Time until tuberculosis recurrence and associated factors in Brazil: a populationbased retrospective cohort study using a linked database.

OBJECTIVE: To calculate the rate of tuberculosis recurrence, estimate its average time until recurrence, and identify factors associated with recurrence in Brazil. METHODS: Retrospective cohort study with a linked database from the Notifiable Diseases Information System. The study included individuals diagnosed with tuberculosis in 2015, focusing on those who experienced their first recurrence within 6.5 years. We estimated the relative risk (RR) and its 95% confidence interval (95%CI), as well as the population attributable fraction (PAF) or the population preventable fraction (PPF) of associated factors. RESULTS: Within a 6.5-year period, 3,253 individuals (6.5%) experienced tuberculosis recurrence, with a median time of 2.2 years. Positively associated factors included: male sex (RR: 1.4; 95%CI 1.3-1.5; PAF: 22.9%), age 30 to 59 years (RR: 3.0; 95%CI 1.6-5.7; PAF: 36.0%), black race (RR: 1.3; 95%CI 1.2-1.5; PAF: 3.5%), mixed race (RR: 1.3; 95%CI 1.2-1.4; PAF: 10.6%), deprivation of liberty (RR: 1.9; 95%CI 1.7-2.1; PAF: 9.1%), pulmonary/mixed clinical form (RR: 1.7; 95%CI 1.4-1.9; PAF: 37.1%), acquired immunodeficiency syndrome diagnosis (RR: 1.8; 95%CI 1.5-1.9; PAF: 4.3%), and alcohol use (RR: 1.2; 95%CI 1.1-1.3; PAF: 2.9%). Negatively associated factors were: 12 or more years of schooling (RR: 0.5; 95%CI 0.4-0.6; PPF: 3.3%) and supervised treatment (RR: 0.9; 95%CI 0.8-0.9; PPF: 4.4%). CONCLUSION: This study revealed high tuberculosis recurrence rates in Brazil, influenced by sociodemographic, compartmental, and social factors, both positively and negatively impacting disease recurrence.

Clusters of heterogeneity of tuberculosis-HIV coinfection in Brazil: a geospatial study.

OBJECTIVE: To analyze the geospatialization of tuberculosis-HIV coinfection in Brazil, from 2010 to 2021, and the correlation with socioeconomic, housing, and health indicators. METHODS: An ecological study of Brazilian municipalities and states, with data from HIV and tuberculosis information systems, previously reported by the Ministry of Health. The crude and smoothed coefficients were calculated by the local empirical Bayesian method of incidence of coinfection per 100,000 inhabitants in the population aged between 18 and 59 years. Univariate (identification of clusters) and bivariate (correlation with 20 indicators) Moran's indices were used. RESULTS: A total of 122,223 cases of coinfection were registered in Brazil from 2010 to 2021, with a mean coefficient of 8.30/100,000. The South (11.44/100,000) and North (9.93/100,000) regions concentrated the highest burden of infections. The coefficients dropped in Brazil, in all regions, in the years of covid-19 (2020 and 2021). The highest coefficients were observed in the municipalities of the states of Rio Grande do Sul, Mato Grosso do Sul, and Amazonas, with high-high clusters in the capitals, border regions, coast of the country. The municipalities belonging to the states of Minas Gerais, Bahia, Paraná, and Piauí showed low-low clusters. There was a direct correlation with human development indices and aids rates, as well as an indirect correlation with the proportion of poor or of those vulnerable to poverty and the Gini index. CONCLUSIONS: The spatial analysis of tuberculosis-HIV coinfection showed heterogeneity in the Brazilian territory and constant behavior throughout the period, revealing clusters with high-burden municipalities, especially in large urban centers and in states with a high occurrence of HIV and/or tuberculosis. These findings, in addition to alerting to the effects of the covid-19 pandemic, can incorporate strategic planning for the control of coinfection, aiming to eliminate these infections as public health problems by 2030.

How has the municipal availability of the GeneXpert®MTB/RIF system affected the detection of drug-resistant tuberculosis in Brazil?

OBJECTIVE: To evaluate the association between the availability of GeneXpert®MTB/RIF in municipalities and the proportion of people who have access to this diagnostic technology for tuberculosis (TB), as well as the resistance detected by the surveillance system in Brazil. METHODS: We analysed 4998 Brazilian municipalities that reported 432,937 new TB cases between 2015 and 2020. We compared municipalities with and without the availability of GeneXpert®MTB/RIF regarding the effective access to GeneXpert®MTB/RIF diagnosis and the prevalence of detected resistance. RESULTS: Municipalities with at least one GeneXpert®MTB/RIF system had three times (95% CI 2.9-3.0) the access to diagnostic tests and 80.4% (95% CI 70.6%-90.2%) higher detection of resistance, compared with municipalities without this technology. We estimated that there have been 1890 cases of undetected resistance during this period in the country. CONCLUSIONS: The availability of GeneXpert®MTB/RIF system in the municipality increased the sensitivity of the surveillance for detecting TB resistance. PUBLIC HEALTH IMPLICATIONS: It is a priority to strengthen laboratory networks and narrow the gap in access to rapid diagnosis in remote areas to improve the detection and control of drug-resistant tuberculosis.

Trends in tuberculosis incidence and mortality coefficients in Brazil, 2011-2019: analysis by inflection points.

