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BACKGROUND: Few studies in routine settings have confirmed the high accuracy of the Xpert MTB/RIF assay for detecting rifampicin resistance (RR) and the first-line probe assay (FL-LPA) for detecting both RR and isoniazid resistance (INHR). METHODS: The performance of Xpert MTB/RIF and MTBDRplus VER 2.0 LPA was evaluated in 180 Mycobacterium tuberculosis samples collected from January 2018 to December 2019 in Rio de Janeiro, Brazil. The results were compared with those from BACTEC MGIT 960 culture and drug susceptibility testing (DST). Whole-genome sequencing was performed on the samples with discordant results. RESULTS: The Xpert MTB/RIF assay showed a sensitivity (Se) of 93.3% and a specificity (Sp) of 97.6%, detecting RR. The performance of FL-LPA to identify RIF and INH resistance was, respectively, (Se) 100% and 83.3% and (Sp) 98.8% and 100%. Among 18 clinical isolates with INHR detected by FL-LPA, mutations in the katG gene were observed in 100% of samples, of which only two (11.1%) had mutations in both katG and inhA genes. Overall, the discordant results were identified in 9 (5%) samples. Among the four Xpert RIF-resistant and DST-sensitive, two harbored mutations in rpoB Leu430Pro. Among the four FL-LPA-sensitive and DST-resistant, one had a mutation in inhA 17G>T. FL-LPA showed high accuracy in detecting RR and INHR. CONCLUSIONS: The MTBDRplus test demonstrated excellent performance in detecting RR, and INHR in clinical isolates under routine conditions at a reference laboratory in Rio de Janeiro, Brazil. Incorporating both tests can improve drug-resistant tuberculosis treatment outcomes and monitor the INHR incidence.

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This study aimed to reinforce the importance of the epidemiological surveillance of multidrug-resistant tuberculosis (MDR-TB) in Rio de Janeiro State (RJ). Here, we reviewed seven articles we published between 2018 and 2022. This study had two phases. The quantitative phase where frequency was used to describe patient characteristics and regressions were used to evaluate the relationship between treatment outcomes and covariates. The qualitative phase where content analysis of the narratives was performed. Secondary (electronic systems) and primary (semi-structured interviews) data were used. We analyzed 2,269 MDR-TB, 58.1% MDR-TB, and 18.6% extensively drug-resistant TB (XDR-TB) cases, of which 44.3% exhibited unfavorable outcomes. Among the 140 patients with XDR-TB, 29.3% had not undergone prior treatment for MDR-TB. The primary resistance rate in MDR-TB cases was 14.7%, revealing significant demographic and clinical disparities, particularly among women, Caucasians, and those with higher education levels. The number of cases increased from 7.69% in 2000 to 38.42% in 2018, showing an increasing trend (AAPC = 9.4; 95% CI 1.4-18.0, p < 0.001), with 25.4% underreporting. A qualitative study confirmed a high proportion of primary resistance (64.5%) and delayed diagnosis of MDR-TB. In RJ, the diagnostic and therapeutic cascade of MDR-TB must be improved using molecular tests to achieve an early diagnosis of resistance and immediate initiation of appropriate treatment, promote social protection for MDR/XDR-TB patients and their families, enhance TB contact tracing, establish and monitor hospital surveillance centers integrated with Primary Care, and unify various information systems through interoperability for better integration.

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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-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.

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ABSTRACT This study aimed to reinforce the importance of the epidemiological surveillance of multidrug-resistant tuberculosis (MDR-TB) in Rio de Janeiro State (RJ). Here, we reviewed seven articles we published between 2018 and 2022. This study had two phases. The quantitative phase where frequency was used to describe patient characteristics and regressions were used to evaluate the relationship between treatment outcomes and covariates. The qualitative phase where content analysis of the narratives was performed. Secondary (electronic systems) and primary (semi-structured interviews) data were used. We analyzed 2,269 MDR-TB, 58.1% MDR-TB, and 18.6% extensively drug-resistant TB (XDR-TB) cases, of which 44.3% exhibited unfavorable outcomes. Among the 140 patients with XDR-TB, 29.3% had not undergone prior treatment for MDR-TB. The primary resistance rate in MDR-TB cases was 14.7%, revealing significant demographic and clinical disparities, particularly among women, Caucasians, and those with higher education levels. The number of cases increased from 7.69% in 2000 to 38.42% in 2018, showing an increasing trend (AAPC = 9.4; 95% CI 1.4−18.0, p < 0.001), with 25.4% underreporting. A qualitative study confirmed a high proportion of primary resistance (64.5%) and delayed diagnosis of MDR-TB. In RJ, the diagnostic and therapeutic cascade of MDR-TB must be improved using molecular tests to achieve an early diagnosis of resistance and immediate initiation of appropriate treatment, promote social protection for MDR/XDR-TB patients and their families, enhance TB contact tracing, establish and monitor hospital surveillance centers integrated with Primary Care, and unify various information systems through interoperability for better integration.

