Tongue swab-based molecular diagnostics for pulmonary tuberculosis and drug resistance in adults: A prospective multicenter diagnostic accuracy study.

BACKGROUND: Tongue swabs have emerged as a promising non-invasive alternative for TB diagnosis. This study aimed to evaluate the diagnostic performance of tongue swab-based assays for detecting Mycobacterium tuberculosis (MTB) and anti-TB drug resistance.

METHODS: We conducted a multicenter study in five TB-designated hospitals in China from May to August 2024. Tongue swabs and sputum samples were collected from 720 adults with symptoms suggestive of pulmonary TB. PCR-based tongue swab testing targeting MTB-specific sequences was evaluated against microbiological reference standards (MRS) and Xpert MTB/RIF. Tongue swab-based targeted next generation sequencing was conducted to diagnose the drug-resistant TB.

RESULTS: Tongue swab testing demonstrated high diagnostic accuracy, with a concordance rate of 95.1% (95% CI: 93.2-96.5) compared to Xpert MTB/RIF, and with a sensitivity of 88.6% (95% CI: 85.3-91.8) and specificity of 98.3% (95% CI: 97.0-99.7) compared to MRS. Tongue swabs supported the detection of drug-resistant MTB using targeted next-generation sequencing, with detection rates of 98.66% for Ct <30, 91.53% for Ct 30-33, and 84.62% for Ct 33-34, declining sharply to 57.14% for Ct 34-35.

CONCLUSION: PCR-based tongue swab testing offers a rapid, non-invasive alternative for TB diagnosis with high accuracy, particularly in paucibacillary cases or individuals unable to provide sputum. Although all participants in this study were able to provide sputum, tongue swabs may offer an alternative in situations where sputum collection is challenging. Further optimization of sampling and molecular techniques is essential to improve reliability and support broader implementation. Integrating tongue swab diagnostics with existing TB control programs could enhance the detection accuracy, improve drug resistance monitoring and reduce transmissions.