ABSTRACT OBJECTIVE Flattening the curve was the most promoted public health strategy worldwide, during the pandemic, to slow down the spread of the SARS-CoV-2 virus, and, consequently, to avoid overloading the healthcare systems. In Brazil, a relative success of public policies was evidenced. However, the association between public policies and the “flatten the curve” objectives remain unclear, as well as the association of different policies to reach this aim. This study aims to verify if the adoption of different public policies was associated with the flattening of the infection and death curves by covid-19 first wave in 2020. METHODS Data from the Sistema de Informação da Vigilância Epidemiológica da Gripe (Influenza Epidemiological Surveillance Information System – SIVEP-Gripe) and the Instituto Brasileiro de Geografia e Estatística (Brazilian Institute of Geography and Statistics – IBGE) were used to compute standardized incidence and mortality rates. The Oxford Covid-19 Government Response Tracker (OxCGRT) was used to obtain information about governmental responses related to the mitigation of pandemic effects, and the Human Development Index (HDI) was used as a measure of socioeconomic status. A non-linear least-square method was used to estimate parameters of the five-parameter sigmoidal curve, obtaining the time to reach the peak and the incremental rate of the curves. Additionally, ordinary least-square linear models were used to assess the correlation between the curves and the public policies adopted. RESULTS Out of 51 municipalities, 261,326 patients had SARS-CoV-2 infection. Stringency Index was associated with reducing covid-19 incremental incidence and death rates,in addition to delaying the time to reach the peak of both pandemic curves. Considering both parameters, economic support policies did not affect the incidence nor the mortality rate curves. CONCLUSION The evidence highlighted the importance and effectiveness of social distancing policies during the first year of the pandemic in Brazil, flattening the curves of mortality and incidence rates. Other policies, such as those focused on economic support, were not effective in flattening the curves but met humanitarian and social outcomes.

BACKGROUND Recurrence is a hallmark of ocular toxoplasmosis (OT), and conditions that influence its occurrence remain a challenge. Natural killer cells (NK) are effectors cells whose primary is cytotoxic function against many parasites, including Toxoplasma gondii. Among the NK cell receptors, immunoglobulin-like receptors (KIR) deserve attention due to their high polymorphism. OBJECTIVES This study aimed to analyse the influence of KIR gene polymorphism in the course of OT infection and its association with recurrences after an active episode. METHODS Ninety-six patients from the Ophthalmologic Clinic of the National Institute of Infectology Evandro Chagas were followed for up to five years. After DNA extraction, genotyping of the patients was performed by polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) utilising Luminex equipment for reading. During follow-up, 60.4% had a recurrence. FINDINGS We identified 25 KIR genotypes and found a higher frequency of genotype 1 (31.7%) with worldwide distribution. We note that the KIR2DL2 inhibitor gene and the gene activator KIR2DS2 were more frequent in patients without recurrence. Additionally, we observed that individuals who carry these genes progressed recurrence episodes slowly compared to individuals who do not carry these genes. MAIN CONCLUSIONS The KIR2DL2 and KIR2DS2 are associated as possible protection markers against ocular toxoplasmosis recurrence (OTR).

ABSTRACT OBJECTIVE Flattening the curve was the most promoted public health strategy worldwide, during the pandemic, to slow down the spread of the SARS-CoV-2 virus, and, consequently, to avoid overloading the healthcare systems. In Brazil, a relative success of public policies was evidenced. However, the association between public policies and the “flatten the curve” objectives remain unclear, as well as the association of different policies to reach this aim. This study aims to verify if the adoption of different public policies was associated with the flattening of the infection and death curves by covid-19 first wave in 2020. METHODS Data from the Sistema de Informação da Vigilância Epidemiológica da Gripe (Influenza Epidemiological Surveillance Information System – SIVEP-Gripe) and the Instituto Brasileiro de Geografia e Estatística (Brazilian Institute of Geography and Statistics – IBGE) were used to compute standardized incidence and mortality rates. The Oxford Covid-19 Government Response Tracker (OxCGRT) was used to obtain information about governmental responses related to the mitigation of pandemic effects, and the Human Development Index (HDI) was used as a measure of socioeconomic status. A non-linear least-square method was used to estimate parameters of the five-parameter sigmoidal curve, obtaining the time to reach the peak and the incremental rate of the curves. Additionally, ordinary least-square linear models were used to assess the correlation between the curves and the public policies adopted. RESULTS Out of 51 municipalities, 261,326 patients had SARS-CoV-2 infection. Stringency Index was associated with reducing covid-19 incremental incidence and death rates,in addition to delaying the time to reach the peak of both pandemic curves. Considering both parameters, economic support policies did not affect the incidence nor the mortality rate curves. CONCLUSION The evidence highlighted the importance and effectiveness of social distancing policies during the first year of the pandemic in Brazil, flattening the curves of mortality and incidence rates. Other policies, such as those focused on economic support, were not effective in flattening the curves but met humanitarian and social outcomes.

