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Genomic-based surveillance reveals high ongoing transmission of multi-drug-resistant Mycobacterium tuberculosis in Southern Brazil

2021-10Artigo científico Acesso aberto
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dc.contributor.authorSalvato, Richard Steiner
dc.contributor.authorReis, Ana Júlia
dc.contributor.authorSchiefelbein, Sun Hee
dc.contributor.authorGómez, Michael Andrés Abril
dc.contributor.authorSalvato, Stéphanie Steiner
dc.contributor.authorda Silva, Larissa Vitória
dc.contributor.authorCosta, Elis Regina Dalla
dc.contributor.authorUnis, Gisela
dc.contributor.authorDias, Claudia Fontoura
dc.contributor.authorViveiros, Miguel
dc.contributor.authorPortugal, Isabel
dc.contributor.authorvon Groll, Andrea
dc.contributor.authorda Silva, Pedro Eduardo Almeida
dc.contributor.authorKritski, Afrânio Lineu
dc.contributor.authorPerdigão, João
dc.contributor.authorRossetti, Maria Lucia Rosa
dc.contributor.institutionTB, HIV and opportunistic diseases and pathogens (THOP)
dc.contributor.institutionInstituto de Higiene e Medicina Tropical (IHMT)
dc.contributor.institutionGlobal Health and Tropical Medicine (GHTM)
dc.contributor.pblElsevier
dc.date.accessioned2022-02-21T23:15:32Z
dc.date.available2022-02-21T23:15:32Z
dc.date.issued2021-10
dc.descriptionFunding Information: Funding: This study was funded, in part, by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (Grant No. 001) and supported by Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (Grant No. 17/1265–8 INCT-TB). JP is supported by Fundação para a Ciência e Tecnologia through Estímulo Individual ao Emprego Científico (CEECIND/00394/2017). Funding Information: The authors wish to thank TGen, C-Path and ReSeqTB for supporting WGS, and the Brazilian Network of Tuberculosis Research for enabling this partnership. The authors would also like to thank the Mycobacteria Laboratory at LACEN-RS/CEVS/SES-RS for performing and providing information on drug susceptibility testing. Funding: This study was funded, in part, by the Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - Brasil (Grant No. 001) and supported by Funda??o de Amparo ? Pesquisa do Estado do Rio Grande do Sul (Grant No. 17/1265?8 INCT-TB). JP is supported by Funda??o para a Ci?ncia e Tecnologia through Est?mulo Individual ao Emprego Cient?fico (CEECIND/00394/2017). Competing interests: None declared. Ethical approval: This project was approved by the Research Ethics Committee of the Funda??o Estadual de Produ??o e Pesquisa em Sa?de (Protocol No. 1.587.621 CAAE: 18269313.0.0000.5320). Data availability: M. tuberculosis genome data were deposited in the NCBI BioProject database (IDs: PRJNA535343, PRJNA639713 and PRJNA692642). Individual accession numbers for genomes analysed in this study are given in the online supplementary material. Publisher Copyright: © 2021 Elsevier Ltd
dc.description.abstractGenomic-based surveillance on the occurrence of drug resistance and its transmission dynamics has emerged as a powerful tool for the control of tuberculosis (TB). A whole-genome sequencing approach, phenotypic testing and clinical-epidemiological investigation were used to undertake a retrospective population-based study on drug-resistant (DR)-TB in Rio Grande do Sul, the largest state in Southern Brazil. The analysis included 305 resistant Mycobacterium tuberculosis strains sampled statewide from 2011 to 2014, and covered 75.7% of all DR-TB cases identified in this period. Lineage 4 was found to be predominant (99.3%), with high sublineage-level diversity composed mainly of 4.3.4.2 [Latin American and Mediterranean (LAM)/RD174], 4.3.3 (LAM/RD115) and 4.1.2.1 (Haarlem/RD182) sublineages. Genomic diversity was also reflected in resistance of the variants to first-line drugs. A large number of distinct resistance-conferring mutations, including variants that have not been reported previously in any other setting worldwide, and 22 isoniazid-monoresistant strains with mutations described as disputed in the rpoB gene but causing rifampicin resistance generally missed by automated phenotypic tests as BACTEC MGIT. Using a cut-off of five single nucleotide polymorphisms, the estimated recent transmission rate was 55.1%, with 168 strains grouped into 28 genomic clusters. The most worrying fact concerns multi-drug-resistant (MDR) strains, of which 73.4% were clustered. Different resistance profiles and acquisition of novel mutations intraclusters revealed important amplification of resistance in the region. This study described the diversity of M. tuberculosis strains, the basis of drug resistance, and ongoing transmission dynamics across the largest state in Southern Brazil, stressing the urgent need for MDR-TB transmission control state-wide.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent1897135
dc.identifier.doi10.1016/j.ijantimicag.2021.106401
dc.identifier.issn0924-8579
dc.identifier.otherPURE: 33308976
dc.identifier.otherPURE UUID: a1155f31-d9f1-4fd9-b101-8a2a7cce8a8e
dc.identifier.otherScopus: 85112516566
dc.identifier.otherPubMed: 34289403
dc.identifier.otherORCID: /0000-0001-9676-6251/work/101864901
dc.identifier.urihttp://hdl.handle.net/10362/133338
dc.identifier.urlhttps://www.scopus.com/pages/publications/85112516566
dc.language.isoeng
dc.peerreviewedyes
dc.subjectDrug resistance
dc.subjectTransmission
dc.subjectTuberculosis
dc.subjectWhole-genome sequencing
dc.subjectMicrobiology (medical)
dc.subjectInfectious Diseases
dc.subjectPharmacology (medical)
dc.subjectSDG 3 - Good Health and Well-being
dc.subjectSDG 12 - Responsible Consumption and Production
dc.subjectSDG 17 - Partnerships for the Goals
dc.titleGenomic-based surveillance reveals high ongoing transmission of multi-drug-resistant Mycobacterium tuberculosis in Southern Brazilen
dc.typejournal article
degois.publication.titleInternational Journal Of Antimicrobial Agents
dspace.entity.typePublication
rcaap.rightsopenAccess

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