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.

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.

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.

The economic burden of households affected by tuberculosis in Brazil: First national survey results, 2019-2021.

BACKGROUND: One of the three main targets of the World Health Organization (WHO) End TB Strategy (2015-2035) is that no tuberculosis (TB) patients or their households face catastrophic costs (defined as exceeding 20% of the annual household income) because of the disease. Our study seeks to determine, as a baseline, the magnitude and main drivers of the costs associated with TB disease for patients and their households and to monitor the proportion of households experiencing catastrophic costs in Brazil. METHODS: A national cross-sectional cluster-based survey was conducted in Brazil in 2019-2021 following WHO methodology. TB patients of all ages and types of TB were eligible for the survey. Adult TB patients and guardians of minors (<18 years old) were interviewed once about costs, time loss, coping measures, income, household expenses, and asset ownership. Total costs, including indirect costs measured as reported household income change, were expressed as a percentage of annual household income. We used descriptive statistics to analyze the cost drivers and multivariate logistic regression to determine factors associated with catastrophic costs. RESULTS: We interviewed 603 patients, including 538 (89%) with drug-sensitive (DS) and 65 (11%) with drug-resistant (DR) TB. Of 603 affected households, 48.1% (95%CI: 43-53.2) experienced costs above 20% of their annual household income during their TB episode. The proportion was 44.4% and 78.5% among patients with DS- and DR-TB, respectively. On average, patients incurred costs of US$1573 (95%CI: 1361.8-1785.0) per TB episode, including pre-diagnosis and post-diagnosis expenses. Key cost drivers were post-diagnosis nutritional supplements (US$317.6, 95%CI: 232.7-402.6) followed by medical costs (US$85.5, 95%CI: 54.3-116.5) and costs of travel for clinic visits during treatment (US$79.2, 95%CI: 61.9-96.5). In multivariate analysis, predictors of catastrophic costs included positive HIV status (aOR = 3.0, 95%CI:1.1-8.6) and self-employment (aOR = 2.7, 95%CI:1.1-6.5); high education was a protective factor (aOR = 0.1, 95%CI:0.0-0.9). CONCLUSIONS: Although the services offered to patients with TB are free of charge in the Brazilian public health sector, the availability of free diagnosis and treatment services does not alleviate patients' financial burden related to accessing TB care. The study allowed us to identify the costs incurred by patients and suggest actions to mitigate their suffering. In addition, this study established a baseline for monitoring catastrophic costs and fostering a national policy to reduce the costs to patients for TB care in Brazil.

Migration and medical screening for tuberculosis.

Vulnerable populations, such as migrants and refugees, have an increased risk of tuberculosis disease, especially in the first years after arrival in the host country. The presence of migrants and refugees in Brazil exponentially grew over the period between 2011 and 2020, and approximately 1.3 million migrants from the Global South were estimated to be residing in Brazil, most of whom from Venezuela and Haiti. Tuberculosis control programs for migrants can be divided into pre- and post-migration screening strategies. Pre-migration screening aims to identify cases of tuberculosis infection (TBI) and can be carried out in the country of origin (pre-entry) or in the destination country (at entry). Pre-migration screening can also detect migrants at an increased risk of developing tuberculosis in the future. High-risk migrants are then followed up in post-migration screening. In Brazil, migrants are considered a priority group for the active search for tuberculosis cases. However, there is no recommendation or plan regarding screening for TBI in migrants and refugees. Ensuring prevention, diagnosis, and treatment for TBI and tuberculosis disease in migrant populations is an important aspect of tuberculosis control and elimination. In this review article, we address epidemiological aspects and access to health care for migrants in Brazil. In addition, the migration medical screening for tuberculosis was reviewed.

Migration and medical screening for tuberculosis / Imigração e triagem médica para tuberculose

ABSTRACT Vulnerable populations, such as migrants and refugees, have an increased risk of tuberculosis disease, especially in the first years after arrival in the host country. The presence of migrants and refugees in Brazil exponentially grew over the period between 2011 and 2020, and approximately 1.3 million migrants from the Global South were estimated to be residing in Brazil, most of whom from Venezuela and Haiti. Tuberculosis control programs for migrants can be divided into pre- and post-migration screening strategies. Pre-migration screening aims to identify cases of tuberculosis infection (TBI) and can be carried out in the country of origin (pre-entry) or in the destination country (at entry). Pre-migration screening can also detect migrants at an increased risk of developing tuberculosis in the future. High-risk migrants are then followed up in post-migration screening. In Brazil, migrants are considered a priority group for the active search for tuberculosis cases. However, there is no recommendation or plan regarding screening for TBI in migrants and refugees. Ensuring prevention, diagnosis, and treatment for TBI and tuberculosis disease in migrant populations is an important aspect of tuberculosis control and elimination. In this review article, we address epidemiological aspects and access to health care for migrants in Brazil. In addition, the migration medical screening for tuberculosis was reviewed.

