In:
Open Forum Infectious Diseases, Oxford University Press (OUP)
Abstract:
An early diagnosis and treatment of invasive fungal disease(IFD) is associated with improved outcome, but the moderate sensitivity of non-invasive diagnostic tests makes this challenging. Invasive diagnostic procedures like bronchoalveolar lavage(BAL) have a higher yield but are not without risk. The detection and sequencing of microbial cell-free DNA(mcfDNA) may facilitate a non-invasive diagnosis. Materials In a prospective observational study, we collected plasma in the 120 hours preceding or following a BAL in patients with hematological malignancies suspected for a pulmonary IFD. The EORTC/MSGERC2020 criteria were used for IFD classification. Sequencing was performed by Karius(Redwood City, California) using their Karius Test® (KT) on plasma and a ‘research use only test'(RUO-KT) on BAL fluid if available. Cases with a probable/proven IFD were identified based on standard diagnostic tests on serum and BAL (microscopy, PCR, GM, culture) and used to calculate the sensitivity, specificity and additional diagnostic value of the KT. Results Of 106 patients enrolled, 39 (37%) had a proven/probable invasive aspergillosis (IA), 7 (7%) a non-Aspergillus IFD and 4 (4%) a mixed IFD. The KT detected fungal mcfDNA in 29 (28%) patients. Compared with usual diagnostic tests, the sensitivity and specificity were 44.0%(95%CI:31.2–57.7%) and 96.6%(95%CI:88.5–99.1%). Sensitivity of the KT was higher in non-Aspergillus IFD (Mucorales:2/3, Pneumocystis jirovecii:3/5). On BAL, the sensitivity was 72.2% (95%CI:62.1–96.3%) and specificity 83.3%(95%CI:49.1–87.5%). Conclusions Sequencing of mcfDNA may facilitate a non-invasive diagnosis of IFD in particular non-Aspergillus IFD. However, on plasma and similar to currently available diagnostics, it cannot be used as a “rule-out” test.
Type of Medium:
Online Resource
ISSN:
2328-8957
DOI:
10.1093/ofid/ofae252
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2024
detail.hit.zdb_id:
2757767-3
