Accuracy of Tongue Swab Testing Using Xpert MTB-RIF Ultra for Tuberculosis Diagnosis.

Tongue dorsum swabs have shown promise as alternatives to sputum for detecting Mycobacterium tuberculosis (MTB) in patients with pulmonary tuberculosis (TB). Some of the most encouraging results have come from studies that used manual quantitative PCR (qPCR) to analyze swabs. Studies using the automated Cepheid Xpert MTB/RIF Ultra qPCR test (Xpert Ultra) have exhibited less sensitivity with tongue swabs, possibly because Xpert Ultra is optimized for testing sputum, not tongue swab samples. Using two new sample preprocessing methods that demonstrated good sensitivity in preliminary experiments, we assessed diagnostic accuracy and semi-quantitative signals of Xpert Ultra performed on tongue swabs collected from 183 adults with presumed TB in Kampala, Uganda. Relative to a sputum Xpert Ultra reference standard, the sensitivity of tongue swab Xpert Ultra was 77.8% (95% confidence interval [CI] 64.4-88.0) and specificity was 100.0% (95% CI, 97.2-100.0). When compared to a microbiological reference standard (MRS) incorporating both sputum Xpert Ultra and sputum mycobacterial culture, sensitivity was 72.4% (95% CI, 59.1-83.3) and specificity remained the same. Semi-quantitative Xpert Ultra results were generally lower with tongue swabs than with sputum, and cycle threshold values were higher. None of the eight sputum Xpert Ultra "trace" or "very low" results were detected using tongue swabs. Tongue swabs should be considered when sputum cannot be collected for Xpert Ultra testing, or in certain mass-screening settings. Further optimization of tongue swab analysis is needed to achieve parity with sputum-based molecular testing for TB.