Evaluation of trace calls by Xpert MTB/RIF ultra for clinical management in low TB burden settings

Abstract

Background Clinical interpretation of trace results by Xpert MTB/RIF Ultra assay (Ultra) used as an initial diagnostic test for tuberculosis (TB) may be challenging. The aim of the study was to evaluate the frequency and epidemiology of trace readouts in routine clinical practice in a low TB prevalence setting and to propose guidance on how to manage patients with trace calls considering the data available (clinical, radiological, bacteriological etc.). Materials and methods A retrospective, observational, monocentric study was conducted at IRCCS Azienda Ospedaliero-Universitaria of Bologna, Italy between November 2017—December 2020. Presumptive TB patients with at least one Ultra trace result during diagnostic workup before treatment were included in the study. Patients with ongoing anti-TB treatment at the time of the trace call result or with no clinical data available were excluded from the study. Results Fifty-nine presumptive TB patients with Ultra trace readouts were included in the study (mean age 37.0 years, 61% males). Four patients had a history of TB in the last 2 years. Twenty-five (42.4%) of the 59 samples with trace results were respiratory material. 57/59 (96.6%) patients started anti-TB treatment soon after obtaining trace results, based on clinical, radiological or other information available, while for two patients with a recent history of TB the trace result did not lead to anti-TB treatment. Culture was positive for M. tuberculosis for 31/59 (52.5%) samples with trace calls: 13/25 (52.0%) were respiratory samples and 18/33 (54.5%) non-respiratory samples. The clinical and/or radiological findings of 47/57 (82.4%) patients given anti-TB therapy improved during treatment. Conclusion In low TB incidence settings, Ultra trace calls in presumptive TB patients should be considered as true-positive and treatment should be started promptly, except in cases of recent history of TB, where careful evaluation of other diagnostic criteria is necessary before starting anti-TB treatment. A decisional algorithm for clinical management is proposed.

Xpert MTB/RIF Ultra Trace Results: Decision Support for the Treatment of Extrapulmonary Tuberculosis in Low TB Burden Countries

“…The relatively high percentage of positive cultures in our series compared to that of Amedeo (71.7% versus 54.5%, respectively), may be due to the lower percentage of lymph node TB (55.9% versus 25%, respectively), that can remain sterile in culture. Severe neuromeningeal, digestive, and bone forms are paradoxically more often documented by culture in our study [9].…”

“…Mazzola et al concluded that false positives results could be easily avoided by not performing the Ultra test on samples from patients with a clinically excluded diagnosis of TB or with a history of TB within 5 years [8]. According to Amedeo's study, trace results in presumptive TB patients should be considered as true positives and treatment should be started promptly, except in cases of recent TB [9].…”

“…Finally, a very recent monocentric study evaluated clinical management of trace results in low TB burden settings [9]. Of the 59 patients included in the analysis, 34 had nonrespiratory samples with 55.9% of lymph node biopsies.…”

“…All the 34 patients had either symptoms and/or radiological findings consistent with TB, meeting the definition of presumptive TB. A total of 57 (96.6%) patients started anti-TB treatment, based on clinical and/or radiological findings and an Ultra trace result with a delay of 4 ± 4.7 days after the trace result [9].…”

Comparison of Analytical Sensitivity (Limit of Detection) of Xpert MTB/RIF and Xpert MTB/RIF Ultra for Non-Sputum Specimens

“…Because Ultra can detect MTB at “trace” levels, this feature can be helpful in establishing TB diagnoses in paucibacillary conditions. Studies have shown that the “trace” calls result in the early diagnosis of TB in smear-negative, culture-positive paucibacillary situations, leading to prompt treatments [ 25 , 26 ]. This highlights the significant clinical impact of Ultra’s “trace” feature in critical situations where the diagnosis could have been missed or delayed otherwise.…”