Diagnosis of Invasive Aspergillosis

Diagnostic Categories

The European Organization for Research in Treatment of Cancer–Mycoses Study Group categorizes invasive aspergillosis into three levels of diagnostic certainty: proven, probable, and possible 2, 3
Proven aspergillosis requires histopathological documentation of infection and a positive culture from a normally sterile site 2, 3
Probable aspergillosis requires fulfillment of criteria in three categories: host factors, clinical manifestations, and microbiological evidence 2, 3

Culture confirmation is important to differentiate aspergillosis from other filamentous fungal infections like fusariosis and scedosporiosis 1, 2
Aspergillus species grow well on standard fungal media and can be identified to species level in most laboratories 1, 4
Blood cultures have limited utility as they are often negative even in disseminated infection 1, 5

Bronchoalveolar lavage (BAL), transthoracic percutaneous needle aspiration, or video-assisted thoracoscopic biopsy are standard procedures for establishing diagnosis 1, 2
Fluid and tissue specimens may reveal characteristic angular dichotomously branching septate hyphae on direct microscopic examination 1, 2

High-resolution CT scan is the diagnostic imaging method of choice and should be performed within 24 hours of clinical suspicion 6
The "halo sign" and "air-crescent sign" on CT are characteristic but not diagnostic of invasive pulmonary aspergillosis 1, 7

Galactomannan enzyme immunoassay (EIA) has been validated as a surrogate marker for invasive aspergillosis 7, 6
Serum galactomannan testing has sensitivity of 74% and specificity of 85% at a cutoff of 0.5 6
Beta-D-glucan (BDG) testing in serum has sensitivity of 50-70% and specificity of 91-99% in patients with hematological malignancies 6

Aspergillus PCR testing of blood or BAL samples can be valuable in immunocompromised patients 6
PCR tests can detect fungal DNA even after antifungal treatment has been initiated 6

The diagnostic algorithm includes performing high-resolution CT scan within 24 hours of clinical suspicion, obtaining serum galactomannan and beta-D-glucan tests, performing bronchoscopy with BAL, considering tissue biopsy, and interpreting results in the context of host factors and clinical manifestations 1, 2, 6, 7