Quantifying gaps in the tuberculosis care cascade in Brazil: A mathematical model study using national program data.

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.

Temporal trend in the incidence of tuberculosis-HIV coinfection in Brazil, by macro-region, Federative Unit, sex and age group, 2010-2021.

OBJECTIVE: To analyze the temporal trend in the incidence of tuberculosis-HIV coinfection in Brazil, by macro-region, Federative Unit, sex and age group, from 2010 to 2021. METHODS: This was a time series study using surveillance data to estimate average annual percentage changes (AAPC), and 95% confidence intervals (95%CI) via joinpoint regression. RESULTS: 122,211 cases of tuberculosis-HIV coinfection were analyzed; a falling trend was identified for Brazil as a whole (AAPC = -4.3; 95%CI -5.1;-3.7), and in the country's Southern (AAPC = -6.2; 95%CI -6.9;-5.5) and Southeast (AAPC = -4.6; 95%CI -5.6;-3.8) regions, even more so during the COVID-19 pandemic (2020-2021); the greatest falling trend was seen in Santa Catarina (AAPC = -9.3; 95%CI -10.1;-8.5), while the greatest rising trend was found in Tocantins (AAPC = 4.1; 95%CI 0.1;8.6); there was a rising trend among males, especially in Sergipe (AAPC = 3.9; 95%CI 0.4;7.9), and those aged 18 to 34 years, especially in Amapá (AAPC = 7.9; 95%CI 5.1;11.5). CONCLUSION: The burden and trends of tuberculosis-HIV coinfection were geographically and demographically disparate.

Temporal trend in the incidence of tuberculosis-HIV coinfection in Brazil, by macro-region, Federative Unit, sex and age group, 2010-2021 / Tendencia temporal de la incidencia de coinfección tuberculosis-VIH en Brasil, por macrorregión, Unidad Federativa, sexo y grupo de edad, 2010-2021 / Tendência temporal da incidência de coinfecção tuberculose-HIV no Brasil, por macrorregião, Unidade da Federação, sexo e faixa etária, 2010-2021

ABSTRACT Objective To analyze the temporal trend in the incidence of tuberculosis-HIV coinfection in Brazil, by macro-region, Federative Unit, sex and age group, from 2010 to 2021. Methods: This was a time series study using surveillance data to estimate average annual percentage changes (AAPC), and 95% confidence intervals (95%CI) via joinpoint regression. Results: 122,211 cases of tuberculosis-HIV coinfection were analyzed; a falling trend was identified for Brazil as a whole (AAPC = -4.3; 95%CI -5.1;-3.7), and in the country's Southern (AAPC = -6.2; 95%CI -6.9;-5.5) and Southeast (AAPC = -4.6; 95%CI -5.6;-3.8) regions, even more so during the COVID-19 pandemic (2020-2021); the greatest falling trend was seen in Santa Catarina (AAPC = -9.3; 95%CI -10.1;-8.5), while the greatest rising trend was found in Tocantins (AAPC = 4.1; 95%CI 0.1;8.6); there was a rising trend among males, especially in Sergipe (AAPC = 3.9; 95%CI 0.4;7.9), and those aged 18 to 34 years, especially in Amapá (AAPC = 7.9; 95%CI 5.1;11.5). Conclusion The burden and trends of tuberculosis-HIV coinfection were geographically and demographically disparate.

