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.

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.

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.

Laboratory-based study of drug resistance and genotypic profile of multidrug-resistant tuberculosis isolates in Salvador, Bahia, Brazil.

BACKGROUND: Surveillance of multidrug resistant/extensively drug-resistant tuberculosis (MDR/XDR-TB) is essential to guide disease dissemination control measures. Brazil contributes to a significant fraction of tuberculosis (TB) cases worldwide, but only few reports addressed MDR/XDR-TB in the country. METHODS: This cross-sectional, laboratory-based study describes the phenotypic resistance profiles of isolates obtained between January 2008 and December 2011 in Bahia, Brazil, and sociodemographic, epidemiological, and clinical characteristics (obtained from mandatory national registries) of the corresponding 204 MDR/XDR-TB patients. We analyzed the mycobacterial spoligotyping and variable number of tandem repeats of mycobacterial interspersed repetitive units in 12-loci profiles obtained from Salvador. RESULTS: MDR/XDR-TB patients were predominantly male, had a median age of 43 years, belonged to black ethnicity, and failed treatment before MDR-TB diagnosis. Nearly one-third of the isolates had phenotypic resistance (evaluated by mycobacteria growth indicator tube assay) to second-line anti-TB drugs (64/204, 31%), of which 22% cases (14/64) were diagnosed as XDR-TB. Death was a frequent outcome among these individuals and was associated with resistance to second-line anti-TB drugs. Most isolates successfully genotyped belonged to the Latin-American Mediterranean (LAM) Family, with an unprecedented high proportion of LAM10-Cameroon subfamily bacilli. More than half of these isolates were assigned to a unique cluster by the genotyping methods performed. Large clusters of identical genotypes were also observed among LAM SIT42 and SIT376 strains. CONCLUSIONS: We highlight the need for strengthening local and national efforts to perform early detection of TB drug resistance and to prevent treatment discontinuation to limit the emergence of drug-resistant strains.

A spatial-mechanistic model to estimate subnational tuberculosis burden with routinely collected data: An application in Brazilian municipalities.

Reliable subnational estimates of TB incidence would allow national policy makers to focus disease control resources in areas of highest need. We developed an approach for generating small area estimates of TB incidence, and the fraction of individuals missed by routine case detection, based on available notification and mortality data. We demonstrate the feasibility of this approach by creating municipality-level burden estimates for Brazil. We developed a mathematical model describing the relationship between TB incidence and TB case notifications and deaths, allowing for known biases in each of these data sources. We embedded this model in a regression framework with spatial dependencies between local areas, and fitted the model to municipality-level case notifications and death records for Brazil during 2016-2018. We estimated outcomes for 5568 municipalities. Incidence rate ranged from 8.6 to 57.2 per 100,000 persons/year for 90% of municipalities, compared to 44.8 (95% UI: 43.3, 46.8) per 100,000 persons/year nationally. Incidence was concentrated geographically, with 1% of municipalities accounting for 50% of incident TB. The estimated fraction of incident TB cases receiving diagnosis and treatment ranged from 0.73 to 0.95 across municipalities (compared to 0.86 (0.82, 0.89) nationally), and the rate of untreated TB ranged from 0.8 to 72 cases per 100,000 persons/year (compared to 6.3 (4.8, 8.3) per 100,000 persons/year nationally). Granular disease burden estimates can be generated using routine data. These results reveal substantial subnational differences in disease burden and other metrics useful for designing high-impact TB control strategies.

Laboratory-based study of drug resistance and genotypic profile of multidrug-resistant tuberculosis isolates in Salvador, Bahia, Brazil

