Accuracy of Rapid Quantitative PCR on Tongue Swabs for Pulmonary Tuberculosis in Sputum-Scarce Patients: A Prospective Multicenter Diagnostic Study

BACKGROUND: The diagnosis of pulmonary tuberculosis (TB) remains challenging in sputum-scarce and sputum-negative patients. Tongue swabs represent a promising non-invasive alternative specimen type that could overcome this diagnostic limitation. This study aimed to evaluate the performance of molecular detection of Mycobacterium tuberculosis (Mtb) from tongue swabs in this clinically challenging population. METHODS: In this study, We enrolled 625 sputum scarce individuals with presumptive TB from four Chinese TB hospitals. For each participant, paired tongue swab and bronchoalveolar lavage fluid (BALF) specimens were collected. Tongue swab specimens were analyzed using MTB-specific PCR assay, while BALF specimens underwent comprehensive evaluation using both microbiological reference standard (MRS) and Xpert MTB/RIF assay. RESULTS: Tongue swab testing demonstrated high diagnostic accuracy with 79.9% sensitivity (95% CI: 73.9-84.8) and 99.5% specificity (95% CI: 98.0-99.9) against the MRS, and 81.7% sensitivity (95% CI: 75.7-86.6) with 97.6% specificity (95% CI: 95.5-98.8) against Xpert MTB/RIF. Notably, simulation modeling revealed that when the proportion of sputum-scarce patients exceeded 10%, the tongue swab PCR strategy outperformed conventional sputum-only Xpert MTB/RIF testing in overall case detection rates. CONCLUSIONS: Tongue swab-based PCR represents a non-invasive, accurate, and highly specific diagnostic approach for tuberculosis, particularly in sputum-scarce or sputum-negative individuals. While this study demonstrates its superior performance in such populations, further optimization of sampling protocols and molecular assays is needed to improve detection sensitivity in cases with low bacillary loads. Integrating tongue swab testing into routine TB diagnostic algorithms could enhance case detection, strengthen drug resistance surveillance, and contribute to reducing transmission.