RESUMEN Objetivo Analizar la tendencia temporal de la incidencia de la coinfección tuberculosis-VIH en Brasil, por Macrorregión, Unidad Federativa, sexo y grupo de edad, 2010-2021. Métodos Estudio de series de tiempo, con datos de vigilancia para la estimación de cambios porcentuales anuales promedio (CPAP) e intervalos de confianza del 95% (IC95%) vía joinpoint regression. Resultados Se analizaron 122.211 casos de coinfección tuberculosis-VIH; se identificó tendencia decreciente en Brasil (CPAP = -4,3; IC95% -5,1;-3,7) y en las regiones Sur (CPAP = -6,2; IC95% -6,9;-5,5) y Sudeste (CPAP = -4,6; IC95% -5,6;-3,8), aumentando durante la pandemia de covid-19; mayor tendencia decreciente ocurrió en Santa Catarina (CPAP = -9,3; IC95% -10,1;-8,5) y creciente en Tocantins (CPAP = 4,1; IC95% 0,1;8,6); hubo tendencia al aumento en el sexo masculino, especialmente Sergipe (CPAP = 3,9; IC95% 0,4;7,9), y en los de 18 a 34 años, especialmente Amapá (CPAP = 7,9; IC95% 5,1;11,5). Conclusión Había disparidades territoriales y demográficas en la carga y las tendencias de la coinfección tuberculosis-VIH.

RESUMO Objetivo Analisar a tendência temporal da incidência da coinfecção tuberculose-HIV no Brasil, por macrorregião, Unidade da Federação, sexo e faixa etária, 2010-2021. Métodos Estudo de séries temporais, com dados de vigilância, para a estimativa de variações percentuais anuais médias (VPAM) e intervalos de confiança de 95% (IC95%), por joinpoint regression. Resultados Foram analisados 122.211 casos de coinfecção tuberculose-HIV; identificou-se tendência decrescente no país (VPAM = -4,3; IC95% 5,1;-3,7) e em suas regiões Sul (VPAM = -6,2; IC95% -6,9;-5,5) e Sudeste (VPAM = -4,6; IC95% -5,6;-3,8), acentuada durante a pandemia de covid-19 (2020-2021); observou-se maior tendência decrescente em Santa Catarina (VPAM = -9,3; IC95% -10,1;-8,5) e maior tendência crescente no Tocantins (VPAM = 4,1; IC95% 0,1;8,6); houve tendência de incremento no sexo masculino, destacando-se Sergipe (VPAM = 3,9; IC95% 0,4;7,9), e na faixa etária de 18-34 anos, sobressaindo-se o Amapá (VPAM = 7,9; IC95% 5,1;11,5). Conclusão Verificaram-se disparidades territoriais e demográficas na carga e nas tendências da coinfecção tuberculose-HIV.

Economic Evaluations and Equity in the Use of Artificial Intelligence in Imaging Exams for Medical Diagnosis in People With Skin, Neurological, and Pulmonary Diseases: Protocol for a Systematic Review.

BACKGROUND: Traditional health care systems face long-standing challenges, including patient diversity, geographical disparities, and financial constraints. The emergence of artificial intelligence (AI) in health care offers solutions to these challenges. AI, a multidisciplinary field, enhances clinical decision-making. However, imbalanced AI models may enhance health disparities. OBJECTIVE: This systematic review aims to investigate the economic performance and equity impact of AI in diagnostic imaging for skin, neurological, and pulmonary diseases. The research question is "To what extent does the use of AI in imaging exams for diagnosing skin, neurological, and pulmonary diseases result in improved economic outcomes, and does it promote equity in health care systems?" METHODS: The study is a systematic review of economic and equity evaluations following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and CHEERS (Consolidated Health Economic Evaluation Reporting Standards) guidelines. Eligibility criteria include articles reporting on economic evaluations or equity considerations related to AI-based diagnostic imaging for specified diseases. Data will be collected from PubMed, Embase, Scopus, Web of Science, and reference lists. Data quality and transferability will be assessed according to CHEC (Consensus on Health Economic Criteria), EPHPP (Effective Public Health Practice Project), and Welte checklists. RESULTS: This systematic review began in March 2023. The literature search identified 9,526 publications and, after full-text screening, 9 publications were included in the study. We plan to submit a manuscript to a peer-reviewed journal once it is finalized, with an expected completion date in January 2024. CONCLUSIONS: AI in diagnostic imaging offers potential benefits but also raises concerns about equity and economic impact. Bias in algorithms and disparities in access may hinder equitable outcomes. Evaluating the economic viability of AI applications is essential for resource allocation and affordability. Policy makers and health care stakeholders can benefit from this review's insights to make informed decisions. Limitations, including study variability and publication bias, will be considered in the analysis. This systematic review will provide valuable insights into the economic and equity implications of AI in diagnostic imaging. It aims to inform evidence-based decision-making and contribute to more efficient and equitable health care systems. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48544.

