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Aspergillus nidulans infection in chronic granulomatous disease
B H Segal1, E S DeCarlo, K J Kwon-Chung
1Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1886, USA.
Abstract:
Chronic granulomatous disease (CGD) is a rare inherited disorder of the NADPH oxidase complex in which phagocytes are defective in generating reactive oxidants. As a result, patients with CGD suffer from recurrent bacterial and fungal infections. The most common fungal infections are caused by Aspergillus species. Aspergillus nidulans is a rare pathogen in most patient populations with quantitative or qualitative neutrophil defects. We have reviewed all cases in which A. nidulans was isolated from patients at the National Institutes of Health (Bethesda, MD) between 1976 and 1997. A. nidulans infection occurred in 6 patients with CGD, but was not a pathogen in any other patient group. Aspergillus fumigatus was a more common pathogen in CGD compared with A. nidulans, but A. nidulans was more virulent. A. nidulans was significantly more likely to result in death compared with A. fumigatus, to involve adjacent bone, and to cause disseminated disease. Patients with A. nidulans received longer courses of amphotericin B therapy than patients with A. fumigatus, and were treated with surgery more often. In contrast to A. fumigatus, A. nidulans was generally refractory to intensive antifungal therapy, suggesting that early surgery may be important. These data show that A. nidulans is a distinct pathogen in CGD and its isolation carries more severe implications than that of A. fumigatus.
Insights
Chronic granulomatous disease (CGD) patients face severe infections from Aspergillus species. Aspergillus nidulans, though rare, is a more virulent pathogen than Aspergillus fumigatus in CGD, often leading to poorer outcomes.
Area of Science:
- Immunology
- Infectious Diseases
- Mycology
Background:
- Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by defective phagocyte NADPH oxidase function.
- This defect leads to recurrent, severe bacterial and fungal infections, with Aspergillus species being common culprits.
Observation:
- This study reviewed cases of Aspergillus nidulans isolation at the National Institutes of Health between 1976 and 1997.
- Aspergillus nidulans was identified as a pathogen exclusively in patients with CGD, unlike other patient groups.
Findings:
- Aspergillus nidulans infections in CGD patients were associated with higher mortality, increased bone involvement, and disseminated disease compared to Aspergillus fumigatus.
- Patients with A. nidulans infections required longer amphotericin B treatment and more frequent surgical interventions.
Implications:
- Aspergillus nidulans represents a distinct and particularly virulent pathogen in the context of CGD.
- The general refractoriness of A. nidulans to antifungal therapy suggests that early surgical intervention may be crucial for patient management.