Early Diagnosis of Invasive Aspergillosis in Hematological Patients Using a PCR-ELISA Assay: A Prospective Validation.

Purpose: Prospective evaluation of a PCR-ELISA method for the early diagnosis of invasive aspergillosis (IA) in hematological patients.

Patients and Methods: The PCR-ELISA assay was evaluated using 1,494 sera samples from 201 hematological adult patients. Monitoring was performed twice weekly during 256 consecutive high-risk treatment periods.

Results: Underlying diseases were acute leukemia 52.7%, lymphoma 20.9%, multiple myeloma 12.4%. Eighty four patients (41.8%) were stem cell transplant recipients. Fifty-five patients were diagnosed with IA. PCR-ELISA positivity (i) preceded the empirical antifungal therapy in 20/31 patients (median 10.5 days), (ii) preceded or was simultaneous to the radiological diagnosis by chest CT in 21/31 patients (median 8 days), (iii) preceded the mycological/histological diagnosis in 7/12 patients (median 70 days) and, (iv) anticipated or was simultaneous to the galactomannan (GM) antigen positivity in 50% (median 16.5 days) and in 89 % of the patients (median 33 days) using a 0.5 and a 1.5 optical density index (ODI) cut-off for the GM assay, respectively. For at least two positive samples the sensitivity, specificity, positive and negative predictive values of the PCR-ELISA assay, were 63.6%, 82.2%, 57.4% and 85.7%, respectively. When the PCR-ELISA and GM detections were combined, values of the combined test for at least two positive samples with either assay were 80%, 47.3%, 36.4%, 86.2% using the 0.5 GM ODI cutoff, and 67.3%, 82.2%, 58.7% and 87% using the 1.5 GM ODI cutoff.

Conclusion: In addition to serial screening with GM antigenemia and chest CT surveillance, the PCR-ELISA assay may improve the early diagnosis of IA.