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Targeted sequencing from cerebrospinal fluid for rapid identification of drug-resistant tuberculous meningitis

Title: Targeted sequencing from cerebrospinal fluid for rapid identification of drug-resistant tuberculous meningitis
Authors: Tram, TTB; Trieu, LPT; Nhat, LTH; Thu, DDA; Quang, NL; Bang, ND; Chau, TTH; Thwaites, GE; Walker, TM; Ha, VTN; Thuong, NTT
Publisher Information: American Society for Microbiology
Publication Year: 2024
Collection: Oxford University Research Archive (ORA)
Description: Mortality from tuberculous meningitis (TBM) remains around 30%, with most deaths occurring within 2 months of starting treatment. Mortality from drug-resistant strains is higher still, making early detection of drug resistance (DR) essential. Targeted next-generation sequencing (tNGS) produces high read depths, allowing the detection of DR-associated alleles with low frequencies. We applied Deeplex Myc-TB-a tNGS assay-to cerebrospinal fluid (CSF) samples from 72 adults with microbiologically confirmed TBM and compared its genomic drug susceptibility predictions to a composite reference standard of phenotypic susceptibility testing (pDST) and whole genome sequencing, as well as to clinical outcomes. Deeplex detected Mycobacterium tuberculosis complex DNA in 24/72 (33.3%) CSF samples and generated full DR reports for 22/24 (91.7%). The read depth generated by Deeplex correlated with semi-quantitative results from MTB/RIF Xpert. Alleles with
Document Type: article in journal/newspaper
Language: English
DOI: 10.1128/jcm.01287-23
Availability: https://doi.org/10.1128/jcm.01287-23; https://ora.ox.ac.uk/objects/uuid:f313575b-71ff-4653-890e-dcc05f03ec50
Rights: info:eu-repo/semantics/openAccess ; CC Attribution (CC BY)
Accession Number: edsbas.7E63C456
Database: BASE