Gene-Based Diagnosis of Tuberculosis from Oral Swabs with a New Generation Pathogen Enrichment Technique in Real-World Practice

Background: A rapid and sensitive diagnosis is crucial for the successful management of tuberculosis (TB). The SLIM assay, a novel label-free pathogen enrichment using a microfluidic system, showed a higher sensitivity than the Xpert MTB/RIF assay in the diagnosis of pulmonary TB (PTB). Here, we evaluated the efficacy of the SLIM assay for oral swab samples in the diagnosis of PTB. Methods: Patients with clinically suspected PTB were prospectively enrolled from May 2019 to October 2020. Oral swab samples were processed using the SLIM assay and the attending physicians were blinded to the results of the SLIM assay. TB cases were defined as those treated with anti-TB chemotherapy for at least 6 months at the discretion of the specialists based on clinical features and conventional laboratory results including the Xpert assay. Findings: A total of 272 patients (TB, n=128 [47·1%]; not TB, n=144 [52·9%]; mean age, 59·8 years) were enrolled. Overall, the sensitivity of the oral swab-based SLIM assay (65·6%) was higher than that of the sputum-based Xpert assay (43·4%; p=0·001). Specifically, the SLIM oral swab assay showed a notably higher sensitivity in culture-negative TB cases compared with the Xpert assay (64·7% vs 9·4%; p=0·001). The specificities of the SLIM and the Xpert were 86·1% and 100%, respectively. Interpretation: The oral swab-based SLIM assay showed a superior sensitivity for TB diagnosis over the sputum-based Xpert assay, especially for culture-negative cases. The novel non-sputum-based diagnostic method may confer a better performance in paucibacillary TB compared with the currently available sputum-based methods. Funding: This work was supported by the Korea Medical Device Development Fund grant funded by the Korean government (Project Number: 202011C07-00), the grants from Asan Institute for Life Sciences (2019-7043) and the Ministry of Science, ICT and Future Planning (MSIP) through the National Research Foundation of Korea (NRF) (2020R1A2C2007148). Declaration of Interest: None to declare. Ethical Approval: The institutional review boards of Asan Medical Center (2018-0020) and Severance hospital (4-2018-0029) approved this study, and the protocols of this study were registered in clinicaltrials.gov (NCT03423550).