Objective: To analyze the temporal trend of tuberculosis incidence and mortality rates in Brazil between 2011 and 2019. Methods: This was an ecological time series study of tuberculosis incidence and mortality rates in Brazil between 2011 and 2019. Data were extracted from the Notifiable Disease Information System and the Mortality Information System, and population estimates were from the Brazilian Institute of Geography and Statistics. Trends were analyzed by Joinpoint regression, which recognizes inflection points for temporal analysis. Results: The average incidence rate of tuberculosis in Brazil in the period was 35.8 cases per 100 000 population. From 2011 to 2015, this coefficient had an annual percentage change of -1.9% (95% CI [-3.4, -0.5]) followed by an increase of 2.4% (95% CI [0.9, 3.9]) until 2019. The average mortality rate between 2011 and 2019 was 2.2 deaths per 100 000 population, with an average annual percentage change of -0.4% (95% CI [-1.0, 0.2]). Amazonas was the only state with an increase in the annual average percentage variation for the incidence rate (3.2%; 95% CI [1.3, 5.1]) and mortality rate (2.7%; 95% CI [1.0, 4.4]) over the years, while Rio de Janeiro state had an increasing inflection for incidence from 2014 to 2019 (2.4%; 95% CI [1.4, 3.5]) and annual average of decreasing percentage variation (-3.5%; 95% CI [-5.0, -1.9]). Conclusions: During the period analyzed, a decreasing trend in incidence was observed between 2011 and 2015, and an increasing trend for the period from 2015 to 2019. On the other hand, no change in the trend for mortality was found in Brazil.

Trends in tuberculosis incidence and mortality coefficients in Brazil, 2011–2019: analysis by inflection points / Tendencias de los coeficientes de incidencia y mortalidad por tuberculosis en Brasil, 2011-2019: análisis por puntos de inflexión / Tendências nos coeficientes de incidência e mortalidade por tuberculose no Brasil, 2011-2019: análise por pontos de inflexão

[ABSTRACT]. Objective. To analyze the temporal trend of tuberculosis incidence and mortality rates in Brazil between 2011 and 2019. Methods. This was an ecological time series study of tuberculosis incidence and mortality rates in Brazil between 2011 and 2019. Data were extracted from the Notifiable Disease Information System and the Mortality Information System, and population estimates were from the Brazilian Institute of Geography and Statistics. Trends were analyzed by Joinpoint regression, which recognizes inflection points for temporal analysis. Results. The average incidence rate of tuberculosis in Brazil in the period was 35.8 cases per 100 000 population. From 2011 to 2015, this coefficient had an annual percentage change of –1.9% (95% CI [–3.4, –0.5]) followed by an increase of 2.4% (95% CI [0.9, 3.9]) until 2019. The average mortality rate between 2011 and 2019 was 2.2 deaths per 100 000 population, with an average annual percentage change of –0.4% (95% CI [–1.0, 0.2]). Amazonas was the only state with an increase in the annual average percentage variation for the incidence rate (3.2%; 95% CI [1.3, 5.1]) and mortality rate (2.7%; 95% CI [1.0, 4.4]) over the years, while Rio de Janeiro state had an increasing inflection for incidence from 2014 to 2019 (2.4%; 95% CI [1.4, 3.5]) and annual average of decreasing percentage variation (–3.5%; 95% CI [–5.0, –1.9]). Conclusions. During the period analyzed, a decreasing trend in incidence was observed between 2011 and 2015, and an increasing trend for the period from 2015 to 2019. On the other hand, no change in the trend for mortality was found in Brazil.

[RESUMEN]. Objetivo. Analizar la tendencia temporal de las tasas de incidencia y mortalidad por tuberculosis en Brasil entre el 2011 y el 2019. Métodos. Este fue un estudio ecológico de series temporales de las tasas de incidencia y mortalidad por tuberculosis en Brasil entre el 2011 y el 2019. Los datos se obtuvieron del Sistema de Información sobre Enfermedades de Notificación Obligatoria y del Sistema de Información sobre Mortalidad, y las estimaciones de población proceden del Instituto Brasileño de Geografía y Estadística. Las tendencias se analizaron mediante el programa de regresión Joinpoint, que reconoce los puntos de inflexión para el análisis temporal. Resultados. La tasa promedio de incidencia de tuberculosis en Brasil para el periodo fue de 35,8 casos por 100 000 habitantes. Entre el 2011 y el 2015, este coeficiente experimentó una variación porcentual anual del -1,9% (intervalo de confianza [IC] del 95% [-3,4, -0,5]), seguida por un aumento del 2,4% (IC 95% [0,9, 3,9]) hasta el 2019. La tasa de mortalidad promedio entre el 2011 y el 2019 fue de 2,2 muertes por cada 100 000 habitantes, con una variación porcentual promedio anual del -0,4% (IC del 95% [-1,0, 0,2]). El estado de Amazonas fue el único que a lo largo de los años presentó un aumento de la variación porcentual promedio anual de la tasa de incidencia (3,2%; IC del 95% [1,3, 5,1]) y de la tasa de mortalidad (2,7%; IC del 95% [1,0, 4,4]), en tanto que, entre el 2014 y el 2019, el estado de Río de Janeiro presentó una inflexión creciente de la incidencia (2,4%; IC del 95% [1,4, 3,5]) y una variación porcentual promedio anual decreciente (-3,5%; IC del 95% [-5,0, -1,9]). Conclusiones. Durante el periodo analizado, se observa una tendencia decreciente de la incidencia entre el 2011 y el 2015, y una tendencia creciente para el periodo comprendido entre el 2015 y el 2019. En cambio, no se encontró ningún cambio en la tendencia de la mortalidad en Brasil.