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

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

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

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

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

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

Trends in occurrences of accidents by venomous animals in brazil: analysis of notifications from 2007 to 2021 / Tendências na ocorrência de acidentes por animais peçonhentos no brasil: análise das notificações de 2007 a 2021 / Tendencias en las ocurrencias de accidentes por animales venenosos en Brasil: análisis de las notificaciones de 2007 a 2021

Os acidentes por animais peçonhentos sãoum problema de saúde pública que apresenta elevado número de casos anuais no Brasil. Objetivo:descrever e analisar as ocorrências de acidentes por animais peçonhentos no Brasil e suas tendências entre 2007 e 2021.Metodologia:oestudo utilizou dados doSistema de Informação de Agravos de Notificação edo Sistema de Informação sobre Mortalidade.A população do estudo foi analisada segundo sexo, faixa etária e região de residência. A análise de tendência da série histórica foi realizada por regressão linear generalizada usando a estimação de Prais-Winsten.Resultados:as taxas de ocorrência padronizadas dobraram no período estudado (53,8/100.000 hab. em 2007 para 111,2/100.000 hab. em 2021). A região Nordeste apresentou a maior taxa de ocorrência padronizada (105,5/100.000 hab.). As regiões Nordeste, Sudeste e Centro-Oeste apresentaram maior taxa bruta de acidentes por escorpiões (75,8, 48,7 e 32,8 acidentes/100.000 hab., respectivamente), enquanto a região Norte por serpentes (54,2 acidentes/100.000 hab.) e a Região Sul por aranhas (60,3 acidentes/100.000 hab.). A taxa de mortalidade observada no período de 2007 a 2020 foi de 1,3 óbitos/1 milhão de hab. Entre as mortes registradas, 39,6% foram por picada de cobra.Conclusões:as tendências no Brasil foram ascendentes para ambos os sexos e para todas as faixas etárias. Apenas as regiões Norte e Sul apresentaram algumas categorias com tendências estacionárias. A análise dos dados epidemiológicos possibilita a identificação de populações-alvo e a elaboração de políticas públicas a fim de prevenir novos acidentes, bem como aprimorar o atendimento às pessoas acometidas por meio do planejamento da distribuição de soros antiofídicos (AU).

Accidents by venomous animals is a public health problem that presents a high number of annual cases in Brazil.Objective:to describe and analyze the occurrences of accidents by venomous animalsin Brazil and their trends between 2007 and 2021.Methodology:the study used Notifiable Diseases Information Systemand Mortality Information Systemdata. The study population wasanalyzed according to sex, age group, and region of residence. Trend analysis of the historical series was performed by generalized linear regression using Prais-Winsten estimation.Results:the standardized occurrence rates doubled during the studied period (53.8/100,000 inhab. in 2007 to 111.2/100,000 inhab. in 2021). The Northeast region had the highest standardized occurrence rate (105.5/100,000 inhab.). The Northeast, Southeast, and Midwest regions had a higher crude rate of accidents caused by scorpions (75.8, 48.7 and 32.8 accidents/100,000 inhab., respectively), while the North region by snakes (54.2 accidents/100,000 inhab.), and the South region by spiders (60.3 accidents/100,000 inhab.). Death rate observed in the period from 2007 to 2020 was 1.3deaths/1 million inhab. Among the deaths registered, 39.6% were from snakebite.Conclusions:trends in Brazil were ascendant for both sexes and for all age groups. Only the North and South regions showed some categories with stationary trends. The analysis of epidemiological data makes it possible the identification of target populations and elaborations of public policies in order to prevent new accidents, as well as the improvement of care for affected people by planning the distribution of antivenom serums (AU).

