ABSTRACT
BACKGROUND: In Brazil, many individuals with tuberculosis (TB) do not receive appropriate care due to delayed or missed diagnosis, ineffective treatment regimens, or loss-to-follow-up. This study aimed to estimate the health losses and TB program costs attributable to each gap in the care cascade for TB disease in Brazil. METHODS AND FINDINGS: We constructed a Markov model simulating the TB care cascade and lifetime health outcomes (e.g., death, cure, postinfectious sequelae) for individuals developing TB disease in Brazil. We stratified the model by age, human immunodeficiency virus (HIV) status, drug resistance, state of residence, and disease severity, and developed a parallel model for individuals without TB that receive a false-positive TB diagnosis. Models were fit to data (adult and pediatric) from Brazil's Notifiable Diseases Information System (SINAN) and Mortality Information System (SIM) for 2018. Using these models, we assessed current program performance and simulated hypothetical scenarios that eliminated specific gaps in the care cascade, in order to quantify incremental health losses and TB diagnosis and treatment costs along the care cascade. TB-attributable disability-adjusted life years (DALYs) were calculated by comparing changes in survival and nonfatal disability to a no-TB counterfactual scenario. We estimated that 90.0% (95% uncertainty interval [UI]: 85.2 to 93.4) of individuals with TB disease initiated treatment and 10.0% (95% UI: 7.6 to 12.5) died with TB. The average number of TB-attributable DALYs per incident TB case varied across Brazil, ranging from 2.9 (95% UI: 2.3 to 3.6) DALYs in Acre to 4.0 (95% UI: 3.3 to 4.7) DALYs in Rio Grande do Sul (national average 3.5 [95% UI: 2.8 to 4.1]). Delayed diagnosis contributed the largest health losses along the care cascade, followed by post-TB sequelae and loss to follow up from TB treatment, with TB DALYs reduced by 71% (95% UI: 65 to 76), 41% (95% UI: 36 to 49), and 10% (95% UI: 7 to 16), respectively, when these factors were eliminated. Total health system costs were largely unaffected by improvements in the care cascade, with elimination of treatment failure reducing attributable costs by 3.1% (95% UI: 1.5 to 5.4). TB diagnosis and treatment of false-positive individuals accounted for 10.2% (95% UI: 3.9 to 21.7) of total programmatic costs but contributed minimally to health losses. Several assumptions were required to interpret programmatic data for the analysis, and we were unable to estimate the contribution of social factors to care cascade outcomes. CONCLUSIONS: In this study, we observed that delays to diagnosis, post-disease sequelae and treatment loss to follow-up were primary contributors to the TB burden of disease in Brazil. Reducing delays to diagnosis, improving healthcare after TB cure, and reducing treatment loss to follow-up should be prioritized to improve the burden of TB disease in Brazil.
Subject(s)
Cost of Illness , Tuberculosis , Adult , Child , Humans , Quality-Adjusted Life Years , Global Health , Brazil/epidemiology , Tuberculosis/diagnosis , Tuberculosis/drug therapy , Tuberculosis/epidemiology , Disease Progression , Global Burden of DiseaseABSTRACT
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.
Subject(s)
Antitubercular Agents , Treatment Failure , Tuberculosis , Humans , Brazil/epidemiology , Male , Female , Adult , Middle Aged , Antitubercular Agents/therapeutic use , Young Adult , Adolescent , Tuberculosis/drug therapy , Tuberculosis/epidemiology , Aged , Directly Observed Therapy , Child , Child, Preschool , Risk Factors , Infant , HIV Infections/drug therapy , HIV Infections/epidemiology , Treatment Outcome , Aged, 80 and overABSTRACT
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.