[RESUMO]. Objetivo. Analisar a tendência temporal das taxas de incidência e mortalidade por tuberculose no Brasil entre 2011 e 2019. Métodos. Estudo ecológico de série temporal das taxas de incidência e mortalidade por tuberculose no Brasil entre 2011 e 2019. Os dados foram extraídos do Sistema de Informação de Agravos de Notificação e do Sistema de Informação sobre Mortalidade, e as estimativas populacionais foram obtidas do Instituto Brasileiro de Geografia e Estatística. As tendências foram analisadas por regressão joinpoint, que reconhece pontos de inflexão para análise temporal. Resultados. A taxa média de incidência da tuberculose no Brasil no período foi de 35,8 casos por 100 mil habitantes. O coeficiente teve uma variação percentual anual de –1,9% (IC 95% [–3,4; –0,5]) de 2011 a 2015, seguida de um aumento de 2,4% (IC 95% [0,9; 3,9]) até 2019. A taxa média de mortalidade entre 2011 e 2019 foi de 2,2 óbitos por 100 mil habitantes, com uma variação percentual anual média de –0,4% (IC 95% [–1,0; 0,2]). Ao longo dos anos, o Amazonas foi o único estado com aumento na variação percentual anual média na taxa de incidência (3,2%; IC 95% [1,3; 5,1]) e na taxa de mortalidade (2,7%; IC 95% [1,0; 4,4]). Já o estado do Rio de Janeiro teve inflexão crescente na incidência de 2014 a 2019 (2,4%; IC 95% [1,4; 3,5]) e média anual de variação percentual decrescente (–3,5%; IC 95% [–5,0; –1,9]). Conclusões. Durante o período analisado, foi observada uma tendência decrescente na incidência entre 2011 e 2015 e crescente entre 2015 e 2019. Por outro lado, não foi encontrada nenhuma mudança na tendência de mortalidade no Brasil.

Treatment of drug-resistant tuberculosis in children and young adolescents in Brazil.

Introduction: Drug-resistant tuberculosis (DR-TB) is a global threat and a challenge for public health authorities worldwide. In children, the diagnosis is even more challenging and DR-TB is poorly described in the literature, as are its treatment outcomes. In this study, we aimed to describe the treatment of drug-resistant TB in children and young adolescents in Brazil. Methods: A descriptive epidemiological study of treatment for DR-TB in children under 15 years of age in Brazil between 2013 and 2020. The primary data source was the Information System for Special Tuberculosis Treatments (SITE-TB). Categorical variables were analyzed using relative frequencies (%) and continuous variables by measures of central tendency to characterize the profile of the cases, namely: sociodemographic, clinical characteristics, procedures, tests performed and treatment success. In order to verify the distribution of cases, a spatial analysis was carried out based on the municipality where the cases resided. Results: Between 2013 and 2020, 19,757 tuberculosis (TB) cases occurred in children aged <15 years in Brazil, and 46 cases of treatment for DR-TB were reported during the same period (annual average of 6 cases). Of these, 73.9% were aged 10-14, 65.2% were male, 4.3% were HIV+ and 43.3% were underweight (BMI<18.5) at the start of treatment. 17.4% had previous contact with TB, 69.6% had primary resistance, 47.8% multidrug resistance. The median duration of treatment was 15 months. DOT and standardized treatment regimen were performed in 52.2% of cases. Bacilloscopy was performed for 97.8% (57.8% positive); culture for 89.1% (75.6% positive), rapid molecular test for 73.9% with proven resistance to rifampicin in 55.8%. Susceptibility testing revealed resistance mainly to isoniazid (87.8%) and rifampicin (60.6%). 73.9% of cases were successfully treated and one death was reported. Cases were treated in 26 Brazilian municipalities, with the majority in Rio de Janeiro (15) and São Paulo (4). Conclusion: DR-TB treatment was recorded in <1% of general TB cases in children and young adolescents, suggesting underreporting of drug-resistant cases in the country. Despite the low number of registered cases, the data reflect the situation of DR-TB in this population and describe important aspects of the problem, as the child needs comprehensive, individualized care, with support from different professionals. We recommend a strengthening of the country's referral services for the care of children with DR-TB so that surveillance and health care services can work together to identify and follow up cases.

Factors associated with post-mortem notification of tuberculosis cases in Brazil, 2014. / Fatores associados à notificação pós-óbito de casos de tuberculose no Brasil, 2014.

According to the World Health Organization (WHO), 1.6 million deaths and 10.6 million cases of tuberculosis (TB) were reported worldwide in 2021. If treated opportunely with the recommended therapy, 85% of patients with TB are healed. The occurrence of death from TB without prior notification of the disease indicates failure in the timely access to this effective treatment. Therefore, this study aimed to identify TB cases with post-mortem notification in Brazil. This is a nested case-control study using a cohort of new TB cases reported to the Braziliam Information System for Notificable Diseases (SINAN). This study analyzed the following variables: selected characteristics of the individual (gender, age, race/color, education), the municipality (Municipality Human Development Index - M-HDI, poverty rate, size, region, and municipality), health services, and underlying or associated cause of death. Logistic regression was estimated using a hierarchical analysis model. People with TB aged 60 years or older (OR = 1.43), with low educational level (OR = 1.67), and with malnutrition (OR = 5.54), living in municipalities with low M-HDI and medium population size (OR = 1.26), located in the North Region of Brazil (OR = 2.42) had a higher chance of post-mortem notification. Protective factors were HIV-TB coinfection (OR = 0.75), malignant neoplasms (OR = 0.62), and living in cities with broad primary care coverage (OR = 0.79). Vulnerable populations should be prioritized in order to address the obstacles to the access to TB diagnosis and treatment in Brazil.

Segundo a Organização Mundial da Saúde (OMS), estima-se que 1,6 milhão de mortes e 10,6 milhões de casos de tuberculose (TB) ocorreram no mundo em 2021. Quando a doença é oportunamente tratada com o esquema terapêutico recomendado, 85% dos pacientes se curam. A ocorrência de óbito por TB sem notificação anterior denuncia falhas no acesso ao tratamento oportuno e efetivo. Sendo assim, este estudo objetivou caracterizar os casos de TB notificados pós-óbito no Brasil. Trata-se de estudo caso-controle aninhado na coorte de casos novos de TB notificados ao Sistema de Informação de Agravos de Notificação (SINAN). As variáveis analisadas foram: características selecionadas do indivíduo (sexo, idade, raça/cor, escolaridade), do município (Índice de Desenvolvimento Humano Municipal - IDH-M, taxa de pobreza, porte municipal, região e município), dos serviços de saúde e causa básica ou associada de morte. Foi estimada regressão logística respeitando um modelo de análise hierárquico. Pessoas com TB de 60 anos de idade ou mais (OR = 1,43), de baixa escolaridade (OR = 1,67), com desnutrição (OR = 5,54), residentes em municípios com baixo IDH-M, de porte populacional médio (OR = 1,26), na Região Norte (OR = 2,42) apresentaram maior chance de notificação pós-óbito. Fatores protetores foram coinfecção HIV-TB (OR = 0,75), neoplasias malignas (OR = 0,62) e residência em municípios com alta cobertura de atenção básica (OR = 0,79). A priorização das populações vulneráveis é necessária para enfrentar as dificuldades de acesso ao diagnóstico e tratamento da TB no Brasil.

