Evaluation of a Urine-Based Rapid Molecular Diagnostic Test with Potential to Be Used at Point-of-Care for Pulmonary Tuberculosis: Cape Town Cohort.

Tuberculosis (TB) diagnosis among sputum-scarce patients is time consuming. Thus, a nonsputum diagnostic alternative is urgently needed. The Mycobacterium tuberculosis-specific transrenal (Tr) DNA from urine is a potential target for TB diagnostics. In this study, a new urine-based Tr-DNA molecular assay was evaluated for diagnosis of pulmonary tuberculosis among 428 adults suspected of having pulmonary TB (164 HIV positive, 263 HIV negative) from Cape Town, South Africa. Tr-DNA was isolated from 4 mL of EDTA urine, and a rapid, double-stranded, primer-based PCR method was performed targeting the Mycobacterium tuberculosis-specific direct repeat region. Each Tr-DNA eluate was tested in triplicate using an automated molecular analyzer with controls included in each test. With liquid culture used as the gold standard, the Tr-DNA assay showed sensitivity of 42.9% (n = 75/175; 95% CI, 35.4%-50.5%) and specificity of 88.6% (n = 210/237; 95% CI, 83.9%-92.4%). Among HIV-infected patients with TB, sensitivity and specificity were 45.2% and 89.0%, respectively. The combination of smear microscopy and Tr-DNA increased the sensitivity to 83.8% (smear microscopy alone, 75.1%), with 96.6% specificity. This study indicates that Tr-DNA has a moderate specificity with low sensitivity for diagnosis of pulmonary TB. Despite low sensitivity, this diagnostic test may have potential in combination with smear microscopy to support TB diagnosis in HIV-endemic regions, where sputum-scarce patients are common.