Detection of Galactomannan Antigenemia by Enzyme Immunoassay for the Diagnosis of Invasive Aspergillosis: Variables That Affect Performance

Abstract

Invasive aspergillosis (IA) is a frequent complication of blood or marrow transplantation. Previous studies have reported that the Aspergillus galactomannan enzyme immunoassay (GM EIA) may be a useful diagnostic tool for IA, but its sensitivity is variable. We examined the performance of the GM EIA in 986 serum samples from 67 patients. Results demonstrated that decreasing the index cutoff for positivity to 0.5 increased its sensitivity, with minimal loss of specificity. The low cutoff increased the duration of test positivity before diagnosis by clinical means. Sensitivity was highest in patients who did not receive preventative mold-active antifungals (87.5%). A rabbit model demonstrated that the level of circulating antigen correlated with the tissue fungus burden. A quantifiable response to antifungal therapy in clinical samples and the rabbit model supports the development of this assay for early diagnosis and therapeutic monitoring. The 0.5 cutoff may allow for better performance as an early diagnostic test.

Analysis of non-relapse mortality and causes of death over 15 years following allogeneic hematopoietic stem cell transplantation

“…19 As for fungal infection, we found a decrease in the number of deaths regardless of GVHD/immunosuppression background (Supplementary Table 1). More prompt diagnosis with the advent of monitoring technology (e.g., galactomannan enzyme immunoassay 20 ), early computed tomography scan policy for suspected fungal infection, and the use of newer anti-fungal agents such as voriconazole may have had a role in the reduced number of deaths from fungal infections, including invasive aspergillosis. 21 We adopted preemptive treatment using ganciclovir or valganciclovir against CMV based on weekly monitoring of C7-HRP (CMVpp65) since 2002.…”

Administration of micafungin as prophylactic antifungal therapy in patients undergoing allogeneic stem cell transplantation

“…Frequent serological examinations for IFI using different methods, including 1-3β-D-glucan and galactomannan antigenemia, are important for early diagnosis. Marr et al reported that the use of a cutoff index of galactomannan reduced to 0.5 facilitated a more specific diagnosis of aspergillosis [19].…”

Retrospective utility of bronchoscopy after hematopoietic stem cell transplant

“…27 Prospective studies are needed to determine the benefit of antigen testing (e.g. galactomannan) of the serum 28,29 and BAL fluid. 30 We suspect that because patients evaluated in our study were accrued during an era with improved prophylaxis against PCP, 12 Candida 10 and CMV 11,13,14 and an increase in the proportion of invasive fungal infections, 31 Aspergillus has become the predominant organism 8 compared to older studies.…”