Prevalence and predictors of tuberculosis in adults and adolescents with sputum trace Ultra results in two 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 disease, 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 three 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 three months, 48% (145/301, 95% CI 43-54%) had been judged by clinicians 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. Having TB symptoms, advanced 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 CRP. Conclusions: Roughly half of PWTS were started on TB therapy. Given the low observed mortality rate, some low-risk people with negative results on widely available diagnostic tests could safely defer treatment. Multimodal testing, repeated evaluations, and longer follow-up duration are needed to fully assess the TB burden in PWTS.