La Organización Mundial de la Salud (OMS) estima que en 2021 se produjeron 1,6 millones de muertes por tuberculosis (TB) y 10,6 millones de casos de esta afección por todo el mundo. Si los pacientes siguen el tratamiento recomendado para la TB, un 85% logran la cura. Las muertes por TB sin notificación previa de caso indican fallas en el acceso a este tratamiento oportuno y efectivo. Por lo tanto, este estudio tuvo como objetivo caracterizar los casos de TB que tuvieron notificación posterior a la muerte en Brasil. Este es un estudio de caso-control anidado dentro de la cohorte de nuevos casos de TB informados al Sistema de Información de Enfermedades de Notificación Obligatoria (SINAN). Las siguientes variables fueron analizadas: características seleccionadas del individuo (sexo, edad, etnia/color, nivel de instrucción) y del municipio (Índice de Desarrollo Humano Municipal -IDH-M, tasa de pobreza, tamaño del municipio, región y municipio), servicios de salud y condiciones y causa de la muerte o su asociación. La regresión logística se estimó desde un modelo de análisis jerárquico. Las personas con TB de 60 años o más (OR = 1,43), con bajo nivel de instrucción (OR = 1,67), con desnutrición (OR = 5,54), residentes en municipios con bajo IDH-M, de tamaño poblacional medio (OR = 1,26) y en la Región Norte (OR = 2,42) tuvieron mayor probabilidad de notificación posterior a la muerte. Los factores protectores fueron la coinfección VIH-TB (OR = 0,75), neoplasias malignas (OR = 0,62) y vivir en ciudades con alta cobertura de atención primaria (OR = 0,79). Es necesario priorizar las poblaciones vulnerables para enfrentar las dificultades de acceso al diagnóstico y tratamiento de la TB en Brasil.

Trends in tuberculosis incidence and mortality coefficients in Brazil, 2011-2019: analysis by inflection points / Tendencias de los coeficientes de incidencia y mortalidad por tuberculosis en Brasil, 2011-2019: análisis por puntos de inflexión / Tendências nos coeficientes de incidência e mortalidade por tuberculose no Brasil, 2011-2019: análise por pontos de inflexão

ABSTRACT Objective. To analyze the temporal trend of tuberculosis incidence and mortality rates in Brazil between 2011 and 2019. Methods. This was an ecological time series study of tuberculosis incidence and mortality rates in Brazil between 2011 and 2019. Data were extracted from the Notifiable Disease Information System and the Mortality Information System, and population estimates were from the Brazilian Institute of Geography and Statistics. Trends were analyzed by Joinpoint regression, which recognizes inflection points for temporal analysis. Results. The average incidence rate of tuberculosis in Brazil in the period was 35.8 cases per 100 000 population. From 2011 to 2015, this coefficient had an annual percentage change of -1.9% (95% CI [-3.4, -0.5]) followed by an increase of 2.4% (95% CI [0.9, 3.9]) until 2019. The average mortality rate between 2011 and 2019 was 2.2 deaths per 100 000 population, with an average annual percentage change of -0.4% (95% CI [-1.0, 0.2]). Amazonas was the only state with an increase in the annual average percentage variation for the incidence rate (3.2%; 95% CI [1.3, 5.1]) and mortality rate (2.7%; 95% CI [1.0, 4.4]) over the years, while Rio de Janeiro state had an increasing inflection for incidence from 2014 to 2019 (2.4%; 95% CI [1.4, 3.5]) and annual average of decreasing percentage variation (-3.5%; 95% CI [-5.0, -1.9]). Conclusions. During the period analyzed, a decreasing trend in incidence was observed between 2011 and 2015, and an increasing trend for the period from 2015 to 2019. On the other hand, no change in the trend for mortality was found in Brazil.

RESUMEN Objetivo. Analizar la tendencia temporal de las tasas de incidencia y mortalidad por tuberculosis en Brasil entre el 2011 y el 2019. Métodos. Este fue un estudio ecológico de series temporales de las tasas de incidencia y mortalidad por tuberculosis en Brasil entre el 2011 y el 2019. Los datos se obtuvieron del Sistema de Información sobre Enfermedades de Notificación Obligatoria y del Sistema de Información sobre Mortalidad, y las estimaciones de población proceden del Instituto Brasileño de Geografía y Estadística. Las tendencias se analizaron mediante el programa de regresión Joinpoint, que reconoce los puntos de inflexión para el análisis temporal. Resultados. La tasa promedio de incidencia de tuberculosis en Brasil para el periodo fue de 35,8 casos por 100 000 habitantes. Entre el 2011 y el 2015, este coeficiente experimentó una variación porcentual anual del -1,9% (intervalo de confianza [IC] del 95% [-3,4, -0,5]), seguida por un aumento del 2,4% (IC 95% [0,9, 3,9]) hasta el 2019. La tasa de mortalidad promedio entre el 2011 y el 2019 fue de 2,2 muertes por cada 100 000 habitantes, con una variación porcentual promedio anual del -0,4% (IC del 95% [-1,0, 0,2]). El estado de Amazonas fue el único que a lo largo de los años presentó un aumento de la variación porcentual promedio anual de la tasa de incidencia (3,2%; IC del 95% [1,3, 5,1]) y de la tasa de mortalidad (2,7%; IC del 95% [1,0, 4,4]), en tanto que, entre el 2014 y el 2019, el estado de Río de Janeiro presentó una inflexión creciente de la incidencia (2,4%; IC del 95% [1,4, 3,5]) y una variación porcentual promedio anual decreciente (-3,5%; IC del 95% [-5,0, -1,9]). Conclusiones. Durante el periodo analizado, se observa una tendencia decreciente de la incidencia entre el 2011 y el 2015, y una tendencia creciente para el periodo comprendido entre el 2015 y el 2019. En cambio, no se encontró ningún cambio en la tendencia de la mortalidad en Brasil.