ABSTRACT
BACKGROUND: Brazil is a signatory to the World Health Organization End TB Strategy and the United Nations Sustainable Development Goals. This study aims to characterize tuberculosis (TB) deaths and TB mortality rates in Brazil for the period 1997-2017. METHODS: We performed an ecological study based on information for TB deaths between 1997 and 2017 extracted from the Mortality Information System of the Brazilian Ministry of Health. Data included gender, age group and geographic regions. The trends in mortality rates were estimated using Joinpoint regression analysis, which identifies years in which there is a change in slope of the time series by the Monte Carlo permutation. RESULTS: Between 1997 and 2017 there were 104 172 recorded TB deaths in Brazil and the mortality rates were higher for men and the elderly. The age-adjusted mortality rate decreased from 4.2 per 100 000 in 1997 to 3.0 per 100 000 in 2003 to 2.0 per 100 000 in 2017. The average percentage reduction from 1997 to 2003 was 6.2% (95% confidence interval [CI] -7.7 to -4.7) per year, while from 2003 to 2017 it was 3.0% (95% CI -3.4 to -2.5) per year, representing a slowdown in the rate of decline. CONCLUSION: The high number of deaths and the slowdown in the decline of mortality rates from TB in Brazil maintain the disease as an important public health concern and an obstacle to reaching goals set by international commitments.
Subject(s)
Tuberculosis , Aged , Brazil/epidemiology , Humans , Male , Mortality , Public Health , Regression Analysis , World Health OrganizationABSTRACT
OBJECTIVE: to evaluate the Brazilian Drug-Resistant Tuberculosis Surveillance System (DRTB-SS). METHODS: this was an evaluative study, following Centers for Disease Control and Prevention guidelines, using national data from the Special Tuberculosis Treatment Information System (SITETB), and the Notifiable Diseases Information System (SINAN), from 2013 to 2017. RESULTS: average data completeness was 95% (schooling [89.1%; 5,417/6,078], nationality [94.7%; 5,754/6,078], race/skin color [99.1%; 6,023/6,078], type of resistance [98.6%; 5,995/6,078], clinical form [100%; 6,078/6,078], and HIV test [87%; 5,289/6,078]); average proportion of cases with sputum cultures performed was 65.7% (culture 1 [94.8%; 5,764/6,078], culture 2 [69.8%; 4,241/6,078], culture 3 [54.7%, 3,324/6,078], and culture 4 [43.6%; 2,652/6,078]); DRTB-SS reported 52% (1,197/2,300) of multi-resistant cases estimated by the World Health Organization in 2015, 41.3% (990/2,400) in 2016, and 45.8% (1,100/2,400) in 2017. CONCLUSION: low DRTB-SS sensitivity suggests the need for improved access to DRTB diagnosis.
Subject(s)
Disease Notification , Health Information Systems/statistics & numerical data , Public Health Surveillance , Tuberculosis, Multidrug-Resistant/epidemiology , Adult , Antitubercular Agents/pharmacology , Brazil/epidemiology , Female , Humans , Male , Sputum/microbiology , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/drug therapy , Young AdultABSTRACT
OBJECTIVES: To estimate the burden of tuberculosis (TB) in reported AIDS cases, to compare the characteristics of TB/HIV subjects with those without TB and to evaluate survival with or without TB in Brazil. METHODS: The data source was the linked database between AIDS (2011-2014) and TB (2011-2014) databases from the Notifiable Diseases Information System (SINAN). The sociodemographic, clinical, laboratory results and use of antiretroviral therapy (ART) data were compared by TB occurrence or not. Survival probability was estimated using the Kaplan-Meier method and associated factors were sought using Cox regression. RESULTS: The proportion of TB diagnosed from 2011 to 2014 among AIDS cases reported between 2006 and 2014 was 6.3%. Subjects coinfected with TB were predominantly male, older, with lower schooling, with lower CD4 count, higher viral load, and higher proportion of ART initiation than those without TB. 57.5% were diagnosed with HIV before TB, 38.2% as concurrent TB/HIV and 4.3% with TB before HIV. 16,466 reported TB cases were not found in the AIDS database, although registered as HIV-infected in the SINAN TB database between 2011 and 2014. Median survival for PLHIV was 581 days, with 582 for those without TB, significantly higher than 547 for those with TB (log-rank teste, p = 0,001). In the Cox multivariate analysis, male gender [aHR = 1.27 (CI 95% 1.22-1.33)], older age [aHR = 1.020 (CI 95% 1.019-1.022)] and TB coinfection [aHR = 1.97 (CI 95% 1.88-2.07)] were positively associated with adjusted hazard of death, whereas CD4 count 200-499 cells [aHR = 0.21 (CI 95% 0.20-0.22)] and receiving ART [aHR = 0.2 2(CI 95% 0.21-0.23)] reduced the risk of death. CONCLUSIONS: HIV-infected subjects should be screened for TB at care entry, to minimize diagnosis and treatment delays when active TB is present or to increase the odds of being offered latent TB infection therapy to prevent TB. On the other hand, TB cases should be promptly tested for HIV. All those will contribute to reduce mortality among people living with AIDS.
