879-024-09109-2 -
Proceedings of the National Academy of... May 2021This paper presents a modular software design for the construction of computational modeling technology that will help implement precision medicine. In analogy to a...
This paper presents a modular software design for the construction of computational modeling technology that will help implement precision medicine. In analogy to a common industrial strategy used for preventive maintenance of engineered products, medical digital twins are computational models of disease processes calibrated to individual patients using multiple heterogeneous data streams. They have the potential to help improve diagnosis, prognosis, and personalized treatment for a wide range of medical conditions. Their large-scale development relies on both mechanistic and data-driven techniques and requires the integration and ongoing update of multiple component models developed across many different laboratories. Distributed model building and integration requires an open-source modular software platform for the integration and simulation of models that is scalable and supports a decentralized, community-based model building process. This paper presents such a platform, including a case study in an animal model of a respiratory fungal infection.
Topics: Algorithms; Animals; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Computational Biology; Humans; Patient-Specific Modeling; Precision Medicine; Software; Spores, Fungal
PubMed: 33972437
DOI: 10.1073/pnas.2024287118 -
Respiratory Medicine Jan 2022Literature regarding trends of mortality, and complications of aspergillosis infection among patients with acute exacerbation of chronic obstructive pulmonary disease...
BACKGROUND
Literature regarding trends of mortality, and complications of aspergillosis infection among patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is limited.
METHODS
Data from the National Readmissions Database (NRD) that constitutes 49.1% of the stratified sample of all hospitals in the United States (US), representing more than 95% of the national population were analyzed for hospitalizations with aspergillosis among AECOPD. Predictors and trends related to aspergillosis in AECOPD were evaluated. A Linear p-trend was used to assess the trends.
RESULTS
Out of the total 7,282,644 index hospitalizations for AECOPD (mean age 69.17 ± 12.04years, 55.3% females), 8209 (11.2/10,000) with primary diagnosis of invasive aspergillosis were recorded in the NRD for 2013-2018. Invasive aspergillosis was strongly associated with mortality (OR 4.47, 95%CI 4.02-4.97, p < 0.001) among AECOPD patients. Malignancy and organ transplant status were predominant predictors of developing aspergillosis among AECOPD patients. The IA-AECOPD group had higher rates of multi-organ manifestations including ACS (3.7% vs 0.44%; p-value0.001), AF (20% vs 18.4%; p-value0.001), PE (4.79% vs1.87%; p-value0.001), AKI (22.3% vs17.5%; p-value0.001), ICU admission (16.5% vs11.9%; p-value0.001), and MV (22.3% vs7.31%; p-value0.001) than the AECOPD group. The absolute yearly trend for mortality of aspergillosis was steady (linear p-trend 0.22) while the yearly rate of IA-AECOPD had decreased from 15/10,000 in 2013 to 9/10,000 in 2018 (linear p-trend 0.02).
INTERPRETATION
Aspergillosis was related with high mortality among AECOD hospitalizations. There has been a significant improvement in the yearly rates of aspergillosis while the mortality trend was steady among aspergillosis subgroups. Improved risk factor management through goal-directed approach may improve clinical outcomes.
Topics: Acute Disease; Aged; Aged, 80 and over; Aspergillosis; Disease Progression; Female; Hospital Mortality; Hospitalization; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; United States
PubMed: 34959147
DOI: 10.1016/j.rmed.2021.106720 -
Journal of Infection and Public Health Feb 2014Invasive Candida infections contribute to significant morbidity and mortality in patients with healthcare-associated infections. They represent a major burden on the... (Review)
Review
Invasive Candida infections contribute to significant morbidity and mortality in patients with healthcare-associated infections. They represent a major burden on the public health system, and are challenging to diagnose and treat. A multidisciplinary expert panel critically reviewed available evidence to provide consensus recommendations for the management of invasive Candida infections in the Middle East. Based on diagnosis, recommendations were provided for the management of Candida infections in non-neutropenic and neutropenic patients. Polyenes (amphotericin B-deoxycholate [AmB-d] and lipid formulations amphotericin B [LFAmB]), triazoles (fluconazole, itraconazole and voriconazole), echinocandins (caspofungin, anidulafungin, and micafungin) and flucytosine are the recommended categories of antifungal agents for treatment of Candida infections. Echinocandins are preferred for treatment of proven and suspected Candida infections, especially in critically ill patients or those with previous exposure to azoles. Recommendations were also provided for infections caused by specific Candida species as well as management of different disease conditions. The experts highlighted that the guidelines should be used along with clinical judgment. Given the paucity of published data from the region, research in the form of randomized clinical trials should be given priority.
