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    F508del CFTR gene mutation in patients with allergic bronchopulmonary aspergillosis.
    J Asthma 2017 Oct 16:1-7. Epub 2017 Oct 16.
    a The National Aspergillosis Centre , University Hospital of South Manchester, The University of Manchester and Manchester Academic Health Science Centre , Manchester , UK.
    Objective: The F508del mutation occurs in approximately 3.5% of Caucasian population of Northern Europe. Heterozygotes have increased risk for asthma and reduced pulmonary function. Read More

    Impact of CYP2C19 Polymorphisms on Serum Concentration of Voriconazole in Iranian Hematological Patients.
    J Res Pharm Pract 2017 Jul-Sep;6(3):151-157
    Hematology-Oncology and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran.
    Objective: This study aimed to determine the portion of Iranian patients who attain therapeutic serum concentrations of voriconazole (VRCZ) following administration of fixed doses. In addition, the effect of CYP2C19 polymorphism on serum levels of VRCZ was also investigated.

    Methods: Forty-eight adult patients of Iranian origin with hematologic malignancies, who received VRCZ for treatment of invasive aspergillosis, were recruited into the study. Read More

    Pentraxin 3 gene polymorphisms and pulmonary aspergillosis in COPD patients.
    Clin Infect Dis 2017 Aug 19. Epub 2017 Aug 19.
    Department of Respiratory and Critical Care Medicine, Jinling Hospital, Southern Medical University, Guangzhou, China, 510515.
    Background: Pentraxin 3 (PTX3) plays an important role in resistance to Aspergillus infections. Previous studies have suggested that PTX3 polymorphisms influence the risk of invasive aspergillosis among transplantation recipients. This study was to investigate the association between PTX3 gene polymorphisms and pulmonary aspergillosis in chronic obstructive pulmonary disease (COPD) population. Read More

    Invasive Fungal Disease in Pediatric Solid Organ Transplant Recipients.
    J Pediatric Infect Dis Soc 2017 Jun 15. Epub 2017 Jun 15.
    Center for Clinical Epidemiology and Biostatistics.
    Background: Solid organ transplant (SOT) recipients are at risk for invasive fungal disease (IFD). Data on IFD burden in pediatric patients are limited. We aimed to determine the incidence and outcome of IFD in a large cohort of pediatric patients who underwent SOT. Read More

    Simulations of CYP51A from Aspergillus fumigatus in a model bilayer provide insights into triazole drug resistance.
    Med Mycol 2017 Sep 9. Epub 2017 Sep 9.
    Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
    Azole antifungal drugs target CYP51A in Aspergillus fumigatus by binding with the active site of the protein, blocking ergosterol biosynthesis. Resistance to azole antifungal drugs is now common, with a leucine to histidine amino acid substitution at position 98 the most frequent, predominantly conferring resistance to itraconazole, although cross-resistance has been reported in conjunction with other mutations. In this study, we create a homology model of CYP51A using a recently published crystal structure of the paralog protein CYP51B. Read More

    Amphotericin B concentrations in healthy mallard ducks (Anas platyrhynchos) following a single intratracheal dose of liposomal amphotericin B using an atomizer.
    Med Mycol 2017 Aug 3. Epub 2017 Aug 3.
    Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, California.
    Aspergillosis is a fungal infection that primarily affects the respiratory tract. Amphotericin B has broad antifungal activity and is commonly used to treat aspergillosis, a fungal pneumonia that is a common sequela in oiled waterfowl as well as other birds in wildlife rehabilitation. Pharmacokinetic parameters of nebulized amphotericin B in an avian model have been reported, but those of direct intratracheal delivery have yet to be established. Read More

    Chronic necrotizing pulmonary aspergillosis in an immunocompetent patient after the surgery of hydatid cyst.
    Tuberk Toraks 2017 Jun;65(2):157-160
    Division of Pediatric Chest Diseases, Faculty of Medicine, Hacettepe University, Children Hospital, Ankara, Turkey.
    Chronic necrotizing pulmonary aspergillosis (CNPA) is a condition caused by the ubiquitous fungus Aspergillus fumigatus in non-immunocompromised individuals. Numerous underlying conditions have been associated with CNPA. Tuberculosis, non-tuberculous mycobacterial infection and allergic bronchopulmonary aspergillosis (ABPA) remain the predominant risk factors for development of CNPA. Read More