Los accidentes por animales venenosos son un problema de salud pública que presenta un elevado número de casos anuales en Brasil. Objetivo: describir y analizar lasocurrencias de accidentes por animales venenosos en Brasil y sus tendencias entre 2007 y 2021.Metodología: el estudio utilizó datos del sistema de información de enfermedades de declaración obligatoria(SINAN, según su sigla en portugués)ydelsistema de información de mortalidad. La población delestudio se analizó según sexo, grupo de edad y región de residencia. El análisis de tendencia de la serie histórica se realizó mediante regresión lineal generalizada utilizando la estimación de Prais-Winsten.Resultados: las tasas de ocurrencia estandarizadas se duplicaron durante el período estudiado (de 53,8/100000 hab. en 2007 a 111,2/100000 hab. en 2021). La región Nordeste presentó la mayor tasa de ocurrencia estandarizada (105,5/100000 hab.). Las regiones Nordeste, Sudeste y Medio Oeste presentaron la mayor tasa bruta de accidentes por alacranes (75,8, 48,7 y 32,8 accidentes/100000 hab., respectivamente), mientras que la región Norte por serpientes (54,2 accidentes/100000 hab.), y la Región Sur por arañas (60,3 accidentes/100000 hab.). La tasa de mortalidad observada en el período de 2007 a 2020 fue de 1,3 muertes/1 millón de hab. Entre las muertes registradas, el 39,6% fueron por mordedura de serpiente.Conclusiones: las tendencias en Brasil fueron ascendentes para ambos sexos y para todos los grupos de edad. Solo las regiones Norte y Sur presentaron algunas categorías con tendencias estacionarias. El análisis de datos epidemiológicos posibilita la identificación de poblaciones objetivo y la elaboración de políticas públicas para la prevención de nuevos accidentes, así como la mejora de la atención a las personas afectadas mediante la planificación de la distribución de sueros antiofídicos (AU).

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

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

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

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

Lutzomyia longipalpis TGF-ß Has a Role in Leishmania infantum chagasi Survival in the Vector.

Despite the increasing number of studies concerning insect immunity, Lutzomyia longipalpis immune responses in the presence of Leishmania infantum chagasi infection has not been widely investigated. The few available studies analyzed the role of the Toll and IMD pathways involved in response against Leishmania and microbial infections. Nevertheless, effector molecules responsible for controlling sand fly infections have not been identified. In the present study we investigated the role a signal transduction pathway, the Transforming Growth Factor-beta (TGF-ß) pathway, on the interrelation between L. longipalpis and L. i. chagasi. We identified an L. longipalpis homolog belonging to the multifunctional cytokine TGF-ß gene family (LlTGF-ß), which is closely related to the activin/inhibin subfamily and potentially involved in responses to infections. We investigated this gene expression through the insect development and in adult flies infected with L. i. chagasi. Our results showed that LlTGF-ß was expressed in all L. longipalpis developmental stages and was upregulated at the third day post L. i. chagasi infection, when protein levels were also higher as compared to uninfected insects. At this point blood digestion is finished and parasites are in close contact with the insect gut. In addition, we investigated the role of LlTGF-ß on L. longipalpis infection by L. i. chagasi using either gene silencing by RNAi or pathway inactivation by addition of the TGF-ß receptor inhibitor SB431542. The blockage of the LlTGF-ß pathway increased significantly antimicrobial peptides expression and nitric oxide levels in the insect gut, as expected. Both methods led to a decreased L. i. chagasi infection. Our results show that inactivation of the L. longipalpis TGF-ß signal transduction pathway reduce L. i. chagasi survival, therefore suggesting that under natural conditions the parasite benefits from the insect LlTGF-ß pathway, as already seen in Plamodium infection of mosquitoes.

Fatal necrotic tracheitis by Aviadenovirus in captive Alagoas curassows (Pauxi mitu) extinct from the wild.

