Rethinking pleural tuberculosis through the lens of cell-free DNA

Tuberculous pleuritis (TBP) remains one of the most diagnostically challenging manifestations of tuberculosis.1 2 Despite its global prevalence, particularly in high-burden settings, confirmation of TBP is frequently elusive. Conventional microbiological techniques perform poorly in pleural fluid,3 4 where mycobacterial burden is low and organisms are often non-viable. Diagnostic confidence is therefore commonly inferred from surrogate markers such as adenosine deaminase (ADA), immunological assays5 6 or clinical response to therapy. The result is a persistent trade-off between diagnostic delay, empirical treatment and invasive pleural biopsy.