    [A case of pulmonary alternariosis complicated with aspergillosis].
    Zhong Nan Da Xue Xue Bao Yi Xue Ban 2017 Sep;42(9):1122-1128
    Department of Respiratory Medicine, Second Xiangya Hospital; Research Unit of Respiratory Disease; Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha 410011, China.
    A 61-year-old woman with pulmonary alternariosis and aspergillosis was reported. The patient presented with recurrent hemoptysis and cough for 3 years. Alternaria was identified by fungal culture. Read More

    Parasitic and fungal infections.
    Handb Clin Neurol 2017 ;145:245-262
    Department of Neuropathology, Charité - Universitätsmedizin Berlin, Berlin, Germany. Electronic address:
    Parasitic infections of the central nervous system (CNS) comprise a plethora of infectious agents leading to a multitude of different disease courses and thus diagnostic and therapeutic challenges. The prevalence of different pathogens is basically dependent on geographic and ethnic backgrounds, its infectious route frequently involving a third party, such as flies or domestic animals. The present review focuses on cerebral malaria due to Plasmodium falciparum infection, and Toxoplasma gondii encephalitis. Read More

    [Aspergillus in airway material : Ignore or treat?]
    Internist (Berl) 2017 Oct 6. Epub 2017 Oct 6.
    Klinische Abteilung für Pulmonologie, Medizinische Universität Graz, Graz, Österreich.
    Fungi of the genus Aspergillus are ubiquitously present. Even though humans inhale Aspergillus spores daily under natural conditions, Aspergillus-associated pulmonary diseases only occur under special circumstances. Whether an Aspergillus-associated disease develops and which type of Aspergillus-associated disease develops depends on the constitution of the host. Read More

    Type III interferon is a critical regulator of innate antifungal immunity.
    Sci Immunol 2017 Oct;2(16)
    Center for Immunity and Inflammation, New Jersey Medical School, Rutgers Biomedical and Health Sciences (RBHS), Newark, NJ 07103, USA.
    Type III interferons (IFN-λs) are the most recently found members of the IFN cytokine family and engage IFNLR1 and IL10R2 receptor subunits to activate innate responses against viruses. We have identified IFN-λs as critical instructors of antifungal neutrophil responses. Using Aspergillus fumigatus (Af) as a model to study antifungal immune responses, we found that depletion of CCR2(+) monocytes compromised the ability of neutrophils to control invasive fungal growth. Read More

    Aspergillus galactomannan detection in exhaled breath condensate compared to bronchoalveolar lavage fluid for the diagnosis of invasive aspergillosis in immunocompromised patients.
    Clin Microbiol Infect 2017 Sep 29. Epub 2017 Sep 29.
    Transplant Infectious Diseases, Multi-Organ Transplant Program, University Health Network, University of Toronto, Toronto, Ontario, Canada; Department of Medicine, University Health Network, Toronto, Ontario, Canada.
    Objective: Exhaled breath condensate (EBC) is a noninvasive means of sampling the airways that has shown significant promise in the diagnosis of many disorders. There have been no reports of its utility for the detection of galactomannan (GM), a component of the cell wall of Aspergillus. The suitability of EBC for the detection of GM for the diagnosis of invasive aspergillosis (IA) using the Platelia(®)Aspergillus enzyme-linked immunosorbent assay (ELISA) was investigated. Read More

    Pharmacodynamics of the Novel Antifungal Agent F901318 for Acute Sinopulmonary Aspergillosis Caused by Aspergillus flavus.
    J Infect Dis 2017 Sep 12. Epub 2017 Sep 12.
    Antimicrobial Pharmacodynamics and Therapeutics, University of Liverpool, Liverpool, UK.
    Background: Aspergillus flavus is one of the most common agents of invasive aspergillosis and is associated with high mortality. The orotomides are a new class of antifungal agents with a novel mechanism of action. An understanding of the pharmacodynamics of the lead compound F901318 is required to plan safe and effective regimens for clinical use. Read More

    Comparative evaluation of galactomannan test with bronchoalveolar lavage and serum for the diagnosis of invasive aspergillosis in patients with hematological malignancies.
    J Lab Physicians 2017 Oct-Dec;9(4):234-238
    Department of Hematology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India.
    Introduction: Invasive pulmonary aspergillosis (IPA) is a major cause of morbidity and mortality in patients with hematological malignancies. In recent years, testing for values of galactomannan (GM) in serum and bronchoalveolar lavage (BAL) fluid has been investigated as a diagnostic test for IPA for such patients, but global experience and consensus on optical density (OD) cutoffs, especially for BAL galactomannan remains lacking.