RESUMO Objetivo. Analisar a tendência temporal das taxas de incidência e mortalidade por tuberculose no Brasil entre 2011 e 2019. Métodos. Estudo ecológico de série temporal das taxas de incidência e mortalidade por tuberculose no Brasil entre 2011 e 2019. Os dados foram extraídos do Sistema de Informação de Agravos de Notificação e do Sistema de Informação sobre Mortalidade, e as estimativas populacionais foram obtidas do Instituto Brasileiro de Geografia e Estatística. As tendências foram analisadas por regressão joinpoint, que reconhece pontos de inflexão para análise temporal. Resultados. A taxa média de incidência da tuberculose no Brasil no período foi de 35,8 casos por 100 mil habitantes. O coeficiente teve uma variação percentual anual de -1,9% (IC 95% [-3,4; -0,5]) de 2011 a 2015, seguida de um aumento de 2,4% (IC 95% [0,9; 3,9]) até 2019. A taxa média de mortalidade entre 2011 e 2019 foi de 2,2 óbitos por 100 mil habitantes, com uma variação percentual anual média de -0,4% (IC 95% [-1,0; 0,2]). Ao longo dos anos, o Amazonas foi o único estado com aumento na variação percentual anual média na taxa de incidência (3,2%; IC 95% [1,3; 5,1]) e na taxa de mortalidade (2,7%; IC 95% [1,0; 4,4]). Já o estado do Rio de Janeiro teve inflexão crescente na incidência de 2014 a 2019 (2,4%; IC 95% [1,4; 3,5]) e média anual de variação percentual decrescente (-3,5%; IC 95% [-5,0; -1,9]). Conclusões. Durante o período analisado, foi observada uma tendência decrescente na incidência entre 2011 e 2015 e crescente entre 2015 e 2019. Por outro lado, não foi encontrada nenhuma mudança na tendência de mortalidade no Brasil.

Fatores associados à notificação pós-óbito de casos de tuberculose no Brasil, 2014 / Factores asociados a la notificación posterior a la muerte por casos de tuberculosis en Brasil, 2014 / Factors associated with post-mortem notification of tuberculosis cases in Brazil, 2014

Resumo: Segundo a Organização Mundial da Saúde (OMS), estima-se que 1,6 milhão de mortes e 10,6 milhões de casos de tuberculose (TB) ocorreram no mundo em 2021. Quando a doença é oportunamente tratada com o esquema terapêutico recomendado, 85% dos pacientes se curam. A ocorrência de óbito por TB sem notificação anterior denuncia falhas no acesso ao tratamento oportuno e efetivo. Sendo assim, este estudo objetivou caracterizar os casos de TB notificados pós-óbito no Brasil. Trata-se de estudo caso-controle aninhado na coorte de casos novos de TB notificados ao Sistema de Informação de Agravos de Notificação (SINAN). As variáveis analisadas foram: características selecionadas do indivíduo (sexo, idade, raça/cor, escolaridade), do município (Índice de Desenvolvimento Humano Municipal - IDH-M, taxa de pobreza, porte municipal, região e município), dos serviços de saúde e causa básica ou associada de morte. Foi estimada regressão logística respeitando um modelo de análise hierárquico. Pessoas com TB de 60 anos de idade ou mais (OR = 1,43), de baixa escolaridade (OR = 1,67), com desnutrição (OR = 5,54), residentes em municípios com baixo IDH-M, de porte populacional médio (OR = 1,26), na Região Norte (OR = 2,42) apresentaram maior chance de notificação pós-óbito. Fatores protetores foram coinfecção HIV-TB (OR = 0,75), neoplasias malignas (OR = 0,62) e residência em municípios com alta cobertura de atenção básica (OR = 0,79). A priorização das populações vulneráveis é necessária para enfrentar as dificuldades de acesso ao diagnóstico e tratamento da TB no Brasil.

Resumen: La Organización Mundial de la Salud (OMS) estima que en 2021 se produjeron 1,6 millones de muertes por tuberculosis (TB) y 10,6 millones de casos de esta afección por todo el mundo. Si los pacientes siguen el tratamiento recomendado para la TB, un 85% logran la cura. Las muertes por TB sin notificación previa de caso indican fallas en el acceso a este tratamiento oportuno y efectivo. Por lo tanto, este estudio tuvo como objetivo caracterizar los casos de TB que tuvieron notificación posterior a la muerte en Brasil. Este es un estudio de caso-control anidado dentro de la cohorte de nuevos casos de TB informados al Sistema de Información de Enfermedades de Notificación Obligatoria (SINAN). Las siguientes variables fueron analizadas: características seleccionadas del individuo (sexo, edad, etnia/color, nivel de instrucción) y del municipio (Índice de Desarrollo Humano Municipal -IDH-M, tasa de pobreza, tamaño del municipio, región y municipio), servicios de salud y condiciones y causa de la muerte o su asociación. La regresión logística se estimó desde un modelo de análisis jerárquico. Las personas con TB de 60 años o más (OR = 1,43), con bajo nivel de instrucción (OR = 1,67), con desnutrición (OR = 5,54), residentes en municipios con bajo IDH-M, de tamaño poblacional medio (OR = 1,26) y en la Región Norte (OR = 2,42) tuvieron mayor probabilidad de notificación posterior a la muerte. Los factores protectores fueron la coinfección VIH-TB (OR = 0,75), neoplasias malignas (OR = 0,62) y vivir en ciudades con alta cobertura de atención primaria (OR = 0,79). Es necesario priorizar las poblaciones vulnerables para enfrentar las dificultades de acceso al diagnóstico y tratamiento de la TB en Brasil.

