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.

Aspergillus fumigatus and Aspergillosis

http://fungi.ro/wp-content/uploads/2013/01/ESCMID_5.pdf

ESCMID guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients.

Candida albicans, a normal component of the mammalian gastrointestinal flora, is responsible for most fungal infections in immunosuppressed patients Candida is normally phagocytosed by macrophages and neutrophils, which secrete cytokines and induce hyphal development in this fungus1,2 Neutropenic patients, deficient in these immune cells, are particularly susceptible to systemic candidiasis3,4 Here we use genome-wide expression profiles of the related yeast Saccharomyces cerevisiae to obtain a signature of the events that take place in the fungus on ingestion by a mammalian macrophage Live S cerevisiae cells isolated from the phagolysosome are induced for genes of the glyoxylate cycle, a metabolic pathway that permits the use of two-carbon compounds as carbon sources In C albicans, phagocytosis also upregulates the principal enzymes of the glyoxylate cycle, isocitrate lyase (ICL1) and malate synthase (MLS1) Candida albicans mutants lacking ICL1 are markedly less virulent in mice than the wild type These findings in fungi, in conjunction with reports that isocitrate lyase is both upregulated and required for the virulence of Mycobacterium tuberculosis5,6, demonstrate the wide-ranging significance of the glyoxylate cycle in microbial pathogenesis

The glyoxylate cycle is required for fungal virulence

PURPOSEThe prognosis of invasive pulmonary aspergillosis (IPA) occurring in neutropenic patients remains poor. We studied whether new strategies for early diagnosis could improve outcome in these patients.PATIENTS AND METHODSTwenty-three histologically proven and 14 highly probable IPAs in 37 hematologic patients (neutropenic in 36) were analyzed retrospectively.RESULTSThe most frequent clinical signs associated with IPA were cough (92%), chest pain (76%), and hemoptysis (54%). Bronchoalveolar lavage (BAL) was positive in 22 of 32 cases. Aspergillus antigen test was positive in 83% of cases when tested on BAL fluid. Since October 1991, early thoracic computed tomographic (CT) scans were systematically performed in febrile neutropenic patients with pulmonary x-ray infiltrates. This approach allowed us to recognize suggestive CT halo signs in 92% of patients, compared with 13% before this date, and the mean time to IPA diagnosis was reduced dramatically from 7 to 1.9 days. Among 36 assessable patients, 10 f...

Improved management of invasive pulmonary aspergillosis in neutropenic patients using early thoracic computed tomographic scan and surgery.

Currently, about 180 hospitals participate in the National Nosocomial Infections Surveillance (NNIS) system. From January 1980 through April 1990, 27,200 fungal isolates causing nosocomial infections were reported from these hospitals; Candida species accounted for 19,621 (72.1%) of these isolates. Immunocompromised patients are at particularly high risk for candidemia. In patients with acute lymphocytic leukemia, treatment with vancomycin and/or imipenem appears to be an independent risk factor for candidemia; colonization of stool by Candida species may be another important predisposing factor in these patients. Rapid detection of invasive candidemia in these high-risk patients is particularly important to the improvement of rates of survival. Methods for rapid detection, such as the measurement of mannan (the major cell-wall polysaccharide of Candida), may be useful for diagnosing invasive candidiasis and for monitoring the response of this infection to antifungal therapy. Further studies of risk factors and the development of new methods for rapid diagnosis and monitoring should help decrease the morbidity and mortality associated with nosocomial fungal infections.

Epidemiology of Nosocomial Fungal Infections, with Emphasis on Candida Species

In an attempt to estimate the frequency of fungal infections among cancer patients, a survey of autopsy examinations was conducted in multiple institutions in Europe, Japan and Canada. Fungal infections were identified most often in leukemic patients and transplant recipients (25% each). Fifty-eight percent of fungal infections were caused by Candida spp. and 30% by Aspergillus spp. There was considerable variability in the frequency of fungal infections in different countries. Nevertheless, this study clearly demonstrates that fungal infections represent a common complication in cancer patients, especially in patients with leukemia.

Fungal infections in cancer patients: an international autopsy survey.

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Fungal infections in cancer patients: an international autopsy survey.