Does IFN-γ play a role on the pathogenesis of non-atopic asthma in Latin America children?

In this work we explore differences in blood cells and cytokine profiles in children according to atopic status and asthma (atopic or non-atopic). The study involved measurement of Th1(IFN-γ) and Th2 (IL-5 and IL-13) cytokines in Dermatophagoides pteronyssinus stimulated peripheral blood leukocytes, blood cell count, skin prick test and specific IgE against common aeroallergens. Atopic status was associated with eosinophilia and production of Th2 type cytokines. Atopic asthma was associated with eosinophilia and non-atopic asthma was associated with IFN-γ and elevated monocytes in blood. IFN-γ and monocytes might play a role in immunopathology of non-atopic asthma in Latin American children.

Epidemiological characteristics and temporal trends of new leprosy cases in Brazil: 2006 to 2017.

Our study aims to describe trends in new case detection rate (NCDR) of leprosy in Brazil from 2006 to 2017 overall and in subgroups, and to analyze the evolution of clinical and treatment characteristics of patients, with emphasis on cases diagnosed with grade 2 physical disabilities. We conducted a descriptive study to analyze new cases of leprosy registered in the Brazilian Information System for Notificable Diseases (SINAN), from 2006-2017. We calculated the leprosy NCDR per 100,000 inhabitants (overall and for individuals aged < 15 and ≥ 15 years) by sex, age, race/ethnicity, urban/rural areas, and Brazilian regions, and estimated the trends using the Mann-Kendall non-parametric test. We analyzed the distributions of cases according to relevant clinical characteristics over time. In Brazil, there was a sharp decrease in the overall NCDR from 23.4/100,000 in 2006 to 10.3/100,000 in 2017; among children < 15 years, from 6.94 to 3.20/100,000. The decline was consistent in all Brazilian regions and race/ethnicity categories. By 2017, 70.2% of the cases were multibacillary, 30.5% had grade 1 (G1D) or 2 (G2D) physical disabilities at diagnosis and 42.8% were not evaluated at treatment completion/discharge; cases with G2D at diagnosis were mostly detected in urban areas (80%) and 5% of cases died during the treatment (leprosy or other causes). Although the frequency of leprosy NCDR decreased in Brazil from 2006 to 2017 across all evaluated population groups, the large number of cases with multibacillary leprosy, physical disabilities or without adequate evaluation, and among children suggest the need to reinforce timely diagnosis and treatment to control leprosy in Brazil.

Methods to evaluate COVID-19 vaccine effectiveness, with an emphasis on quasi-experimental approaches. / Métodos para avaliação da efetividade de vacinas para COVID-19 com ênfase em abordagens quase-experimentais.

The evaluation of vaccine effectiveness is conducted with real-world data. They are essential to monitor the performance of vaccination programmes over time, and in the context of the emergence of new variants. Until now, the effectiveness of COVID-19 vaccines has been assessed based on classic methods, such as cohort and test-negative case-control studies, which may often not allow for adequate control of inherent biases in the assignment of vaccination campaigns. The aim of this review was to discuss the study designs available to evaluate vaccine effectiveness, highlighting quasi-experimental studies, which seek to mimic randomized trials, by introducing an exogenous component to allocate to treatment, in addition to the advantages, limitations, and applicability in the context of Brazilian data. The use of quasi-experimental approaches, such as interrupted time series, difference-in-differences, propensity scores, instrumental variables, and regression discontinuity design, are relevant due to the possibility of providing more accurate estimates of COVID-19 vaccine effectiveness. This is especially important in scenarios such as the Brazilian, which characterized by the use of various vaccines, with the respective numbers and intervals between doses, applied to different age groups, and introduced at different times during the pandemic.