Abstract: According to the World Health Organization (WHO), 1.6 million deaths and 10.6 million cases of tuberculosis (TB) were reported worldwide in 2021. If treated opportunely with the recommended therapy, 85% of patients with TB are healed. The occurrence of death from TB without prior notification of the disease indicates failure in the timely access to this effective treatment. Therefore, this study aimed to identify TB cases with post-mortem notification in Brazil. This is a nested case-control study using a cohort of new TB cases reported to the Braziliam Information System for Notificable Diseases (SINAN). This study analyzed the following variables: selected characteristics of the individual (gender, age, race/color, education), the municipality (Municipality Human Development Index - M-HDI, poverty rate, size, region, and municipality), health services, and underlying or associated cause of death. Logistic regression was estimated using a hierarchical analysis model. People with TB aged 60 years or older (OR = 1.43), with low educational level (OR = 1.67), and with malnutrition (OR = 5.54), living in municipalities with low M-HDI and medium population size (OR = 1.26), located in the North Region of Brazil (OR = 2.42) had a higher chance of post-mortem notification. Protective factors were HIV-TB coinfection (OR = 0.75), malignant neoplasms (OR = 0.62), and living in cities with broad primary care coverage (OR = 0.79). Vulnerable populations should be prioritized in order to address the obstacles to the access to TB diagnosis and treatment in Brazil.

Excess tuberculosis cases and deaths following an economic recession in Brazil: an analysis of nationally representative disease registry data.

BACKGROUND: In 2019, tuberculosis incidence and mortality in Brazil were 46 and 3·3 per 100 000 population, respectively, and the country has reported rising tuberculosis case rates since 2016, following an economic crisis beginning in mid-2014. We aimed to estimate the number of excess tuberculosis cases and deaths during the recession period, and assessed potential causes. METHODS: In this multi-level regression modelling study, we extracted tuberculosis case notifications from Brazil's National Notifiable Disease Information System (known as SINAN), and tuberculosis deaths from the Mortality Information System (known as SIM), for all ages. We fitted mixed-effects regression models estimating trends in these outcomes-stratified by sex, age group, and state-during the pre-recession period (Jan 1, 2010-Dec 31, 2014). We calculated excess cases and deaths between Jan 1, 2015, and Dec 31, 2019 (the recession period) as the difference between reported values and a counterfactual of continued pre-recession trends. We examined the relationship between excess cases and possible explanatory factors using ordinary least squares regression. We tested the robustness of our findings to alternative model specifications related to the pre-recession period and criteria for defining tuberculosis deaths. FINDINGS: We estimated 22 900 excess tuberculosis cases (95% uncertainty interval 18 100-27 500) during 2015-19. By 2019, reported cases were 12% (10-13) higher than predicted by historical trends. 54% (44-66) of excess cases occurred among 20-29-year-old men. In this group, reported cases in 2019 were 30% (25-36) higher than predicted. Excess cases were positively associated with an increasing fraction of cases among incarcerated individuals (p=0·001) and higher unemployment (p=0·04) at the state level. Estimated excess deaths for 2015-19 were not statistically significant from 0 (-600 [-2100 to 1000]). These results were robust to alternative definitions of the pre-recession period and criteria for defining tuberculosis deaths. INTERPRETATION: Tuberculosis cases in Brazil rose substantially in 2015-19 during the recession, largely affecting young men. This increase seems to be linked to increasing tuberculosis transmission among incarcerated populations. Rising tuberculosis case rates threaten tuberculosis control in Brazil, and highlight the threat posed by prison-based tuberculosis transmission. FUNDING: US National Institutes of Health. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Environmental factors associated with the time to tuberculosis diagnosis in prisoners in São Paulo, Brazil.

BACKGROUND: Environmental conditions play an important role in the high incidence of tuberculosis in prisons. We estimated the effect of environmental factors, including measurements based on cell dimensions, on the time to tuberculosis diagnosis in prison population of Brazil. METHODS: This is a retrospective cohort of 2,257 prisoners diagnosed with tuberculosis in 2014 and 2015. We collected environmental data from 105 prisons and linked with routine tuberculosis surveillance and prison data. We estimated tuberculosis-free survival time with Cox risk models, guided by a validated directed acyclic graph. RESULTS: The median disease-free time was 1.71 years (95% confidence interval [95% CI] 1.64-1.78). Each 50% increase in occupancy-rate, increased the tuberculosis speed incidence by 16% (95% CI 8%-25%) in the first 2 years, and 9% (95% CI 3%-16%) up to 5 years. An increase in the cell area per person (ln[m2/person]) reduced the hazard of tuberculosis by 13% (95% CI 3%-23%) for up to 2, and 12% (95% CI 3%-21%) for up to 5 years. DISCUSSION: Most tuberculosis cases were diagnosed within 2 years of incarceration. Prison overcrowding and physical space per person in the cell were associated with the tuberculosis-free disease time. CONCLUSIONS: Interventions to reduce overcrowding or increase physical space are crucial to prevent tuberculosis in prisons.

Brazilian cohort study of risk factors associated with unsuccessful outcomes of drug resistant tuberculosis.

