Comprehensive genomic surveillance reveals transmission profiles of extensively drug-resistant tuberculosis cases in Pará, Brazil
Bedaquiline, an antimicrobial used to treat drug-resistant tuberculosis (DR-TB), was introduced in Brazil in October 2021. Monitoring the emergence and transmission of DR-TB is crucial for implementing public health to control the spread of DR strains of Mycobacterium tuberculosis. To measure its im...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1514862/full |
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| author | Davi Josué Marcon Davi Josué Marcon Abhinav Sharma Alex Brito Souza Alex Brito Souza Rafaella Bonfim Barros Valnete das Graças Dantas Andrade Ricardo José de Paula Souza Guimarães Luana Nepomuceno Gondim Lima Luana Nepomuceno Gondim Lima Lúcia Helena Martins Tavares Monteiro Ana Judith Pires Garcia Quaresma Ana Judith Pires Garcia Quaresma Layana Rufino Ribeiro Layana Rufino Ribeiro Philip Noel Suffys Robin Mark Warren Carlos Augusto Abreu Alberio Karla Valéria Batista Lima Karla Valéria Batista Lima Emilyn Costa Conceição |
| author_facet | Davi Josué Marcon Davi Josué Marcon Abhinav Sharma Alex Brito Souza Alex Brito Souza Rafaella Bonfim Barros Valnete das Graças Dantas Andrade Ricardo José de Paula Souza Guimarães Luana Nepomuceno Gondim Lima Luana Nepomuceno Gondim Lima Lúcia Helena Martins Tavares Monteiro Ana Judith Pires Garcia Quaresma Ana Judith Pires Garcia Quaresma Layana Rufino Ribeiro Layana Rufino Ribeiro Philip Noel Suffys Robin Mark Warren Carlos Augusto Abreu Alberio Karla Valéria Batista Lima Karla Valéria Batista Lima Emilyn Costa Conceição |
| author_sort | Davi Josué Marcon |
| collection | DOAJ |
| description | Bedaquiline, an antimicrobial used to treat drug-resistant tuberculosis (DR-TB), was introduced in Brazil in October 2021. Monitoring the emergence and transmission of DR-TB is crucial for implementing public health to control the spread of DR strains of Mycobacterium tuberculosis. To measure its impact on the multi-drug treatment scheme in the state of Pará, we aimed to conduct genomic surveillance of DR-TB after bedaquiline was introduced in Brazil. Individuals treated for DR-TB between October 2021 and December 2022, in the reference hospital to treat DR-TB cases from the state of Pará, were included in the study. Clinical and bacteriological information was obtained from the National Laboratory Management Environment and the Special TB Treatment Information System. Genomic DNA was extracted from bacterial cultures performed at the Pará Central Laboratory (LACEN-PA). Whole-genome sequencing (WGS) was obtained using Illumina Nextera-XT and NextSeq 550 and genomes were analyzed using the MAGMA and TB-Profiler pipelines interpreted according to the World Health Organization (WHO) mutations catalog 2nd edition. Geoprocessing was performed based on the patient’s residences. Cutoffs of 5–12 single nucleotide polymorphisms (SNPs) were used for transmission analysis. From the 103 patients reported as DR-TB, viable cultures were obtained from 67. Forty isolates were selected randomly for WGS. Among these, a mixed infection of M. tuberculosis L1 and L4 and a co-infection of M. tuberculosis and Mycobacterium chelonae were observed. The genotypic drug susceptibility profile of TB stains (39/40) was as follows: sensitive (1/2, 5%), rifampicin mono-resistant (RR) (4/10%), isoniazid mono-resistant (1/2%), multidrug-resistant (MDR) (21/52%), extensively drug-resistant (XDR) (3/7%), pre-XDR (8/20%), and other (1/2%). Among the 38 isolates of M. tuberculosis strains without mixed infection, using a cutoff of 12 SNPs and suggestive of recent TB transmission, 14 (37%) were grouped into five clusters (C1–C5) and included RR (C5), MDR (C3, C4, C5), pre-XDR, and XDR (C2) strains. We recommend greater attention from the regional public health authorities to detect and track resistance to new drugs, especially in areas with pre-XDR and XDR cases. This is the first report on the detection and transmission of XDR-TB in Pará, Brazil, after the recent re-definition of XDR-TB by the WHO in 2021. |
