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Clinical Microbiology Reviews Dec 2019is a saprotrophic fungus; its primary habitat is the soil. In its ecological niche, the fungus has learned how to adapt and proliferate in hostile environments. This... (Review)
Review
is a saprotrophic fungus; its primary habitat is the soil. In its ecological niche, the fungus has learned how to adapt and proliferate in hostile environments. This capacity has helped the fungus to resist and survive against human host defenses and, further, to be responsible for one of the most devastating lung infections in terms of morbidity and mortality. In this review, we will provide (i) a description of the biological cycle of ; (ii) a historical perspective of the spectrum of aspergillus disease and the current epidemiological status of these infections; (iii) an analysis of the modes of immune response against in immunocompetent and immunocompromised patients; (iv) an understanding of the pathways responsible for fungal virulence and their host molecular targets, with a specific focus on the cell wall; (v) the current status of the diagnosis of different clinical syndromes; and (vi) an overview of the available antifungal armamentarium and the therapeutic strategies in the clinical context. In addition, the emergence of new concepts, such as nutritional immunity and the integration and rewiring of multiple fungal metabolic activities occurring during lung invasion, has helped us to redefine the opportunistic pathogenesis of .
Topics: Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Disease Susceptibility; History, 21st Century; Host-Pathogen Interactions; Humans; Immunity; Immunocompromised Host; Public Health Surveillance; Treatment Outcome; Virulence
PubMed: 31722890
DOI: 10.1128/CMR.00140-18 -
Clinical Infectious Diseases : An... Aug 2016It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with...
It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Azoles; Echinocandins; Humans; Infectious Disease Medicine; Societies, Medical; United States
PubMed: 27365388
DOI: 10.1093/cid/ciw326 -
Clinical Microbiology Reviews Apr 1999Aspergillus fumigatus is one of the most ubiquitous of the airborne saprophytic fungi. Humans and animals constantly inhale numerous conidia of this fungus. The conidia... (Review)
Review
Aspergillus fumigatus is one of the most ubiquitous of the airborne saprophytic fungi. Humans and animals constantly inhale numerous conidia of this fungus. The conidia are normally eliminated in the immunocompetent host by innate immune mechanisms, and aspergilloma and allergic bronchopulmonary aspergillosis, uncommon clinical syndromes, are the only infections observed in such hosts. Thus, A. fumigatus was considered for years to be a weak pathogen. With increases in the number of immunosuppressed patients, however, there has been a dramatic increase in severe and usually fatal invasive aspergillosis, now the most common mold infection worldwide. In this review, the focus is on the biology of A. fumigatus and the diseases it causes. Included are discussions of (i) genomic and molecular characterization of the organism, (ii) clinical and laboratory methods available for the diagnosis of aspergillosis in immunocompetent and immunocompromised hosts, (iii) identification of host and fungal factors that play a role in the establishment of the fungus in vivo, and (iv) problems associated with antifungal therapy.
Topics: Animals; Antigens, Fungal; Aspergillosis; Aspergillus fumigatus; Disease Models, Animal; Humans; Serologic Tests; Virulence
PubMed: 10194462
DOI: 10.1128/CMR.12.2.310 -
Molecular Aspects of Medicine Dec 2023Invasive fungal diseases are common complications in critically ill patients and in those with significant underlying imbalanced immune systems. Fungal co-, and/or... (Review)
Review
Invasive fungal diseases are common complications in critically ill patients and in those with significant underlying imbalanced immune systems. Fungal co-, and/or super-infections are emerging and have become a rising concern within the last few years. In Europe, cases of candidiasis and aspergillosis dominate, followed by mucormycosis in India. Epidemiological studies show an increasing trend in the incidence of all three entities. Parallel to this, a shift within the underlying fungal pathogens is observed. More non-albicans Candida infections and aspergillosis with cryptic species are on the rise; cryptic species may cover intrinsic resistance to azoles and other antifungal drugs. The recent COVID-19 pandemic led to a significantly increasing incidence of invasive fungal diseases among hospitalized patients.
Topics: Humans; Pandemics; Mycoses; Antifungal Agents; Aspergillosis
PubMed: 37804792
DOI: 10.1016/j.mam.2023.101215 -
Virulence Dec 2023Pulmonary infections caused by the mould pathogen are a major cause of morbidity and mortality globally. Compromised lung defences arising from immunosuppression,... (Review)
Review
Pulmonary infections caused by the mould pathogen are a major cause of morbidity and mortality globally. Compromised lung defences arising from immunosuppression, chronic respiratory conditions or more recently, concomitant viral or bacterial pulmonary infections are recognised risks factors for the development of pulmonary aspergillosis. In this review, we will summarise our current knowledge of the mechanistic basis of pulmonary aspergillosis with a focus on emerging at-risk populations.
