Background: Reported sensitivity of the galactomannan enzyme immunoassay as an early diagnostic test for invasive aspergillosis (IA) has been widely variable, ranging from 29% to 100% in earlier clinical studies.
Methods: Studies performed to date have analyzed performance using per-patient calculations, limiting their ability to measure the impact of clinical variables that change over time, such as receipt of preventive antifungal therapy. In our study, performance of the test was calculated in per-patient and per-test analyses in a large cohort of patients at high risk for IA from 2 North American centers. A total of 272 serum samples obtained from 46 patients with IA and 3005 serum samples obtained from 269 control patients were analyzed using multiple index cutoff values to define positivity.
Results: Per-patient calculations yielded sensitivities of 43% and 70% using index cutoff values of 1.5 and 0.5, respectively; specificity decreased from 93% with use of the 1.5 index cutoff to 70% with use of the 0.5 index cutoff. Per-test calculations yielded sensitivities of 31% and 59% and specificities of 99% and 92% using index cutoff values of 1.5 and 0.5, respectively. Receipt of mold-active antifungal drugs on the day of testing decreased sensitivity; samples obtained from patients not receiving prophylactic or empirical antifungal drugs yielded a sensitivity of 89% and a specificity of 92% (with use of an index cutoff value of 0.5).
Conclusions: These findings have direct implications for preventive strategies, because the diagnostic utility of the antigen assay is compromised during receipt of prophylactic or empirical antifungal therapies.