Abstract Background: Surveillance of multidrug resistant/extensively drug-resistant tuberculosis (MDR/XDR-TB) is essential to guide disease dissemination control measures. Brazil contributes to a significant fraction of tuberculosis (TB) cases worldwide, but only few reports addressed MDR/XDR-TB in the country. Methods: This cross-sectional, laboratory-based study describes the phenotypic resistance profiles of isolates obtained between January 2008 and December 2011 in Bahia, Brazil, and sociodemographic, epidemiological, and clinical characteristics (obtained from mandatory national registries) of the corresponding 204 MDR/XDR-TB patients. We analyzed the mycobacterial spoligotyping and variable number of tandem repeats of mycobacterial interspersed repetitive units in 12-loci profiles obtained from Salvador. Results: MDR/XDR-TB patients were predominantly male, had a median age of 43 years, belonged to black ethnicity, and failed treatment before MDR-TB diagnosis. Nearly one-third of the isolates had phenotypic resistance (evaluated by mycobacteria growth indicator tube assay) to second-line anti-TB drugs (64/204, 31%), of which 22% cases (14/64) were diagnosed as XDR-TB. Death was a frequent outcome among these individuals and was associated with resistance to second-line anti-TB drugs. Most isolates successfully genotyped belonged to the Latin-American Mediterranean (LAM) Family, with an unprecedented high proportion of LAM10-Cameroon subfamily bacilli. More than half of these isolates were assigned to a unique cluster by the genotyping methods performed. Large clusters of identical genotypes were also observed among LAM SIT42 and SIT376 strains. Conclusions: We highlight the need for strengthening local and national efforts to perform early detection of TB drug resistance and to prevent treatment discontinuation to limit the emergence of drug-resistant strains.

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.

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.

[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.

Notifiable Diseases Information System (SINAN): main features of tuberculosis notification and data analysis. / Sistema de Informação de Agravos de Notificação (Sinan): principais características da notificação e da análise de dados relacionada à tuberculose.

The Notifiable Diseases Information System (SINAN) enables knowledge of the profile of people with active tuberculosis (TB) in a country of continental dimensions such as Brazil. Available in all Brazilian municipalities and states, the system enables continuous consolidation of data, evaluation and monitoring of actions related to TB control in the country. The purpose of this paper is to present the specificities of SINAN-Net related to TB, including the follow-up screen, the record linkage and the follow-up report. Additionally, we describe the main variables and indicators and the challenges and limitations of the system.

O Sistema de Informação de Agravos de Notificação (Sinan) possibilita conhecer o perfil das pessoas com tuberculose (TB) ativa em um país continental como o Brasil. Disponível em todos os municípios e estados, o sistema permite contínua consolidação dos dados, avaliação e monitoramento das ações relacionadas ao controle da doença no país. O objetivo deste estudo foi apresentar as especificidades do Sinan-Net referentes à TB, entre elas a tela de acompanhamento, a rotina de vinculação e o boletim de acompanhamento. Adicionalmente, são descritas as principais variáveis e indicadores, os desafios e limitações do sistema.

El Sistema de Información de Agravamientos de Notificación (Sinan) posibilita conocer el perfil de las personas con tuberculosis (TB) activa en un país continental como Brasil. Disponible en todos los municipios y estados, el sistema posibilita una continua consolidación de los datos, evaluación y monitoreo de las acciones relacionadas al control de la enfermedad en el país. El objetivo de este trabajo es presentar las especificidades del Sinan-Net con relación a la TB, entre ellas la pantalla de acompañamiento, la rutina de vinculación y el boletín de acompañamiento. Adicionalmente, describimos las principales variables e indicadores y los desafíos y limitaciones del sistema.

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.

Special Tuberculosis Treatment Information System (SITE-TB) in Brazil: background, description and perspectives. / Sistema de Informação de Tratamentos Especiais de Tuberculose (SITE-TB): histórico, descrição e perspectivas.

The Special Tuberculosis Treatment Information System (SITE-TB) arose mainly from the need to routinely monitor all persons with drug-resistant tuberculosis (DR-TB) in Brazil, as well as to qualify tuberculosis' drug control. Developed by the Professor Hélio Fraga Reference Center and the Management Sciences for Health/Brazil Project, this online system was implemented in 2013 in all Brazilian states. In addition to DR-TB, the system registers people with drug-sensitive tuberculosis with special regimen indications, and those with nontuberculous mycobacterial infections identified by differential diagnosis of tuberculosis. All confirmed tuberculosis cases should be notified on the Notifiable Diseases Information System (SINAN). In situations where treatment with special regimens is necessary, the case is closed on SINAN and notified on SITE-TB. Professionals from tuberculosis reference centers report and monitor these cases on the system, as well as manage tuberculosis' drugs.

