Progress towards developing sensitive non-sputum based TB diagnostic tests: the promise of urine cell-free DNA.

MacLean, Emily; Nathavitharana, Ruvandhi R

A highly accurate, non-sputum based test for tuberculosis (TB) detection is a key priority for the field of TB diagnostics. A recent study in Journal of Clinical Microbiology by Oreskovic and colleagues (J Clin Microbiol 59:e00074-21, 2021, https://doi.org/10.1128/JCM.00074-21) reports the performance of an optimized urine cell-free DNA (cfDNA) using sequence-specific purification combined with short-target PCR to improve the accuracy of TB detection. Their retrospective clinical study utilized frozen urine samples (n=73) from study participants diagnosed with active pulmonary TB in South Africa and the USA in an early phase validation study. Overall, this cfDNA technique detected TB with sensitivity of 83.7% (95% CI:71.0-91.5) and specificity of 100% (95% CI:86.2-100), which meet the World Health Organization's published performance criteria. Sensitivity was 73.3% in people without HIV (95% CI:48.1-89.1) and 76% in people with smear negative TB (95% CI:56.5-88.5). In this commentary, we discuss the results of this optimized urine TB cfDNA assay within the larger context of TB diagnostics and pose additional questions for further research.