Using droplet digital polymerase chain reaction for cell-free DNA to diagnose tuberculous pleural effusion.
Journal
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
Journal Volume
168
Start Page
Article number 108743
ISSN
1878-3511
Date Issued
2026-07
Author(s)
Abstract
Objectives Tuberculous pleural effusion (TPE) remains a diagnostic challenge. We aimed to evaluate droplet digital polymerase chain reaction (ddPCR) for detecting Mycobacterium tuberculosis (Mtb)-derived cell-free deoxyribonucleic acid (cfDNA) in pleural effusion. Methods Pleural effusion samples were prospectively collected from two hospitals in Taiwan. ddPCR targeting the IS6110 sequence of Mtb was performed to quantify cfDNA levels. Diagnostic performance was compared with Xpert Ultra. Results Of 91 participants, 29 were diagnosed with TPE and 62 with non-TPE causes. ddPCR showed significantly higher Mtb cfDNA levels in TPE compared with the non-TPE group (1.49 vs 0.35-0.44 copies/µL, P < 0.001). The optimal cutoff of ≥10 positive droplets yielded a sensitivity of 83% and specificity of 84%. In contrast, Xpert Ultra showed only 31.8% sensitivity despite 100% specificity. The area under the receiver operating characteristic curve for ddPCR (area under the curve = 0.861) outperformed Xpert. Conclusion ddPCR of Mtb-derived cfDNA in pleural effusion offers a sensitive and specific non-invasive diagnostic tool for TPE, outperforming conventional molecular diagnostics.
Subjects
Cell-free DNA
Droplet digital polymerase chain reaction
Mycobacterium tuberculosis
Tuberculous pleural effusion
Type
journal article