O Sistema de Informação de Tratamentos Especiais de Tuberculose (SITE-TB) surgiu da necessidade principal de monitorar, rotineiramente, todas as pessoas com tuberculose drogarresistente (TBDR) no Brasil, e qualificar o controle dos fármacos antituberculose. Desenvolvido pelo Centro de Referência Professor Hélio Fraga e pelo projeto Management Sciences for Health/Brasil, esse sistema online foi implantado em 2013, em todas as Unidades da Federação. Além da TBDR, no SITE-TB são registradas pessoas com tuberculose sensível com indicação de esquema especial, e aquelas com micobacterioses não tuberculosas identificadas por diagnóstico diferencial de tuberculose. Toda pessoa com tuberculose confirmada deve ser notificada no Sistema de Informação de Agravos de Notificação (Sinan). Em situações nas quais se faz necessário tratamento com esquema especial, o caso é encerrado no Sinan e notificado no SITE-TB. Profissionais das unidades de referência para tuberculose fazem a notificação e acompanhamento desses casos no sistema, assim como a gestão dos medicamentos.

El Sistema de Información de Tratamientos Especiales de Tuberculosis (SITE-TB) surgió principalmente de la necesidad de monitorear rutinariamente todas las personas con tuberculosis drogorresistente (TB-DR) en Brasil y cualificar el control de drogas antituberculosis. Desarrollado por el Centro de Referencia Profesor Hélio Fraga y el proyecto Management Sciences for Health/Brasil, este sistema online fue implantado en 2013 en todos los estados del país. Además de TB-DR, el SITE-TB registra personas con tuberculosis sensible con indicación de régimen especial, y aquellas con micobacteriosis no tuberculosas identificadas por diagnóstico diferencial de tuberculosis. Toda persona con tuberculosis confirmada debe ser notificada en el Sistema de Información de Agravamientos de Notificación (SINAN). Para situaciones en las que se hace necesario tratamiento con régimen especial, el caso se cierra en el SINAN y se notifica en el SITE-TB. Los profesionales de las unidades de referencia para TB son los que hacen la notificación y seguimiento de estos casos en el sistema, así como la gestión de las drogas antituberculosis.

The impact of a cash transfer programme on tuberculosis treatment success rate: a quasi-experimental study in Brazil.

BACKGROUND: Evidence suggests that social protection policies such as Brazil's Bolsa Família Programme (BFP), a governmental conditional cash transfer, may play a role in tuberculosis (TB) elimination. However, study limitations hamper conclusions. This paper uses a quasi-experimental approach to more rigorously evaluate the effect of BFP on TB treatment success rate. METHODS: Propensity scores were estimated from a complete-case logistic regression using covariates from a linked data set, including the Brazil's TB notification system (SINAN), linked to the national registry of those in poverty (CadUnico) and the BFP payroll. RESULTS: The average effect of treatment on the treated was estimated as the difference in TB treatment success rate between matched groups (ie, the control and exposed patients, n=2167). Patients with TB receiving BFP showed a treatment success rate of 10.58 percentage points higher (95% CI 4.39 to 16.77) than patients with TB not receiving BFP. This association was robust to sensitivity analyses. CONCLUSIONS: This study further confirms a positive relationship between the provision of conditional cash transfers and TB treatment success rate. Further research is needed to understand how to enhance access to social protection so to optimise public health impact.

[Brazilian National Registry of Healthcare Establishments as a tool for the analysis of decentralization of tuberculosis treatment to basic care services]. / Cadastro Nacional de Estabelecimentos de Saúde como ferramenta de análise da descentralização do atendimento da tuberculose para a atenção básica.

This study aimed to validate a method for classification of healthcare services in Brazil (basic care vs. other levels) and describe the decentralization of tuberculosis (TB) care to basic services (2002 to 2016). The healthcare services that reported and followed TB cases were classified as either "basic care" or "other levels" based on the type of establishment registered in the Brazilian National Registry of Healthcare Establishments (CNES, in Portuguese). The study estimated the agreement between this classification with a previous classification performed in 2013 by Brazil's state and local tuberculosis programs. Using the CNES registry, the authors then calculated the percentage of TB patients treated in basic care from 2002 to 2016. Agreement was 94.4%, and overall kappa index was 0.86. There was a relative increment of 31.2% in TB care provided by basic services (from 50.9% in 2002 to 66.8% in 2016). All regions of Brazil showed an increase in this percentage, except the South. The classification based on the CNES registry allowed analyzing the trend in decentralization of TB treatment to basic healthcare services in Brazil.

