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BMJ Case Reports Mar 2022Invasive aspergillosis (IA) is a serious fungal infection that primarily affects patients with prolonged and profound neutropenia, and compromised cell-mediated...
Invasive aspergillosis (IA) is a serious fungal infection that primarily affects patients with prolonged and profound neutropenia, and compromised cell-mediated immunity. Aspergillosis of the oesophagus and gastrointestinal tract is uncommon but seen in advanced cases of disseminated IA. However, it is difficult to diagnose antemortem due to the poor specificity of the symptoms and the absence of characteristic imaging findings. Therefore, the reported cases of gastrointestinal aspergillosis have been associated with high morbidity and mortality, and frequently diagnosed postmortem. Here we present a successful outcome in a patient with relapsed and refractory multiple myeloma who had presented with febrile neutropenia, cough and dysphagia, and was diagnosed with disseminated IA comprising of pulmonary and oesophageal involvement. This case highlights the need for a high index of suspicion and the importance of invasive procedures for histopathology and molecular diagnostics to ensure an early diagnosis and therapeutic intervention.
Topics: Aspergillosis; Esophagus; Humans; Invasive Fungal Infections; Invasive Pulmonary Aspergillosis; Multiple Myeloma
PubMed: 35318199
DOI: 10.1136/bcr-2021-246403 -
Journal of Molecular Biology Oct 2019The genus Aspergillus is ubiquitous in the environment and contains a number of species, primarily A. fumigatus, that cause mold-associated disease in humans. Humans... (Review)
Review
The genus Aspergillus is ubiquitous in the environment and contains a number of species, primarily A. fumigatus, that cause mold-associated disease in humans. Humans inhale several hundred to several thousand Aspergillus conidia (i.e., vegetative spores) daily and typically clear these in an asymptomatic manner. In immunocompromised individuals, Aspergillus conidia can germinate into tissue-invasive hyphae, disseminate, and cause invasive aspergillosis. In this review, we first discuss novel concepts in host defense against Aspergillus infections and emphasize new insights in fungal recognition and signaling, innate immune activation, and fungal killing. Second, the review focuses on novel concepts of Aspergillus pathogenesis and highlights emerging knowledge regarding fungal strain heterogeneity, stress responses, and metabolic adaptations on infectious outcomes. Mechanistic insight into the host-pathogen interplay is thus critical to define novel druggable fungal targets and to exploit novel immune-based strategies to improve clinical outcomes associated with aspergillosis in vulnerable patient populations.
Topics: Animals; Aspergillosis; Aspergillus; Cell Wall; Humans; Immunity, Innate; Mycology
PubMed: 30954573
DOI: 10.1016/j.jmb.2019.03.027 -
Cold Spring Harbor Perspectives in... Nov 2014Survival rates among immunocompromised patients with invasive mold infections have markedly improved over the last decade with earlier diagnosis and new antifungal... (Review)
Review
Survival rates among immunocompromised patients with invasive mold infections have markedly improved over the last decade with earlier diagnosis and new antifungal treatment options. Yet, increasing antifungal resistance, breakthrough infections with intrinsically resistant fungi, and potentially life-threatening adverse effects and drug interactions are becoming more problematic, especially with prolonged therapy. Evidence-based recommendations for treating invasive aspergillosis and mucormycosis provide excellent guidance on the initial workup and treatment of these molds, but they cannot address all of the key management issues. Herein, we discuss 10 general treatment principles in the management of invasive mold disease in immunocompromised patients and discuss how these principles can be integrated to develop an effective, individualized treatment plan.
