Clinical Information

Invasive aspergillosis (IA) is a severe infection that occurs in patients with prolonged neutropenia following transplantation or in conjunction with aggressive immunosuppressive regimens (eg, prolonged corticosteroid use, chemotherapy). The incidence of IA is reported to vary from 5% to 20% depending on the patient population. IA has an extremely high mortality rate of 50% to 80%, due in part to the rapid progression of the infection (ie, 1-2 weeks from onset to death). Approximately 30% of cases remain undiagnosed and untreated at death.

Definitive diagnosis of IA requires histopathological evidence of deep-tissue invasion or a positive culture. However, this evidence is often difficult to obtain due to the critically ill nature of the patient and the fact that severe thrombocytopenia often precludes the use of invasive procedures to obtain a quality specimen. The sensitivity of culture in this setting also is low, reportedly ranging from 30% to 60% for bronchoalveolar lavage (BAL) fluid. Accordingly, the diagnosis is often based on nonspecific clinical symptoms (unexplained fever, cough, chest pain, dyspnea) in conjunction with radiologic evidence (computed tomography [CT] scan), and a definitive diagnosis is often not established before fungal proliferation becomes overwhelming and refractory to therapy.

Recently, a serologic assay was approved by the FDA for the detection of galactomannan, a molecule found in the cell wall of Aspergillus species. Serum galactomannan (Aspergillus antigen) can often be detected a mean of 7 to 14 days before other diagnostic clues become apparent, and monitoring of Aspergillus antigen can potentially allow initiation of preemptive antifungal therapy before life-threatening infection occurs.

The clinical utility of Aspergillus antigen testing in BAL specimens as an early prognostic indicator of IA has recently been assessed. These studies demonstrated equivalent or higher sensitivity compared to detection of Aspergillus antigen in serum.(1-4) This assay may be useful in the assessment of therapeutic response as antigen levels typically decline in response to effective antimicrobial therapy.