Invasive Aspergillosis (IA) is now the leading infectious cause of mortality in patients with haematological malignancies. Studies have identified those patient groups and the time-periods associated with high-risk for IA. The current management strategies for IA include prophylaxis and empiric antifungal therapy (EAFT). The rationale for prophylaxis in high-risk patients exists...
Invasive fungal infections, such as invasive aspergillosis (IA) represent a major threat to immunocompromised patients, especially patients with hematological malignancies or who receive hematopoietic stem cell transplantation. Hence, prevention of IA is a critical strategy that requires a clear understanding of the mould's environmental sources and how it is transmitted to...
In patients with invasive aspergillosis (IA), there are numerous clinical settings where stable disease or progression of findings or deterioration of the patient's condition does not indicate failure, and subsequent response to a ‘salvage’ antifungal is not necessarily attributable to this drug. Many patients, in whom pulmonary aspergillosis emerges during profound neutropenia...
The original trials of empiric intravenous amphotericin-B in the 1980s failed to prove conclusively its efficacy in the treatment of febrile neutropenia. Despite that, all subsequent studies of the therapy of presumed, possible, probable and proven invasive aspergillosis have assumed that this drug, either as deoxycholate or in lipid-based form, is the gold standard treatment...
Randomized trials in invasive aspergillosis have evolved over the past decade. Definitions of disease now include specifics of the underlying disease and how this affects interpretation of certain tests, including high resolution computed tomography and smears or cultures of sputum and bronchoalveolar lavage. Study hypotheses have changed from underpowered superiority trials to...
Invasive aspergillosis (IA) continues to represent a significant challenge for physicians in charge of immunocompromised patients. Voriconazole, caspofungin, itraconazole, and the different formulations of amphotericin B (AmB) are all approved for therapy of IA. To collect information on the effect of high dose of antifungals in the treatment of IA, data from the available...
The main challenge in patient recruitment for invasive aspergillosis (IA) trials is to include a maximum number of patients for a minimum length of time, bearing in mind that the final objective is to improve the prognosis of patients with IA. Theoretically, all that is needed is a good drug and a good strategy. The analysis of patient recruitment rates in the most recent...
Assessment of the health effects of indoor moulds is complicated by the diversity of mould species found in homes and the limitations of current methods to determine exposure. Thus it is difficult to establish whether there is a relationship between mould exposure and disease. Allergic respiratory diseases are commonly caused by Alternaria, Aspergillus, Cladosporium and...
The European Organization for Research and Treatment of Cancer (EORTC)/ Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (MSG) consensus definitions for opportunistic invasive fungal infections have achieved their objective in fostering better communication between researchers but their limitations...
Allergic fungal rhinosinusitis is a relatively newly characterized disease entity that commands a great deal of interest. Large amounts of information are being generated addressing the underlying etiology of the disease, its clinical presentation, and forms of treatment. Although controversy still exists, recent evidence supports the theory that AFRS represents an immunologic...
Treatment of allergic bronchopulmonary aspergillosis (ABPA) emerged from uncontrolled published series of patients on prolonged oral glucocorticosteroids. Oral steroids remain the mainstay of treatment, but dose regime and duration have never been standardized. Oral steroids are problematic due to frequency of relapse, lack of steroid action on airway fungal burden and toxicities...
In the United Kingdom the prevalence of asthma has been rising. While some of this rise has been attributed to re-labelling of respiratory disease there is
Exposure to fungi, particularly in water damaged indoor environments, has been thought to exacerbate a number of adverse health effects, ranging from subjective symptoms such as fatigue, cognitive difficulties or memory loss to more definable diseases such as allergy, asthma and hypersensitivity pneumonitis. Understanding the role of fungal exposure in these environments has been...
The outcome of the Th1/Th2 balance is a critical determinant of the outcome in invasive aspergillosis. The innate immune system encounters the pathogen first. Dendritic cells (DC) appear to be the critical fulcrum at the intersection of the innate immune system, and which receptors are engaged, particularly which Toll-like receptors are triggered by the pathogen, likely...
Aspergillus fumigatus is a pathogenic mould that can cause severe and life-threatening infections in immunocompromised patients. Apart from novel and improved antifungals, additional strategies are required to protect patients at risk from developing invasive aspergillosis. Given the problems in diagnosis of this disease, important perspectives lie in attempts to elicit and...
Invasive pulmonary aspergillosis (IPA) usually occurs in severely immunocompromised patients. The expanded use of glucocorticoids (GC) in clinical practice accounts for the increasing number of fungal infections reported in mildly or non-immunocompromised hosts. We report a series of 8 patients with fungal pneumonia in whom long term high dose GC treatment was the only risk...
Effective management of invasive aspergillosis (IA) requires early and accurate diagnosis. Microscopy and culture of appropriate specimens remain the gold standard of mycological diagnosis. High-resolution computed tomography serially performed constitutes a sensitive mode of diagnosis of pulmonary IA in hematological patients, but similar data is lacking for children. While...
The G-test was developed in 1992 by Obayashi et al. as a serological diagnostic test for the measurement of β-D-glucan (BDG). A multicenter clinical study demonstrated the utility of the G-test for the diagnosis of deep mycosis with a sensitivity of 90% and specificity of 100%. Determination of BDG has found wide application in Japan, particularly in the fields of hematological...
Within the past decade detection of the aspergillus antigen galactomannan has become an important and reliable tool for the early diagnosis of invasive aspergillosis. The galactomannan molecule, that is detected by the commercial sandwich ELISA (Platelia Aspergillus, Biorad), was found not to be a single molecule, but a family of molecules that have the epitope that reacts with...
Aspergillus spp. have been the subject of numerous epidemiological studies. The most useful typing techniques are DNA based methods including the random amplified polymorphic DNA technique, microsatellite length polymorphisms, restriction fragment length polymorphism (RFLP) analysis using retrotransposon-like sequences as probes, and multilocus sequence typing. The results of...
As the number of cases of aspergillosis grows, the number of species reported to cause the disease is increasing. Historically, classification and identification of aspergilli was accomplished using morphological characteristics. A number of molecular, immunological and biochemical methods are now available. For the most part, the results of the various approaches concur...
Programmed cell death (PCD), in which cells actively participate in their own death through the activation of defined pathways, has long been established as an important developmental pathway in metazoan systems but it is only recently that evidence for a primitive form of PCD in the fungi has come to light. While much of the evidence for this comes from studies in the yeast...
Reactive oxygen species (ROS) such as hydrogen peroxide, produced externally or during normal metabolism, can damage different cell components and usually trigger a counteracting antioxidant response. The fact that animals and humans utilize ROS and related nitrogen reactive species to prevent fungal infection has generated great interest in defining the components of the...
The present paper describes 22 cases of chromoblastomycosis (CBM) caused by Cladophialophora carrionii in children and adolescents (2–19 years old). The patients were seen between 1992 and 2004 and all resided in a CBM endemic area in the semi-arid zone of the Falcón state, Venezuela. Twelve of the 22 patients (54.55%) had close relatives who also had CBM and 19 (86.36%) were...
Little is known about the relationships between metabolic activity and fungal biomass or time of incubation for medically important fungal pathogens. Understanding these relationships may be especially relevant for rapidly growing organisms, such as zygomycetes. A range of inocula of five clinical isolates of zygomycetes (one each of Rhizopus oryzae,Rhizopus microsporus...