A avalição da efetividade de vacinas é feita com dados do mundo real e é essencial para monitorar o desempenho dos programas de vacinação ao longo do tempo bem como frente a novas variantes. Até o momento, a avaliação da efetividade das vacinas para COVID-19 tem sido baseada em métodos clássicos como estudos de coorte e caso controle teste-negativo, que muitas vezes podem não permitir o adequado controle dos vieses intrínsecos da alocação das campanhas de vacinação. O objetivo dessa revisão foi discutir os desenhos de estudo disponíveis para avaliação de efetividade das vacinas, enfatizando os estudos quase-experimentais, que buscam mimetizar os estudos aleatorizados ao introduzir um componente exógeno para atribuição ao tratamento, bem como suas vantagens, limitações e aplicabilidade no contexto dos dados brasileiros. O emprego de métodos quase-experimentais, incluindo as séries temporais interrompidas, o método de diferença em diferenças, escore de propensão, variáveis instrumentais e regressão descontínua, são relevantes pela possibilidade de gerar estimativas mais acuradas da efetividade de vacinas para COVID-19 em cenários como o brasileiro, que se caracteriza pelo uso de várias vacinas, com respectivos número e intervalos entre doses, aplicadas em diferentes faixas etárias e em diferentes momentos da pandemia.

Chronic intestinal helminth infections are associated with immune hyporesponsiveness and induction of a regulatory network.

Helminth infections have been associated with protection against allergy and autoimmune diseases. We investigated the effects of chronic infections with Ascaris lumbricoides and Trichuris trichiura (measured twice over a 5-year period) on cytokine and antibody responses. We collected blood from 1,060 children aged 4 to 11 years living in a poor urban area of Brazil and measured Th1 (gamma interferon [IFN-gamma]) and Th2 (interleukin-5 [IL-5] and IL-13) cytokines and the regulatory cytokine IL-10 in unstimulated and stimulated (with mitogen or A. lumbricoides antigens) cultures of peripheral blood leukocytes and levels of total IgE and anti-A. lumbricoides IgG4 and IgE in serum. Intestinal helminth infections were associated with an increased proportion of children producing IL-5 in response to A. lumbricoides and producing IL-10 spontaneously, especially among coinfected and chronically infected children. Helminth infections were associated with a generalized suppression of cytokine responses to mitogen. Levels of total IgE and anti-A. lumbricoides IgG4 and IgE were especially elevated in chronically infected children. In conclusion, intestinal helminth infections were associated with a typical Th2 immune response profile and with the induction of immune hyporesponsiveness that was associated with greater frequencies of the production of spontaneous IL-10.

Epidemiological characteristics and temporal trends of new leprosy cases in Brazil: 2006 to 2017 / Características epidemiológicas e tendências temporais de casos novos de hanseníase no Brasil: 2006 a 2017 / Características epidemiológicas y tendencias temporales de nuevos casos de lepra en Brasil: de 2006 a 2017

Abstract: Our study aims to describe trends in new case detection rate (NCDR) of leprosy in Brazil from 2006 to 2017 overall and in subgroups, and to analyze the evolution of clinical and treatment characteristics of patients, with emphasis on cases diagnosed with grade 2 physical disabilities. We conducted a descriptive study to analyze new cases of leprosy registered in the Brazilian Information System for Notificable Diseases (SINAN), from 2006-2017. We calculated the leprosy NCDR per 100,000 inhabitants (overall and for individuals aged < 15 and ≥ 15 years) by sex, age, race/ethnicity, urban/rural areas, and Brazilian regions, and estimated the trends using the Mann-Kendall non-parametric test. We analyzed the distributions of cases according to relevant clinical characteristics over time. In Brazil, there was a sharp decrease in the overall NCDR from 23.4/100,000 in 2006 to 10.3/100,000 in 2017; among children < 15 years, from 6.94 to 3.20/100,000. The decline was consistent in all Brazilian regions and race/ethnicity categories. By 2017, 70.2% of the cases were multibacillary, 30.5% had grade 1 (G1D) or 2 (G2D) physical disabilities at diagnosis and 42.8% were not evaluated at treatment completion/discharge; cases with G2D at diagnosis were mostly detected in urban areas (80%) and 5% of cases died during the treatment (leprosy or other causes). Although the frequency of leprosy NCDR decreased in Brazil from 2006 to 2017 across all evaluated population groups, the large number of cases with multibacillary leprosy, physical disabilities or without adequate evaluation, and among children suggest the need to reinforce timely diagnosis and treatment to control leprosy in Brazil.