    Methods: We performed a prospective case-control study to determine an optimal BAL GM OD cutoff for IPA in at-risk patients. Read More

    Comparison of serum PCR assay and histopathology for the diagnosis of invasive aspergillosis and mucormycosis in immunocompromised patients with sinus involvement.
    Curr Med Mycol 2016 Dec;2(4):46-48
    Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
    Background And Purpose: Invasive fungal infections cause morbidity and mortality in patients with hematologic malignancies and immunosuppression. Although these infections are commonly caused by Candida and Aspergillus species, infections caused by Mucoralean fungi are also on a growing trend. The definitive diagnosis of mucormycosis includes visualization of non-septate hyphae on pathology or growth of Mucoralean fungi culture. Read More

    Quantitative Analysis of Proteome Modulations in Alveolar Epithelial Type II Cells in Response to Pulmonary Aspergillus fumigatus Infection.
    Mol Cell Proteomics 2017 Sep 26. Epub 2017 Sep 26.
    Inst. for Experimental Immunology and Imaging, University Duisburg-Essen, University Hospital, Institute for Experimental Immunology and Imaging, Germany
    The ubiquitous mold Aspergillus fumigatus threatens immunosuppressed patients as inducer of lethal invasive aspergillosis. A. fumigatus conidia are airborne and reach the alveoli, where they encounter alveolar epithelial cells (AEC). Read More

    Acute hypoxemic respiratory failure in immunocompromised patients: the Efraim multinational prospective cohort study.
    Intensive Care Med 2017 Sep 25. Epub 2017 Sep 25.
    ECSTRA Team, Biostatistics and Clinical Epidemiology, UMR 1153, INSERM, Paris Diderot Sorbonne University and Service de Biostatistique et Information Médicale AP-HP, Hôpital Saint-Louis, Paris, France.
    Background: In immunocompromised patients with acute hypoxemic respiratory failure (ARF), initial management aims primarily to avoid invasive mechanical ventilation (IMV).

    Methods: To assess the impact of initial management on IMV and mortality rates, we performed a multinational observational prospective cohort study in 16 countries (68 centers).

    Results: A total of 1611 patients were enrolled (hematological malignancies 51. Read More

    Eosinophils release extracellular DNA traps in response to Aspergillus fumigatus.
    J Allergy Clin Immunol 2017 Sep 21. Epub 2017 Sep 21.
    Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil. Electronic address:
    Background: Eosinophils mediate the immune response in different infection conditions. The release of extracellular DNA traps (ETs) by leukocytes has been described as an innate immune response mechanism that is relevant in many disorders including fungal diseases. Different stimuli induce human eosinophil ETs (EETs) release. Read More

    Voriconazole in lung transplant recipients - how worried should we be?
    Am J Transplant 2017 Sep 23. Epub 2017 Sep 23.
    Division of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University in Saint Louis, MO, United States.
    Invasive aspergillosis (IA) is the most common invasive mold infection in solid organ transplant (SOT) recipients, occurring in 1-15% of recipients, with a 12-week mortality rate of 20-60%.(1) Lung transplant (LTx) recipients are at the highest risk for IA among all SOT recipients, ranging from ulcerative tracheobronchitis, anastomotic site involvement and airway wall necrosis, to pneumonia, mediastinitis, empyema and disseminated fungemia. Additionally, Aspergillus colonization is an independent risk factor for chronic lung allograft dysfunction. Read More

    The evolving landscape of new diagnostic tests for invasive aspergillosis in hematology patients: strengths and weaknesses.
    Curr Opin Infect Dis 2017 Sep 21. Epub 2017 Sep 21.
    aDepartment of Internal Medicine - Hematology and Oncology, Mannheim University Hospital, Heidelberg University, Heidelberg bSecond Department of Internal Medicine, Brandenburg University Hospital, Brandenburg, Germany cDivision of Infectious Diseases, Department of Medicine, University of California -San Diego, San Diego, California, USA dSection of Infectious Diseases and Tropical Medicine, Department of Internal Medicine eDivision of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
    Purpose Of Review: The diagnosis of invasive aspergillosis in hematologic patients is a complex composite of clinical preconditions and features, imaging findings, biomarker combinations from appropriate clinical samples and microbiological and/or histological findings.