| format | Article |
| id | doaj-art-892e9d226943455d921222ad5ab159ed |
| institution | Kabale University |
| issn | 1664-302X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Microbiology |
| spelling | doaj-art-892e9d226943455d921222ad5ab159ed2025-01-22T07:11:26ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-01-011510.3389/fmicb.2024.15148621514862Comprehensive genomic surveillance reveals transmission profiles of extensively drug-resistant tuberculosis cases in Pará, BrazilDavi Josué Marcon0Davi Josué Marcon1Abhinav Sharma2Alex Brito Souza3Alex Brito Souza4Rafaella Bonfim Barros5Valnete das Graças Dantas Andrade6Ricardo José de Paula Souza Guimarães7Luana Nepomuceno Gondim Lima8Luana Nepomuceno Gondim Lima9Lúcia Helena Martins Tavares Monteiro10Ana Judith Pires Garcia Quaresma11Ana Judith Pires Garcia Quaresma12Layana Rufino Ribeiro13Layana Rufino Ribeiro14Philip Noel Suffys15Robin Mark Warren16Carlos Augusto Abreu Alberio17Karla Valéria Batista Lima18Karla Valéria Batista Lima19Emilyn Costa Conceição20Programa de Pós-Graduação em Biologia Parasitária na Amazônia, Belém, BrazilSeção de Bacteriologia do Instituto Evandro Chagas, Ananindeua, Pará, BrazilSouth African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South AfricaPrograma de Pós-Graduação em Biologia Parasitária na Amazônia, Belém, BrazilSeção de Bacteriologia do Instituto Evandro Chagas, Ananindeua, Pará, BrazilLaboratório Central do Estado do Pará, Belém, Pará, BrazilLaboratório Central do Estado do Pará, Belém, Pará, BrazilSeção de Epidemiologia do Instituto Evandro Chagas, Ananindeua, Pará, BrazilPrograma de Pós-Graduação em Biologia Parasitária na Amazônia, Belém, BrazilSeção de Bacteriologia do Instituto Evandro Chagas, Ananindeua, Pará, BrazilSecretaria de Estado da Saúde do Pará, Belém, Pará, BrazilPrograma de Pós-Graduação em Biologia Parasitária na Amazônia, Belém, BrazilSeção de Bacteriologia do Instituto Evandro Chagas, Ananindeua, Pará, BrazilSeção de Bacteriologia do Instituto Evandro Chagas, Ananindeua, Pará, BrazilPrograma de Pós-graduação em Epidemiologia e Vigilância em Saúde, Ananindeua, BrazilLaboratório de Biologia Molecular Aplicada a Micobactérias, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, BrazilSouth African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South AfricaHospital Universitário João de Barros Barreto, Ambulatório de Tuberculose Multiressistente, Universidade Federal do Pará, Belém, Pará, BrazilPrograma de Pós-Graduação em Biologia Parasitária na Amazônia, Belém, BrazilSeção de Bacteriologia do Instituto Evandro Chagas, Ananindeua, Pará, BrazilSouth African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South AfricaBedaquiline, an antimicrobial used to treat drug-resistant tuberculosis (DR-TB), was introduced in Brazil in October 2021. Monitoring the emergence and transmission of DR-TB is crucial for implementing public health to control the spread of DR strains of Mycobacterium tuberculosis. To measure its impact on the multi-drug treatment scheme in the state of Pará, we aimed to conduct genomic surveillance of DR-TB after bedaquiline was introduced in Brazil. Individuals treated for DR-TB between October 2021 and December 2022, in the reference hospital to treat DR-TB cases from the state of Pará, were included in the study. Clinical and bacteriological information was obtained from the National Laboratory Management Environment and the Special TB Treatment Information