Extinct from nature, captive young Alagoas curassows (Pauxi mitu) were found agonizing or dead with respiratory disease. Intranuclear inclusion bodies were found in the epithelia of the trachea, associated with marked necrotic tracheitis. An Aviadenovirus was isolated in chicken eggs and characterized genetically with 99% identity to the fowl Aviadenovirus A, as based on the hexon protein gene. This is the first report of respiratory disease caused by Aviadenovirus in any cracid species in Brazil, recommending for stricter biosecurity in the conservation premises. RESEARCH HIGHLIGHTS Fatal tracheitis in curassows extinct from nature was associated with Aviadenovirus A. Seven-month-old Alagoas curassows (Aves: Cracidae) died with haemorrhagic tracheitis. Aviadenovirus A with 99% identity to fowl adenovirus 1 was detected in dead curassows. Fatal tracheitis by Aviadenovirus was described in Pauxi mitu (Aves: Cracidae).

Investigação de possíveis grupos de risco para tuberculose humana por Mycobacterium bovis no estado de São Paulo / Investigation of possible risk groups for human tuberculosis caused by Mycobacterium bovis in the state of São Paulo

Objetivos: Identificar e comparar grupos de pacientes potencialmente de risco para tuberculose zoonótica (TBz), investigando a existência de fatores associados. Apresentar a distribuição espacial dos casos de tuberculose (TB) em bovinos e dos casos humanos. Método: Trata-se de estudo descritivo de casos confirmados de TB por todas as formas clínicas, residentes no estado de São Paulo, do período de 2006 a 2015. Definiram-se seis grupos potenciais de risco para TBz conforme critérios estabelecidos pela literatura. A análise descritiva foi realizada separadamente para pacientes menores de 15 anos e pacientes com 15 anos ou mais de idade, comparando os grupos identificados com a população de estudo por meio do teste do Qui-quadrado/Exato de Fisher. A existência de associação entre TB intestinal e/ou ganglionar (aceita como proxy de caso suspeito de TBz) e as exposições de interesse foi investigada pelas estimativas da odds ratio bruta e ajustada, com os respectivos intervalos de 95% de confiança, usando regressão logística. . A distribuição dos casos suspeitos foram apresentados em mapas temáticos. Resultados: Aplicados os critérios estabelecidos para o estudo, foram incluídos 190.368 casos de TB por todas as formas clínicas. Dentre estes: 134 tinham menos de 15 anos e residiam em municípios com até 20.000 habitantes (grupo A); os demais tinham 15 anos ou mais, sendo 1.238 trabalhadores rurais (grupo B); 201 magarefes (grupo C); 1.012 residiam em municípios com até 20.000 habitantes e com rebanhos infectados pela TB (grupo D); 2.776 imigrantes sul americanos (grupo E); e 160 imigrantes africanos (grupo F). Os grupos B e F foram os que mais apresentaram características semelhantes à TBz descrita na literatura, destacando-se no grupo B as maiores proporções de casos de residentes em municípios com caso de TB em bovinos e das formas intestinal e ganglionar periférica. Enquanto que no grupo F verificou-se maior proporção de casos com a forma clínica ganglionar periférica e de coinfecção HIV/TB. Os grupos A, C e D também apresentaram características distintas em relação ao total de casos de TB e associadas à TBz segundo a literatura, porém de maneira menos nítida. O grupo E não apresentou características relacionadas aos casos típicos da TBz. Dentre os pacientes menores de 15 anos de idade, após ajustes, destacaram-se como fatores associados à TB ganglionar e/ou intestinal, residir em município com menores índices de urbanização e com casos de TB em bovino conforme registro oficial. Entte os pacientes com 15 anos ou mais de idade, destacaram-se as associações com a ocupação de trabalhador rural e com a de magarefe. A distribuição dos tipos de rebanhos bovinos foi ampla sendo registrados casos da doença em animais em praticamente todas as regiões do estado. Conclusões: Os dados de vigilância da TB humana e animal, permitiram identificar grupos de pacientes com características associadas à TBz, salietando a importância da aplicação da proposta de Saúde Única, além de oferecerem subsídios para o desenvolvimento de um componente para TBz na vigilância da TB no estado de São Paulo, assim como, para pesquisas sobre o tema