Os objetivos deste artigo foram validar um método de classificação dos serviços de saúde (atenção básica vs. outros níveis) e descrever a descentralização do atendimento da tuberculose (TB) para a atenção básica no Brasil no período de 2002 a 2016. Os serviços de saúde que notificaram e acompanharam pessoas com TB foram classificados como "atenção básica" ou "outros níveis", considerando-se o tipo de estabelecimento registrado no Cadastro Nacional de Estabelecimentos de Saúde (CNES). Foi estimada a concordância entre essa classificação e uma realizada em 2013 pelos programas estaduais e municipais de TB. Posteriormente, utilizando-se o CNES, calculou-se o percentual de pessoas com TB atendidas na atenção básica no período de 2002 a 2016. A concordância foi de 94,4% e o índice kappa global foi 0,86. Houve um incremento relativo de 31,2% do atendimento de TB na atenção básica (50,9% em 2002 para 66,8% em 2016). Todas as regiões apresentaram aumento desse percentual, exceto a Região Sul. A classificação baseada no CNES permitiu analisar a evolução da descentralização do atendimento da TB para a atenção básica no Brasil.

Los objetivos de este artículo fueron validar un método de clasificación de los servicios de salud (atención básica vs. otros niveles) y describir la descentralización del cuidado de la tuberculosis (TB) hacia los servicios de atención básica en Brasil, durante el período de 2002 a 2016. Los servicios de salud que notificaron y efectuaron el seguimiento a personas con TB fueron clasificados como "atención básica" u "otros niveles", considerándose el tipo de establecimiento registrado en el Registro Nacional de Establecimientos de Salud (CNES). Se estimó la concordancia entre esta clasificación y una realizada en 2013 por los programas estatales y municipales de TB. Posteriormente, utilizando el CNES, se calculó el porcentaje de personas con TB atendidas en la atención básica durante el período de 2002 a 2016. La concordancia fue de 94,4% y el índice kappa global fue 0,86. Hubo un incremento relativo de un 31,2% del manejo de la TB en la atención básica (de un 50,9% en 2002 hasta un 66,8% en 2016). Todas las regiones presentaron un aumento de ese porcentaje, excepto la región Sur. La clasificación, basada en el CNES, permitió analizar la evolución de la descentralización del manejo de la TB hacia la atención básica en Brasil.

Identifying socioeconomic, epidemiological and operational scenarios for tuberculosis control in Brazil: an ecological study.

OBJECTIVES: To identify scenarios based on socioeconomic, epidemiological and operational healthcare factors associated with tuberculosis incidence in Brazil. DESIGN: Ecological study. SETTINGS: The study was based on new patients with tuberculosis and epidemiological/operational variables of the disease from the Brazilian National Information System for Notifiable Diseases and the Mortality Information System. We also analysed socioeconomic and demographic variables. PARTICIPANTS: The units of analysis were the Brazilian municipalities, which in 2015 numbered 5570 but 5 were excluded due to the absence of socioeconomic information. PRIMARY OUTCOME: Tuberculosis incidence rate in 2015. DATA ANALYSIS: We evaluated as independent variables the socioeconomic (2010), epidemiological and operational healthcare indicators of tuberculosis (2014 or 2015) using negative binomial regression. Municipalities were clustered by the k-means method considering the variables identified in multiple regression models. RESULTS: We identified two clusters according to socioeconomic variables associated with the tuberculosis incidence rate (unemployment rate and household crowding): a higher socioeconomic scenario (n=3482 municipalities) with a mean tuberculosis incidence rate of 16.3/100 000 population and a lower socioeconomic scenario (2083 municipalities) with a mean tuberculosis incidence rate of 22.1/100 000 population. In a second stage of clusterisation, we defined four subgroups in each of the socioeconomic scenarios using epidemiological and operational variables such as tuberculosis mortality rate, AIDS case detection rate and proportion of vulnerable population among patients with tuberculosis. Some of the subscenarios identified were characterised by fragility in their information systems, while others were characterised by the concentration of tuberculosis cases in key populations. CONCLUSION: Clustering municipalities in scenarios allowed us to classify them according to the socioeconomic, epidemiological and operational variables associated with tuberculosis risk. This classification can support targeted evidence-based decisions such as monitoring data quality for improving the information system or establishing integrative social protective policies for key populations.

Offer of primary care services and detection of tuberculosis incidence in Brazil.