BACKGROUND: Treatment outcomes were evaluated of a cohort of new pulmonary tuberculosis (TB) cases that were rifampicin resistant, multidrug-resistant, or extensively resistant during 2013 and 2014 in Brazil. The objective of this study is to identify factors associated with unfavorable treatment outcomes for drug-resistant TB cases. METHODS: The Brazilian Special Tuberculosis Treatment Information System (SITE-TB) was the main data source. The independent variables were classified into four blocks (block I: individual characteristics; block II: clinical characteristics and proposed treatment; block III: treatment follow-up characteristics; and block IV: TB history). The category of successful therapeutic outcome was compared with lost to follow-up, failure, and death. Considering the multiple outcomes as the dependent variable, the odds ratios (OR) and its respective 95% confidence interval (95% CI) were estimated by multinomial logistic regression. RESULTS: After applying the exclusion criteria, 980 (98.8%) individuals were included in the study. Of these, 621 (63.4%) had successful treatment, 163 (16.6%) lost to follow-up, 76 (7.8%) failed, and 120 (12.2%) died. Important factors associated with lost to follow-up in the final model included use of illicit drugs (OR = 2.5 95% CI: 1.57-3.82). Outcome failure was associated with having disease in both lungs (OR = 2.0; 95% CI: 1.09-3.62) and using more than one or not using injectable medication (OR = 2.8; 95% CI: 1.05-7.69). Major factors for the death outcome were at least 60 years old (OR = 3.4; 95% CI: 1.90-6.03) and HIV positive (OR = 2.7; 95% CI: 1.45-4.83). CONCLUSIONS: The factors associated with unfavorable treatment outcomes were different. Some of these factors are specific to each outcome, which reflects the complexity of providing care to these individuals.

Factors Associated with Unsuccessful Outcomes of Tuberculosis Treatment in 125 Municipalities in Colombia 2014 to 2016.

Our aim was to identify the risk factors associated with unsuccessful outcomes of tuberculosis (TB) treatment in patients diagnosed between 2014 and 2016 in the 125 municipalities of Antioquia, Colombia. We studied a retrospective cohort of patients with TB diagnosed between 2014 and 2016, from national routine surveillance systems, in 125 municipalities of Antioquia. Factors associated with unsuccessful tuberculosis treatment outcomes (treatment failed, lost to follow up, or death) were identified utilizing a Poisson regression with robust variance. Over 3 years, of the 6,739 drug-susceptible tuberculosis patients, 73.4% had successful treatment and 26.6% unsuccessful outcomes (17% lost to follow up, 8.9% deaths, and 0.7% treatment failures). Patients with subsidized health insurance (Relative risk [RR]: 2.4; 95% CI: 2.1-2.8) and without health insurance (RR: 2.5; 95% CI: 2.1-3.0) had a higher risk for unsuccessful tuberculosis treatment compared to those with contributive health insurance. Other risk factors included age over 15 years, male sex, homelessness, people living with HIV, previous treatment, and primary diagnosis during hospitalization. Protective factors were living in a rural area and extrapulmonary disease. It is important to generate strategies that improves tuberculosis diagnosis in primary healthcare institutions. In addition, it is imperative to initiate new research about the barriers and obstacles related to patients, healthcare workers and services, and the health system, including the analysis of urban violence, to understand why the goal of TB treatment success has not been reached.

Bayesian evidence synthesis to estimate subnational TB incidence: An application in Brazil.

BACKGROUND: Evidence on local disease burden and the completeness of case detection represent important information for TB control programs. We present a new method for estimating subnational TB incidence and the fraction of individuals with incident TB who are diagnosed and treated in Brazil. METHODS: We compiled data on TB notifications and TB-related mortality in Brazil and specified an analytic model approximating incidence as the number of individuals exiting untreated active disease (sum of treatment initiation, death before treatment, and self-cure). We employed a Bayesian inference approach to synthesize data and adjust for known sources of bias. We estimated TB incidence and the fraction of cases treated, for each Brazilian state and the Federal District over 2008-2017. FINDINGS: For 2017, TB incidence was estimated as 41.5 (95 % interval: 40.7, 42.5) per 100 000 nationally, and ranged from 11.7-88.3 per 100 000 across states. The fraction of cases treated was estimated as 91.9 % (89.6 %, 93.7 %) nationally and ranged 86.0 %-94.8 % across states, with an estimated 6.9 (5.3, 9.2) thousand cases going untreated in 2017. Over 2008-2017, incidence declined at an average annual rate of 1.4 % (1.1 %, 1.9 %) nationally, and -1.1%-4.2 % across states. Over this period there was a 0.5 % (0.2 %, 0.9 %) average annual increase in the fraction of incident TB cases treated. INTERPRETATION: Time-series estimates of TB burden and the fraction of cases treated can be derived from routinely-collected data and used to understand variation in TB outcomes and trends.

Trends in Untreated Tuberculosis in Large Municipalities, Brazil, 2008-2017.

We adapted a mathematical modeling approach to estimate tuberculosis (TB) incidence and fraction treated for 101 municipalities of Brazil during 2008-2017. We found the average TB incidence rate decreased annually (0.95%), and fraction treated increased (0.30%). We estimated that 9% of persons with TB did not receive treatment in 2017.

Regional coordinators of Sao Paulo State prisons in tuberculosis and HIV coinfection care.

OBJECTIVES: to analyze the care provided to individuals with Tuberculosis (TB)-HIV coinfection in prison units in the state of São Paulo, according to the regional coordination of prisons. METHODS: cross-sectional study conducted between 2016 and 2018. A structured questionnaire was applied to 112 directors or health professionals from 168 prison units. Data were analyzed by frequency distribution and multiple correspondence analysis. RESULTS: 92.9% of participants reported active search for respiratory symptoms, 89.3% offer the directly observed treatment (DOT) for all TB cases, 95.5% anti-HIV testing for all inmates, 92.9% offer HIV follow-up in specialized care services and 59.8% antiretroviral drugs for cases of coinfection. An association was identified between the Northwest and Central regional coordinations and deficient human resources and low performance of actions for the diagnosis and follow-up of cases. CONCLUSIONS: although most prison units perform planned actions for the care of coinfected persons, some places need support to guarantee access to these actions.

