Half treated, few confirmed: TB after trace Ultra results

Some people who test trace-positive on the molecular test Xpert MTB/RIF Ultra (called "Ultra") do not actually have active tuberculosis disease, and that uncertainty can make clinical decisions difficult. To better understand what a trace result means in practice, researchers led by Caitlin Visek enrolled adults and adolescents who had a trace-positive sputum result during initial TB diagnostic evaluation in two high-burden settings: Uganda and South Africa. The group, described in this study, called people with trace sputum (PWTS), were examined closely at the time they entered the study. When clinicians could not decide whether someone had TB, those participants were not immediately treated but were followed off treatment with repeat clinical evaluations over a period of up to three months. The goal was to measure how common true TB disease was in this group, to describe clinical features that were linked to disease, and to see how well additional, widely available tests helped clarify who had TB and who did not.

The study enrolled 311 PWTS and used standard tools such as sputum culture and the Xpert MTB/RIF Ultra ("Ultra") assay, along with clinical assessment, chest x-ray, and blood C-reactive protein (CRP) testing. At enrollment, sputum culture identified TB in 20% of participants (61/311, 95% CI 15-24%). Over a three-month period, clinicians judged that 48% (145/301, 95% CI 43-54%) of participants warranted TB treatment. When the researchers looked at those who were followed until microbiologic outcomes, 30% (68/227, 95% CI 24-36%) had a positive culture and 41% (99/240, 95% CI 35-47%) had either a positive culture or a positive Ultra result. Certain characteristics were associated with microbiologically-confirmed TB disease: having TB symptoms, advanced HIV, and no recent history of TB. In people without recent TB, an abnormal chest x-ray or an elevated CRP were also linked to confirmed disease. The observed mortality rate in the group was low.

These findings highlight a challenging balancing act for clinicians working in high-burden settings. Roughly half of people with trace-positive Ultra results were started on TB therapy, yet a substantially smaller share had microbiologic confirmation at enrollment or during follow-up. That suggests many patients with trace results may be treated empirically, while others with low risk and negative widely available tests — such as sputum culture, chest x-ray, and CRP — might safely defer immediate treatment and instead receive close monitoring. The study supports using a multimodal approach: combining symptom assessment, HIV status, chest x-ray, CRP, and repeated testing to better identify who truly has TB. It also underscores the need for longer follow-up and repeated evaluations to fully measure the TB burden among PWTS and to avoid both missed diagnoses and unnecessary treatment.