Topics: Antifungal Agents; Aspergillosis; Disease Management; Fungi; Humans; Immunocompromised Host; Mucormycosis
PubMed: 25377139
DOI: 10.1101/cshperspect.a019737 -
Future Microbiology May 2012Invasive fungal infections are a major problem in solid organ transplant (SOT) recipients. Overall, the most common fungal infection in SOT is candidiasis, followed by... (Review)
Review
Invasive fungal infections are a major problem in solid organ transplant (SOT) recipients. Overall, the most common fungal infection in SOT is candidiasis, followed by aspergillosis and cryptococcosis, except in lung transplant recipients, where aspergillosis is most common. Development of invasive disease hinges on the interplay between host factors (e.g., integrity of anatomical barriers, innate and acquired immunity) and fungal factors (e.g., exposure, virulence and resistance to prophylaxis). In this article, we describe the epidemiology and clinical features of the most common fungal infections in organ transplantation. Within this context, we review recent advances in diagnostic modalities and antifungal chemotherapy, and their impact on evolving prophylaxis and treatment paradigms.
Topics: Aspergillosis; Candidiasis; Cryptococcosis; Fungemia; Humans; Immunocompromised Host; Transplants
PubMed: 22568718
DOI: 10.2217/fmb.12.28 -
BMC Ophthalmology Jan 2021Orbital aspergillosis is a rare sight- and life-threatening fungal infection affecting immunocompromised or otherwise healthy patients. It is often misdiagnosed due to... (Review)
Review
BACKGROUND
Orbital aspergillosis is a rare sight- and life-threatening fungal infection affecting immunocompromised or otherwise healthy patients. It is often misdiagnosed due to its unspecific clinical and radiologic appearance. Therapeutic delay can have dramatic consequences. However, progress in microbiological diagnostic techniques and therapeutic experience from case series help improve the management of this disease.
CASE PRESENTATION
A 78-year-old immunocompetent woman presented at an eye clinic for subacute swelling, reddening, and ptosis of her left upper eyelid. Based on radiologic and histologic considerations, she was treated for idiopathic orbital inflammation, but her condition worsened. After a second biopsy of the orbital mass, aspergillosis was diagnosed. Her condition improved promptly after initiation of an oral voriconazole treatment. Additionally, using a polymerase chain reaction (PCR) assay, A. fumigatus was identified on tissue of both biopsies and its azole susceptibility was examined simultaneously.
CONCLUSIONS
In the case described here, oral antifungal treatment was sufficient for the therapy of invasive orbital aspergillosis. Performing fungal PCR on orbital tissue can accelerate the diagnostic process and should be performed in ambiguous cases of slowly growing orbital mass. Finally, interdisciplinary management is the key to optimal treatment of orbital tumours and infections.
Topics: Aged; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Female; Humans; Voriconazole
PubMed: 33419395
DOI: 10.1186/s12886-020-01773-7 -
Medicine Jul 2015Invasive aspergillosis (IA) has poor prognosis in immunocompromised patients. Skin manifestations, when present, should contribute to an early diagnosis. The authors... (Observational Study)
Observational Study Review
Invasive aspergillosis (IA) has poor prognosis in immunocompromised patients. Skin manifestations, when present, should contribute to an early diagnosis. The authors aimed to provide prevalence data and a clinical and histologic description of cutaneous manifestations of primary cutaneous IA (PCIA) and secondary CIA (SCIA) in a unique clinical series of IA and present the results of an exhaustive literature review of CIA. Cases of proven and probable IA with cutaneous manifestations were retrospectively extracted from those registered between 2005 and 2010 in a prospective multicenter aspergillosis database held by the National Reference Center for Invasive Mycoses and Antifungals, Pasteur Institute, France. Patients were classified as having PCIA (i.e., CIA without extracutaneous manifestations) or SCIA (i.e., disseminated IA). Among the 1,410 patients with proven or probable IA, 15 had CIA (1.06%), 5 PCIA, and 10 SCIA. Hematological malignancies were the main underlying condition (12/15). Patients with PCIA presented infiltrated and/or suppurative lesions of various localizations not related to a catheter site (4/5), whereas SCIA was mainly characterized by disseminated papules and nodules but sometimes isolated nodules or cellulitis. Histologic data were available for 11 patients, and for 9, similar for PCIA and SCIA, showed a dense dermal polymorphic inflammatory infiltrate, with the epidermis altered in PCIA only. Periodic acid Schiff and Gomori-Grocott methenamine silver nitrate staining for all but 2 biopsies revealed hyphae compatible with Aspergillus. Aspergillus flavus was isolated in all cases of PCIA, with Aspergillus fumigatus being the most frequent species (6/10) in SCIA. Two out 5 PCIA cases were treated surgically. The 3-month survival rate was 100% and 30% for PCIA and SCIA, respectively. Our study is the largest adult series of CIA and provides complete clinical and histologic data for the disease. Primary cutaneous IA should be recognized early, and cases of extensive necrosis should be treated surgically; its prognosis markedly differs from that for SCIA. Any suppurative, necrotic, papulonodular, or infiltrated skin lesion in an immunocompromised patient should lead to immediate biopsy for histologic analysis and mycological skin direct examination and culture.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; Aspergillosis; Child; Child, Preschool; Female; France; Humans; Infant; Male; Middle Aged; Prevalence; Retrospective Studies; Skin; Young Adult
PubMed: 26131805
DOI: 10.1097/MD.0000000000001018 -
Medical Mycology Journal 2016Invasive aspergillosis (IA) is still one of the leading causes of morbidity and mortality in hematological patients, although its outcome has been improving. Prolonged... (Review)
Review
Invasive aspergillosis (IA) is still one of the leading causes of morbidity and mortality in hematological patients, although its outcome has been improving. Prolonged and profound neutropenia in patients receiving intensive chemotherapy for acute leukemia and stem cell transplantation is a major risk factor for IA. Allogeneic stem cell transplant recipients with graft-versus-host disease and corticosteroid use are also at high risk. Management in a protective environment with high efficiency particular air (HEPA) filter is generally recommended to prevent aspergillosis in patients with prolonged and profound neutropenia. Antifungal prophylaxis against Aspergillus species should be considered in patients with past history of aspergillosis or colonization of Aspergillus species, at facilities with high incidence of IA and those without a protective environment. Early diagnosis and prompt antifungal treatment is important to improve outcome. Imaging studies such as computed tomography and biomarkers such as galactomannan antigen and β-D-glucan are useful for early diagnosis. Empirical antifungal treatment based on persistent or recurrent fever during neutropenia despite broad-spectrum antibiotic therapy is generally recommended in high-risk patients. Alternatively, a preemptive treatment strategy has recently been proposed in the context of progress in the early diagnosis of IA based on the results of imaging studies and biomarkers. Voriconazole is recommended for initial therapy for IA. Liposomal amphotericin B is considered as alternative initial therapy. Combination antifungal therapy of echinocandin with voriconazole or liposomal amphotericin B could be a choice for refractory cases.
Topics: Amphotericin B; Antifungal Agents; Antineoplastic Agents; Aspergillosis; Biomarkers; Echinocandins; Hematologic Neoplasms; Humans; Neutropenia; Opportunistic Infections; Risk Factors; Stem Cell Transplantation; Tomography, X-Ray Computed; Voriconazole
PubMed: 27251320
DOI: 10.3314/mmj.57.J77 -
Current Opinion in Infectious Diseases Apr 2022Invasive pulmonary aspergillosis (IPA) can affect patients with severe coronavirus disease 2019 (COVID-19), but many questions remain open about its very variable... (Review)
Review
PURPOSE OF REVIEW
Invasive pulmonary aspergillosis (IPA) can affect patients with severe coronavirus disease 2019 (COVID-19), but many questions remain open about its very variable incidence across the world, the actual link between the viral infection and the fungal superinfection, the significance of Aspergillus recovery in a respiratory sample, and the management of such cases. This review addresses these questions and aims at providing some clues for the practical diagnostic and therapeutic approaches of COVID-19-associated pulmonary aspergillosis (CAPA) in a clinical perspective.