    Recent Findings: Recent developments in the evolving landscape of diagnostic tests for invasive aspergillosis in adult hematology patients are highlighted.

    Summary: Novel approaches and tools are currently under development. Read More

    A suspected case of autoinduction of voriconazole metabolism in a patient with cerebral aspergillosis.
    Drug Healthc Patient Saf 2017 8;9:89-91. Epub 2017 Sep 8.
    Department of Transplantation, Urology and Nephrology, Beaumont Hospital Kidney Centre, Dublin, Ireland.
    Objective: This study aims to report a case of accelerated metabolism of voriconazole in a patient with cerebral aspergillosis.

    Case Summary: A 36-year-old woman developed cerebral aspergillosis after immunosuppressive treatment for suspected atypical hemolytic uremic syndrome/thrombotic thrombocytopenic purpura. She was treated with voriconazole using therapeutic drug monitoring to guide dosing. Read More

    A rare coexistence of aspergillosis with actinomycosis.
    J Oral Maxillofac Pathol 2017 May-Aug;21(2):277-281
    Department of Oral and Maxillofacial Pathology, GSL Dental College, Rajahmundry, Andhra Pradesh, India.
    Aspergillosis is a common systemic mycosis which affects immunocompromised and immunocompetent hosts. Aspergillus spp. is wide spread in the environment in most countries, which renders an invasive form of disease. Read More

    Sensitive and selective quantification of total and free itraconazole and hydroxyitraconazole in human plasma using ultra-performance liquid chromatography coupled to tandem mass spectrometry.
    Clin Biochem 2017 Sep 18. Epub 2017 Sep 18.
    Department of Clinical Pharmacy, Oita University Hospital, Hasama-machi, Oita, Japan.
    Objectives: Protein-free (unbound) drug concentrations have been reported to be better biomarker of pharmacodynamics compared with total drug concentrations. In this study, we developed and validated an assay for the quantification of total and free itraconazole and hydroxyitraconazole, a main metabolite with antifungal activity, in human plasma using ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS).

    Design & Methods: Plasma sample was ultra-filtrated for the measurement of free itraconazole and hydroxyitraconazole concentrations. Read More

    Recognition and Clinical Presentation of Invasive Fungal Disease in Neonates and Children.
    J Pediatric Infect Dis Soc 2017 Sep;6(suppl_1):S12-S21
    Aberdeen Fungal Group, Medical Research Council Centre for Medical Mycology, Institute of Medical Sciences, University of Aberdeen, and the Royal Aberdeen Children's Hospital, United Kingdom.
    Invasive fungal diseases (IFDs) are devastating opportunistic infections that result in significant morbidity and death in a broad range of pediatric patients, particularly those with a compromised immune system. Recognizing them can be difficult, because nonspecific clinical signs and symptoms or isolated fever are frequently the only presenting features. Therefore, a high index of clinical suspicion is necessary in patients at increased risk of IFD, which requires knowledge of the pediatric patient population at risk, additional predisposing factors within this population, and the clinical signs and symptoms of IFD. Read More

    Epidemiology of Invasive Fungal Disease in Children.
    J Pediatric Infect Dis Soc 2017 Sep;6(suppl_1):S3-S11
    Division of Infectious Diseases and Center for Pediatric Clinical Effectiveness Research, Children's Hospital of Philadelphia, Pennsylvania.
    Considerable progress has been made in the prevention, diagnosis, and management of pediatric patients with invasive fungal disease (IFD). The reported decreasing trend in the incidence of invasive candidiasis (IC) over the past 15 years in both neonates and children has been encouraging. Nevertheless, due to the growing number of immunocompromised children at risk for IFD, this disease continues to be associated with significant morbidity and death and with increased financial burden to the health care system. Read More

