| Disease Introduction Mechanism | Aspergillus fumigatus is a ubiquitous filamentous fungus in the environment. On average, humans inhale hundreds of Aspergillus conidia daily. These conidia can be eliminated efficiently by innate immune mechanisms in immunocompetent hosts, but could germinate and colonize in immunocompromised hosts. Because of the increasing use of transplantation for end-organ disease, the use of immunosuppressive and myeloablative therapies for autoimmune and neoplastic diseases, and the progressing human immunodeficiency virus (AIDS) pandemic, the number of immunocompromised patients is steadily expanding. In these patients, the conidia of A. fumigatus with diameters (3 to 5 μm) that allow them to traverse the terminal respiratory airways and reach the pulmonary alveoli could escape the host defense and germinate in the lung, causing pulmonary aspergillosis. In severely immunocompromised humans, the fungi are able to penetrate the lung tissue or sinuses with invasive hyphae and disseminate throughout the body via the bloodstream, which cause life-threatening infections of the brain or other organs, including the eye, the heart, the kidneys, and the skin. Such disseminated infections are known as invasive aspergillosis (IA). The incidence of IA can reach as high as 50 % in acute leukemia if the patients are exposed to increased environmental doses of Aspergillus spores, such as during building/construction work. The mortality rate is often around 50 %, but could reach 95 % with delayed diagnosis. Since the signs and symptoms of IA are nonspecific, early clinical diagnosis of this infection is often difficult. The “gold standard” for “proven” diagnosis is Aspergillus isolation in laboratory culture or histological evidence of mycelial growth in biopsy specimens. However, owing to its invasiveness, biopsy is often precluded from patients in critical conditions. A. fumigatus cultures from blood or respiratory specimens are often negative, especially during early stages of the disease. As an adjunctive measure to microbiological methods, antibody detection is usually performed for the diagnosis of IA, but these assays are usually insufficient, owing to limits of their sensitivity and specificity. False-negative results are frequent because of the fulminant nature of the disease and the poor immunological status of the host, and positive antibodies are also exist in healthy individuals because of their frequent environmentally prolonged exposure to the conidia. |
