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BACKGROUND: BCG vaccination, originally used to prevent tuberculosis, is known to "train" the immune system to improve defence against viral respiratory infections. We investigated whether a previous BCG vaccination is associated with less severe clinical progression of COVID-19 METHODS: A case-control study comparing the proportion with a BCG vaccine scar (indicating previous vaccination) in cases and controls presenting with COVID-19 to health units in Brazil. Cases were subjects with severe COVID-19 (O2 saturation < 90%, severe respiratory effort, severe pneumonia, severe acute respiratory syndrome, sepsis, and septic shock). Controls had COVID-19 not meeting the definition of "severe" above. Unconditional regression was used to estimate vaccine protection against clinical progression to severe disease, with strict control for age, comorbidity, sex, educational level, race/colour, and municipality. Internal matching and conditional regression were used for sensitivity analysis. RESULTS: BCG was associated with high protection against COVID-19 clinical progression, over 87% (95% CI 74-93%) in subjects aged 60 or less and 35% (95% CI - 44-71%) in older subjects. CONCLUSIONS: This protection may be relevant for public health in settings where COVID-19 vaccine coverage is still low and may have implications for research to identify vaccine candidates for COVID-19 that are broadly protective against mortality from future variants. Further research into the immunomodulatory effects of BCG may inform COVID-19 therapeutic research.

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BACKGROUND: Children with congenital Zika syndrome (CZS) have severe damage to the peripheral and central nervous system (CNS), greatly increasing the risk of death. However, there is no information on the sequence of the underlying, intermediate, immediate, and contributing causes of deaths among these children. The aims of this study are describe the sequence of events leading to death of children with CZS up to 36 months of age and their probability of dying from a given cause, 2015 to 2018. METHODS AND FINDINGS: In a population-based study, we linked administrative data on live births, deaths, and cases of children with CZS from the SINASC (Live Birth Information System), the SIM (Mortality Information System), and the RESP (Public Health Event Records), respectively. Confirmed and probable cases of CZS were those that met the criteria established by the Brazilian Ministry of Health. The information on causes of death was collected from death certificates (DCs) using the World Health Organization (WHO) DC template. We estimated proportional mortality (PM%) among children with CZS and among children with non-Zika CNS congenital anomalies (CA) by 36 months of age and proportional mortality ratio by cause (PMRc). A total of 403 children with confirmed and probable CZS who died up to 36 months of age were included in the study; 81.9% were younger than 12 months of age. Multiple congenital malformations not classified elsewhere, and septicemia unspecified, with 18 (PM = 4.5%) and 17 (PM = 4.2%) deaths, respectively, were the most attested underlying causes of death. Unspecified septicemia (29 deaths and PM = 11.2%) and newborn respiratory failure (40 deaths and PM = 12.1%) were, respectively, the predominant intermediate and immediate causes of death. Fetuses and newborns affected by the mother's infectious and parasitic diseases, unspecified cerebral palsy, and unspecified severe protein-caloric malnutrition were the underlying causes with the greatest probability of death in children with CZS (PMRc from 10.0 to 17.0) when compared to the group born with non-Zika CNS anomalies. Among the intermediate and immediate causes of death, pneumonitis due to food or vomiting and unspecified seizures (PMRc = 9.5, each) and unspecified bronchopneumonia (PMRc = 5.0) were notable. As contributing causes, fetus and newborn affected by the mother's infectious and parasitic diseases (PMRc = 7.3), unspecified cerebral palsy, and newborn seizures (PMRc = 4.5, each) were more likely to lead to death in children with CZS than in the comparison group. The main limitations of this study were the use of a secondary database without additional clinical information and potential misclassification of cases and controls. CONCLUSION: The sequence of causes and circumstances involved in the deaths of the children with CZS highlights the greater vulnerability of these children to infectious and respiratory conditions compared to children with abnormalities of the CNS not related to Zika.

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OBJECTIVE: To evaluate the performance of tuberculosis control in Brazilian municipalities. METHODS: This is an ecological study on Brazilian municipalities that notified at least four new cases of tuberculosis, with a minimum of one new case of pulmonary tuberculosis between 2015 and 2018. The municipalities were stratified according to the population in < 50 thousand, 50-100 thousand, 100-300 thousand, and > 300 thousand inhabitants, and the k-means method was used to group them within each population range according to the performance of six indicators of the disease. RESULTS: A total of 2,845 Brazilian municipalities were included, comprising 98.5% (208,007/211,174) of new tuberculosis cases in the period. For each population range, three groups (A, B, and C) of municipalities were identified according to the performance of the indicators: A, the most satisfactory; B, the intermediates; and C, the least satisfactory. Municipalities in group A with < 100 thousand inhabitants presented results above the targets for laboratory confirmation (≥ 72%), abandonment (≤ 5%), and cure (≥ 90%), and comprised 2% of new cases of the disease. Conversely, municipalities of groups B and C presented at least five indicators with results below the targets - HIV testing (< 100%), contact investigation (< 90%), directly observed therapy (< 90%), abandonment (> 5%), and cure (< 90%) -, and corresponded to 66.7% of new cases of tuberculosis. In group C of municipalities with > 300 thousand inhabitants, which included 19 of the 27 capitals and 43.1% of new cases of tuberculosis, the lowest percentages of contact investigation (mean = 56.4%) and directly observed therapy (mean = 15.4%) were verified, in addition to high abandonment (mean = 13.9%) and low coverage of primary health care (mean = 66.0%). CONCLUSIONS: Most new cases of tuberculosis occurred in municipalities with unsatisfactory performance for disease control. Expanding the coverage of primary health care in these places can reduce abandonment and increase the contact investigation and directly observed therapy.