Topics: Adult; Aspergillosis; Candidiasis, Invasive; Humans; Practice Guidelines as Topic
PubMed: 24035607
DOI: 10.1016/j.jiph.2013.08.002 -
Journal of Zoo and Wildlife Medicine :... Mar 2022Aspergillosis remains a difficult disease to diagnose antemortem in many species, especially avian species. In the present study, banked plasma samples from various...
Aspergillosis remains a difficult disease to diagnose antemortem in many species, especially avian species. In the present study, banked plasma samples from various avian species were examined for gliotoxin (GT), which is a recognized key virulence factor produced during the replication of species hyphae and a secondary metabolite bis(methyl)gliotoxin (bmGT). Initially, liquid chromatography-tandem mass spectrometry methods for detecting GT and bmGT were validated in a controlled model using sera obtained from rats experimentally infected with . The minimum detection level for both measurements was determined to be 3 ng/ml, and the assay was found to be accurate and reliable. As proof of concept, GT was detected in 85.7% (30/35) of the samples obtained from birds with confirmed aspergillosis and in 60.7% (17/28) of samples from birds with probable infection but only in one of those from clinically normal birds (1/119). None of the birds were positive for bmGT. Repeated measures from birds under treatment suggests results may have prognostic value. Further studies are needed to implement quantitative methods and to determine the utility of this test in surveillance screening in addition to its use as a diagnostic test in birds with suspected aspergillosis.
Topics: Animals; Aspergillosis; Aspergillus; Aspergillus fumigatus; Birds; Gliotoxin; Rats
PubMed: 35339150
DOI: 10.1638/2021-0070 -
Disease Models & Mechanisms Mar 2022Invasive pulmonary aspergillosis (IPA) caused by the mold Aspergillus fumigatus is one of the most important life-threatening infections in immunocompromised patients....
Invasive pulmonary aspergillosis (IPA) caused by the mold Aspergillus fumigatus is one of the most important life-threatening infections in immunocompromised patients. The alarming increase of isolates resistant to the first-line recommended antifungal therapy urges more insights into triazole-resistant A. fumigatus infections. In this study, we systematically optimized a longitudinal multimodal imaging-compatible neutropenic mouse model of IPA. Reproducible rates of pulmonary infection were achieved through immunosuppression (sustained neutropenia) with 150 mg/kg cyclophosphamide at day -4, -1 and 2, and an orotracheal inoculation route in both sexes. Furthermore, increased sensitivity of in vivo bioluminescence imaging for fungal burden detection, as early as the day after infection, was achieved by optimizing luciferin dosing and through engineering isogenic red-shifted bioluminescent A. fumigatus strains, one wild type and two triazole-resistant mutants. We successfully tested appropriate and inappropriate antifungal treatment scenarios in vivo with our optimized multimodal imaging strategy, according to the in vitro susceptibility of our luminescent fungal strains. Therefore, we provide novel essential mouse models with sensitive imaging tools for investigating IPA development and therapy in triazole-susceptible and triazole-resistant scenarios.
Topics: Animals; Aspergillosis; Aspergillus fumigatus; Female; Humans; Invasive Pulmonary Aspergillosis; Male; Mice; Multimodal Imaging; Triazoles
PubMed: 35352801
DOI: 10.1242/dmm.049165 -
Oncology (Williston Park, N.Y.) Aug 2001The incidence of invasive aspergillosis is increasing parallel to the intensity of immunosuppressive and myelosuppressive anticancer treatments. Successful management is... (Review)
Review
The incidence of invasive aspergillosis is increasing parallel to the intensity of immunosuppressive and myelosuppressive anticancer treatments. Successful management is linked to an understanding of the pathogenesis and recognition of risk factors. Identifying the patients and clinical circumstances associated with the highest risk for invasive aspergillosis and managing patients in protected environments remain the most effective means of prevention. Early accurate diagnosis continues to be a challenge; however, newer non-culture-based methods are encouraging and have been incorporated into standardized case definitions. Unacceptably high mortality rates persist with current treatment of established infection. Among the newer potentially less toxic antifungal therapies are the triazoles, and lipid-based polyene-formulations that target the fungal cell membrane and 1,3-beta-D-glucan synthase inhibitors that target the fungal cell wall. These agents are currently in clinical trials. Host defense augmentation using hematopoietic growth factors with or without other cytokines such as interferon-gamma or hematopoietic growth factor-stimulated neutrophil transfusions remain controversial strategies that have yet to be tested in well-designed randomized controlled trials.
Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Fungemia; Humans; Immunocompromised Host; Itraconazole; Risk Factors
PubMed: 11548975
DOI: No ID Found -
The Israel Medical Association Journal... May 2007
Topics: Antifungal Agents; Aspergillosis; Combined Modality Therapy; Humans; Hyperbaric Oxygenation; Mucormycosis
PubMed: 17591380
DOI: No ID Found