Resumo: O estudo teve com objetivos descrever as tendências na taxa de detecção de casos novos (TDCN) de hanseníase no Brasil em 2006-2017, global e por subgrupos, e analisar a evolução das características clínicas e terapêuticas dos pacientes, com ênfase nos casos diagnosticados com incapacidade física grau 2. Realizamos um estudo descritivo par analisar casos novos de hanseníase registrados no Sistema de Informação de Agravos de Notificação (SINAN), 2006-2017. Calculamos a TDCN de hanseníase por 100.000 habitantes (global e para indivíduos < 15 e ≥ 15 anos de idade) por sexo, idade, raça/etnicidade, área urbana/rural e macrorregião do Brasil e estimamos as tendências com o teste não paramétrico de Mann-Kendall. Analisamos as distribuições de casos de acordo com características clínicas relevantes ao longo do tempo. No Brasil, houve uma queda marcante na TDCN global, de 23,4/100.000 em 2006 para 10,3/100.000 em 2017; entre crianças < 15 anos, de 6,94 para 3,20/100.000. A queda foi consistente em todas a regiões brasileiras e em todas as categorias de raça/etnicidade. Até 2017, 70,2% dos casos eram multibacilares, 30,5% apresentavam incapacidades físicas grau 1 (G1D) ou grau 2 (G2D) ao diagnóstico e 42,8% não foram avaliados ao encerramento do tratamento ou alta; os casos com G2D ao diagnóstico foram detectados majoritariamente nas áreas urbanas (80%), e 5% dos casos faleceram durante o tratamento (devido à hanseníase ou por outras causas). Embora a frequência da TDCN da hanseníase tenha diminuído no Brasil entre 2006 e 2017 em todos os grupos avaliados, o número grande de casos com hanseníase multibacilar, incapacidades físicas ou sem avaliação adequada e entre crianças sugere a necessidade de reforçar o diagnóstico e tratamento oportunos para controlar a hanseníase no Brasil.

Resumen: Se realizó este trabajo con el fin de describir la tendencia general y en subgrupos de la tasa de detección de nuevos casos de lepra (NCDR por sus siglas en inglés) en Brasil, entre 2006-2017, así como para analizar la evolución de las características clínicas y de tratamiento de los pacientes, con énfasis en los casos diagnosticados con un grado 2 de discapacidad física. Realizamos un estudio descriptivo para analizar los nuevos casos de lepra registrados en el Sistema Brasileño de Información de Enfermedades de Notificación (SINAN), 2006-2017. Calculamos la NCDR de lepra por cada 100.000 habitantes (general e individuos con una edad < 15 y ≥ 15 años) por sexo, edad, raza/etnicidad, áreas urbanas/rurales y regiones brasileñas, y estimamos las tendencias usando el test no paramétrico de Mann-Kendall. Analizamos las distribuciones de casos según las características clínicas relevantes a lo largo del tiempo. En Brasil, hubo una drástica disminución en general de NCDR de los 23,4/100.000 en 2006, a los 10,3/100.000 en 2017; entre niños < 15 años, desde los 6,94 a los 3,20/100.000. El decremento fue consistente en todas las regiones brasileñas y categorías de raza/etnicidad. En 2017, un 70,2% de los casos fueron multibacilares, un 30,5% tenían grado 1 (G1D) o 2 (G2D) discapacidad física en el diagnóstico y un 42,8% no fueron evaluados al completar el tratamiento/ser dados de alta; casos con G2D en el diagnóstico fueron en su mayoría detectados en áreas urbanas (80%) y un 5% de los casos murieron durante el tratamiento (lepra u otras causas). A pesar de la frecuencia de lepra los NCDR decrecieron en Brasil de 2006 a 2017, a través de todos los grupos de población evaluados, el elevado número de casos con lepra multibacilar, discapacidad física o sin una adecuada evaluación, y entre niños sugiere la necesidad de reforzar a tiempo el diagnóstico y tratamiento para controlar la lepra en Brasil.