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ABSTRACT OBJECTIVE To evaluate the performance of tuberculosis control in Brazilian municipalities. METHODS This is an ecological study on Brazilian municipalities that notified at least four new cases of tuberculosis, with a minimum of one new case of pulmonary tuberculosis between 2015 and 2018. The municipalities were stratified according to the population in < 50 thousand, 50-100 thousand, 100-300 thousand, and > 300 thousand inhabitants, and the k-means method was used to group them within each population range according to the performance of six indicators of the disease. RESULTS A total of 2,845 Brazilian municipalities were included, comprising 98.5% (208,007/211,174) of new tuberculosis cases in the period. For each population range, three groups (A, B, and C) of municipalities were identified according to the performance of the indicators: A, the most satisfactory; B, the intermediates; and C, the least satisfactory. Municipalities in group A with < 100 thousand inhabitants presented results above the targets for laboratory confirmation (≥ 72%), abandonment (≤ 5%), and cure (≥ 90%), and comprised 2% of new cases of the disease. Conversely, municipalities of groups B and C presented at least five indicators with results below the targets - HIV testing (< 100%), contact investigation (< 90%), directly observed therapy (< 90%), abandonment (> 5%), and cure (< 90%) -, and corresponded to 66.7% of new cases of tuberculosis. In group C of municipalities with > 300 thousand inhabitants, which included 19 of the 27 capitals and 43.1% of new cases of tuberculosis, the lowest percentages of contact investigation (mean = 56.4%) and directly observed therapy (mean = 15.4%) were verified, in addition to high abandonment (mean = 13.9%) and low coverage of primary health care (mean = 66.0%). CONCLUSIONS Most new cases of tuberculosis occurred in municipalities with unsatisfactory performance for disease control. Expanding the coverage of primary health care in these places can reduce abandonment and increase the contact investigation and directly observed therapy.

RESUMO OBJETIVO Avaliar o desempenho no controle da tuberculose dos municípios brasileiros. MÉTODOS Estudo ecológico com municípios brasileiros que notificaram pelo menos quatro casos novos de tuberculose, com no mínimo um caso novo de tuberculose pulmonar entre 2015 e 2018. Os municípios foram estratificados de acordo com a população em < 50 mil, 50-100 mil, 100-300 mil e > 300 mil habitantes e foi utilizado o método k-médias para agrupá-los dentro de cada faixa populacional segundo desempenho de seis indicadores da doença. RESULTADOS Foram incluídos 2.845 municípios brasileiros abrangendo 98,5% (208.007/211.174) dos casos novos de tuberculose do período. Para cada faixa populacional identificou-se três grupos (A, B e C) de municípios segundo desempenho dos indicadores: A os mais satisfatórios, B os intermediários e C os menos satisfatórios. Municípios do grupo A com < 100 mil habitantes apresentaram resultados acima das metas para confirmação laboratorial (≥ 72%), abandono (≤ 5%) e cura (≥ 90%), e abrangeram 2% dos casos novos da doença. Por outro lado, os municípios dos grupos B e C apresentaram pelo menos cinco indicadores com resultados abaixo das metas - testagem HIV (< 100%), exame de contatos (< 90%), tratamento diretamente observado (< 90%), abandono (> 5%) e cura (< 90%) -, e corresponderam a 66,7% dos casos novos de tuberculose. Já no grupo C dos municípios com > 300 mil habitantes, que incluiu 19 das 27 capitais e 43,1% dos casos novos de tuberculose, encontrou-se os menores percentuais de exames de contatos (média = 56,4%) e tratamento diretamente observado (média = 15,4%), elevado abandono (média = 13,9%) e baixa cobertura da atenção básica (média = 66,0%). CONCLUSÕES Grande parte dos casos novos de tuberculose ocorreu em municípios com desempenho insatisfatório para o controle da doença, onde expandir a cobertura da atenção básica pode reduzir o abandono e elevar o exame de contatos e tratamento diretamente observado.