OBJECTIVE To evaluate the association between the health services offered by primary care teams and the detection of new tuberculosis cases in Brazil. METHODS This was an ecological study covering all Brazilian municipalities that registered at least one new tuberculosis case (diagnosed between 2012 to 2014 and notified in the Information System of Notifiable Diseases) and with at least one primary care team evaluated by the second cycle of the National Program for Improving Access and Quality of Primary Care (PMAQ-AB). The variables of the PMAQ-AB were classified as proximal or distal, according to their relation with the tuberculosis diagnosis. Then, they were tested hierarchically in multiple models (adjusted by States) using negative binomial regression. RESULTS An increase of 10% in the primary health care coverage was associated with a decrease of 2.24% in the tuberculosis detection rate (95%CI -3.35- -1.11). Regarding the proximal variables in relation to diagnosis, in the multiple model, the detection of tuberculosis was associated with the proportion of teams that conduct contact investigation (increase in Incidence Rate Ratio [IRR] = 2.97%, 95%CI 2.41-3.53), carry out tuberculosis active case finding (increase in IRR = 2.17%, 95%CI 1.48-2.87), and request culture for mycobacteria (increase in IRR = 1.87%, 95%CI 0.98-2.76). CONCLUSIONS The variables related to the search actions were positively associated with the detection of new tuberculosis cases, which suggests a significant contribution to the strengthening of the sensitivity of the surveillance system. On the other hand, primary care coverage was inversely associated with the tuberculosis detection rate, which could represent the overall effect of the primary care on transmission control, probably from the identification and early treatment of cases.

Cadastro Nacional de Estabelecimentos de Saúde como ferramenta de análise da descentralização do atendimento da tuberculose para a atenção básica / Brazilian National Registry of Healthcare Establishments as a tool for the analysis of decentralization of tuberculosis treatment to basic care services / Registro Nacional de Establecimientos de Salud como herramienta de análisis de la descentralización de la atención a la tuberculosis en la atención básica

Resumo: Os objetivos deste artigo foram validar um método de classificação dos serviços de saúde (atenção básica vs. outros níveis) e descrever a descentralização do atendimento da tuberculose (TB) para a atenção básica no Brasil no período de 2002 a 2016. Os serviços de saúde que notificaram e acompanharam pessoas com TB foram classificados como "atenção básica" ou "outros níveis", considerando-se o tipo de estabelecimento registrado no Cadastro Nacional de Estabelecimentos de Saúde (CNES). Foi estimada a concordância entre essa classificação e uma realizada em 2013 pelos programas estaduais e municipais de TB. Posteriormente, utilizando-se o CNES, calculou-se o percentual de pessoas com TB atendidas na atenção básica no período de 2002 a 2016. A concordância foi de 94,4% e o índice kappa global foi 0,86. Houve um incremento relativo de 31,2% do atendimento de TB na atenção básica (50,9% em 2002 para 66,8% em 2016). Todas as regiões apresentaram aumento desse percentual, exceto a Região Sul. A classificação baseada no CNES permitiu analisar a evolução da descentralização do atendimento da TB para a atenção básica no Brasil.

Abstract: This study aimed to validate a method for classification of healthcare services in Brazil (basic care vs. other levels) and describe the decentralization of tuberculosis (TB) care to basic services (2002 to 2016). The healthcare services that reported and followed TB cases were classified as either "basic care" or "other levels" based on the type of establishment registered in the Brazilian National Registry of Healthcare Establishments (CNES, in Portuguese). The study estimated the agreement between this classification with a previous classification performed in 2013 by Brazil's state and local tuberculosis programs. Using the CNES registry, the authors then calculated the percentage of TB patients treated in basic care from 2002 to 2016. Agreement was 94.4%, and overall kappa index was 0.86. There was a relative increment of 31.2% in TB care provided by basic services (from 50.9% in 2002 to 66.8% in 2016). All regions of Brazil showed an increase in this percentage, except the South. The classification based on the CNES registry allowed analyzing the trend in decentralization of TB treatment to basic healthcare services in Brazil.