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OBJECTIVE: To understand patients' narratives about the barriers they faced in the diagnosis and treatment of multidrug-resistant tuberculosis, and their consequences in Rio de Janeiro State, Brazil. METHODS: This is a qualitative cross-sectional study with non-probabilistic sampling. A theoretical saturation criterion was considered for composing the number of interviewees. Semi-structured interviews were conducted from August to December 2019 with 31 patients undergoing treatment for multidrug-resistant tuberculosis at an outpatient referral center in Rio de Janeiro. Data were transcribed and processed with the aid of the NVIVO software. Interviews were evaluated by content analysis, and their themes, cross-referenced with participants' characterization data. RESULTS: Our main findings were: a) participants show a high proportion of primary drug resistance, b) patients experience delays in the diagnosis and effective treatment of multidrug-resistant tuberculosis ; c) healthcare providers fail to value or seek the diagnosis of drug-resistant tuberculosis, thus beginning the inadequate treatment for drug-susceptible tuberculosis, d) primary health units show low report rates of active case-finding and contact monitoring, and e) patients show poor knowledge about the disease. CONCLUSIONS: We need to improve referral systems, and access to the diagnosis and effective treatment of multidrug-resistant tuberculosis; conduct an active investigation of contacts; intensify the training of healthcare providers, in collaboration with medical and nursing schools, in both public and private systems; and promote campaigns to educate the population on tuberculosis signs and symptoms.

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ABSTRACT OBJECTIVE To understand patients' narratives about the barriers they faced in the diagnosis and treatment of multidrug-resistant tuberculosis, and their consequences in Rio de Janeiro State, Brazil. METHODS This is a qualitative cross-sectional study with non-probabilistic sampling. A theoretical saturation criterion was considered for composing the number of interviewees. Semi-structured interviews were conducted from August to December 2019 with 31 patients undergoing treatment for multidrug-resistant tuberculosis at an outpatient referral center in Rio de Janeiro. Data were transcribed and processed with the aid of the NVIVO software. Interviews were evaluated by content analysis, and their themes, cross-referenced with participants' characterization data. RESULTS Our main findings were: a) participants show a high proportion of primary drug resistance, b) patients experience delays in the diagnosis and effective treatment of multidrug-resistant tuberculosis ; c) healthcare providers fail to value or seek the diagnosis of drug-resistant tuberculosis, thus beginning the inadequate treatment for drug-susceptible tuberculosis, d) primary health units show low report rates of active case-finding and contact monitoring, and e) patients show poor knowledge about the disease. CONCLUSIONS We need to improve referral systems, and access to the diagnosis and effective treatment of multidrug-resistant tuberculosis; conduct an active investigation of contacts; intensify the training of healthcare providers, in collaboration with medical and nursing schools, in both public and private systems; and promote campaigns to educate the population on tuberculosis signs and symptoms.

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INTRODUCTION: We analyzed the trends in primary multidrug-resistant tuberculosis (MDR-TB). METHODS: We performed a time series analysis of primary MDR-TB cases reported in the State of Rio de Janeiro (RJ) during 2000-2019. The annual percent change and the average annual percentage change (AAPC) were computed using joinpoint regression analysis. RESULTS: The percentage of cases increased from 7.69% in 2000 to 38.42% in 2018. We observed an upward trend during this period (AAPC = 9.4; 95% confidence interval 1.4-18.0, p < 0.001). CONCLUSIONS: The trend indicates the increasing occurrence of MDR-TB transmission sources in RJ during 2000-2019.

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[ABSTRACT]. Objective. To identify clinical and demographic factors associated with unfavorable treatment outcomes in patients with primary and acquired multidrug-resistant tuberculosis (MDR-TB) in Rio de Janeiro State. Methods. Retrospective cohort study using data on 2 269 MDR-TB cases in 2000–2016. Factors associated with unsuccessful, loss to follow-up, and death outcomes in patients with primary and acquired resistance were investigated with bivariate and multivariate regression. Results. Primary resistance was 14.7% among MDR-TB cases. The unfavorable outcomes proportion was 30.3% in the primary resistance group and 46.7% in the acquired resistance group. There were significant differences in demographic and clinical characteristics between the two groups. Proportionally, the group with primary resistance had more cases among women (46.4% vs. 33.5% in the acquired resistance group), Caucasians (47.3% and 34%), and those with ≥8 years of schooling (37.7% and 27.4%). Extensively drug-resistant TB patients had 12.2-fold higher odds of unsuccessful outcome than MDR-TB patients, and comorbidities had 2-fold higher odds in the primary resistance group. Extensively drug-resistant TB had 5.43-fold higher odds in the acquired MDR-TB group. Bilateral disease and <8 years of schooling were associated with unsuccessful outcome in both groups. Being an inmate had 8-fold higher odds of loss to follow-up in the primary resistance group. Culture conversion by the sixth month was a protective factor for all outcomes. Conclusions. Primary resistance cases of MDR-TB constitute a different transmission reservoir, which is related to other chronic diseases associated with higher acquisition of TB. The poor results observed in Rio de Janeiro State can contribute to increasing the transmission of primary MDR-TB, thus favoring drug resistance.

