Invasive aspergillosis is a severe opportunistic fungal infection caused by Aspergillus species, most commonly A. fumigatus (>90% of cases), with A. flavus, A. niger, and A. terreus less frequent. Aspergillus is a ubiquitous environmental mold producing airborne conidia that are inhaled but cleared by intact immune defenses (alveolar macrophages, neutrophils). In the setting of severe immunosuppression, conidia germinate into invasive hyphae demonstrating angioinvasive growth, producing characteristic hemorrhagic infarction with surrounding hemorrhage and necrosis. The disease primarily affects the lungs (75%), but dissemination to brain, sinuses, skin, eyes, and other organs occurs.
Risk factors are critical to recognition and stratification. Highest risk populations include hematologic malignancy patients with prolonged neutropenia (>10 days), hematopoietic stem cell transplant recipients (especially during pre-engraftment and graft-versus-host disease), solid organ transplant recipients (lung > heart > liver > kidney), patients on high-dose corticosteroids (>20 mg prednisone equivalent for >3 weeks), and those receiving newer biologics (ibrutinib, alemtuzumab, JAK inhibitors). Other risk groups include advanced HIV, severe COPD, ICU patients, and increasingly recognized COVID-19-associated pulmonary aspergillosis (CAPA) and influenza-associated pulmonary aspergillosis (IAPA).
Modern diagnosis utilizes multiple non-culture biomarkers due to the difficulty of obtaining tissue diagnosis in critically ill patients. Serum galactomannan (GM) is a cell wall component of Aspergillus, with positive cutoff index ≥0.5 in serum and ≥1.0 in BAL fluid showing high sensitivity and specificity. Beta-D-glucan is more sensitive but less specific. Aspergillus-specific PCR is increasingly available. Imaging shows characteristic features: early halo sign (ground-glass opacity surrounding nodule), reverse halo sign, and late air crescent sign on chest CT. Definitive diagnosis requires tissue biopsy or sterile site culture. Voriconazole (loading dose 6 mg/kg twice daily, then 4 mg/kg twice daily with therapeutic drug monitoring targeting 1-5 μg/mL trough) and isavuconazole (no TDM needed, better tolerated) are first-line therapy. Liposomal amphotericin B is alternative therapy for intolerance or breakthrough disease. Treatment duration is minimum 6-12 weeks, with response monitored by clinical, radiographic, and biomarker follow-up. Reduction of immunosuppression when possible improves outcomes.