Emerging Aspergillus Species Almost Exclusively Associated With Primary Immunodeficiencies

Area of Science:

• Medical Mycology
• Immunology
• Infectious Diseases

Background:

• Invasive aspergillosis (IA) is a severe mold infection, particularly in immunocompromised individuals.
• Primary immunodeficiency (PID) patients face significant IA morbidity and mortality, often from common Aspergillus species like *A. fumigatus*.
• Emerging rare *Aspergillus* species are increasingly identified in PID patients, distinct from those affecting iatrogenically immunosuppressed individuals.

Purpose of the Study:

• To summarize current understanding of rare *Aspergillus* species causing IA in PID patients.
• To highlight the distinct clinical presentation and challenges of IA in PID compared to acquired immunosuppression.
• To differentiate the etiological agents and disease patterns of IA in PID.

Main Methods:

• Review of literature on *Aspergillus* species identified in patients with primary immunodeficiency.
• Analysis of clinical characteristics and disease progression patterns in IA cases within PID cohorts.
• Comparison of IA epidemiology and treatment responses between PID and iatrogenic immunosuppression.

Main Results:

• Several rare *Aspergillus* species (*A. udagawae, A. quadrilineatus*, etc.) are reported almost exclusively in PID patients.
• IA in PID patients can present as chronic, extrapulmonary disease with contiguous dissemination.
• Infections in PID patients are often more refractory to standard antifungal therapies.

Conclusions:

• Rare *Aspergillus* species represent a significant etiological group for IA in PID.
• PID-associated IA exhibits unique clinical and epidemiological features.
• Understanding these rare species and their distinct disease patterns is crucial for improved diagnosis and management in PID.