Background:The diagnosis of tuberculous pleurisy (TP) presents a significant challenge due to the low bacterial load in pleural effusion (PE) samples. Cell-free Mycobacterium tuberculosis DNA (cf-TB) in PE samples is considered an optimal biomarker for diagnosing TP. This study aimed to evaluate the applicability of cf-TB testing across diverse research sites with a relatively large sample size.Methods:Patients suspected of TP and presenting with clinical symptoms and radiological evidence of PE were consecutively enrolled by treating physicians from 11 research sites across 6 provinces in China between April 2020 and August 2022. Following centrifugation, sediments obtained from PE were used for Xpert MTB/RIF (Xpert) and mycobacterial culture, while the supernatants were subjected to cf-TB testing. This study employed a composite reference standard to definite TP, which was characterized by any positive result for Mycobacterium tuberculosis (MTB) through either PE culture, PE Xpert, or pleural biopsy.Results:A total of 1412 participants underwent screening, and 1344 (95.2%) were subsequently enrolled in this study. Data from 1241 (92.3%) participants were included, comprising 284 with definite TP, 677 with clinically diagnosed TP, and 280 without TP. The sensitivity of cf-TB testing in definite TP was 73.6% (95% CI 68.2%–78.4%), significantly higher than both Xpert (40.8%, 95% CI 35.3%–46.7%, P<0.001) and mycobacterial culture (54.2%, 95% CI 48.4%–59.9%, P<0.001). When clinically diagnosed TP was incorporated into the composite reference standard for sensitivity analysis, cf-TB testing showed a sensitivity of 46.8% (450/961, 95% CI 43.7%–50.0%), significantly higher than both Xpert (12.1%, 116/961, 95% CI 10.2%–14.3%, P<0.001) and mycobacterial culture (16.0%, 154/961, 95% CI 13.8%–18.5%, P<0.001). The specificities of cf-TB testing, Xpert, and mycobacterial culture were all 100.0%.Conclusions:The performance of cf-TB testing is significantly superior to that of Xpert and mycobacterial culture methods, indicating that it can be considered as the primary diagnostic approach for improving TP detection.

Cell-free Mycobacterium tuberculosis DNA (cf-TB);Pleural effusion (PE);Tuberculous pleurisy (TP);diagnosis