The diagnostic value of targeted next-generation sequencing for smear-negative and sputum-scarce pulmonary tuberculosis

OBJECTIVE: To evaluate the diagnostic performance of targeted next-generation sequencing (tNGS) in pulmonary tuberculosis (PTB). METHODS: This retrospective study included 164 suspected PTB patients admitted to Anhui Chest Hospital between October 2022 and October 2024. All patients were smear-negative or sputum-scarce. Clinical specimens were tested simultaneously with tNGS, SAT-TB, GeneXpert MTB/RIF, and Mycobacterium tuberculosis (MTB) culture. RESULTS: Among 108 diagnosed PTB patients, the sensitivity of tNGS was significantly superior to that of other methods. The negative predictive value (NPV) and accuracy of tNGS were 66.67% and 82.93%, which were superior to other methods. In bronchoalveolar lavage fluid (BALF) specimens, the positive detection rate of tNGS reached 48.12%, significantly higher than that of other methods (P<0.0001). In pleural effusion specimens, the positive detection rate of tNGS was 38.10%, which was significantly better than that of SAT-TB and GeneXpert MTB/RIF (P<0.01). ROC curve analysis showed that the AUC value of tNGS reached 0.87, significantly higher than that of the culture method, GeneXpert MTB/RIF, and SAT-TB. The combined detection strategy further increased the sensitivity to 79.63%, and the overall diagnostic accuracy reached 86.59%. CONCLUSIONS: tNGS demonstrates superior diagnostic performance for tuberculosis diagnosis, particularly in alternative specimens such as BALF and pleural effusion.