Progress toward Developing Sensitive Non-Sputum-Based Tuberculosis Diagnostic Tests: the Promise of Urine Cell-Free DNA.

ABSTRACT

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 the Journal of Clinical Microbiology by Oreskovic and colleagues (J Clin Microbiol 59e00074-21, 2021, https//doi.org/10.1128/JCM.00074-21) reports the performance of an optimized urine cell-free DNA (cfDNA) test 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 compared results to non-TB patients in South Africa and the United States in an early-phase validation study. Overall, this cfDNA technique detected TB with a sensitivity of 83.7% (95% CI 71.0 to 91.5) and specificity of 100% (95% CI 86.2 to 100), which meet the World Health Organization's published performance criteria. Sensitivity was 73.3% in people without HIV (95% CI 48.1 to 89.1) and 76% in people with smear-negative TB (95% CI 56.5 to 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.