Subject(s)
Acquired Immunodeficiency Syndrome/complications , Databases, Factual , Tuberculosis/complications , Tuberculosis/epidemiology , Adult , Brazil/epidemiology , Female , Humans , Male , Survival AnalysisABSTRACT
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.
ABSTRACT
Objetivo: avaliar o Sistema de Vigilância da Tuberculose Drogarresistente (SV-TBDR)/Brasil. Métodos: estudo avaliativo, segundo diretrizes do Centro de Controle e Prevenção de Doenças, sobre dados nacionais do Sistema de Informação de Tratamentos Especiais de Tuberculose (SITETB) e do Sistema de Informação de Agravos de Notificação (Sinan) de 2013-2017. Resultados: a completitude média dos dados foi de 95% (escolaridade [89,1%; 5.417/6.078]; nacionalidade [94,7%; 5.754/6.078]; raça/cor da pele [99,1%; 6.023/6.078]; tipo de resistência [98,6%; 5.995/6.078]; forma clínica [100%; 6.078/6.078]; e teste para HIV [87%; 5.289/6.078]); a proporção média de casos com culturas realizadas foi de 65,7% (cultura 1 [94,8%; 5.764/6.078]; cultura 2 [69,8%; 4.241/6.078]; cultura 3 [54,7%; 3.324/6.078]; e cultura 4 [43,6%; 2.652/6.078]); em 2015, o SV-TBDR notificou 52% (1.197/2.300) dos casos multirresistentes estimados pela Organização Mundial da Saúde, 41,3% (990/2.400) em 2016 e 45,8% (1.100/2.400) em 2017. Conclusão: a baixa sensibilidade do SV-TBDR recomenda melhorias no acesso ao diagnóstico da TBDR.
Objetivo: evaluar el Sistema de Vigilancia de la Tuberculosis Drogorresistente (SV-TB -DR)/Brasil. Métodos: estudio evaluativo, según directrices del Centro de Control y Prevención de Enfermedades, sobre datos nacionales del Sistema de Información de Tratamientos Especiales de Tuberculosis (SITETB) y del Sistema Nacional de Agravamientos de Notificación (Sinan) entre 2013 y 2017. Resultados: la completitud promedio de los datos fue de 95% (escolaridad [89,1%; 5.417/6.078]; nacionalidad [94,7%; 5.754/6.078]; raza/color de la piel [99,1%; 6.023/6.078]; tipo de resistencia [98,6%; 5.995/6.078]; forma clínica [100%; 6.078/6.078]; y prueba de VIH [87%; 5.289/6.078]); la proporción promedio de los casos con cultivos realizados fue 65,7% (cultivo 1 [94,8%; 5.764/6.078]; cultivo 2 [69,8%; 4.241/6.078]; cultivo 3 [54,7%; 3.324/6.078]; y cultivo 4 [43,6%; 2.652/6.078]); el SV-TB-DR reportó en 2015 52% (1.197/2.300) de los casos multirresistentes estimados por la Organización Mundial de la Salud, 41,3% (990/2.400) en 2016 y 45,8% (1.100/2.400) en 2017. Conclusión: la baja sensibilidad del SV-TB-DR sugiere la necesidad de mejorar el acceso al diagnóstico de TB-DR.
