Mass incarceration as a driver of the tuberculosis epidemic in Latin America and projected effects of policy alternatives: a mathematical modelling study.

BACKGROUND: Tuberculosis incidence is increasing in Latin America, where the incarcerated population has nearly quadrupled since 1990. We aimed to quantify the impact of historical and future incarceration policies on the tuberculosis epidemic, accounting for effects in and beyond prisons. METHODS: In this modelling study, we calibrated dynamic compartmental transmission models to historical and contemporary data from Argentina, Brazil, Colombia, El Salvador, Mexico, and Peru, which comprise approximately 80% of the region's incarcerated population and tuberculosis burden. The model was fit independently for each country to incarceration and tuberculosis data from 1990 to 2023 (specific dates were country dependent). The model does not include HIV, drug resistance, gender or sex, or age structure. Using historical counterfactual scenarios, we estimated the transmission population attributable fraction (tPAF) for incarceration and the excess population-level burden attributable to increasing incarceration prevalence since 1990. We additionally projected the effect of alternative incarceration policies on future population tuberculosis incidence. FINDINGS: Population tuberculosis incidence in 2019 was 29·4% (95% uncertainty interval [UI] 23·9-36·8) higher than expected without the rise in incarceration since 1990, corresponding to 34 393 (28 295-42 579) excess incident cases across countries. The incarceration tPAF in 2019 was 27·2% (20·9-35·8), exceeding estimates for other risk factors like HIV, alcohol use disorder, and undernutrition. Compared with a scenario where incarceration rates remain stable at current levels, a gradual 50% reduction in prison admissions and duration of incarceration by 2034 would reduce population tuberculosis incidence by over 10% in all countries except Mexico. INTERPRETATION: The historical rise in incarceration in Latin America has resulted in a large excess tuberculosis burden that has been under-recognised to date. International health agencies, ministries of justice, and national tuberculosis programmes should collaborate to address this health crisis with comprehensive strategies, including decarceration. FUNDING: National Institutes of Health.

Cost-effectiveness and health impact of screening and treatment of Mycobacterium tuberculosis infection among formerly incarcerated individuals in Brazil: a Markov modelling study.

BACKGROUND: Individuals who were formerly incarcerated have high tuberculosis incidence, but are generally not considered among the risk groups eligible for tuberculosis prevention. We investigated the potential health impact and cost-effectiveness of Mycobacterium tuberculosis infection screening and tuberculosis preventive treatment (TPT) for individuals who were formerly incarcerated in Brazil. METHODS: Using published evidence for Brazil, we constructed a Markov state transition model estimating tuberculosis-related health outcomes and costs among individuals who were formerly incarcerated, by simulating transitions between health states over time. The analysis compared tuberculosis infection screening and TPT, to no screening, considering a combination of M tuberculosis infection tests and TPT regimens. We quantified health effects as reductions in tuberculosis cases, tuberculosis deaths, and disability-adjusted life-years (DALYs). We assessed costs from a tuberculosis programme perspective. We report intervention cost-effectiveness as the incremental costs per DALY averted, and tested how results changed across subgroups of the target population. FINDINGS: Compared with no intervention, an intervention incorporating tuberculin skin testing and treatment with 3 months of isoniazid and rifapentine would avert 31 (95% uncertainty interval 14-56) lifetime tuberculosis cases and 4·1 (1·4-5·8) lifetime tuberculosis deaths per 1000 individuals, and cost US$242 per DALY averted. All test and regimen combinations were cost-effective compared with no screening. Younger age, longer incarceration, and more recent prison release were each associated with significantly greater health benefits and more favourable cost-effectiveness ratios, although the intervention was cost-effective for all subgroups examined. INTERPRETATION: M tuberculosis infection screening and TPT for individuals who were formerly incarcerated appears cost-effective, and would provide valuable health gains. FUNDING: National Institutes of Health. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Mass incarceration as a driver of the tuberculosis epidemic in Latin America and projected impacts of policy alternatives: A mathematical modeling study.

