Epidemiology and clinical manifestations of invasive aspergillosis
- Kieren A Marr, MD
Kieren A Marr, MD
- Section Editor — Compromised Host Infections; Fungal Infections
- Professor of Medicine and Oncology
- Johns Hopkins University School of Medicine
The term "aspergillosis" refers to illness due to allergy, airway or lung invasion, cutaneous infection, or extrapulmonary dissemination caused by species of Aspergillus, most commonly A. fumigatus, A. flavus, and A. terreus. Aspergillus species are ubiquitous in nature, and inhalation of infectious conidia is a frequent event. Tissue invasion is uncommon and occurs most frequently in the setting of immunosuppression associated with therapy for hematologic malignancies, hematopoietic cell transplantation, or solid organ transplantation.
The pathogenesis, epidemiology, clinical manifestations, and differential diagnosis of invasive aspergillosis (specifically that occurring in people who are immunocompromised after transplant and/or treatment of hematologic malignancies) will be reviewed here. The diagnosis and treatment of invasive aspergillosis are discussed separately; other syndromes caused by Aspergillus species, including invasive aspergillosis in HIV-infected patients, are also presented elsewhere. (See "Diagnosis of invasive aspergillosis" and "Treatment and prevention of invasive aspergillosis" and "Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis" and "Clinical manifestations and diagnosis of chronic pulmonary aspergillosis" and "Treatment of chronic pulmonary aspergillosis" and "Epidemiology and clinical manifestations of pulmonary aspergillosis and invasive disease in HIV-infected patients" and "Diagnosis and treatment of invasive pulmonary aspergillosis in HIV-infected patients".)
Inhaled conidia are met by the innate defenses provided by resident phagocytes, specifically airway epithelial cells and alveolar macrophages [1,2]. Little is known about the contribution of epithelial cells in clearing conidia. Relatively more is known about macrophages, which contribute to both conidial clearance and the production of secondary inflammation. These cells secrete inflammatory mediators after recognition of key cell wall components (eg, beta-D-glucan) exposed after conidial germination into hyphal forms. These mediators result in neutrophil recruitment and the activation of cellular immunity, which are important in killing potentially invasive microbial forms (hyphae) and determining the extent and nature of the immune response. Hence, risks for disease and the type of disease that occurs are the combined result of multiple cellular functions that impact proximal events in conidial clearance, production of inflammation, and killing of invasive forms .
Microbial factors that impact disease potential include toxins, proteases, and secondary metabolites that exert multiple effects on the host's local pulmonary and systemic defense. These include cellular products that:
●Inhibit phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, a key component in host defense against filamentous fungi
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- MICROBIAL EPIDEMIOLOGY
- Species prevalence
- RISK FACTORS
- CLINICAL FEATURES
- Pulmonary aspergillosis
- - Imaging
- Chronic necrotizing and chronic cavitary pulmonary aspergillosis
- Disseminated infection
- Central nervous system infection
- Cutaneous aspergillosis
- Gastrointestinal aspergillosis
- DIFFERENTIAL DIAGNOSIS
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS