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

SUMMARY 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.

Secreted proteases from pathogenic fungi.

Despite significant advances in the management of immunosuppressed patients, invasive aspergillosis remains an important life-threatening complication. In the past two decades, the incidence of invasive aspergillosis in this population has continued to increase. Factors that predispose patients to develop invasive aspergillosis include prolonged granulocytopenia, the development of graft-versus-host disease, immunosuppressive therapy, the use of adrenal corticosteroids, and the prolonged impairment of host defenses associated with diseases such as chronic granulomatous disease. Environmental factors also play a key part in the pathogenesis of this infection, and therefore, infection control measures play a critical role in reducing exposure of patients to Aspergillus. New exciting developments in the early diagnosis of invasive aspergillosis and the acceleration of antifungal drug discovery offer promise for the future.

Invasive aspergillosis in 2002: an update.

Few among the millions of fungal species fulfill four basic conditions necessary to infect humans: high temperature tolerance, ability to invade the human host, lysis and absorption of human tissue, and resistance to the human immune system. In previously healthy individuals, invasive fungal disease is rare because animals' sophisticated immune systems evolved in constant response to fungal challenges. In contrast, fungal diseases occur frequently in immunocompromised patients. Paradoxically, successes of modern medicine have put increasing numbers of patients at risk for invasive fungal infections. Uncontrolled HIV infection additionally makes millions vulnerable to lethal fungal diseases. A concerted scientific and social effort is needed to meet these challenges.

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The Spectrum of Fungi That Infects Humans

During a seven month period, 367 molds were isolated from hospital air and 23 from patients. Aspergillus niger accounted for 56% of air isolates, but for only 17% of patient isolates. Aspergillus fumigatus was rarely found in air (0.3%), but was the dominant isolate among our patients (44%). We conclude, that different Aspergillus species may have a varied aptitude to colonize immunocompromised patients.

Aspergillus species from hospital air and from patients.

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Aspergillus species from hospital air and from patients.