[RESUMEN]. Objetivo. Determinar cuáles son los factores clínicos o demográficos asociados con resultados desfavorables del tratamiento en pacientes con tuberculosis multirresistente (TB-MDR) primaria o adquirida en el estado de Rio de Janeiro. Métodos. Estudio retrospectivo de cohorte con datos de 2 269 casos de TB-MDR entre el 2000 y el 2016. Se analizaron los factores asociados con resultados desfavorables, pacientes perdidos en el seguimiento o muerte en pacientes con resistencia primaria o adquirida mediante modelos de regresión bifactorial y multifactorial. Resultados. En los casos de TB-MDR, la resistencia primaria fue de 14,7%. La proporción de resultados desfavorables fue de 30,3% en el grupo con resistencia primaria y de 46,7% en el grupo con resistencia adquirida. Las diferencias en las características demográficas y clínicas de los dos grupos fueron significativas. Proporcionalmente, el grupo con resistencia primaria tuvo más casos en las mujeres (46,4% frente a 33,5% en el grupo con resistencia adquirida), las personas caucásicas (47,3% frente a 34%) y en aquellas personas con 8 o más años de escolarización (37,7% frente a 27,4%). Los pacientes con tuberculosis extensamente resistente tenían 12,2 veces más probabilidades de tener un resultado desfavorable que los pacientes con TB-MDR. La comorbilidad fue 2 veces mayor en el grupo con resistencia primaria. El grupo con TB-MDR adquirida tenía 5,43 veces más probabilidades de tener tuberculosis extremadamente resistente. En ambos grupos, se asoció la enfermedad bilateral y menos de 8 años de escolarización con resultados desfavorables. En el grupo con resistencia primaria, las probabilidades de perder al paciente en el seguimiento fueron 8 veces mayores en los presidiarios. La conversión del cultivo a los seis meses fue un factor protector en todos los resultados. Conclusiones. Los casos de resistencia primaria de TB-MDR constituyen un reservorio de transmisión diferente, que está relacionado con otras enfermedades crónicas asociadas con una mayor adquisición de tuberculosis. Los resultados insatisfactorios observados en el estado de Rio de Janeiro pueden contribuir a aumentar la transmisión de la TB-MDR primaria, y por lo tanto favorecer la farmacorresistencia.

[RESUMO]. Objetivo. Identificar fatores demográficos e clínicos associados a desfechos desfavoráveis do tratamento em pacientes com tuberculose multirresistente primária e adquirida no Estado do Rio de Janeiro. Métodos. Estudo de coorte retrospectivo baseado em dados de 2.269 casos de tuberculose multirresistente no período 2000–2016. Fatores associados aos desfechos de falha terapêutica, perda de seguimento e óbito em pacientes com resistência primária e adquirida foram analisados em modelos de regressão bivariada e multivariada. Resultados. Observou-se resistência primária em 14,7% dos casos de tuberculose multirresistente. Desfechos desfavoráveis ocorreram em 30,3% no grupo com resistência primária e 46,7% no grupo com resistência adquirida. Verificaram-se diferenças significativas quanto às características demográficas e clínicas entre os dois grupos. Proporcionalmente, o grupo com resistência primária apresentou mais casos em pacientes do sexo feminino (46,4% vs. 33,5% no grupo de resistência adquirida), caucasianos (47,3% vs. 34%) e com escolaridade ≥8 anos (37,7% vs. 27,4%). A tuberculose extensivamente resistente foi associada a uma chance 12,2 vezes maior de falha terapêutica que a tuberculose multirresistente e a chance de presença de comorbidades foi 2 vezes maior no grupo com resistência primária. A chance de ocorrência de tuberculose extensivamente resistente foi 5,43 maior no grupo com tuberculose multirresistente adquirida. Doença bilateral e escolaridade <8 anos foram associados à falha terapêutica em ambos os grupos. Estar encarcerado foi associado a uma chance 8 vezes maior de perda de seguimento no grupo com resistência primária. A conversão da cultura após seis meses de tratamento foi um fator de proteção para todos os desfechos. Conclusões. Os casos de tuberculose multirresistente com resistência primária constituem um reservatório de transmissão distinto que está relacionado a outras doenças crônicas associadas a uma taxa maior de tuberculose. Os resultados ruins observados no Estado do Rio de Janeiro podem contribuir para aumentar a transmissão da tuberculose multirresistente primária, favorecendo a resistência aos medicamentos.

