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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Feliciano, Cinara Silva [1] ; Namburete, Evangelina Inacio [1] ; Placa, Jessica Rodrigues [2] ; Peronni, Kamila [2] ; Dippenaar, Anzaan [3] ; Warren, Robin Mark [3] ; Silva, Jr., Wilson Araujo [2, 4] ; Bollela, Valdes Roberto [1]
Total Authors: 8
Affiliation:
[1] Univ Sao Paulo FMRP USP, Ribeirao Preto Med Sch, Dept Internal Med, Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo FMRP USP, Ribeirao Preto Med Sch, Clin Hosp, Ctr Med Genom, Ribeirao Preto, SP - Brazil
[3] Stellenbosch Univ, DST NRF Ctr Excellence Biomed TB Res, SAMRC Ctr TB Res, Div Mol Biol & Human Genet, Fac Med & Hlth Sci, Stellenbosch - South Africa
[4] Univ Sao Paulo FMRP USP, Ribeirao Preto Med Sch, Dept Genet, Ribeirao Preto, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: TUBERCULOSIS; v. 110, p. 59-67, MAY 2018.
Web of Science Citations: 2
Abstract

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-SIRETM) and genotypic (Xpert-MTB/RIFTTM, Genotype-MTBDRplus(TM), and MTBDRal(TM)) 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. (AU)

FAPESP's process: 15/13333-3 - Molecular epidemiology of multidrug resistant tuberculosis through whole genome sequencing
Grantee:Valdes Roberto Bollela
Support Opportunities: Regular Research Grants