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BACKGROUND: The rate of tuberculosis (TB) infection among the prison population (PP) in Brazil is 28 times higher than that in the general population, and prison environment favors the spread of TB. OBJECTIVE: To describe TB transmission dynamics and drug resistance profiles in PP using whole-genome sequencing (WGS). METHODS: This was a retrospective study of Mycobacterium tuberculosis cultivated from people incarcerated in 55 prisons between 2016 and 2019; only one isolate per prisoner was included. Information about movement from one prison to another was tracked. Clinical information was collected, and WGS was performed on isolates obtained at the time of TB diagnosis. RESULTS: Among 134 prisoners included in the study, we detected 16 clusters with a total of 58 (43%) cases of M. tuberculosis. Clusters ranged from two to seven isolates with five or fewer single nucleotide polymorphism (SNP) differences, suggesting a recent transmission. Six (4.4%) isolates were resistant to at least one anti-TB drug. Two of these clustered together and showed resistance to rifampicin, isoniazid, and fluoroquinolones, with 100% concordance between WGS and phenotypic drug-susceptibility testing. Prisoners with clustered isolates had a high amount of movement between prisons (two to eight moves) during the study period. CONCLUSIONS: WGS demonstrated the recent transmission of TB within prisons in Brazil. The high movement among prisoners seems to be related to the transmission of the same M. tuberculosis strain within the prison system. Screening for TB before and after the movement of prisoners using rapid molecular tests could play a role in reducing transmission.
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Tuberculosis Latente , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis , Humanos , Prisiones , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Brasil/epidemiología , Estudios Retrospectivos , Tuberculosis/diagnóstico , Antituberculosos/uso terapéutico , Mycobacterium tuberculosis/genética , Pruebas de Sensibilidad MicrobianaRESUMEN
ABSTRACT Background: The rate of tuberculosis (TB) infection among the prison population (PP) in Brazil is 28 times higher than that in the general population, and prison environment favors the spread of TB. Objective: To describe TB transmission dynamics and drug resistance profiles in PP using whole-genome sequencing (WGS). Methods: This was a retrospective study of Mycobacterium tuberculosis cultivated from people incarcerated in 55 prisons between 2016 and 2019; only one isolate per prisoner was included. Information about movement from one prison to another was tracked. Clinical information was collected, and WGS was performed on isolates obtained at the time of TB diagnosis. Results: Among 134 prisoners included in the study, we detected 16 clusters with a total of 58 (43%) cases of M. tuberculosis. Clusters ranged from two to seven isolates with five or fewer single nucleotide polymorphism (SNP) differences, suggesting a recent transmission. Six (4.4%) isolates were resistant to at least one anti-TB drug. Two of these clustered together and showed resistance to rifampicin, isoniazid, and fluoroquinolones, with 100% concordance between WGS and phenotypic drug-susceptibility testing. Prisoners with clustered isolates had a high amount of movement between prisons (two to eight moves) during the study period. Conclusions: WGS demonstrated the recent transmission of TB within prisons in Brazil. The high movement among prisoners seems to be related to the transmission of the same M. tuberculosis strain within the prison system. Screening for TB before and after the movement of prisoners using rapid molecular tests could play a role in reducing transmission.
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Molecular-typing can help in unraveling epidemiological scenarios and improvement for disease control strategies. A literature review of Mycobacterium tuberculosis transmission in Brazil through genotyping on 56 studies published from 1996-2019 was performed. The clustering rate for mycobacterial interspersed repetitive units - variable tandem repeats (MIRU-VNTR) of 1,613 isolates were: 73%, 33% and 28% based on 12, 15 and 24-loci, respectively; while for RFLP-IS6110 were: 84% among prison population in Rio de Janeiro, 69% among multidrug-resistant isolates in Rio Grande do Sul, and 56.2% in general population in São Paulo. These findings could improve tuberculosis (TB) surveillance and set up a solid basis to build a database of Mycobacterium genomes.
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Repeticiones de Minisatélite/genética , Mycobacterium tuberculosis/genética , Polimorfismo de Longitud del Fragmento de Restricción/genética , Técnicas de Tipificación Bacteriana , Brasil/epidemiología , Genotipo , Humanos , Epidemiología Molecular , Mycobacterium tuberculosis/aislamiento & purificación , Secuenciación Completa del GenomaRESUMEN
Molecular-typing can help in unraveling epidemiological scenarios and improvement for disease control strategies. A literature review of Mycobacterium tuberculosis transmission in Brazil through genotyping on 56 studies published from 1996-2019 was performed. The clustering rate for mycobacterial interspersed repetitive units - variable tandem repeats (MIRU-VNTR) of 1,613 isolates were: 73%, 33% and 28% based on 12, 15 and 24-loci, respectively; while for RFLP-IS6110 were: 84% among prison population in Rio de Janeiro, 69% among multidrug-resistant isolates in Rio Grande do Sul, and 56.2% in general population in São Paulo. These findings could improve tuberculosis (TB) surveillance and set up a solid basis to build a database of Mycobacterium genomes.
