Whole genome sequencing of M. tuberculosis for detection of drug resistance: a systematic review
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
OBJECTIVES: We conducted a systematic review to determine the diagnostic accuracy of Whole Genome Sequencing (WGS) of M. tuberculosis for the detection of resistance to first and second line anti-tuberculosis (TB) drugs. METHODS: The study was conducted according to the criteria of the Preferred Reporting Items for Systematic Reviews group. A total of 20 publications were included. The sensitivity, specificity, PPV and NPV of WGS using phenotypic Drug Susceptibility Testing (DST) methods as a gold standard were determined. RESULTS: Anti-TB agents tested included all first line drugs, a variety of reserve drugs, as well as new drugs. Polymorphisms in a total of 53 genes were tested for associations with drug resistance. Pooled sensitivity and specificity values for detection of resistance to selected first line drugs were 0.98 (95% CI, 0.93 to 0.98) and 0.98 (95% CI, 0.98 to 1.00) for rifampicin and 0.97 (95% CI, 0.94 to 0.99) and 0.93 (95% CI 0.91 to 0.96) for isoniazid, respectively. Due to high heterogeneity in studies' design, lack of data, knowledge of resistance mechanisms and clarity on exclusion of phylogenetic markers, there was a significant variation in analytical performance of WGS for the remaining first-line, reserved drugs and new drugs. CONCLUSIONS: WGS could be considered a promising alternative to existing phenotypic and molecular DST methods for rifampicin and isoniazid pending standardization of analytical pipelines. To ensure clinical relevance of WGS for detection of M. tuberculosis complex drug resistance, future studies should include information on clinical outcomes.
Date Issued
2016-09-22
Date Acceptance
2016-09-15
Citation
Clinical Microbiology and Infection, 2016, 23 (2), pp.61-68
ISSN
1469-0691
Publisher
Wiley
Start Page
61
End Page
68
Journal / Book Title
Clinical Microbiology and Infection
Volume
23
Issue
2
Copyright Statement
Crown Copyright © 2016 Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. All rights reserved. You may re-use this document/publication (not including logos) free of charge in any format or medium, under the terms of the Open Government Licence v3.0. To view this licence visit http://www.nationalarchives.gov.uk/doc/open-government-licence
Identifier
http://www.ncbi.nlm.nih.gov/pubmed/27665704
PII: S1198-743X(16)30395-0
Subjects
Drug resistance
Genetic polymorphisms
Laboratory diagnostics
Performance characteristics
Tuberculosis
Whole genome sequencing
Antitubercular Agents
Drug Resistance, Bacterial
Genes, Bacterial
Genome, Bacterial
Genomics
Humans
Mutation
Mycobacterium tuberculosis
Phylogeny
Polymorphism, Genetic
Microbiology
1103 Clinical Sciences
Publication Status
Published