RECENT FINDINGS
Definitions have been proposed for possible/probable/proven CAPA, but distinction between colonization and invasive fungal infection is difficult and not possible in most cases in the absence of histopathological proof or positive galactomannan in serum. Most importantly, the recovery of an Aspergillus by a direct (culture, PCR) or indirect (galactomannan) test in a respiratory sample is an indicator of worse outcome, which justifies a screening for early detection and initiation of preemptive antifungal therapy in such cases.
SUMMARY
The COVID-19 pandemic has increased our awareness of IPA among ICU patients. Although current recommendations are mainly based on experts' opinions, prospective studies are needed to get more evidence-based support for the diagnostic approach and management of CAPA.
Topics: COVID-19; Humans; Invasive Pulmonary Aspergillosis; Pandemics; Pulmonary Aspergillosis; SARS-CoV-2
PubMed: 34980831
DOI: 10.1097/QCO.0000000000000812 -
Microbial Biotechnology Mar 2017Fungi of the genus Aspergillus are widespread in the environment. Some Aspergillus species, most commonly Aspergillus fumigatus, may lead to a variety of allergic... (Review)
Review
Fungi of the genus Aspergillus are widespread in the environment. Some Aspergillus species, most commonly Aspergillus fumigatus, may lead to a variety of allergic reactions and life-threatening systemic infections in humans. Invasive aspergillosis occurs primarily in patients with severe immunodeficiency, and has dramatically increased in recent years. There are several factors at play that contribute to aspergillosis, including both fungus and host-related factors such as strain virulence and host pulmonary structure/immune status, respectively. The environmental tenacity of Aspergilllus, its dominance in diverse microbial communities/habitats, and its ability to navigate the ecophysiological and biophysical challenges of host infection are attributable, in large part, to a robust stress-tolerance biology and exceptional capacity to generate cell-available energy. Aspects of its stress metabolism, ecology, interactions with diverse animal hosts, clinical presentations and treatment regimens have been well-studied over the past years. Here, we synthesize these findings in relation to the way in which some Aspergillus species have become successful opportunistic pathogens of human- and other animal hosts. We focus on the biophysical capabilities of Aspergillus pathogens, key aspects of their ecophysiology and the flexibility to undergo a sexual cycle or form cryptic species. Additionally, recent advances in diagnosis of the disease are discussed as well as implications in relation to questions that have yet to be resolved.
Topics: Animals; Aspergillosis; Aspergillus; Biophysical Phenomena; Diagnostic Tests, Routine; Ecosystem; Host-Pathogen Interactions; Humans
PubMed: 27273822
DOI: 10.1111/1751-7915.12367 -
Journal of Feline Medicine and Surgery Jul 2013Aspergillosis is a sporadic mycosis that occurs worldwide in mammals and birds and leads to a usually chronic, and only rarely acute, disease that mainly affects the... (Review)
Review
OVERVIEW
Aspergillosis is a sporadic mycosis that occurs worldwide in mammals and birds and leads to a usually chronic, and only rarely acute, disease that mainly affects the nasal cavity and sinuses.
INFECTION
Aspergillus species infections are commonly associated with predisposing local or systemic factors. Local disease can spread and involve the central nervous system or the lungs. Some Aspergillus species can also disseminate, causing systemic infections. In contrast to dogs, in which (nasal) aspergillosis is relatively common, aspergillosis is rare in cats, but considered an emerging infection.
CLINICAL SIGNS
There are two clinical forms of aspergillosis in cats, the sinonasal form (characterised by signs of chronic nasal infection) and the newly emerging, more invasive sino-orbital form (characterised by signs of orbital and surrounding tissue invasion). Sino-orbital involvement has been described now in approximately half of the reported cases.
DISEASE MANAGEMENT
Treatment should consist of local and systemic antifungal therapy.
Topics: Animals; Antifungal Agents; Aspergillosis; Cat Diseases; Cats
PubMed: 23813825
DOI: 10.1177/1098612X13489223