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Humanos , Polimorfismo de Longitud del Fragmento de Restricción/genética , Repeticiones de Minisatélite/genética , Mycobacterium tuberculosis/genética , Brasil/epidemiología , Técnicas de Tipificación Bacteriana , Epidemiología Molecular , Secuenciación Completa del Genoma , Genotipo , Mycobacterium tuberculosis/aislamiento & purificaciónRESUMEN
INTRODUCTION: Mozambique is one of three countries with high prevalence of tuberculosis (TB), TB/human immunodeficiency virus coinfection, and multidrug-resistant TB. We aimed to describe Mycobacterium tuberculosis spoligotypes circulating among drug resistant (DR) strains from Beira, Mozambique comparing them with genotypes in the country. METHODS: We performed spoligotyping of 79 M. tuberculosis suspected of DR-TB compared all spoligotype patterns published on the international database and PubMed. RESULTS: Both in Beira and Mozambique (n=578), the main clades were Latin-American-Mediterranean, East-African-Indian, Beijing and T, with no extensively DR TB cases. CONCLUSIONS: Beira and Mozambique share the same population genetic structure of M. tuberculosis.
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Variación Genética/genética , Mycobacterium tuberculosis/genética , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Técnicas de Tipificación Bacteriana , Genotipo , Humanos , Mozambique , Mutación/genética , FilogeniaRESUMEN
Effective treatment of tuberculosis (TB) remains a serious public health problem in many countries, including Brazil, especially when considering drug-resistant disease. Xpert MTB/RIF has been implemented in many countries to reduce the time to TB diagnosis and to rapidly detect rifampicin resistance. The study aimed to describe and evaluate Xpert MTB/RIF performance in diagnosing pulmonary TB and rifampicin resistance in a tertiary healthcare facility in Brazil. A cross-sectional study was performed, which included all isolates of confirmed pulmonary TB patients from 2015 to 2018. Both Xpert MTB/RIF and GenoType MTBDRplus assays were performed to detect rifampicin and isoniazid resistance. In addition, isolates with detected resistance to rifampicin and/or isoniazid were analysed by phenotypic testing using MGIT-960 SIRE kit and whole-genome sequencing (WGS) using Illumina MiSeq Sequencing System. 2148 respiratory specimens tested with Xpert MTB/RIF were included: n=1556 sputum, n=348 bronchoalveolar lavage and n=244 gastric washing. The overall Xpert MTB/RIF sensitivity in sputum was 94% and the overall specificity was 98%. The negative predictive value in sputum of all the patients was 99% with a positive predictive value of 89%. The concordance between Xpert MTB/RIF and phenotypic susceptibility test was 94.1%, while its concordance with WGS was 78.9%. Xpert MTB/RIF is a rapid and accurate diagnostic strategy for pulmonary TB, which can contribute to improvement in TB control. However, detection of rifampicin resistance might be associated with false-positive results.
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Abstract INTRODUCTION Mozambique is one of three countries with high prevalence of tuberculosis (TB), TB/human immunodeficiency virus coinfection, and multidrug-resistant TB. We aimed to describe Mycobacterium tuberculosis spoligotypes circulating among drug resistant (DR) strains from Beira, Mozambique comparing them with genotypes in the country. METHODS: We performed spoligotyping of 79 M. tuberculosis suspected of DR-TB compared all spoligotype patterns published on the international database and PubMed. RESULTS: Both in Beira and Mozambique (n=578), the main clades were Latin-American-Mediterranean, East-African-Indian, Beijing and T, with no extensively DR TB cases. CONCLUSIONS: Beira and Mozambique share the same population genetic structure of M. tuberculosis.
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Humanos , Variación Genética/genética , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Mycobacterium tuberculosis/genética , Filogenia , Técnicas de Tipificación Bacteriana , Genotipo , Mozambique , Mutación/genéticaRESUMEN
From 2012 to 2013, 300 adults under investigation of tuberculous meningitis (TBM) were tested with polymerase chain reaction (PCR) in central spinal fluid (CSF), followed by TBM score calculation. There were 33(11%) confirmed TBM cases based on clinical findings, CSF-culture; biopsy/necropsy exams and clinical improvement after tuberculosis specific treatment. Other 267 adults were classified as non-TBM. Based on the original score there were 143 possible cases (6≤score≤11) and 20(60.6%) out of 33 TBM; among 27 probable TBM (score≥12) there were 13/33 (39.4%) confirmed cases. The CSF-PCR detected 48% (16/33) of TBM. Based on these findings, a new cut-off point was proposed to differentiate probable (score≥10) from possible (6≤score≤9) TBM. After score adjustment, there were 61 probable TBM with 26/33 (78.8%) TBM, and among the 109 possible TBM there were 7/33(21.2%) confirmed cases. In both systems, there were 130 non-TBM (score≤5) and no confirmed TBM. The association of adjusted score (≥10) and CSF-PCR showed high sensitivity (90.9%) and specificity (86.9%), positive and negative predictive value of 46.2% and 98.9%, respectively. The combination of CSF-PCR and TBM score is a useful tool for the management of adults under investigation of TBM, but the best cut-off point may need local/regional adjustments.