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Invasive aspergillosis is distinguished by its setting in immunocompromised individuals and its rapid progression to death. The typical patient is one with leukemia or under immunosuppression for a bone marrow transplant. The appearance of fever and a dry cough may be the only signs until pulmonary infiltrates are demonstrated radiologically. Until Aspergillus hyphae are demonstrated, almost any of the causes of pneumonia could be responsible.
Aspergillus species are widely distributed in nature and found throughout the world. Theyseem to adapt to a wide range of environmental conditions, and the heat-resistant conidia provide a good mechanism for dispersal. Like bacteria spores, the conida survive well in the environment and their inhalation is the mode of infection. Hospital air and air ducts have received attention as sources of nosocomial Aspergillus isolates. Occasionally, con-struction, remodeling, or other kinds of major environmental disruption have been associ-ated with increased frequency of Aspergillus contamination, colonization, or infection.
Aspergillus conidia are small enough to readily reach the alveoli when inhaled, but diseaseis rare in those without compromised defenses. Factors that aid the fungus in the initial stages are not known, but the ability of proteins on the surface of the conidia to bind fi-brinogen and laminin probably contribute to adherence. Production of extracellular elas-tase, proteinases, and phospholipases has been associated with the more virulent species. The appearance of antibodies to these enzymes during and following invasive aspergillosis argues for their importance, but the pathogenic role of these enzymes remains to be demonstrated. Most species produce aflatoxins and other toxic secondary metabolites but their role in infection is also unknown.
Macrophages, particularly pulmonary macrophages, are the first line of defense against inhaled Aspergillus conidia phagocytosing and killing them by nonoxidative mechanisms. For the conidia that survive and germinate, PMNs become the primary defense. They are able to attach to the growing hyphae, generate an oxidative burst, and secrete reactive oxygen intermediates. Little is known of adaptive immunity in humans. Antibodies are formed but their protective value is unknown. Although AIDS patients do develop Aspergillus infections, the association with T-cell deficiencies is not strong enough to draw conclusions about their importance.
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