System. Genomic DNA was extracted from bacterial cultures performed at the Pará Central Laboratory (LACEN-PA). Whole-genome sequencing (WGS) was obtained using Illumina Nextera-XT and NextSeq 550 and genomes were analyzed using the MAGMA and TB-Profiler pipelines interpreted according to the World Health Organization (WHO) mutations catalog 2nd edition. Geoprocessing was performed based on the patient’s residences. Cutoffs of 5–12 single nucleotide polymorphisms (SNPs) were used for transmission analysis. From the 103 patients reported as DR-TB, viable cultures were obtained from 67. Forty isolates were selected randomly for WGS. Among these, a mixed infection of M. tuberculosis L1 and L4 and a co-infection of M. tuberculosis and Mycobacterium chelonae were observed. The genotypic drug susceptibility profile of TB stains (39/40) was as follows: sensitive (1/2, 5%), rifampicin mono-resistant (RR) (4/10%), isoniazid mono-resistant (1/2%), multidrug-resistant (MDR) (21/52%), extensively drug-resistant (XDR) (3/7%), pre-XDR (8/20%), and other (1/2%). Among the 38 isolates of M. tuberculosis strains without mixed infection, using a cutoff of 12 SNPs and suggestive of recent TB transmission, 14 (37%) were grouped into five clusters (C1–C5) and included RR (C5), MDR (C3, C4, C5), pre-XDR, and XDR (C2) strains. We recommend greater attention from the regional public health authorities to detect and track resistance to new drugs, especially in areas with pre-XDR and XDR cases. This is the first report on the detection and transmission of XDR-TB in Pará, Brazil, after the recent re-definition of XDR-TB by the WHO in 2021.https://www.frontiersin.org/articles/10.3389/fmicb.2024.1514862/fullbedaquilinedrug-resistant tuberculosisextensively drug-resistant tuberculosisgenomic surveillancewhole-genome sequencing |
| spellingShingle | Davi Josué Marcon Davi Josué Marcon Abhinav Sharma Alex Brito Souza Alex Brito Souza Rafaella Bonfim Barros Valnete das Graças Dantas Andrade Ricardo José de Paula Souza Guimarães Luana Nepomuceno Gondim Lima Luana Nepomuceno Gondim Lima Lúcia Helena Martins Tavares Monteiro Ana Judith Pires Garcia Quaresma Ana Judith Pires Garcia Quaresma Layana Rufino Ribeiro Layana Rufino Ribeiro Philip Noel Suffys Robin Mark Warren Carlos Augusto Abreu Alberio Karla Valéria Batista Lima Karla Valéria Batista Lima Emilyn Costa Conceição Comprehensive genomic surveillance reveals transmission profiles of extensively drug-resistant tuberculosis cases in Pará, Brazil Frontiers in Microbiology bedaquiline drug-resistant tuberculosis extensively drug-resistant tuberculosis genomic surveillance whole-genome sequencing |
| title | Comprehensive genomic surveillance reveals transmission profiles of extensively drug-resistant tuberculosis cases in Pará, Brazil |
| title_full | Comprehensive genomic surveillance reveals transmission profiles of extensively drug-resistant tuberculosis cases in Pará, Brazil |
| title_fullStr | Comprehensive genomic surveillance reveals transmission profiles of extensively drug-resistant tuberculosis cases in Pará, Brazil |
| title_full_unstemmed | Comprehensive genomic surveillance reveals transmission profiles of extensively drug-resistant tuberculosis cases in Pará, Brazil |
| title_short | Comprehensive genomic surveillance reveals transmission profiles of extensively drug-resistant tuberculosis cases in Pará, Brazil |
| title_sort | comprehensive genomic surveillance reveals transmission profiles of extensively drug resistant tuberculosis cases in para brazil |
| topic | bedaquiline drug-resistant tuberculosis extensively drug-resistant tuberculosis genomic surveillance whole-genome sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1514862/full |
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