Accuracy of Plasma Cell-Free DNA Polymerase Chain Reaction for Diagnosis of Coccidioidomycosis

BACKGROUND: Coccidioidomycosis is the most prevalent endemic mycosis in the United States. Diagnosis of coccidioidomycosis can be challenging due to limitations of conventional diagnostics. Detection of fungal plasma cell-free DNA (cfDNA) is a novel non-invasive testing modality for the diagnosis of invasive fungal disease. In this study, we characterized the performance of Coccidioides plasma cfDNA PCR. METHODS: A retrospective study was conducted in patients with suspected coccidioidomycosis who underwent plasma cfDNA PCR testing and conventional fungal testing for C. immitis and C. posadasii. Patients were categorized per the EORTC/MSGERC case definitions as proven or probable for sensitivity analyses and no coccidioidomycosis for specificity analyses. RESULTS: Overall, 362 plasma samples from unique patients were included in this study. The overall sensitivity, specificity, and positive and negative predictive values of Coccidioides plasma cfDNA PCR at 0.04% prevalence were 57.5% (27/47; 95% CI, 42.2-71.7), 100% (315/315; 95% CI, 98.8-100), 100% (95% CI, 87.2-100), and 99.9% (95% CI, 100-100), respectively. The sensitivity was 33.3% (2/6; 95% CI, 4.3-77.7) in patients with pulmonary focal disease, 66.7% (14/21; 95% CI, 43.0-85.4; P≥0.05) in patients with pulmonary multifocal disease, and 52.6% (10/19; 95% CI, 39.6-77.9; P≥0.05) in patients with disseminated coccidioidomycosis. In patients with concurrent antigen results, the sensitivity of cfDNA PCR was 58.3% (14/24; 95% CI, 39.6-77.9) compared with 37.5% (9/24; 95% CI, 18.8-59.4; P≥0.05) for antigen. CONCLUSIONS: Coccidioides plasma cfDNA PCR is modestly sensitive but highly specific which can be useful for rapid and non-invasive diagnosis of coccidioidomycosis.