RESUMO Populações vulneráveis, como imigrantes e refugiados, apresentam maior risco de tuberculose doença, especialmente nos primeiros anos após a chegada ao país de acolhimento. A presença de imigrantes e refugiados no Brasil cresceu exponencialmente no período entre 2011 e 2020, sendo estimado que aproximadamente 1,3 milhão de imigrantes do Sul Global residiam no Brasil, a maioria proveniente da Venezuela e do Haiti. Os programas de controle da tuberculose para imigrantes podem ser divididos em estratégias de triagem pré- e pós-migração. A triagem pré-migração visa identificar casos de tuberculose infecção (TBI) e pode ser realizada no país de origem (pré-entrada) ou no país de destino (no momento da entrada). A triagem pré-migração também pode detectar imigrantes com maior risco de desenvolver tuberculose no futuro. Os imigrantes de alto risco são então acompanhados na triagem pós-migração. No Brasil, os imigrantes são considerados um grupo prioritário para a busca ativa de casos de tuberculose. No entanto, não há recomendação ou plano sobre triagem para TBI em imigrantes e refugiados. Garantir a prevenção, o diagnóstico e o tratamento da TBI e da tuberculose doença em populações imigrantes é um aspecto importante do controle e eliminação da tuberculose. Neste artigo de revisão, abordamos aspectos epidemiológicos e acesso à saúde para imigrantes no Brasil. Além disso, revisou-se a triagem médica de imigrantes para tuberculose.

[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.

Lacunas na vigilância da tuberculose drogarresistente: relacionando sistemas de informação do Brasil / Gaps in drug-resistant tuberculosis surveillance: probabilistic database linkage in Brazil / Lagunas en la vigilancia de la tuberculosis resistente a fármacos: relacionando sistemas de información en Brasil

Resumo: O objetivo do trabalho foi avaliar a cobertura e a confiabilidade do encerramento dos casos de tuberculose drogarresistente (TB DR), do Sistema de Informação de Tratamentos Especiais de Tuberculose (SITE-TB), que ocorreram no Brasil no período de 2013 a 2016, a partir de relacionamentos probabilísticos com o Sistema de Informação de Agravos de Notificação (SINAN), Gerenciador de Ambiente Laboratorial (GAL) e Sistema de Informações sobre Mortalidade (SIM). Os casos de TB DR com início de tratamento entre 2013 e 2016 no Brasil constituíram a população do estudo. O relacionamento com o SINAN avaliou a cobertura e estimou a subnotificação dos casos de TB DR. Aplicou-se o método de captura-recaptura, com uso do estimador de Chapman. O relacionamento com o GAL identificou casos diagnosticados pelo laboratório que não estavam notificados no SITE-TB. O relacionamento com o SIM avaliou a confiabilidade do encerramento óbito no SITE-TB, utilizando o coeficiente kappa. Estimou-se uma população de 2.945 (IC95%: 2.365-3.602) casos novos de TB DR com o estimador de Chapman. No GAL, foram encontrados 1.626 indivíduos não notificados no SITE-TB, mesmo com exame laboratorial confirmatório de resistência aos medicamentos antiTB. Classificou-se como excelente, PABAK (prevalance and bias adjusted kappa) de 0,86 (IC95%: 0,85-0,87), a concordância entre o desfecho óbito do SITE-TB e o SIM. Os resultados mostraram que ainda temos lacunas relacionadas ao diagnóstico e ao tratamento da TB DR no Brasil. A subnotificação no SITE-TB de casos de TB DR representa um desafio para o controle da doença. A localização desses indivíduos e o início precoce do tratamento devem constituir uma ação priorizada nos serviços de saúde.

Abstract: 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.

Resumen: El objetivo de este trabajo fue evaluar la cobertura y fiabilidad del cierre de casos de tuberculosis resistente a multiple medicamentos (TB DR; por sus siglas en portugués) en el Sistema de Información de Tratamientos Especiales de Tuberculosis (SITE-TB), que se produjeron en Brasil durante el período de 2013 a 2016, a partir de relaciones probabilísticas con el Sistema de Información de Enfermedades de Notificación (SINAN por sus siglas en portugués), Gestor de Ambiente de Laboratorio (GAL) y Sistema de Información sobre Mortalidad (SIM). La población del estudio fueron los casos de TB DR con inicio de tratamiento entre 2013 y 2016 en Brasil. La relación con el SINAN evaluó la cobertura y estimó la subnotificación de los casos de TB DR. Se aplicó el método de captura-recaptura, utilizando el estimador de Chapman. La relación con el GAL identificó casos diagnosticados por el laboratorio que no estaban notificados en el SITE-TB. La relación con el SIM evaluó la fiabilidad del cierre óbito en el SITE-TB, utilizando el coeficiente kappa. Se estimó que para una población de 2.945 (IC95%: 2.365-3.602) casos nuevos de TB DR con el estimador de Chapman. Se encontraron en el GAL a 1.626 individuos no notificados en el SITE-TB, incluso con examen de laboratorio confirmatorio de resistencia a los medicamentos antiTB. Se clasificó como excelente, PABAK (prevalance and bias adjusted kappa) de 0,86 (IC95%: 0,85-0,87), la concordancia entre el resultado óbito del SITE-TB y el SIM. Los resultados mostraron que todavía existen lagunas relacionadas con el diagnóstico y el tratamiento de la TB DR en Brasil. La subnotificación en el SITE-TB de casos de TB DR representa un desafío para el control de la enfermedad. La localización de esos individuos y el inicio precoz del tratamiento debe ser una acción priorizada en los servicios de salud.