ena-STUDY-UNIVERSITY OF S*O PAULO-27-11-2017-13:10:39:643-213
Whole Genome Sequencing compared with phenotypic (MGIT) and commercial molecular tests for drug resistant Mycobacterium tuberculosis isolated from patients in Brazil and Mozambique.
This study aimed to use WGS to describe the mutations conferring resistance in clinical isolates of M. tuberculosis from Brazil and Mozambique and to compare these results to those obtained by phenotypic and commercial genotypic DST.Methods: This cross-sectional study evaluated 30 isolates from patients with DR-TB from Brazil and Mozambique. All the isolates were evaluated with phenotypic (MGIT-SIRE) and genotypic (Xpert-MTB/RIF, Genotype-MTBDRplus and MTBDRsl) DST. Any isolate with detected resistance to at least one first- or second-line drug went to WGS, followed by the analysis with TB profiler online tool database. Results: Compared to the phenotypic DST WGS sensitivity and specificity for rifampicin resistance detection was 87.5% and 92.3%; for isoniazid sensitivity was 91.3% and the specificity 100%; for streptomycin sensitivity was 85.7% and specificity 93.3%. Regarding ethambutol sensitivity was 100% and specificity 77.2%. The concordance between WGS and phenotypic DST was 89.6% for rifampicin and streptomycin; 93.1% for isoniazid and 82.7% for ethambutol. In two isolates from Mozambique, there was a mutation in rpoB gene (Val170Phe) which was neither detected by Xpert-MTB/RIF, nor Genotype-MTBDRplus. Conclusion: WGS showed good performance and a great potential to provide more accurate information about the M. tuberculosis resistance in two high-burden areas without previous WGS information.
This study aimed to use WGS to describe the mutations conferring resistance in clinical isolates of M. tuberculosis from Brazil and Mozambique and to compare these results to those obtained by phenotypic and commercial genotypic DST.Methods: This cross-sectional study evaluated 30 isolates from patients with DR-TB from Brazil and Mozambique. All the isolates were evaluated with phenotypic (MGIT-SIRE) and genotypic (Xpert-MTB/RIF, Genotype-MTBDRplus and MTBDRsl) DST. Any isolate with detected resistance to at least one first- or second-line drug went to WGS, followed by the analysis with TB profiler online tool database. Results: Compared to the phenotypic DST WGS sensitivity and specificity for rifampicin resistance detection was 87.5% and 92.3%; for isoniazid sensitivity was 91.3% and the specificity 100%; for streptomycin sensitivity was 85.7% and specificity 93.3%. Regarding ethambutol sensitivity was 100% and specificity 77.2%. The concordance between WGS and phenotypic DST was 89.6% for rifampicin and streptomycin; 93.1% for isoniazid and 82.7% for ethambutol. In two isolates from Mozambique, there was a mutation in rpoB gene (Val170Phe) which was neither detected by Xpert-MTB/RIF, nor Genotype-MTBDRplus. Conclusion: WGS showed good performance and a great potential to provide more accurate information about the M. tuberculosis resistance in two high-burden areas without previous WGS information.