TY - JOUR
T1 - First insights into circulating XDR and pre-XDR Mycobacterium tuberculosis in Southern Brazil
AU - Salvato, Richard Steiner
AU - Costa, Elis Regina Dalla
AU - Reis, Ana Júlia
AU - Schiefelbein, Sun Hee
AU - Halon, Maria Laura
AU - Barcellos, Regina Bones
AU - Unis, Gisela
AU - Dias, Cláudia Fontoura
AU - Viveiros, Miguel
AU - Portugal, Isabel
AU - da Silva, Pedro Eduardo Almeida
AU - Kritski, Afrânio Lineu
AU - Perdigão, João
AU - Rossetti, Maria Lucia Rosa
N1 - Funding Information:
This study was approved by the Research Ethics Committee of the Fundação Estadual de Produção e Pesquisa em Saúde (FEPPS/RS), protocol number 1.587.621 CAAE: 18269313.0.0000.5320. 3
Funding Information:
This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES), (grant number: 001 ), and supported by Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), (grant number: FAPERGS/MS/CNPq/SESRS n. 03/2017 – PPSUS ).
Funding Information:
We are grateful to TGen, C-Path and ReSeqTB for supporting whole genome sequencing and to Brazilian Network of Tuberculosis Research (REDE-TB) for enabling this partnership. The authors would like to thank Centro de Desenvolvimento Científico e Tecnológico (CDCT)/CEVS/SES/RS for the support and infrastructure. Appendix A
Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/3
Y1 - 2019/3
N2 - Drug-resistant tuberculosis (DR-TB) is major problem in the fight against TB. Multidrug resistant (MDR) TB patients have a reduced treatment success rates and for, extensively drug-resistant (XDR) TB the cure rate does not exceed 25% in many countries. To evaluate the pre-XDR-TB and XDR-TB prevalence and transmission in Rio Grande do Sul State, in southern Brazil, we performed a retrospective WGS-based analysis of 87 MDR-TB cases, aiming to identify resistance-conferring mutations and its phylogenetic distinctiveness. Using a five SNP threshold for genomic clustering, 60 strains were genomically linked within 10 clusters, including 14 likely transmission events identified by retrospective conventional epidemiological investigation. Moreover, five likely transmission events involved 17 patients deprived of liberty in the same prison establishment. Mutations associated with isoniazid and rifampicin resistance were identified respectively in 97.70% and 98.85% of MDR M.tb strains, more frequently in katG and rpoB genes. In total, we identified eight (9.19%) pre-XDR and four (4.59%) XDR M.tb strains. Resistance to ofloxacin was observed in seven (8.04%) strains, all of them presenting resistance-conferring mutations. Phenotypic resistance from capreomycin and kanamycin was found in seven (8.04%) and four (4.59%) strains respectively, but no classic mutations associated with resistance to these drugs was identified. The results put in evidence a scenario involving multiple phylogenetically distinctive clades associated with pre-XDR and XDR-TB in the largest state of southern Brazil, while stressing the potential of using WGS to predict anti-TB drug resistance and need to halt MDR-TB transmission in the region.
AB - Drug-resistant tuberculosis (DR-TB) is major problem in the fight against TB. Multidrug resistant (MDR) TB patients have a reduced treatment success rates and for, extensively drug-resistant (XDR) TB the cure rate does not exceed 25% in many countries. To evaluate the pre-XDR-TB and XDR-TB prevalence and transmission in Rio Grande do Sul State, in southern Brazil, we performed a retrospective WGS-based analysis of 87 MDR-TB cases, aiming to identify resistance-conferring mutations and its phylogenetic distinctiveness. Using a five SNP threshold for genomic clustering, 60 strains were genomically linked within 10 clusters, including 14 likely transmission events identified by retrospective conventional epidemiological investigation. Moreover, five likely transmission events involved 17 patients deprived of liberty in the same prison establishment. Mutations associated with isoniazid and rifampicin resistance were identified respectively in 97.70% and 98.85% of MDR M.tb strains, more frequently in katG and rpoB genes. In total, we identified eight (9.19%) pre-XDR and four (4.59%) XDR M.tb strains. Resistance to ofloxacin was observed in seven (8.04%) strains, all of them presenting resistance-conferring mutations. Phenotypic resistance from capreomycin and kanamycin was found in seven (8.04%) and four (4.59%) strains respectively, but no classic mutations associated with resistance to these drugs was identified. The results put in evidence a scenario involving multiple phylogenetically distinctive clades associated with pre-XDR and XDR-TB in the largest state of southern Brazil, while stressing the potential of using WGS to predict anti-TB drug resistance and need to halt MDR-TB transmission in the region.
U2 - 10.1016/j.meegid.2019.104127
DO - 10.1016/j.meegid.2019.104127
M3 - Article
C2 - 31783187
SN - 1567-1348
VL - 78
SP - 104127
JO - Infection, Genetics and Evolution
JF - Infection, Genetics and Evolution
M1 - 104127
ER -