Topics: Humans; Aspergillus fumigatus; Virulence; Aspergillosis; Virulence Factors; Pulmonary Aspergillosis
PubMed: 36752587
DOI: 10.1080/21505594.2023.2172264 -
European Respiratory Review : An... Sep 2011Aspergillus is a mould which may lead to a variety of infectious, allergic diseases depending on the host's immune status or pulmonary structure. Invasive pulmonary... (Review)
Review
Aspergillus is a mould which may lead to a variety of infectious, allergic diseases depending on the host's immune status or pulmonary structure. Invasive pulmonary aspergillosis occurs primarily in patients with severe immunodeficiency. The significance of this infection has dramatically increased with growing numbers of patients with impaired immune state associated with the management of malignancy, organ transplantation, autoimmune and inflammatory conditions; critically ill patients and those with chronic obstructive pulmonary disease appear to be at an increased risk. The introduction of new noninvasive tests, combined with more effective and better-tolerated antifungal agents, has resulted in lower mortality rates associated with this infection. Chronic necrotising aspergillosis is a locally invasive disease described in patients with chronic lung disease or mild immunodeficiency. Aspergilloma is usually found in patients with previously formed cavities in the lung, whereas allergic bronchopulmonary aspergillosis, a hypersensitivity reaction to Aspergillus antigens, is generally seen in patients with atopy, asthma or cystic fibrosis. This review provides an update on the evolving epidemiology and risk factors of the major manifestations of Aspergillus lung disease and the clinical manifestations that should prompt the clinician to consider these conditions. Current approaches for the diagnosis and management of these syndromes are discussed.
Topics: Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Humans; Invasive Pulmonary Aspergillosis; Predictive Value of Tests; Pulmonary Aspergillosis; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 21881144
DOI: 10.1183/09059180.00001011 -
Mycopathologia Oct 2023Despite improvements in treatment and diagnostics over the last two decades, invasive aspergillosis (IA) remains a devastating fungal disease. The number of... (Review)
Review
Despite improvements in treatment and diagnostics over the last two decades, invasive aspergillosis (IA) remains a devastating fungal disease. The number of immunocompromised patients and hence vulnerable hosts increases, which is paralleled by the emergence of a rise in IA cases. Increased frequencies of azole-resistant strains are reported from six continents, presenting a new challenge for the therapeutic management. Treatment options for IA currently consist of three classes of antifungals (azoles, polyenes, echinocandins) with distinctive advantages and shortcomings. Especially in settings of difficult to treat IA, comprising drug tolerance/resistance, limiting drug-drug interactions, and/or severe underlying organ dysfunction, novel approaches are urgently needed. Promising new drugs for the treatment of IA are in late-stage clinical development, including olorofim (a dihydroorotate dehydrogenase inhibitor), fosmanogepix (a Gwt1 enzyme inhibitor), ibrexafungerp (a triterpenoid), opelconazole (an azole optimized for inhalation) and rezafungin (an echinocandin with long half-life time). Further, new insights in the pathophysiology of IA yielding immunotherapy as a potential add-on therapy. Current investigations show encouraging results, so far mostly in preclinical settings. In this review we discuss current treatment strategies, give an outlook on possible new pharmaceutical therapeutic options, and, lastly, provide an overview of the ongoing research in immunotherapy for IA.
Topics: Humans; Aspergillosis; Antifungal Agents; Mycoses; Invasive Fungal Infections; Azoles; Drug Resistance, Fungal
PubMed: 37100963
DOI: 10.1007/s11046-023-00727-z -
Clinical Infectious Diseases : An... Aug 2016It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with...
It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Azoles; Echinocandins; Humans; Infectious Disease Medicine; Practice Guidelines as Topic; Societies, Medical; United States
PubMed: 27481947
DOI: 10.1093/cid/ciw444 -
Seminars in Respiratory and Critical... Feb 2024The filamentous fungus causes a wide spectrum of diseases in the human lung, with being the most pathogenic and allergenic subspecies. The broad range of clinical... (Review)
Review
The filamentous fungus causes a wide spectrum of diseases in the human lung, with being the most pathogenic and allergenic subspecies. The broad range of clinical syndromes that can develop from the presence of in the respiratory tract is determined by the interaction between host and pathogen. In this review, an oversight of the different clinical entities of pulmonary aspergillosis is given, categorized by their main pathophysiological mechanisms. The underlying immune processes are discussed, and the main clinical, radiological, biochemical, microbiological, and histopathological findings are summarized.
Topics: Humans; Lung; Aspergillus; Pulmonary Aspergillosis; Aspergillus fumigatus
PubMed: 38286136
DOI: 10.1055/s-0043-1777259 -
International Journal of Molecular... May 2022Invasive aspergillosis (IA) is a life-threatening fungal disease that causes high morbidity and mortality in immunosuppressed patients. Early and accurate diagnosis and... (Review)
Review
Invasive aspergillosis (IA) is a life-threatening fungal disease that causes high morbidity and mortality in immunosuppressed patients. Early and accurate diagnosis and treatment of IA remain challenging. Given the broad range of non-specific clinical symptoms and the shortcomings of current diagnostic techniques, most patients are either diagnosed as "possible" or "probable" cases but not "proven". Moreover, because of the lack of sensitive and specific tests, many high-risk patients receive an empirical therapy or a prolonged treatment of high-priced antifungal agents, leading to unnecessary adverse effects and a high risk of drug resistance. More precise diagnostic techniques alongside a targeted antifungal treatment are fundamental requirements for reducing the morbidity and mortality of IA. Monoclonal antibodies (mAbs) with high specificity in targeting the corresponding antigen(s) may have the potential to improve diagnostic tests and form the basis for novel IA treatments. This review summarizes the up-to-date application of mAb-based approaches in assisting IA diagnosis and therapy.
Topics: Antibodies, Monoclonal; Antifungal Agents; Antineoplastic Agents, Immunological; Aspergillosis; Humans; Invasive Fungal Infections; Mycoses
PubMed: 35628374
DOI: 10.3390/ijms23105563