Testing pleural fluid for tuberculosis DNA to diagnose pleural tuberculosis

Trial details

Who runs it

Chinese University of Hong Kong

Trial code

NCT06439810

Record updated

31 March 2026

Original description

Tuberculosis (TB) is one of the major global health threats and is the second leading infectious cause of death after COVID-19 in 2022. Extrapulmonary TB (EPTB), amongst which tuberculous pleuritis (TBP) is one of the most common subtypes, poses additional obstacles to global TB control due to its difficulty in diagnosis.Read full original descriptionShow less

Diagnostic Utility of Mycobacterium Tuberculosis Cell-free DNA (MTB cfDNA) in Tuberculous and Non-tuberculous Pleural Effusion

Tuberculosis (TB) is one of the major global health threats and is the second leading infectious cause of death after COVID-19 in 2022. Extrapulmonary TB (EPTB), amongst which tuberculous pleuritis (TBP) is one of the most common subtypes, poses additional obstacles to global TB control due to its difficulty in diagnosis.

The diagnosis of TBP is challenging. The ideal way of confirming TBP is by direct detection of TB bacteria or its specific component in the pleural space. However, the performance of available diagnostic tests is far from satisfactory, and no single test can achieve multiple diagnostic goals simultaneously, including high detection sensitivity, high specificity to exclude other diseases, low invasiveness and detection of drug resistance. The inability to diagnose TBP early leads to unnecessary invasive pleural procedures and delayed curative treatment. There is a pressing need for a better diagnostic test to diagnose TBP confidently.

When TB bacteria die or break down, the DNA materials shed into the pleural space, forming Mycobacterium tuberculosis cell-free DNA (MTB cfDNA), which may aid in diagnosing TBP. However, only limited literature explored this aspect, and the sensitivity rates reported were still suboptimal due to the scarcity of DNA materials in the pleural fluid. Based on a small patient cohort, our group has recently developed a new laboratory assay measuring MTB cfDNA to overcome this problem, with a superior diagnostic performance to conventional tests. This assay can potentially capture the genes harbouring drug resistance towards anti-TB medications.

There are three aims in this research proposal. First, the diagnostic accuracy of the new MTB cfDNA assay in diagnosing TBP will be determined using a large cohort containing pleural fluid samples of various causes from countries with different TB burdens. Second, the clinical and laboratory factors determining the pleural fluid MTB cfDNA level will be identified. Third, the ability of the assay to capture different anti-TB drug-resistance genes will be explored.

This new diagnostic method will significantly enhance the pickup rate of TBP, benefit patients with less invasive procedures, shorter hospital stays and timely treatment.

Inclusion: New-onset pleural effusion planning for thoracentesis; Age 18 years or above; Able to give informed consent.

Exclusion: Concomitant use of at least two anti-TB medications (including isoniazid, rifampicin, pyrazinamide, ethambutol, amikacin, streptomycin, levofloxacin, moxifloxacin, linezolid) for more than consecutive 7 days in the past 3 months; History of TBP or intrapleural therapy (including talc and fibrinolytic) in the ipsilateral pleural space. Patients with a history of TB outside the pleural space completed anti-TB treatment can be included; History of surgical intervention (including decortication, pleurodesis, lung resection) in the ipsilateral pleural space; Consent not obtained from the participants.

ClinicalTrials.gov NCT06439810