Prevalence and Predictors of Tuberculosis in Adults and Adolescents With Sputum Trace Ultra Results in 2 High-Burden Clinical Settings

Background Some patients who test trace positive on Xpert MTB/RIF Ultra ("Ultra"), a highly sensitive molecular diagnostic platform, may not have tuberculosis (TB) disease. A better understanding of the prevalence of TB, associated clinical characteristics, and utility of additional diagnostic tests among people with trace sputum (PWTS) could aid clinical decision-making. Methods We enrolled adults and adolescents with trace-positive sputum on initial TB diagnostic evaluation in Uganda and South Africa. Participants were extensively evaluated at enrollment; those with uncertain TB status were followed off treatment, with interval reevaluations by TB clinicians, for up to 3 months. We assessed TB prevalence and associated patient characteristics and diagnostic results. Results Among 311 PWTS, TB was identified by sputum culture at enrollment in 20% of participants (61/311, 95% CI 15%-24%). Within 3 months, 48% (145/301, 95% CI 43%-54%) had been judged to warrant TB treatment, and among those followed until microbiologic outcomes, 30% (68/227, 95% CI 24%-36%) had positive culture and 41% (99/240, 95% CI 35%-47%) had positive culture or Ultra. Two participants died. Having TB symptoms, advanced human immunodeficiency virus (HIV), and no recent TB history were associated with microbiologically confirmed TB disease, as were an abnormal chest X-ray (in those without recent TB) or elevated C-reactive protein (CRP). Conclusions Roughly half of PWTS were recommended TB therapy. This prevalence supports treating most PWTS when multimodal testing and repeated clinical evaluations are infeasible. However, given low observed mortality, some people with low-risk characteristics and negative results on other widely available diagnostic tests could safely defer treatment with clinical follow-up.