Trends in primary multidrug-resistant tuberculosis in the State of Rio de Janeiro: a retrospective study conducted during 2000-2019

Bhering, Marcela; Kritski, Afrânio Lineu

doi:10.1590/0037-8682-0086-2021

Cited by 6 publications

(7 citation statements)

References 8 publications

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“…The majority of clusters were identified in Rio de Janeiro, and although sampling from this state was clearly over represented in our setting, this may represent higher levels of recent infection and drug resistant TB transmission, differing of TB cases due to reactivation of latent infection [31,32]. In this Brazilian State, an increase of primary MDR-TB has been described as associated with low TB control performance [5]. Studies in other Brazilian States also shown important ongoing transmission of MDR-TB, as observed in Sao Paulo [33,34] and Santa Catarina [35] and also, in a genome-based study [36], in Rio Grande do Sul.…”

Section: Resistance Mutation Genotypic Profile Resistance Phenotypic ...mentioning

confidence: 86%

“…In addition, due to the COVID-19 pandemic, it is estimated that after a decade of decline, TB mortality has increased in Brazil and globally [3]. An additional concern for TB control in Brazil is the considerable number of DR-TB patients; in 2018 around 2.500 MDR/RR-TB cases were estimated [4], including an increase of MDR-TB among patients that had not previously been treated in Rio de Janeiro State [5].…”

Section: Introductionmentioning

confidence: 99%

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Genetic Characterization and Population Structure of Drug Resistant <em>Mycobacterium tuberculosis </em>Isolated from Brazilian Patients Using Whole-Genome Sequencing

Esteves,

Gomes,

Brites

et al. 2024

Preprint

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The present study aimed to determine the genetic diversity of isolates of Mycobacterium tuberculosis (Mtb) from presumed drug resistant tuberculosis patients from several states of Brazil. The isolates had been submitted to conventional drug susceptibility testing for first- and second-line drugs. Multidrug-resistant (MDR-TB) (54.8%) was the most frequent phenotypic resistance profile, in addition to an important high frequency of pre-extensively resistant (p-XDR-TB) (9.2%). Using whole-genome sequencing (WGS), we characterized 298 Mtb isolates from Brazil. Besides analysis of genotype distribution and possible correlations between molecular and clinical data, we determined the performance of an in-house WGS pipeline with other online pipelines for Mtb lineages and drug resistance profile definition. Sub-lineage 4.3 (52%) was the most frequent genotype and the genomic approach revealed a p-XDR-TB level of 22.5%. We detected 20 novel mutations in three resistance genes, and six of these were observed in eight phenotypically resistant isolates. Cluster analysis of 170 isolates showed that 43.5% of the TB patients belonged to 24 genomic clusters, suggesting considerable ongoing transmission of DR-TB, including two interstate transmissions. The in-house WGS pipeline showed the best overall performance in drug-resistance prediction, presenting the best accuracy values to five of nine drugs tested. Significant associations were observed between suffering from fatal disease and genotypic p-XDR-TB (p = 0.03) and either phenotypic (p = 0.006) and genotypic (p = 0.0007) ethambutol resistance. The use of WGS analysis improved our understanding of the population structure of MTBC in Brazil, genetic and clinical data correlations and demonstrating its utility for surveillance efforts for spread of DR-TB, hopefully helping to avoid the emergence of even more resistant strains and to reduce TB incidence and mortality rates.

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Section: Resistance Mutation Genotypic Profile Resistance Phenotypic ...mentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Genetic Characterization and Population Structure of Drug Resistant <em>Mycobacterium tuberculosis </em>Isolated from Brazilian Patients Using Whole-Genome Sequencing

Esteves,

Gomes,

Brites

et al. 2024

Preprint

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“…On the contrary, an upward trend of primary MDR-TB in Brazil from 2000 to 2019 was reported. [25] The possible reason for the downward trend in the current study was the implementation of effective strategies for TB control in China. Directly observed treatment short-course, which had been put forward in China since the 1990s, still plays an important role in controlling DR-TB prevalence, in terms of supervising TB patients to complete their treatments.…”

Section: Discussionmentioning

confidence: 98%

Patterns and trends of primary drug-resistant tuberculosis in Chongqing, China, from 2012 to 2020

