Purpose: Early diagnosis of invasive pulmonary aspergillosis and initiation of antifungal therapy improves outcomes in patients with this opportunistic infection. Assays are available for the detection of the surrogate markers (1,3)-β -D-glucan and galactomannan within the serum. Recent studies have reported the utility of detecting galactomannan within the bronchial alveolar lavage (BAL) fluid for the diagnosis of invasive pulmonary aspergillosis. Our objective was to measure (1,3)-β -D-glucan and galactomannan within the BAL fluid in a guinea pig model of invasive pulmonary aspergillosis and compare these results to those obtained within serum. Methods: Guinea pigs were immunosuppressed with cyclophosphamide (250 mg/kg IP) and cortisone acetate (250 mg/kg SC), and inoculated with A. fumigatus clinical isolate AF293 using an established aerosol chamber. Blood and BAL fluid were collected in 5 infected animals at 1 hour post-inoculation and on days 3, 5, and 7. (1,3)-β -D-glucan was assayed using the commercially available Fungitell assay, and galactomannan was measured using the Platelia Aspergillus assay. These biomarkers were measured in both infected and uninfected animals. Pulmonary fungal burden was assessed by colony-forming units. Results: At 1 hour post-inoculation (1,3)-β -D-glucan and galactomannan levels were below the threshold of positivity ((1,3)-β -D-glucan 80 pg/mL and galactomannan index [GMI] 0.5, respectively) in both the BAL and serum from 4 of 5 animals. Increases within the BAL fluid were detected in 5/5 animals for (1,3)-β -D-glucan and 3/5 for galactomannan on day 3 (median beta-glucan 466 pg/mL and GMI 1.29, respectively) and remained elevated on days 5 and 7. These results are in agreement with the pulmonary fungal burden data, which was elevated on day 3 (median 3.85 log10 CFU/g) and remained elevated on days 5 and 7. In contrast, increases in these biomarkers within the serum were not detected until day 7 (157 pg/mL and GMI 4.98, respectively) with 4/5 samples positive by both assays. (1,3)-β -D-glucan and galactomannan remained below their respective thresholds for positivity within the BAL fluid in uninfected animals. Conclusions: The biomarkers (1,3)-β -D-glucan and galactomannan were detectable earlier within the BAL fluid compared to serum from guinea pigs with invasive pulmonary aspergillosis. These findings may have clinical implications as the diagnosis of invasive pulmonary aspergillosis may be made earlier when biomarkers are assayed within the BAL fluid.
Full conference title:
4th Advances Against Aspergillosis
- AAA 4th (2010)