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OBJECTIVE: To identify clinical and demographic factors associated with unfavorable treatment outcomes in patients with primary and acquired multidrug-resistant tuberculosis (MDR-TB) in Rio de Janeiro State. METHODS: Retrospective cohort study using data on 2 269 MDR-TB cases in 2000-2016. Factors associated with unsuccessful, loss to follow-up, and death outcomes in patients with primary and acquired resistance were investigated with bivariate and multivariate regression. RESULTS: Primary resistance was 14.7% among MDR-TB cases. The unfavorable outcomes proportion was 30.3% in the primary resistance group and 46.7% in the acquired resistance group. There were significant differences in demographic and clinical characteristics between the two groups. Proportionally, the group with primary resistance had more cases among women (46.4% vs. 33.5% in the acquired resistance group), Caucasians (47.3% and 34%), and those with ≥8 years of schooling (37.7% and 27.4%). Extensively drug-resistant TB patients had 12.2-fold higher odds of unsuccessful outcome than MDR-TB patients, and comorbidities had 2-fold higher odds in the primary resistance group. Extensively drug-resistant TB had 5.43-fold higher odds in the acquired MDR-TB group. Bilateral disease and <8 years of schooling were associated with unsuccessful outcome in both groups. Being an inmate had 8-fold higher odds of loss to follow-up in the primary resistance group. Culture conversion by the sixth month was a protective factor for all outcomes. CONCLUSIONS: Primary resistance cases of MDR-TB constitute a different transmission reservoir, which is related to other chronic diseases associated with higher acquisition of TB. The poor results observed in Rio de Janeiro State can contribute to increasing the transmission of primary MDR-TB, thus favoring drug resistance.

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SETTING: The State of Rio de Janeiro stands out as having the second highest incidence and the highest mortality rate due to TB in Brazil. This study aims at identifying the factors associated with the unfavourable treatment of MDR/XDR-TB patients in that State. METHOD: Data on 2269 MDR-TB cases reported in 2000-2016 in Rio de Janeiro State were collected from the Tuberculosis Surveillance System. Bivariate and multivariate logistic regressions were run to estimate the factors associated with unfavourable outcomes (failure, default, and death) and, specifically, default and death. RESULTS: The proportion of unfavourable outcomes was 41.9% among MDR-TB and 81.5% among XDR-TB. Having less than 8 years of schooling, and being an Afro-Brazilian, under 40 years old and drug user were associated with unfavourable outcome and default. Bilateral disease, HIV positive, and comorbidities were associated with death. XDR-TB cases had a 4.7-fold higher odds of an unfavourable outcome, with 29.3% of such cases being not treated for multidrug resistance in the past. CONCLUSION: About 30% of XDR-TB cases may have occurred by primary transmission. The high rates of failure and death in this category reflect the limitation of treatment options. This highlights the urgency to incorporate new drugs in the treatment.

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Introdução: a população idosa, com 60 anos ou mais, tem aspectos peculiares que a diferencia da mais jovem e que implicam em alterações fisiológicas e maior vulnerabilidade às infecções. O presente trabalho tem como objetivo avaliar o comportamento da tuberculose (Tb) em pacientes idosos internados no maior hospital de referência para a doença no Estado do Rio de Janeiro. Metodologia: estudo descritivo, retrospectivo, realizado por meio do levantamento de prontuários de pacientes com mais de 60 anos, portadores de Tb, internados entre janeiro de 2001 e dezembro de 2003 no Hospital Estadual Santa Maria. Resultados: dos 61 prontuários revisados, 77% eram de pacientes do sexo masculino, predominando a faixa etária entre 60 e 65 anos (42,6%). O mau estado geral foi o principal motivo de internação, em 39,9% dos casos, e a Tb pulmonar o diagnóstico da internação em 93,4% dos casos. Com relação à realização de tratamentos anteriores para Tb, 42,6% eram retratamento sendo que destes 65,4% tinham história de abandono. No momento da internação, 39,9% apresentaram baciloscopia positiva. O diabetes foi a comorbidade presente em 16,4% dos casos. O tempo médio de permanência foi de 61 dias ou mais em 59% dos pacientes. Quanto à alta hospitalar, 54,1% dos pacientes saíram de alta por decisão médica e 31,1% evoluíram para óbito. Conclusões: a tuberculose no idoso apresenta um exaurimento progressivo da competência imunológica, o que justifica os principais motivos de internação, a freqüência de apresentações atípicas, a presença de comorbidades e o longo tempo de internação.

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