Accuracy of whole genome sequencing versus phenotypic (MGIT) and commercial molecular tests for detection of drug-resistant Mycobacterium tuberculosis isolated from patients in Brazil and Mozambique.

Autor: Feliciano CS; Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo (FMRP-USP), Brazil., Namburete EI; Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo (FMRP-USP), Brazil., Rodrigues Plaça J; Center for Medical Genomics, Clinics Hospital at Ribeirão Preto Medical School, University of São Paulo (FMRP-USP), Brazil., Peronni K; Center for Medical Genomics, Clinics Hospital at Ribeirão Preto Medical School, University of São Paulo (FMRP-USP), Brazil., Dippenaar A; DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa., Warren RM; DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa., Silva WA Jr; Center for Medical Genomics, Clinics Hospital at Ribeirão Preto Medical School, University of São Paulo (FMRP-USP), Brazil; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo (FMRP-USP), Brazil., Bollela VR; Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo (FMRP-USP), Brazil; Center for Medical Genomics, Clinics Hospital at Ribeirão Preto Medical School, University of São Paulo (FMRP-USP), Brazil. Electronic address: vbollela@fmrp.usp.br.
Jazyk: angličtina
Zdroj: Tuberculosis (Edinburgh, Scotland) [Tuberculosis (Edinb)] 2018 May; Vol. 110, pp. 59-67. Date of Electronic Publication: 2018 Apr 05.
DOI: 10.1016/j.tube.2018.04.003
Abstrakt: Background: The fast and accurate diagnosis of drug-resistant tuberculosis (DR-TB) is critical to reducing the spread of disease. Although commercial genotypic drug-susceptibility tests (DST) are close to the goal, they are still not able to detect all relevant DR-TB related mutations. Whole genome sequencing (WGS) allows better comprehension of DR-TB with a great discriminatory power. We aimed to evaluate WGS in M. tuberculosis isolates compared with phenotypic and genotypic DST.
Methods: This cross-sectional study evaluated 30 isolates from patients with detected DR-TB in Brazil and Mozambique. They were evaluated with phenotypic (MGIT-SIRE™) and genotypic (Xpert-MTB/RIF™, Genotype-MTBDRplus™, and MTBDRsl™) DST. Isolates with resistance to at least one first- or second-line drug were submitted to WGS and analyzed with TB profiler database.
Results: WGS had the best performance among the genotypic DST, compared to the phenotypic test. There was a very good concordance with phenotypic DST for rifampicin and streptomycin (89.6%), isoniazid (96.5%) and ethambutol (82.7%). WGS sensitivity and specificity for detection resistance were respectively 87.5 and 92.3% for rifampicin; 95.6 and 100% for isoniazid; 85.7 and 93.3% for streptomycin while 100 and 77.2% for ethambutol. Two isolates from Mozambique showed a Val170Phe rpoB mutation which was neither detected by Xpert-MTB/RIF nor Genotype-MTBDRplus.
Conclusion: WGS was able to provide all the relevant information about M. tuberculosis drug susceptibility in a single test and also detected a mutation in rpoB which is not covered by commercial genotypic DST.
(Copyright © 2018 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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