Clinical utility of target amplicon sequencing test for rapid diagnosis of drug-resistant Mycobacterium tuberculosis from respiratory specimens.

Autor:	Leung KS; Department of Microbiology, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Tam KK; Department of Microbiology, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Ng TT; Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China., Lao HY; Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China., Shek RC; Department of Microbiology, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Ma OCK; KingMed Diagnostics, Science Park, Kwun Tong, Hong Kong SAR, China., Yu SH; Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease, Guangzhou, China., Chen JX; Guangzhou KingMed Diagnostics Group, Guangzhou, China., Han Q; Guangzhou KingMed Diagnostics Group, Guangzhou, China., Siu GK; Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China., Yam WC; Department of Microbiology, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Jazyk:	angličtina
Zdroj:	Frontiers in microbiology [Front Microbiol] 2022 Sep 09; Vol. 13, pp. 974428. Date of Electronic Publication: 2022 Sep 09 (Print Publication: 2022).
DOI:	10.3389/fmicb.2022.974428
Abstrakt:	An in-house-developed target amplicon sequencing by next-generation sequencing technology (TB-NGS) enables simultaneous detection of resistance-related mutations in Mycobacterium tuberculosis (MTB) against 8 anti-tuberculosis drug classes. In this multi-center study, we investigated the clinical utility of incorporating TB-NGS for rapid drug-resistant MTB detection in high endemic regions in southeast China. From January 2018 to November 2019, 4,047 respiratory specimens were available from patients suffering lower respiratory tract infections in Hong Kong and Guangzhou, among which 501 were TB-positive as detected by in-house IS6110-qPCR assay with diagnostic sensitivity and specificity of 97.9 and 99.2%, respectively. Preliminary resistance screening by GenoType MTBDR plus and MTBDR sl identified 25 drug-resistant specimens including 10 multidrug-resistant TB. TB-NGS was performed using MiSeq on all drug-resistant specimens alongside 67 pan-susceptible specimens, and demonstrated 100% concordance to phenotypic drug susceptibility test. All phenotypically resistant specimens with dominating resistance-related mutations exhibited a mutation frequency of over 60%. Three quasispecies were identified with mutation frequency of less than 35% among phenotypically susceptible specimens. They were well distinguished from phenotypically resistant cases and thus would not complicate TB-NGS results interpretations. This is the first large-scale study that explored the use of laboratory-developed NGS platforms for rapid TB diagnosis. By incorporating TB-NGS with our proposed diagnostic algorithm, the workflow would provide a user-friendly, cost-effective routine diagnostic solution for complicated TB cases with an average turnaround time of 6 working days. This is critical for timely management of drug resistant TB patients and expediting public health control on the emergence of drug-resistant TB. Competing Interests: OM, S-HY, J-XC and QH were employed by KingMed Diagnostics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Leung, Tam, Ng, Lao, Shek, Ma, Yu, Chen, Han, Siu and Yam.)
Databáze:	MEDLINE
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