Objective: to evaluate the Brazilian Drug-Resistant Tuberculosis Surveillance System (DRTB-SS). Methods: this was an evaluative study, following Centers for Disease Control and Prevention guidelines, using national data from the Special Tuberculosis Treatment Information System (SITETB), and the Notifiable Diseases Information System (SINAN), from 2013 to 2017. Results: average data completeness was 95% (schooling [89.1%; 5,417/6,078], nationality [94.7%; 5,754/6,078], race/skin color [99.1%; 6,023/6,078], type of resistance [98.6%; 5,995/6,078], clinical form [100%; 6,078/6,078], and HIV test [87%; 5,289/6,078]); average proportion of cases with sputum cultures performed was 65.7% (culture 1 [94.8%; 5,764/6,078], culture 2 [69.8%; 4,241/6,078], culture 3 [54.7%, 3,324/6,078], and culture 4 [43.6%; 2,652/6,078]); DRTB-SS reported 52% (1,197/2,300) of multi-resistant cases estimated by the World Health Organization in 2015, 41.3% (990/2,400) in 2016, and 45.8% (1,100/2,400) in 2017. Conclusion: low DRTB-SS sensitivity suggests the need for improved access to DRTB diagnosis.
Subject(s)
Humans , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/epidemiology , Health Information Systems/organization & administration , Health Information Systems/statistics & numerical data , Data Accuracy , Brazil/epidemiology , Disease Notification , Qualitative Research , Public Health Surveillance , Epidemiological MonitoringABSTRACT
De acordo com o Programa Nacional de Controle da Tuberculose (TB), em 2006 foram registrados aproximadamente 72 mil casos de TB. No Rio de Janeiro/ (RJ), foram notificados 5.769 casos, representando 8% do total. O propósito de avaliar um Sistema de Vigilância (SV) é identificar os problemas na vigilância de agravos de importância em saúde pública e confirmar se eles estão sendo monitorados de maneira eficiente e efetiva. O objetivo deste trabalho foi avaliar o Sistema da Vigilância da Tuberculose (SVTB) no Rio de Janeiro/ (RJ), de 2001 a 2006. Utilizaram-se as Diretrizes para Avaliação de Sistemas de Vigilância propostas pelo Centers for Disease Control and Prevention (CDC). Essas diretrizes propõem descrever o SV e avaliá-lo quanto aos atributos quantitativos, qualitativos e à utilidade. O SV foi considerado complexo, com qualidade dos dados excelente na ficha de notificação/investigação e regular na ficha de acompanhamento, aceitabilidade boa, baixa sensibilidade, representativo e com oportunidade e estabilidade regular. Considerou-se útil o SV quando avaliamos sua capacidade de oferecer dados que possibilitem aos profissionais conhecer o perfil da doença e planejar suas ações. A assistência e a rede laboratorial precisam ser avaliadas para reconhecermos outros possíveis problemas que fazem com que o agravo ainda acometa de forma importante o município.
The Brazilian National Tuberculosis (TB) Control Program reported 72 thousand cases of TB in 2006. In Rio de Janeiro/ (RJ), Brazil, 5,769 cases were reported, representing 8% of the total. The purpose of evaluating a surveillance system (SS) is to identify problems in surveillance of diseases of public health significance and confirm whether they are being monitored efficiently and effectively. The aim of this study was to evaluate the Surveillance System of Tuberculosis (SSTB) in Rio de Janeiro, between 2001 and 2006. We used Centers for Disease Control and Prevention (CDC) Updated Guidelines for Evaluating Public Health Surveillance Systems, describing the SS and evaluating its quantitative and qualitative attributes and utility. We found the SS to be complex, with excellent data quality in notification/investigation reporting and fair in monitoring reporting, good acceptability, low sensitivity, representative, and regular timeliness and stability. The SS was considered useful when evaluating the ability to provide data characterizing disease epidemiology and facilitating planning control actions. Clinical care and laboratory network function must be evaluated to detect other possible problems that make the disorder continuously affect the municipality.