Diagnostic accuracy of tongue swab testing in persons with sputum Xpert Ultra Trace results

Abstract Background Molecular amplification of tongue swab samples is a non-sputum-based investigational approach to diagnose pulmonary tuberculosis (pTB). An improved manual qPCR method for tongue swabs recently achieved >90% sensitivity overall in diagnosing TB, compared to a sputum microbiologic reference standard. Performance characteristics in persons with low-positive results on sputum molecular tests are unknown. Methods Adults in South Africa and Uganda with sputum Xpert MTB/RIF Ultra Trace (TR+) results were recruited for confirmatory evaluation and follow-up. They underwent symptom evaluation, examination, chest X-ray, further sputum testing (repeat Xpert Ultra and two solid and liquid mycobacterial cultures), and two tongue swabs. Tongue swabs were tested using qPCR amplification of the IS6110 gene. A single copy detected on >=1 swab was considered TB-positive. TR+ persons not diagnosed with TB at baseline were re-evaluated at 1 and 3 months. We determined the sensitivity and specificity of tongue swabs against TB culture alone, a microbiologic reference standard (MRS: any positive result from Xpert Ultra or TB culture) and a composite reference standard (CRS: a clinical recommendation for TB treatment or any positive culture) at baseline. Results 225 enrolled TR+ participants (115 (51%) women, median age 38 [IQR 30-47], 130 (58%) people living with HIV (PWH)) provided at least 1 tongue swab at baseline. With a culture reference standard, 45 (20%) were positive for TB at baseline testing; 58 (26%) were positive for TB by MRS and 83 (37%) by CRS. Sensitivity and specificity of tongue swabs against culture were 25% [95% CI 13-40%] and 94% [90-97%], vs. MRS were 25% [95% CI 14-38%] and 96% [91-98%], and vs. CRS were 16% [9-26%] and 94% [89-98%]. Conclusion Tongue swabs had low sensitivity and moderately high specificity for TB in persons with a Trace Xpert Ultra result. Tongue swabs have limited value for diagnosing people with low-positive molecular test results of uncertain clinical significance.