Background: Tuberculosis incidence is increasing in Latin America, where the incarcerated population has nearly quadrupled since 1990. The full impact of incarceration on the tuberculosis epidemic, accounting for effects beyond prisons, has never been quantified. Methods: We calibrated dynamic compartmental transmission models to historical and contemporary data from Argentina, Brazil, Colombia, El Salvador, Mexico, and Peru, which comprise approximately 80% of the region's incarcerated population and tuberculosis burden. Using historical counterfactual scenarios, we estimated the transmission population attributable fraction (tPAF) for incarceration and the excess population-level burden attributable to increasing incarceration prevalence since 1990. We additionally projected the impact of alternative incarceration policies on future population tuberculosis incidence. Findings: Population tuberculosis incidence in 2019 was 29.4% (95% UI, 23.9-36.8) higher than expected without the rise in incarceration since 1990, corresponding to 34,393 (95% UI, 28,295-42,579) excess incident cases across countries. The incarceration tPAF in 2019 was 27.2% (95% UI, 20.9-35.8), exceeding estimates for other risk factors like HIV, alcohol use disorder, and undernutrition. Compared to a scenario where incarceration rates remain stable at current levels, a gradual 50% reduction in prison admissions and duration of incarceration by 2034 would reduce population tuberculosis incidence by over 10% in all countries except Mexico. Interpretation: The historical rise in incarceration in Latin America has resulted in a large excess tuberculosis burden that has been under-recognized to-date. International health agencies, ministries of justice, and national tuberculosis programs should collaborate to address this health crisis with comprehensive strategies, including decarceration. Funding: National Institutes of Health.

Predictors of unsuccessful tuberculosis treatment outcomes in Brazil: an analysis of 259,484 patient records.

INTRODUCTION: Tuberculosis (TB) causes over 1 million deaths annually. Providing effective treatment is a key strategy for reducing TB deaths. In this study, we identified factors associated with unsuccessful treatment outcomes among individuals treated for TB in Brazil. METHODS: We obtained data on individuals treated for TB between 2015 and 2018 from Brazil's National Disease Notification System (SINAN). We excluded patients with a history of prior TB disease or with diagnosed TB drug resistance. We extracted information on patient-level factors potentially associated with unsuccessful treatment, including demographic and social factors, comorbid health conditions, health-related behaviors, health system level at which care was provided, use of directly observed therapy (DOT), and clinical examination results. We categorized treatment outcomes as successful (cure, completed) or unsuccessful (death, regimen failure, loss to follow-up). We fit multivariate logistic regression models to identify factors associated with unsuccessful treatment. RESULTS: Among 259,484 individuals treated for drug susceptible TB, 19.7% experienced an unsuccessful treatment outcome (death during treatment 7.8%, regimen failure 0.1%, loss to follow-up 11.9%). The odds of unsuccessful treatment were higher with older age (adjusted odds ratio (aOR) 2.90 [95% confidence interval: 2.62-3.21] for 85-100-year-olds vs. 25-34-year-olds), male sex (aOR 1.28 [1.25-1.32], vs. female sex), Black race (aOR 1.23 [1.19-1.28], vs. White race), no education (aOR 2.03 [1.91-2.17], vs. complete high school education), HIV infection (aOR 2.72 [2.63-2.81], vs. no HIV infection), illicit drug use (aOR 1.95 [1.88-2.01], vs. no illicit drug use), alcohol consumption (aOR 1.46 [1.41-1.50], vs. no alcohol consumption), smoking (aOR 1.20 [1.16-1.23], vs. non-smoking), homelessness (aOR 3.12 [2.95-3.31], vs. no homelessness), and immigrant status (aOR 1.27 [1.11-1.45], vs. non-immigrants). Treatment was more likely to be unsuccessful for individuals treated in tertiary care (aOR 2.20 [2.14-2.27], vs. primary care), and for patients not receiving DOT (aOR 2.35 [2.29-2.41], vs. receiving DOT). CONCLUSION: The risk of unsuccessful TB treatment varied systematically according to individual and service-related factors. Concentrating clinical attention on individuals with a high risk of poor treatment outcomes could improve the overall effectiveness of TB treatment in Brazil.

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.

Time until tuberculosis recurrence and associated factors in Brazil: a population-based retrospective cohort study using a linked database / Tempo até a recorrência da tuberculose e fatores associados no Brasil: um estudo de coorte retrospectiva de base populacional usando dados de linkage

ABSTRACT 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.

