Abstract

Invasive aspergillosis (IA) in immunocompromised hosts carries a high morbidity and mortality. Diagnosis is often delayed as definitive diagnosis requires invasive specimen collection while non-invasive testing with galactomannan is moderately accurate. Plasma cell-free DNA PCR represents a novel testing modality for the non-invasive diagnosis of invasive fungal disease (IFD). We directly compared the performance of Aspergillus plasma cfDNA PCR to serum galactomannan for the diagnosis of IFA during routine clinical practice.We conducted a retrospective study of all patients with suspected IFD who had Aspergillus plasma cfDNA PCR testing at Stanford Health Care from September 1st, 2020 - October 30th, 2022. Patients were categorized into proven, probable, possible and no IA based on the EORTC/MSG 2020 definitions. Primary outcomes included the clinical sensitivity and specificity for Aspergillus plasma cfDNA PCR and galactomannan.Overall, 238 unique patients with Aspergillus plasma cfDNA PCRs test results, including 63 positives and 175 non-consecutive negatives, were included in this study. Majority were immunosuppressed (89.9%) with a 22.3% 30-day all-cause mortality. The overall sensitivity and specificity of Aspergillus plasma cfDNA PCR was 86.0% (37/43; 95% CI, 72.7-95.7) and 93.1% (121/130; 95% CI, 87.4-96.3). The sensitivity and specificity of serum galactomannan in hematologic malignancies/stem cell transplants was 67.9% (19/28; 95% CI, 49.3-82.1) and 89.8% (53/59; 95% CI, 79.5-95.3), respectively. The sensitivity of cfDNA PCR was 93.0% (40/43; 95% CI, 80.9-98.5) in patients with a new diagnosis of IA.Aspergillus plasma cfDNA PCR represents a more sensitive alternative to serum galactomannan for non-invasive diagnosis of IA.

View details for DOI 10.1093/cid/ciad420

View details for PubMedID 37450614