Objectives: To identify and compare groups of patients potentially at risk for zoonotic tuberculosis (zTB), investigating the existence of associated factors. To present the spatial distribution of cases of tuberculosis (TB) in cattle and human cases. Method: This is a descriptive study of confirmed cases of TB by all clinical forms, residents in the state of São Paulo, from 2006 to 2015. Six potential risk groups for zTB were defined according to literature. The descriptive analysis was performed separately for patients younger than 15 years and patients 15 years of age or older, comparing the groups identified with the study population using the Chi-square / Fisher\'s Exact test. The existence of an association between intestinal and/or ganglion TB (accepted as a proxy for a suspected zTB case) and the exposures of interest was investigated by the estimates of the crude and adjusted odds ratio, with the respective 95% confidence intervals, using logistic regression. The distribution of suspected cases was presented in thematic maps. Results: After applying the criteria established for the study, 190,368 TB cases were included in all clinical forms. Among them: 134 were less than 15 years old and lived in municipalities with up to 20,000 inhabitants (group A); the others were 15 years old or over, with 1,238 rural workers (group B); 201 magarefes (group C); 1,012 resided in municipalities with up to 20,000 inhabitants and with herds infected by TB (group D); 2,776 South American immigrants (group E); and 160 African immigrants (group F). Groups B and F were the ones that presented the most similar characteristics to the zTB described in the literature. In group B, the highest proportions of cases of residents in municipalities with cases of TB in cattle and of the intestinal and peripheral ganglion forms were highlighted. While in the F group there was a higher proportion of cases with peripheral ganglionic form and HIV / TB co-infection. Groups A, C and D also presented distinct characteristics in relation to total TB cases and associated with TB, according to the literature, but less clearly. Group E did not present characteristics related to typical zTB cases. Among patients younger than 15 years of age, after adjustments, they were identified as factors associated with lymph node and/or intestinal TB, living in a municipality with lower rates of urbanization and with cases of TB in cattle according to official records. Among the patients aged 15 years and over, the associations with the occupation of rural workers and magarefe stood out. The distribution of bovine herd types was extensive and cases of the disease were recorded in animals in practically all regions of the state. Conclusions: Human and animal TB surveillance data allowed the identification of groups of patients with characteristics associated with zTB, stressing the importance of applying the One Health proposal, as well as providing subsidies for the development of a component for zTB in TB surveillance in the state of São Paulo, as well as for research on the subject

Molecular characterization of infectious laryngotracheitis virus in naturally infected egg layer chickens in a multi-age flock in Brazil.

The virus responsible for an outbreak of infectious laryngotracheitis (ILT) in a multi-age flock of egg layer chickens under quarantine in Brazil was characterized. Layer chickens from this area with circulating gallid herpesvirus 1 (GaHV 1) were evaluated using histopathology and molecular characterization techniques based on sequences of infected-cell polypeptide 4 (ICP4) and thymidine kinase (TK) genes. The infected chickens that were analyzed were PCR-positive for GaHV-1 in the trachea and negative in most trigeminal ganglia. The lack of ILT lesions in the conjunctiva and respiratory tissues, combined with detection of viral DNA in the trachea, was found to be associated with latent infection. The sequences from five farms obtained in the present study were identical, and there were no deletions within the 272- to 283-bp region of the ICP4 gene, as observed in the sequences of vaccine strains (CEO and TCO). The lack of a deletion in the ICP4 fragment analyzed in this study indicates that the chickens were infected with a field virus. The absence of the T252M mutation in a fragment of the TK gene, in addition to the low mortality rate observed, suggests that the outbreak in the state of Minas Gerais was not caused by a highly virulent strain but rather by a field virus of lower virulence. In addition, using phylogenetic reconstructions, it was found that this field strain was grouped together in a separate branch, apart from the previously characterized Brazilian strains. The introduction of vectored vaccines apparently has been effective in reducing clinical disease and lesions, and preventing new outbreaks of disease.