Resumen: Los objetivos de este artículo fueron validar un método de clasificación de los servicios de salud (atención básica vs. otros niveles) y describir la descentralización del cuidado de la tuberculosis (TB) hacia los servicios de atención básica en Brasil, durante el período de 2002 a 2016. Los servicios de salud que notificaron y efectuaron el seguimiento a personas con TB fueron clasificados como "atención básica" u "otros niveles", considerándose el tipo de establecimiento registrado en el Registro Nacional de Establecimientos de Salud (CNES). Se estimó la concordancia entre esta clasificación y una realizada en 2013 por los programas estatales y municipales de TB. Posteriormente, utilizando el CNES, se calculó el porcentaje de personas con TB atendidas en la atención básica durante el período de 2002 a 2016. La concordancia fue de 94,4% y el índice kappa global fue 0,86. Hubo un incremento relativo de un 31,2% del manejo de la TB en la atención básica (de un 50,9% en 2002 hasta un 66,8% en 2016). Todas las regiones presentaron un aumento de ese porcentaje, excepto la región Sur. La clasificación, basada en el CNES, permitió analizar la evolución de la descentralización del manejo de la TB hacia la atención básica en Brasil.

Offer of primary care services and detection of tuberculosis incidence in Brazil / Oferta de serviços pela atenção básica e detecção da incidência de tuberculose no Brasil

ABSTRACT OBJECTIVE To evaluate the association between the health services offered by primary care teams and the detection of new tuberculosis cases in Brazil. METHODS This was an ecological study covering all Brazilian municipalities that registered at least one new tuberculosis case (diagnosed between 2012 to 2014 and notified in the Information System of Notifiable Diseases) and with at least one primary care team evaluated by the second cycle of the National Program for Improving Access and Quality of Primary Care (PMAQ-AB). The variables of the PMAQ-AB were classified as proximal or distal, according to their relation with the tuberculosis diagnosis. Then, they were tested hierarchically in multiple models (adjusted by States) using negative binomial regression. RESULTS An increase of 10% in the primary health care coverage was associated with a decrease of 2.24% in the tuberculosis detection rate (95%CI -3.35- -1.11). Regarding the proximal variables in relation to diagnosis, in the multiple model, the detection of tuberculosis was associated with the proportion of teams that conduct contact investigation (increase in Incidence Rate Ratio [IRR] = 2.97%, 95%CI 2.41-3.53), carry out tuberculosis active case finding (increase in IRR = 2.17%, 95%CI 1.48-2.87), and request culture for mycobacteria (increase in IRR = 1.87%, 95%CI 0.98-2.76). CONCLUSIONS The variables related to the search actions were positively associated with the detection of new tuberculosis cases, which suggests a significant contribution to the strengthening of the sensitivity of the surveillance system. On the other hand, primary care coverage was inversely associated with the tuberculosis detection rate, which could represent the overall effect of the primary care on transmission control, probably from the identification and early treatment of cases.

RESUMO OBJETIVO Avaliar a associação entre os serviços de saúde ofertados por equipes de atenção básica e a detecção de casos novos de tuberculose no Brasil. MÉTODOS Estudo ecológico, abrangendo todos os municípios brasileiros que registraram pelo menos um caso novo de tuberculose (diagnosticado entre 2012 a 2014 e notificado no Sistema de Informação de Agravos de Notificação) e com pelo menos uma equipe de atenção básica avaliada pelo segundo ciclo do Programa Nacional de Melhoria do Acesso e da Qualidade da Atenção Básica (PMAQ-AB). As variáveis do PMAQ-AB foram classificadas como próximais ou distais, segundo a sua relação com o diagnóstico de tuberculose. Em seguida, foram testadas hierarquicamente em modelos múltiplos (ajustados por Unidade Federada), usando regressão binomial negativa. RESULTADOS Um incremento de 10% na cobertura da atenção básica esteve associado à redução de 2,24% na taxa de detecção de tuberculose (IC95% -3,35- -1,11). No que se refere às variáveis proximais ao diagnóstico, no modelo múltiplo, a detecção da tuberculose esteve associada à proporção de equipes que: realizam vigilância de contatos (incremento na Razão de Taxas de Incidência [RTI] = 2,97%; IC95% 2,41-3,53); fazem busca ativa de casos de tuberculose (incremento na RTI = 2,17%; IC95% 1,48-2,87); e, ofertam cultura para micobactérias (incremento na RTI = 1,87%; IC95% 0,98-2,76). CONCLUSÕES As variáveis relacionadas às ações de detecção estiveram positivamente associadas à detecção de casos novos de tuberculose, sugerindo uma contribuição significativa ao fortalecimento da sensibilidade do sistema de vigilância. Por outro lado, a cobertura da atenção básica esteve inversamente associada à taxa de detecção de tuberculose, o que poderia representar o efeito global da atenção básica sobre o controle da transmissão, provavelmente, através da identificação e tratamento precoce de casos.