The value of targeted next-generation sequencing in the diagnosis and differential diagnosis of paucibacillary pulmonary tuberculosis.

Background: The diagnostic utility of broad-spectrum pathogen-specific targeted next-generation sequencing (tNGS) for paucibacillary pulmonary tuberculosis (PTB) in general hospital settings remains insufficiently characterized compared to validated Mycobacterium-specific tNGS.

Objective: To investigate the clinical value of broad-spectrum pathogen-specific tNGS in diagnosing and differentially diagnosing paucibacillary PTB in real-world clinical practice.

Methods: This retrospective study analyzed data from 423 patients admitted to the First Affiliated Hospital of Chongqing Medical University from January 1, 2024, to October 31, 2024. Patients underwent bronchoalveolar lavage fluid (BALF) testing, including acid-fast staining, culture, Xpert MTB/RIF, and tNGS. 47 participants were excluded based on predefined criteria.

Results: Among 83 microbiologically confirmed PTB cases, tNGS exhibited significantly higher sensitivity compared to Xpert and culture (91.6 % vs. 79.5 % for Xpert and 73.5 % for culture; p<0.001), albeit with marginally lower specificity than Xpert (95.6 % vs. 98.6 %; p=0.01). For 293 non-TB patients, tNGS detected pathogens in 86.7 % (254/293) of BAL samples, identifying 300 pathogens with 47.3 % (142/300) concordance to clinical diagnoses.

Conclusion: Broad-spectrum pathogen-specific tNGS demonstrated enhanced sensitivity for diagnosing paucibacillary PTB but slightly reduced specificity relative to Xpert. While it achieved high pathogen detection rates in non-TB pulmonary diseases, its concordance with clinical diagnoses was suboptimal.