    IL-12 Influence mTOR to Modulate CD8(+) T Cells Differentiation through T-bet and Eomesodermin in Response to Invasive Pulmonary Aspergillosis.
    Int J Med Sci 2017 18;14(10):977-983. Epub 2017 Aug 18.
    Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, China.
    Objective: To investigate whether mTOR signaling pathway regulate the proliferation and differentiation of CD8(+) T cells by transcription factors T-bet and Eomes, and explore the role of IL-12 in this biological procedure. Methods: Aspergillus fumigatus spore suspension nasal inhalation was used to establish the invasive pulmonary aspergillosis (IPA) mouse model. After inoculation, rapamycin (2mg/kg) each day or IL-12 (5ug/kg) every other day was given for 7 days. Read More

    Exposure-Response Relationships for Isavuconazole in Patients with Invasive Aspergillosis and Other Filamentous Fungi.
    Antimicrob Agents Chemother 2017 Sep 18. Epub 2017 Sep 18.
    Astellas Pharma Global Development, Inc., Northbrook, Illinois, USA.
    Isavuconazole, the active moiety of the water-soluble prodrug isavuconazonium sulfate, is a triazole antifungal agent for the treatment of invasive fungal infections. The purpose of this analysis was to characterize the isavuconazole exposure-response relationship for measures of efficacy and safety in patients with invasive aspergillosis and other filamentous fungi from the SECURE trial. Two hundred and thirty one patients who received the clinical dosing regimen and had exposure parameters were included in this analysis. Read More

    Emergence of Echinocandin Resistance due to a Point Mutation in the fks1 Gene of Aspergillus fumigatus in a Patient with Chronic Pulmonary Aspergillosis.
    Antimicrob Agents Chemother 2017 Sep 18. Epub 2017 Sep 18.
    Public Health Research Institute-New Jersey Medical School-Rutgers Biomedical Health Sciences, Newark, NJ, USA.
    We have identified the first case of a fks1 hot spot 1 point mutation causing echinocandin resistance in a clinical Aspergillus fumigatus isolate recovered from a chronic pulmonary aspergillosis patient with an aspergilloma who first failed azole and polyene therapy, and then subsequently failed micafungin treatment. Read More

    Innate and adaptive immune response to chronic pulmonary infection of hyphae of Aspergillus fumigatus in a new murine model.
    J Med Microbiol 2017 Oct 19;66(10):1400-1408. Epub 2017 Sep 19.
    1​Department of Dermatology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, PR China.
    Purpose: The pathogenesis of chronic pulmonary aspergillosis (CPA) has seldom been studied due partly to a lack of animal models. Since hypha is the main morphology colonizing the airway in CPA, it's critical to study the immune reaction to chronic pulmonary infection of hyphae of Aspergillus fumigatus, which also has seldom been studied in vivo before.

    Methodology: We established a novel murine model of chronic pulmonary infection of hyphae by challenging immunocompetent mice with tightly-structured hyphae balls intratracheally, and described the ensuing immunoreaction to hyphae and conidia, and the pathogenesis of CPA. Read More

    Clinical evaluation of the newly formatted lateral-flow device for invasive pulmonary aspergillosis.
    Mycoses 2017 Sep 18. Epub 2017 Sep 18.
    Section of Infectious Diseases and Tropical Medicine, Medical University of Graz, Graz, Austria.
    The study evaluated the newly formatted Aspergillus-specific lateral-flow-device (LFD), and compared its performance to the original prototype "old" LFD test using BALF samples from 28 patients (14 patients with probable/proven invasive pulmonary aspergillosis [IPA] and 14 patients with no evidence for IPA). A total of 10/14 (71%) of BALF samples from patients with probable/proven IPA resulted positive with the new LFD, including 8/9 with true-positive and 2/5 with false-negative results with the old LFD. All 14 samples from patients without IPA resulted negative with the new LFD; specificity of the new LFD was significantly improved compared to the old LFD. Read More

    Defective calcineurin/NFAT signaling in myeloid cells and susceptibility to aspergillosis in post-transplant patients.
    Virulence 2017 Sep 18. Epub 2017 Sep 18.
    a Molecular Microbiology Section, Laboratory of Clinical Immunology and Microbiology , National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) , Bethesda , Maryland , United States of America.

