Whole genome sequencing of Mycobacterium tuberculosis for detection of drug resistance: a systematic review

Abstract Background The emergence of drug-resistant tuberculosis (DR-TB) is a persistent threat to public health. The detection of DR-TB requires culture-based drug susceptibility testing (DST) or rapid molecular assays for targeted genes. The recent advances in Whole-genome sequencing (WGS) technology have offered a new capacity to identify resistance-conferring mutations in Mycobacterium tuberculosis (MTB). This study reviews and quantifies the emerging evidence on the association between genomic markers of drug resistance in MTB identified by WGS and treatment outcomes for DR-TB. Methods A literature search will be conducted in NCBI PubMed, Scopus, Cochrane Library, Web of Science, and CINAHL (Ebsco) to retrieve all the relevant original reports from 2000 onwards. Clinical trials and observational studies describing different applications of WGS to genotypic resistance testing for TB and detection of MDR-TB/ XDR-TB as well as treatment outcomes of the patients will be included. Two primary reviewers will separately screen and select papers for data extraction, risk of bias, and assess the quality. Any disagreement between the reviewers' will be clarified by a third reviewer. The I2 statistics will be used to assess the heterogeneity of the included studies and if the data are sufficiently homogenous, a meta-analysis will be performed. The Egger's test and visual representation of the funnel plot will be used to monitor for publication bias. Narrative data synthesis will be conducted for all the included studies if performing meta-analysis is not possible. Discussion This systematic review will examine the evidence on the feasibility and added value of WGS in improving treatment outcomes in DR-TB patients. The rapid detection of drug-resistance conferring mutations and selection of appropriate drug regimens is likely to improve the cure rates while minimizing adverse events and treatment costs. Hence, the outcome of this systematic review will inform policy-making and will guide clinical laboratory practice to improve drug resistance diagnostic capacity and treatment outcomes. Systematic review registration: PROSPERO CRD42020197099.

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Whole genome sequencing data of 1110 Mycobacterium tuberculosis isolates identifies insertions and deletions associated with drug resistance

BMC Genomics ◽

10.1186/s12864-018-4734-6 ◽

2018 ◽

Vol 19 (1) ◽

Cited By ~ 3

Author(s):

Xi Zeng ◽

Jamie Sui-Lam Kwok ◽

Kevin Yi Yang ◽

Kenneth Siu-Sing Leung ◽

Mai Shi ◽

...

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Whole Genome Sequencing Data ◽

Whole Genome ◽

Sequencing Data ◽

Insertions And Deletions

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Comprehensive Whole-Genome Sequencing and Reporting of Drug Resistance Profiles on Clinical Cases of Mycobacterium tuberculosis in New York State

Journal of Clinical Microbiology ◽

10.1128/jcm.00298-17 ◽

2017 ◽

Vol 55 (6) ◽

pp. 1871-1882 ◽

Cited By ~ 46

Author(s):

Joseph Shea ◽

Tanya A. Halse ◽

Pascal Lapierre ◽

Matthew Shudt ◽

Donna Kohlerschmidt ◽

...

Keyword(s):

New York ◽

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Predictive Value ◽

New York State ◽

Whole Genome ◽

Content Type ◽

York State

ABSTRACTWhole-genome sequencing (WGS) is a newer alternative for tuberculosis (TB) diagnostics and is capable of providing rapid drug resistance profiles while performing species identification and capturing the data necessary for genotyping. Our laboratory developed and validated a comprehensive and sensitive WGS assay to characterizeMycobacterium tuberculosisand otherM. tuberculosiscomplex (MTBC) strains, composed of a novel DNA extraction, optimized library preparation, paired-end WGS, and an in-house-developed bioinformatics pipeline. This new assay was assessed using 608 MTBC isolates, with 146 isolates during the validation portion of this study and 462 samples received prospectively. In February 2016, this assay was implemented to test all clinical cases of MTBC in New York State, including isolates and early positive Bactec mycobacterial growth indicator tube (MGIT) 960 cultures from primary specimens. Since the inception of the assay, we have assessed the accuracy of identification of MTBC strains to the species level, concordance with culture-based drug susceptibility testing (DST), and turnaround time. Species identification by WGS was determined to be 99% accurate. Concordance between drug resistance profiles generated by WGS and culture-based DST methods was 96% for eight drugs, with an average resistance-predictive value of 93% and susceptible-predictive value of 96%. This single comprehensive WGS assay has replaced seven molecular assays and has resulted in resistance profiles being reported to physicians an average of 9 days sooner than with culture-based DST for first-line drugs and 32 days sooner for second-line drugs.

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