Evidence for Tuberculosis in Individuals With Xpert Ultra "Trace" Sputum During Screening of High-Burden Communities

Abstract

Background: "Trace" results on Xpert MTB/RIF Ultra ("Ultra"; Cepheid) -a molecular diagnostic test for tuberculosis (TB)-are often interpreted as an indication for TB treatment, but may also represent detection of nonviable bacilli or analytical error. In community-screening settings where individual TB risk is low, there is limited guidance on how to interpret Ultra-trace results.

Methods: We conducted systematic Ultra TB screening of adults and adolescents (≥15 years) in Kampala, Uganda, through door-to-door and event-based sputum collection. We enrolled individuals with trace-positive sputum for detailed clinical, radiographic, and microbiological (including 2 sputum cultures, repeat Ultra, and for people with HIV, urine lipoarabinomannan) evaluation, and compared those findings with similar evaluations in controls with Ultra-negative and Ultra-positive (non-trace) sputum.

Results: Of 21 957 people screened with Ultra, 211 (1.0%) tested positive, including 96 (46% of positives) with trace results. Of 92 people enrolled with trace-positive sputum; 12% (11/92) were HIV-positive and 14% (13/92) had prior TB. The prevalence of TB among participants with trace-positive sputum results was 14% (13/92) by culture, 24% (22/92) using broader microbiological criteria, and 26% (24/92) after accounting for clinical diagnosis. The prevalence of cough and of abnormal chest computed tomography (CT) findings were 32% and 26%, respectively, if Ultra-negative; 34% and 54% if trace-positive/non-microbiologically confirmed; 72% and 95% if trace-positive/microbiologically confirmed; and 71% and 93% if Ultra-positive (more than trace).

Conclusions: Most individuals with trace-positive sputum in Ugandan communities did not have microbiologically confirmed TB but had more symptoms and chest CT abnormalities than people with Ultra-negative sputum.

Keywords: Xpert MTB/RIF Ultra; Xpert Ultra; community screening; trace; tuberculosis.

Graphical Abstract

This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/evidence-for-tuberculosis-in-individuals-with-xpert-ultra-trace-sputum-during-screening-of-high-burden-communities

Figure 1.

Results of microbiological evaluation of community-screened individuals, by initial sputum Ultra result. Bars show the proportions of participants with Ultra-negative (left), Ultra-trace (middle), and Ultra-positive (right) screening results whose subsequent microbiological evaluations were positive as judged by a repeat sputum Ultra test result greater than trace (dark gray), a sputum culture positive for Mycobacterium tuberculosis (Mtb) (light gray), or any microbiological confirmation (black). The tests considered for microbiological confirmation included Ultra (greater than trace), culture, and urine LAM. Urine LAM testing was only performed for participants with a trace-positive screening result and HIV, and participants with a positive (> trace) or negative screening result had culture performed on only 1 sputum specimen (obtained after treatment initiation for 5/91 [5%] of those with positive screening results), whereas 2 culture specimens were obtained from participants with trace-positive screening results. The 22 microbiological confirmations among participants with trace screening results include 2 with positive LAM results (18% of 11 participants tested), both of which occurred among participant with negative repeat Ultra and negative culture results. The 1 participant with a negative screening Ultra result whose repeat Ultra result was positive had a negative culture result and a history of prior TB treatment. Two participants with trace-positive Ultra screening results were missing repeat Ultra results, and 8 and 1 participants with negative and positive screening Ultra results, respectively, had no interpretable culture results. Abbreviations: HIV, human immunodeficiency virus; LAM, lipoarabinomannan; TB, tuberculosis.