et al. 2023

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Primary drug-resistant tuberculosis (DR-TB) contributes significantly to the global TB epidemic, particularly in countries with high TB burdens. This study aimed to investigate the characteristics of primary DR-TB prevalence in Chongqing, China, from 2012 to 2020. A total of 4546 newly diagnosed and 2769 relapse TB patients admitted to the hospital from 2012 to 2020 were included. Categorical variables were compared using Pearson chi-square test or Fisher exact test, as appropriate. Logistic regression analysis was performed to determine factors associated with primary DR-TB. The rate of primary DR-TB was 24.5%, whereas that of acquired DR-TB was 67.8%. Among newly diagnosed TB cases, the percentage of DR-TB (from 48.9 to 44.2%), monoresistant TB (from 11.8 to 9.7%), multidrug-resistant TB (MDR-TB; from 25.3 to 6.9%), and pre-extensive drug-resistant TB (from 13.7 to 5.8%) showed a decreasing trend from 2012 to 2020. Age from 15 to 64 years was a risk factor for the development of primary DR-TB (15-44 years: adjusted odds ratio = 2.227, 95% confidence interval: 1.053-4.710; 45-64 years: adjusted odds ratio = 2.223, 95% confidence interval: 1.048-4.717). The rates of primary DR-TB (P = .041) and MDR-TB (P = .007) were significantly higher in the age group of 15 to 64 years than in the age groups of ≤14 years and ≥65 years. Noticeably, rising trends of primary DR-TB (from 0 to 27.3%) and MDR-TB (from 0 to 9.1%) in the population of ≤14 years were observed from 2012 to 2020. Although the rate of primary DR-TB showed a downward trend, a rising drug-resistance rate among some particular subgroups was still observed. Further control of primary DR-TB should focus more on TB patients aged 15 to 64 years. Abbreviations: aOR = adjusted odds ratio, DR = drug-resistant, DST = drug susceptibility testing, INH = isoniazid, MDR = multidrug-resistant, MR = mono-resistant, PDR = polydrug-resistant, pre-XDR = pre-extensive drug-resistant, RFP = rifampicin, RR = rifampicin-resistant, TB = tuberculosis.

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“…The majority of clusters were identified in Rio de Janeiro, and although sampling from this state was clearly over-represented in our setting, this may represent higher levels of recent infection and drug-resistant TB transmission, differing from TB cases due to the reactivation of a latent infection [ 36 , 37 ]. In this Brazilian state, an increase in primary MDR-TB has been described as being associated with low TB control performance [ 5 ]. Studies in other Brazilian states have also shown significant ongoing transmission of MDR-TB, as observed in Sao Paulo [ 38 , 39 ] and Santa Catarina [ 40 ], and Rio Grande do Sul in a genome-based study [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, due to the COVID-19 pandemic, it is estimated that after a decade of decline, TB mortality has increased in Brazil and globally [ 3 ]. An additional concern for TB control in Brazil is the considerable number of DR-TB patients; in 2018, around 2.500 MDR/RR-TB cases were estimated [ 4 ], including an increase in MDR-TB among patients that had not previously been treated in the Rio de Janeiro State [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic Characterization and Population Structure of Drug-Resistant Mycobacterium tuberculosis Isolated from Brazilian Patients Using Whole-Genome Sequencing

Esteves,

Gomes,

Brites

et al. 2024

Antibiotics

Self Cite

View full text Add to dashboard Cite

The present study aimed to determine the genetic diversity of isolates of Mycobacterium tuberculosis (Mtb) from presumed drug-resistant tuberculosis patients from several states of Brazil. The isolates had been submitted to conventional drug susceptibility testing for first- and second-line drugs. Multidrug-resistant (MDR-TB) (54.8%) was the most frequent phenotypic resistance profile, in addition to an important high frequency of pre-extensive resistance (p-XDR-TB) (9.2%). Using whole-genome sequencing (WGS), we characterized 298 Mtb isolates from Brazil. Besides the analysis of genotype distribution and possible correlations between molecular and clinical data, we determined the performance of an in-house WGS pipeline with other online pipelines for Mtb lineages and drug resistance profile definitions. Sub-lineage 4.3 (52%) was the most frequent genotype, and the genomic approach revealed a p-XDR-TB level of 22.5%. We detected twenty novel mutations in three resistance genes, and six of these were observed in eight phenotypically resistant isolates. A cluster analysis of 170 isolates showed that 43.5% of the TB patients belonged to 24 genomic clusters, suggesting considerable ongoing transmission of DR-TB, including two interstate transmissions. The in-house WGS pipeline showed the best overall performance in drug resistance prediction, presenting the best accuracy values for five of the nine drugs tested. Significant associations were observed between suffering from fatal disease and genotypic p-XDR-TB (p = 0.03) and either phenotypic (p = 0.006) or genotypic (p = 0.0007) ethambutol resistance. The use of WGS analysis improved our understanding of the population structure of MTBC in Brazil and the genetic and clinical data correlations and demonstrated its utility for surveillance efforts regarding the spread of DR-TB, hopefully helping to avoid the emergence of even more resistant strains and to reduce TB incidence and mortality rates.

show abstract

Trends in primary multidrug-resistant tuberculosis in the State of Rio de Janeiro: a retrospective study conducted during 2000-2019

Cited by 6 publications

References 8 publications

Genetic Characterization and Population Structure of Drug Resistant <em>Mycobacterium tuberculosis </em>Isolated from Brazilian Patients Using Whole-Genome Sequencing

Genetic Characterization and Population Structure of Drug Resistant <em>Mycobacterium tuberculosis </em>Isolated from Brazilian Patients Using Whole-Genome Sequencing

Patterns and trends of primary drug-resistant tuberculosis in Chongqing, China, from 2012 to 2020

Genetic Characterization and Population Structure of Drug-Resistant Mycobacterium tuberculosis Isolated from Brazilian Patients Using Whole-Genome Sequencing

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