    Clinical significance of Aspergillus species isolated from respiratory specimens in patients with Mycobacterium avium complex lung disease.
    Eur J Clin Microbiol Infect Dis 2017 Sep 17. Epub 2017 Sep 17.
    Department of Respiratory Medicine, Ohara Memorial Kurashiki Healthcare Foundation, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, Okayama, 710-8602, Japan.
    Chronic pulmonary aspergillosis (CPA) is associated with mortality in patients with Mycobacterium avium complex lung disease (MAC-LD). An Aspergillus-positive respiratory specimen often reflects colonization, and thus the clinical significance of Aspergillus isolation in MAC-LD patients is not well understood. The objective of this study was to investigate the clinical characteristics and outcomes of MAC-LD patients in whom Aspergillus was isolated from respiratory specimens. Read More

    Aspergillus fumigatus morphology and dynamic host interactions.
    Nat Rev Microbiol 2017 Nov 18;15(11):661-674. Epub 2017 Sep 18.
    Unité des Aspergillus, Institut Pasteur, 25-28 Rue du Dr Roux, 75015 Paris, France.
    Aspergillus fumigatus is an environmental filamentous fungus that can cause life-threatening disease in immunocompromised individuals. The interactions between A. fumigatus and the host environment are dynamic and complex. Read More

    [Mycological and parasitological examinations in the management of lung infections].
    Rev Mal Respir 2017 Sep 14. Epub 2017 Sep 14.
    Laboratoire de parasitologie-mycologie, CHU Pontchaillou, 2, rue Henri-Le-Guillou, 35033 Rennes cedex 09, France.
    Pulmonary parasitic diseases are rare whereas pulmonary fungal infections are increasing. The diversity of clinical presentations requires laboratory tests to confirm the diagnosis. Direct examination of lung samples and antibody detection are the basis of parasitological diagnosis. Read More

    [Allergic bronchopulmonary aspergillosis in patients with asthma: Results of a prospective study].
    Ter Arkh 2017 ;89(8):13-16
    I.I. Mechnikov North-Western State Medical University Ministry of Health of Russia, Saint Petersburg, Russia.
    Aim: To estimate the frequency of fungal sensitization and the incidence of allergic bronchopulmonary aspergillosis (ABPA) in asthmatic patients.

    Subjects And Methods: A total of 140 asthmatic patients were examined. They underwent allergologic (skin tests for fungal allergens, estimation of total and fungal allergen-specific IgE levels) and mycological (microscopy and inoculation of respiratory biosubstrates) examinations. Read More

    A young immunocompetent patient with spontaneous Aspergillus empyema who developed severe eosinophilia.
    Respir Med Case Rep 2017 30;22:220-223. Epub 2017 Aug 30.
    Department of Pulmonary Medicine, Jichi Medical University Saitama Medical Center, Saitama, Japan.
    Aspergillus empyema is usually reported as a complication of surgical procedures, and spontaneous cases are quite rare. Here, we describe the case of a 16-year-old man who suddenly developed dyspnea despite previously being healthy. Chest computed tomography showed multiple mass-containing cavity lesions, pneumothorax, and pleural effusion in the left thorax. Read More

    Towards Translational ImmunoPET/MR Imaging of Invasive Pulmonary Aspergillosis: The Humanised Monoclonal Antibody JF5 Detects Aspergillus Lung Infections In Vivo.
    Theranostics 2017 11;7(14):3398-3414. Epub 2017 Aug 11.
    ISCA Diagnostics Ltd. and Biosciences, College of Life & Environmental Sciences, University of Exeter, Exeter, United Kingdom.
    Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease of hematological malignancy or bone marrow transplant patients caused by the ubiquitous environmental fungus Aspergillus fumigatus. Current diagnostic tests for the disease lack sensitivity as well as specificity, and culture of the fungus from invasive lung biopsy, considered the gold standard for IPA detection, is slow and often not possible in critically ill patients. In a previous study, we reported the development of a novel non-invasive procedure for IPA diagnosis based on antibody-guided positron emission tomography and magnetic resonance imaging (immunoPET/MRI) using a [(64)Cu]DOTA-labeled mouse monoclonal antibody (mAb), mJF5, specific to Aspergillus. Read More