Comparação de diferentes comprimentos de onda do laser de baixa potência no sóleo de ratos Wistar após lesão nervosa / Comparación entre diferentes longitudes de onda de láser de baja potencia en el sóleo de ratas Wistar tras lesión nerviosa / Comparison of different low-level laser therapy wavelengths in the soleus of Wistar rats after nerve injury

RESUMO Os músculos esqueléticos podem ser afetados por lesões do sistema nervoso periférico, levando a fraqueza e atrofia muscular. Na tentativa de recuperar a funcionalidade dos músculos, existem vários recursos terapêuticos utilizados, dentre os quais o laser de baixa potência (LBP). Este estudo comparou o efeito do LBP em dois comprimentos de onda (660 nm e 830 nm), em características morfológicas do tecido muscular após axonotmese de nervos isquiáticos de ratos Wistar. Para tanto, foram utilizados 32 ratos Wistar, divididos em quatro grupos, sendo G1 (controle), G2 (lesão), G3 (lesão e tratamento com LBP de 660 nm) e G4 (lesão e tratamento com LBP de 830 nm). Os animais de G2, G3 e G4 foram submetidos à lesão do nervo isquiático e, três dias após a lesão, G3 e G4 realizaram tratamento com LBP de 660 nm e 830 nm, respectivamente. Após o tratamento, todos os animais foram eutanasiados e os músculos sóleos coletados para confecção das lâminas histológicas, visando a realização de análises morfológicas do tecido. Constatou-se que os animais submetidos à lesão sofreram alterações morfológicas na fibra, resultando em sua atrofia. Foi percebido também que o LBP com comprimento de onda de 830 nm apresentou ligeiros sinais de recuperação das características morfométricas analisadas.

RESUMEN Las lesiones en el sistema nervioso periférico pueden afectar los músculos esqueléticos y provocar debilidad y atrofia muscular. Para recuperar la funcionalidad de los músculos, se utilizan varios recursos terapéuticos, entre los cuales el láser de baja potencia (LBP). Este estudio comparó el efecto del LBP en dos longitudes de onda (660 nm y 830 nm) sobre las características morfológicas del tejido muscular después de la axonotmesis de los nervios ciáticos en ratas Wistar. Para ello, se utilizaron 32 ratas Wistar, divididas en cuatro grupos: G1 (control), G2 (lesión), G3 (lesión y tratamiento con LBP de 660 nm) y G4 (lesión y tratamiento con LBP de 830 nm). Los animales de G2, G3 y G4 se sometieron a lesión del nervio ciático y, tres días después de la lesión, el G3 y G4 se sometieron al tratamiento con LBP de 660 nm y 830 nm, respectivamente. Después del tratamiento, todos los animales fueron sacrificados y se recogieron los músculos sóleos para la preparación de placas histológicas, con el fin de realizar análisis morfológicos del tejido. Se encontró que los animales sometidos a lesión sufrieron cambios morfológicos en la fibra, lo que resultó en atrofia. También se observó que el LBP con la longitud de onda de 830 nm presentó leves signos de recuperación de las características morfométricas analizadas.

ABSTRACT Skeletal muscles may be affected by peripheral nervous system injuries, leading to muscle weakness and atrophy. Several therapeutic resources may be used in the attempt to recover the functionality of muscles, such as low-level laser therapy (LLLT). This study compared the effect of LLLT of two wavelengths (660 nm and 830 nm) on morphological characteristics of muscle tissue after axonotmesis of ischiatic nerves of Wistar rats. A total of 32 Wistar rats were divided into four groups: G1 (control), G2 (injury), G3 (injury and treatment with 660 nm LLLT) and G4 (injury and treatment with 830 nm LLLT). G2, G3, and G4 animals were submitted to sciatic nerve damage and, three days after the injury, G3 and G4 were treated with LLLT of 660 nm and 830 nm, respectively. After the treatment, all animals were euthanized, and the soles muscles were collected to perform morphological analyzes of the tissue using histological slides. We verified that animals submitted to the lesion underwent morphological changes in the fiber, resulting in their atrophy. We also noticed that LLLT with a wavelength of 830 nm presented slight signs of recovery of the morphometric characteristics analyzed.

[Gaps in drug-resistant tuberculosis surveillance: probabilistic database linkage in Brazil]. / Lacunas na vigilância da tuberculose drogarresistente: relacionando sistemas de informação do Brasil.

The study aimed to assess the coverage and reliability of drug-resistant tuberculosis (DR-TB) case closure in the Information System on Special Treatments for Tuberculosis (SITE-TB in Portuguese) in Brazil from 2013 to 2016, based on probabilistic linkage with the Information System on Diseases of Notification (SINAN), Laboratory Environment Manager (GAL), and Mortality Information System (SIM). The study population consisted of DR-TB cases that initiated treatment from 2013 to 2016 in Brazil. Linkage with SINAN assessed the coverage and estimated underreporting of DR-TB cases. The capture-recapture method was applied, using the Chapman estimator. Linkage with GAL identified cases diagnosed by the laboratory that had not been reported to SITE-TB. Linkage with SIM assessed the reliability of case closure by death in SITE-TB, using the kappa coefficient. We estimated a population of 2,945 (95%CI: 2,365-3,602) new cases of DR-TB with the Chapman estimator. We located 1,626 individuals in the GAL database that had not been reported to SITE-TB, even with laboratory confirmation of drug resistance. PABAK (prevalance and bias adjusted kappa) of 0.86 (95%CI: 0.85-0.87) was classified as excellent for the agreement in death as the outcome between the SITE-TB and SIM databases. The results pointed to persistent gaps related to diagnosis and treatment of DR-TB in Brazil. Underreporting of DR-TB cases in the SITE-TB database poses a challenge for TB control. Identification of these individuals and early start of treatment should be prioritized in health services.