The term "aspergillosis" comprises several categories of infection: invasive aspergillosis; chronic necrotizing aspergillosis; aspergilloma, or fungus ball; and allergic bronchopulmonary aspergillosis. In 24 medical centers, we examined the impact of a culture positive for Aspergillus species on the diagnosis, risk factors, management, and outcome associated with these diseases. Most Aspergillus culture isolates from nonsterile body sites do not represent disease. However, for high-risk patients, such as allogeneic bone marrow transplant recipients (60%), persons with hematologic cancer (50%), and those with signs of neutropenia (60%) or malnutrition (30%), a positive culture result is associated with invasive disease. When such risk factors as human immunodeficiency virus infection (20%), solid-organ transplantation (20%), corticosteroid use (20%), or an underlying pulmonary disease (10%) are associated with a positive culture result, clinical judgment and better diagnostic tests are necessary. The management of invasive aspergillosis remains suboptimal: only 38% of patients are alive 3 months after diagnosis. Chronic necrotizing aspergillosis, aspergilloma, and allergic bronchopulmonary aspergillosis have variable management strategies and better short-term outcomes.

Oropharyngeal and esophageal candidiases remain significant causes of morbidity in human immunodeficiency virus (HIV)-infected patients, despite the dramatic ability of antiretroviral therapy to reconstitute immunity. Notable advances have been achieved in understanding, at the molecular level, the relationships between the progression of HIV infection, the acquisition, maintenance, and clonality of oral candidal populations, and the emergence of antifungal resistance. However, the critical immunological defects which are responsible for the onset and maintenance of mucosal candidiasis in patients with HIV infection have not been elucidated. The devastating impact of HIV infection on mucosal Langerhans' cell and CD4+ cell populations is most probably central to the pathogenesis of mucosal candidiasis in HIV-infected patients. However, these defects may be partly compensated by preserved host defense mechanisms (calprotectin, keratinocytes, CD8+ T cells, and phagocytes) which, individually or together, may limit Candida albicans proliferation to the superficial mucosa. The availability of CD4C/HIV transgenic mice expressing HIV-1 in immune cells has provided the opportunity to devise a novel model of mucosal candidiasis that closely mimics the clinical and pathological features of candidal infection in human HIV infection. These transgenic mice allow, for the first time, a precise cause-and-effect analysis of the immunopathogenesis of mucosal candidiasis in HIV infection under controlled conditions in a small laboratory animal

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In order to approximate and adhere to mucosal epithelial cells, Candida must traverse the overlying mucus layer. Interactions of Candida species with mucin and human buccal epithelial cells (BECs) were thus investigated in vitro. Binding of the Candida species to purified small intestinal mucin showed a close correlation with their hierarchy of virulence. Significant differences (P < 0.05) were found among three categories of Candida species adhering highly (C. dubliniensis, C. tropicalis, and C. albicans), moderately (C. parapsilosis and C. lusitaniae) or weakly (C. krusei and C. glabrata) to mucin. Adherence of C. albicans to BECs was quantitatively inhibited by graded concentrations of mucin. However, inhibition of adherence was reversed by pretreatment of mucin with pronase or C. albicans secretory aspartyl proteinase Sap2p but not with sodium periodate. Saturable concentration-and time-dependent binding of mucin to C. albicans was abrogated by pronase or Sap2p treatment of mucin but was unaffected by ␤-mercaptoethanol, sodium periodate, neuraminidase, lectins, or potentially inhibitory sugars. Probing of membrane blots of the mucin with C. albicans revealed binding of the yeast to the 66-kDa cleavage product of the 118-kDa C-terminal glycopeptide of mucin. Although no evidence was found for the participation of C. albicans cell surface mannoproteins in specific receptor-ligand binding to mucin, inhibition of binding by p-nitrophenol (1 mM) and tetramethylurea (0.36 M) revealed that hydrophobic interactions are involved in adherence of C. albicans to mucin. These results suggest that C. albicans may both adhere to and enzymatically degrade mucins by the action of Saps, and that both properties may act to modulate Candida populations in the oral cavity and gastrointestinal tract.