Accuracy of tongue swab testing using Xpert MTB-RIF Ultra for tuberculosis diagnosis

Abstract 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 yielded less encouraging results with tongue swabs, possibly because Xpert Ultra is optimized for testing sputum, not tongue swab samples. Using two new sample processing methods that demonstrated good sensitivity in preliminary experiments, we assessed diagnostic accuracy and semi-quantitative signals of 183 tongue swab samples using Xpert Ultra in a clinical setting. Relative to a sputum Xpert Ultra reference standard, the sensitivity of tongue swab Xpert Ultra was 68.5% (95% CI 54.4-80.5) 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 culture, sensitivity was 64.9 (95% CI 51.1-77.1) and specificity remained the same. Higher sensitivity was observed (77.8% CI 64.4-88.0) when “trace” Xpert results were included among positive swabs. Semi-quantitative Xpert Ultra results were generally lower with swabs than with sputum. 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.