RESUMO Objetivo: Calcular a taxa de recorrência de tuberculose, estimar seu tempo médio e identificar seus fatores associados no Brasil. Métodos: Estudo de coorte retrospectiva com dados de linkage do Sistema de Informação de Agravos de Notificação. Incluímos pessoas diagnosticadas com tuberculose em 2015, com foco naquelas que tiveram sua primeira recorrência em 6,5 anos. Estimamos o risco relativo (RR) e seus intervalos de confiança de 95% (IC95%), assim como a fração atribuível populacional (FAP) ou a fração prevenível populacional (FPP) dos fatores associados. Resultados: No período de 6,5 anos, 3.253 indivíduos (6,5%) tiveram recorrência de tuberculose, com tempo médio de 2,2 anos. Fatores positivamente associados incluíram: sexo masculino (RR: 1,4; IC95% 1,3-1,5; FAP: 22,9%), idade de 30 a 59 anos (RR: 3,0; IC95% 1,6-5,7; FAP: 36,0%), raça/cor preta (RR: 1,3; IC95% 1,2-1,5; FAP: 3,5%) ou raça/cor parda (RR: 1,3; IC95% 1,2-1,4; FAP: 10,6%), privação de liberdade (RR: 1,9; IC95% 1,7-2,1; FAP: 9,1%), forma clínica pulmonar/mista (RR: 1,7; IC95% 1,4-1,9; FAP: 37,1%), diagnóstico de síndrome da imunodeficiência adquirida (RR: 1,8; IC95% 1,5-1,9; FAP: 4,3%) e uso de álcool (RR: 1,2; IC95% 1,1-1,3; FAP: 2,9%). Fatores negativamente associados foram: 12 ou mais anos de estudo (RR: 0,5; IC95% 0,4-0,6; FPP: 3,3%) e tratamento supervisionado (RR: 0,9; IC95% 0,8-0,9; FPP: 4,4%). Conclusão: Revelamos taxas elevadas de recorrência de tuberculose no Brasil, com fatores sociodemográficos, comportamentais e sociais influenciando na recorrência da doença.

Clusters of heterogeneity of tuberculosis-HIV coinfection in Brazil: a geospatial study / Clusters da heterogeneidade da coinfecção tuberculose-HIV no Brasil: um estudo geoespacial

ABSTRACT 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.

RESUMO OBJETIVO Analisar a geoespacialização da coinfecção tuberculose-HIV no Brasil, de 2010 a 2021, e a correlação com indicadores socioeconômicos, habitacionais e sanitários. MÉTODOS Estudo ecológico dos municípios e estados brasileiros, com dados dos sistemas de informação do HIV e da tuberculose, previamente relacionados pelo Ministério da Saúde. Foram calculados os coeficientes brutos e suavizados pelo método bayesiano empírico local de incidência da coinfecção, por 100 mil habitantes, na população entre 18 e 59 anos. Empregaram-se os índices de Moran univariado (identificação de clusters) e bivariado (correlação com 20 indicadores). RESULTADOS Foram registrados 122.223 casos de coinfecção no Brasil, de 2010 a 2021, com coeficiente médio de 8,30/100 mil. As regiões Sul (11,44/100 mil) e Norte (9,93/100 mil) concentraram a maior carga das infecções. Houve queda dos coeficientes no Brasil, em todas as regiões, nos anos de covid-19 (2020 e 2021). Os maiores coeficientes foram visualizados nos municípios do Rio Grande do Sul, do Mato Grosso do Sul e do Amazonas, com aglomerados alto-alto nas capitais, em regiões de fronteira e no litoral do país. Os municípios pertencentes aos estados de Minas Gerais, da Bahia, do Paraná e do Piauí apresentaram clusters baixo-baixo. Houve correlação direta com os índices de desenvolvimento humano e as taxas de aids, bem como indireta com a proporção de pobres ou vulneráveis à pobreza e o índice de Gini. CONCLUSÕES A análise espacial da coinfecção tuberculose-HIV demonstrou heterogeneidade no território brasileiro e comportamento constante ao longo do período, revelando clusters com municípios de alta carga, principalmente nos grandes centros urbanos e nos estados com ocorrência elevada do HIV e/ou da tuberculose. Esses achados, além de trazerem um alerta para os efeitos da pandemia da covid-19, podem incorporar o planejamento estratégico para o controle da coinfecção, visando à eliminação dessas infecções como problemas de saúde pública até 2030.

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.

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.

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.

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.

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.