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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.

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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.

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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.

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OBJECTIVE: To analyse how testing the population influences the health indicators used to monitor the COVID-19 pandemic in the 50 countries with the highest number of diagnosed cases. METHODS: This was an ecological study using secondary data retrieved on 8/19/2020. Cumulative incidence, mortality rate, case-fatality rate, and proportion of positive tests were calculated. The data were described and presented graphically, with their respective Spearman Correlation Coefficients. RESULTS: The testing rate varied enormously between countries. Cumulative incidence and the proportion of positive tests were correlated with the number of tests, while the mortality rate and case-fatality rate showed low correlation with this indicator. CONCLUSION: Most countries do not test enough to ensure adequate monitoring of the pandemic, and this is reflected in the quality of the indicators. Expanding the number of tests is essential, but it needs to be accompanied by other measures, such as isolation of diagnosed cases and contact tracing.

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BACKGROUND: Leprosy continues to be an important cause of physical disability in endemic countries such as Brazil. Knowledge of determinants of these events may lead to better control measures and targeted interventions to mitigate its impact on affected individuals. This study investigated such factors among the most vulnerable portion of the Brazilian population. METHODS: A large cohort was built from secondary data originated from a national registry of applicants to social benefit programs, covering the period 2001-2015, including over 114 million individuals. Data were linked to the leprosy notification system utilizing data from 2007 until 2014. Descriptive and bivariate analyses lead to a multivariate analysis using a multinomial logistic regression model with cluster-robust standard errors. Associations were reported as Odds Ratios with their respective 95% confidence intervals. RESULTS: Among the original cohort members 21,565 new leprosy cases were identified between 2007 and 2014. Most of the cases (63.1%) had grade zero disability. Grades 1 and 2 represented 21 and 6%, respectively. Factors associated with increasing odds of grades 1 and 2 disability were age over 15 years old (ORs 2.39 and 1.95, respectively), less schooling (with a clear dose response effect) and being a multibacillary patient (ORs 3.5 and 8.22). Protective factors for both grades were being female (ORs 0.81 and 0.61) and living in a high incidence municipality (ORs 0.85 and 0.67). CONCLUSIONS: The findings suggest that the developing of physical disabilities remains a public health problem which increases the burden of leprosy, mainly for those with severe clinical features and worse socioeconomic conditions. Early diagnosis is paramount to decrease the incidence of leprosy-related disability and our study points to the need for strengthening control actions in non-endemic areas in Brazil, where cases may be missed when presented at early stages in disease. Both actions are needed, to benefit patients and to achieve the WHO goal in reducing physical disabilities among new cases of leprosy.

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There is increasing evidence that the use of masks is an indispensable protective measure against COVID-19, given the high transmissibility of the new coronavirus through the respiratory system, including by asymptomatic individuals. The use of cloth masks in public places has been established as a protective measure to be adopted alongside social distancing and hand hygiene. This narrative review aims to systematize the scientific evidence that informs the widespread use of cloth masks as a preventive measure against COVID-19 and to describe the evolution of positions contrary to or in favor of its use outside the home, in view of the advance of the new coronavirus pandemic globally. The scientific articles, technical notes, governmental decrees and other documents analyzed indicate that widespread use of masks has the potential to reduce the spread of the new coronavirus. We recommend that the Brazilian government adopt strategies to increase the supply of reusable cloth masks to the public, especially to vulnerable populations and to support studies on the impact of this measure to control the pandemic in the country. Finally, it is imperative to ensure that use of masks does not exacerbate stigmatization of racial groups that already face prejudice.

Acumulam-se evidências de que o uso de máscaras é uma medida indispensável de proteção à COVID-19, devido ao alto poder de transmissão do novo coronavírus por via respiratória, inclusive por indivíduos assintomáticos. Por sua vez, o uso das máscaras de tecido em locais públicos tem se consolidado como medida adicional de proteção às medidas de distanciamento social e higienização das mãos. Objetivou-se sistematizar as evidências científicas que justificam o amplo uso de máscaras de tecido como prevenção à COVID-19 e descrever a evolução dos posicionamentos contrários ou favoráveis ao seu uso em ambientes extradomiciliares, diante do avanço da pandemia do novo coronavírus pelo mundo. A triagem de artigos e documentos oficiais do Brasil e de outros países indica que o uso de máscaras em locais públicos tornou-se uma intervenção essencial graças ao potencial de reduzir a velocidade de propagação do novo coronavírus. Recomenda-se que o poder público adote estratégias para aumentar a oferta deste produto e fomente estudos para avaliação do impacto da medida no controle da pandemia no Brasil. É imperativo assegurar disponibilidade de máscaras a grupos socioeconomicamente desfavorecidos e garantir que determinados grupos raciais não sejam estigmatizados diante do uso de máscaras em ambientes extradomiciliares.

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