    Animal Models for Studying Triazole Resistance in Aspergillus fumigatus.
    J Infect Dis 2017 Aug;216(suppl_3):S466-S473
    Department of Medical Microbiology, Radboud University Medical Center.
    Infections caused by triazole-resistant Aspergillus fumigatus are associated with a higher probability of treatment failure and mortality. Because clinical experience in managing these infections is still limited, mouse models of invasive aspergillosis fulfill a critical void for studying treatment regimens designed to overcome resistance. The type of immunosuppression, the route of infection, the timing of antifungal administration, and the end points used to assess antifungal activity affect the interpretation of data from these models. Read More

    Azole-Resistant Aspergillosis: Epidemiology, Molecular Mechanisms, and Treatment.
    J Infect Dis 2017 Aug;216(suppl_3):S436-S444
    Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital.
    Aspergillus fumigatus remains the most common species in all pulmonary syndromes, followed by Aspergillus flavus which is a common cause of allergic rhinosinusitis, postoperative aspergillosis and fungal keratitis. The manifestations of Aspergillus infections include invasive aspergillosis, chronic pulmonary aspergillosis and bronchitis. Allergic manifestations of inhaled Aspergillus include allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization. Read More

    Testing the performance of a prototype lateral flow device using bronchoalveolar lavage fluid for the diagnosis of invasive pulmonary aspergillosis in high-risk patients.
    Mycoses 2017 Sep 14. Epub 2017 Sep 14.
    Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA.
    The diagnosis of invasive pulmonary aspergillosis (IPA) increasingly relies on non-culture-based biomarkers in bronchoalveolar lavage (BAL) fluid. The Aspergillus lateral flow device (LFD) is a rapid immunoassay that uses a novel Aspergillus monoclonal antibody to gain specificity. The objective of the study is to compare specificity and sensitivity of the prototype LFD and the galactomannan (GM) enzyme immunoassay in BAL fluid in high-risk patients. Read More

    Toll-like receptor 2 induced cytotoxic T-lymphocyte-associated protein 4 regulates Aspergillus-induced regulatory T-cells with pro-inflammatory characteristics.
    Sci Rep 2017 Sep 13;7(1):11500. Epub 2017 Sep 13.
    Department of Experimental Internal Medicine and Radboud Center for Infectious diseases (RCI), Radboud University Medical Center, Geert Grooteplein zuid 8, 6525GA, Nijmegen, The Netherlands.
    Patients with cystic fibrosis, chronic obstructive pulmonary disease, severe asthma, pre-existing pulmonary lesions, and severely immunocompromised patients are susceptible to develop infections with the opportunistic pathogenic fungus Aspergillus fumigatus, called aspergillosis. Infections in these patients are associated with persistent pro-inflammatory T-helper (TH)2 and TH17 responses. Regulatory T-cells, natural suppressor cells of the immune system, control pro-inflammatory T-cell responses, but can also contribute to disease by shifting to a pro-inflammatory TH17-like phenotype. Read More

    Molecular Tools for the Detection and Deduction of Azole Antifungal Drug Resistance Phenotypes in Aspergillus Species.
    Clin Microbiol Rev 2017 Oct;30(4):1065-1091
    Institute for Medical Microbiology, University Medical Center Göttingen, Göttingen, Germany
    The incidence of azole resistance in Aspergillus species has increased over the past years, most importantly for Aspergillus fumigatus. This is partially attributable to the global spread of only a few resistance alleles through the environment. Secondary resistance is a significant clinical concern, as invasive aspergillosis with drug-susceptible strains is already difficult to treat, and exclusion of azole-based antifungals from prophylaxis or first-line treatment of invasive aspergillosis in high-risk patients would dramatically limit drug choices, thus increasing mortality rates for immunocompromised patients. Read More

    Fungal Infections of the Central Nervous System in Children.
    J Pediatric Infect Dis Soc 2017 Sep;6(3):e123-e133
    Transplantation-Oncology Infectious Diseases Program, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, New York, New York.
    Although uncommon in children, fungal infections of the central nervous system can be devastating and difficult to treat. A better understanding of basic mycologic, immunologic, and pharmacologic processes has led to important advances in the diagnosis and management of these diseases, but their mortality rates remain unacceptably high. In this focused review, we examine the epidemiology and clinical features of the most common fungal pathogens of the central nervous system in children and explore recent advances in diagnosis and antifungal therapy. Read More

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