Métodos para avaliação da efetividade de vacinas para COVID-19 com ênfase em abordagens quase-experimentais / Methods to evaluate COVID-19 vaccine effectiveness, with an emphasis on quasi-experimental approaches

Resumo A avalição da efetividade de vacinas é feita com dados do mundo real e é essencial para monitorar o desempenho dos programas de vacinação ao longo do tempo bem como frente a novas variantes. Até o momento, a avaliação da efetividade das vacinas para COVID-19 tem sido baseada em métodos clássicos como estudos de coorte e caso controle teste-negativo, que muitas vezes podem não permitir o adequado controle dos vieses intrínsecos da alocação das campanhas de vacinação. O objetivo dessa revisão foi discutir os desenhos de estudo disponíveis para avaliação de efetividade das vacinas, enfatizando os estudos quase-experimentais, que buscam mimetizar os estudos aleatorizados ao introduzir um componente exógeno para atribuição ao tratamento, bem como suas vantagens, limitações e aplicabilidade no contexto dos dados brasileiros. O emprego de métodos quase-experimentais, incluindo as séries temporais interrompidas, o método de diferença em diferenças, escore de propensão, variáveis instrumentais e regressão descontínua, são relevantes pela possibilidade de gerar estimativas mais acuradas da efetividade de vacinas para COVID-19 em cenários como o brasileiro, que se caracteriza pelo uso de várias vacinas, com respectivos número e intervalos entre doses, aplicadas em diferentes faixas etárias e em diferentes momentos da pandemia.

Abstract The evaluation of vaccine effectiveness is conducted with real-world data. They are essential to monitor the performance of vaccination programmes over time, and in the context of the emergence of new variants. Until now, the effectiveness of COVID-19 vaccines has been assessed based on classic methods, such as cohort and test-negative case-control studies, which may often not allow for adequate control of inherent biases in the assignment of vaccination campaigns. The aim of this review was to discuss the study designs available to evaluate vaccine effectiveness, highlighting quasi-experimental studies, which seek to mimic randomized trials, by introducing an exogenous component to allocate to treatment, in addition to the advantages, limitations, and applicability in the context of Brazilian data. The use of quasi-experimental approaches, such as interrupted time series, difference-in-differences, propensity scores, instrumental variables, and regression discontinuity design, are relevant due to the possibility of providing more accurate estimates of COVID-19 vaccine effectiveness. This is especially important in scenarios such as the Brazilian, which characterized by the use of various vaccines, with the respective numbers and intervals between doses, applied to different age groups, and introduced at different times during the pandemic.

Reducing occurrence of Giardia duodenalis in children living in semiarid regions: impact of a large scale rainwater harvesting initiative.

BACKGROUND: In Brazil, about two million people living in rural semiarid regions were benefited with the construction of rainwater cement cisterns, as an initiative from the program "One Million Cisterns" (P1MC). Nevertheless, few epidemiological studies have been conducted to assess health risks or protection effects associated with consumption of this water source. The aim of this study was to evaluate whether access to rainwater harvesting cisterns is associated with the decrease in the occurrence of Giardia duodenalis infections in children, compared to other children living in households supplied by other water sources. METHODOLOGY/PRINCIPAL FINDINGS: A quasi-experimental study with two concurrent cohorts was developed in two rural municipalities of the semiarid region of Brazil. A sample of 664 children, aged between 4 months and 5 years old, was followed up, of which 332 had access to rainwater cisterns (cistern group) and 332 did not, having water supplied from alternative sources (comparison group). In a period of approximately one year (2010) intestinal parasites were investigated in feces three times. The prevalence of G. duodenalis in children from the cistern group ranged from 4.8 to 10.5%, while the prevalence in the comparison group ranged from 7.6 to 16.7%. Multivariate analysis (GEE) showed a higher risk of G. duodenalis infection in children who did not have access to rainwater cisterns, when compared to children who did (OR 1.72; 95% CI 1.14-2.59). The other variables associated with G. duodenalis infection were: number of rooms per house (OR 0.89; 95% CI 0.80-0.99); family income (OR0.48; 95% CI 0.26-0.88); birth order (OR 1.72; 95% CI 1.17-2.51); preterm children (OR 1.70; 95% CI 1.19-2.43); and improper hand hygiene prior to food preparation (OR 4.78; 95% CI 1.95-11.76). CONCLUSIONS/SIGNIFICANCE: Ownership of a rainwater cistern is associated with a lower prevalence of G. duodenalis infection in children after adjustment for environmental and family-related factors. Nevertheless, the study suggests the necessity to complement physical interventions with actions related to personal and domestic hygiene to enable further reductions in parasite infections affecting mainly the underprivileged populations.