RESUMO Objetivo o diagnóstico da tuberculose pleural (TBpl) é um desafio devido à sua natureza paucibacilar e à necessidade de procedimentos invasivos. Este estudo visou identificar variáveis facilmente disponíveis, bem como construir um modelo preditivo para o diagnóstico da TBpl que possa permitir a utilização de uma estratégia alternativa precoce e acessível em unidades de cuidados básicos de saúde. Métodos um estudo transversal observacional comparou pacientes com TB e não TB seguidos em um hospital terciário brasileiro entre 2010 e 2018. Foi realizada uma análise de regressão logística incondicional que foi validado e aplicado em um modelo de classificação de árvore de decisão (CAD) em pacientes com diagnóstico empírico de TB. Foram calculados precisão (Prec), sensibilidade (Se), especificidade (Esp), assim como os valores preditivos positivos e negativos. Resultados de 1.135 pacientes com diagnóstico de TB, 160 foram considerados para análise (111 com TBpl confirmada e 49 com TBpl não confirmada. 58 pacientes não TB foram considerados como controles. Hiporexia [odds ratio ajustado (ORa) 27,39 (95% IC 6,26-119,89)] e características celulares/bioquímicas do líquido pleural (LP) (polimorfonuclear em duas categorias: 3%-14% ORa 26,22, 95% IC 7,11-96,68; e < 3% ORa 28,67, 95% IC 5,51-149,25; e proteína ≥ 5g/dL ORa 7,24, 95% IC 3,07-17,11) foram associadas a um risco mais elevado de tuberculose. O diagnóstico de CAD construído ao empregar essas variáveis mostrou valores de Prec = 87,6%, Se = 89,2%, Esp = 84,5% para o diagnóstico de TB e foi aplicado com sucesso em doentes com TB não confirmada. Conclusão o modelo CAD mostrou um excelente desempenho para o diagnóstico de TB e pode ser considerado como estratégia alternativa de diagnóstico, utilizando padrões clínicos em associação com características celulares/bioquímicas do LP, que são acessíveis e facilmente realizados em unidades de cuidados básicos de saúde.

ABSTRACT Objectives Pleural tuberculosis (PlTB) diagnosis is a challenge due to its paucibacillary nature and to the need of invasive procedures. This study aimed to identify easily available variables and build a predictive model for PlTB diagnosis which may allow earlier and affordable alternative strategy to be used in basic health care units. Methods An observational cross-sectional study compared PlTB and non-TB patients followed at a tertiary Brazilian hospital between 2010 and 2018. Unconditional logistic regression analysis was performed and a Decision Tree Classifier (DTC) model was validated and applied in additional PlTB patients with empiric diagnosis. The accuracy (Acc), sensitivity (Se), specificity (Sp), positive and negative predictive values were calculated. Results From 1,135 TB patients, 160 were considered for analysis (111 confirmed PlTB and 49 unconfirmed PlTB). Indeed, 58 non-TB patients were enrolled as controls. Hyporexia [adjusted odds ratio (aOR) 27.39 (95% CI 6.26 – 119.89)] and cellular/biochemical characteristics on pleural fluid (PF) (polimorphonuclear in two categories: 3-14% aOR 26.22, 95% CI 7.11 – 96.68 and < 3% aOR 28.67, 95% CI 5.51 – 149.25; and protein ≥ 5g/dL aOR 7.24, 95% CI 3.07 – 17.11) were associated with higher risk for TB. The DTC constructed using these variables showed Acc=87.6%, Se=89.2%, Sp=84.5% for PlTB diagnosis and was successfully applied in unconfirmed PlTB patients. Conclusion The DTC model showed an excellent performance for PlTB diagnosis and can be considered as an alternative diagnostic strategy by using clinical patterns in association with PF cellular/biochemical characteristics, which were affordable and easily performed in basic health care units.

BACKGROUND Distinct N-acetyltransferase 2 (NAT2) slow acetylators genotypes have been associated with a higher risk to develop anti-tuberculosis drug-induced hepatotoxicity (DIH). However, studies have not pointed the relevance of different acetylation phenotypes presented by homozygotes and compound heterozygotes slow acetylators on a clinical basis. OBJECTIVES This study aimed to investigate the association between NAT2 genotypes and the risk of developing DIH in Brazilian patients undergoing tuberculosis treatment, focusing on the discrimination of homozygotes and compound heterozygotes slow acetylators. METHODS/FINDINGS The frequency of NAT2 genotypes was analysed by DNA sequencing in 162 patients undergoing tuberculosis therapy. The mutation analyses revealed 15 variants, plus two new NAT2 mutations, that computational simulations predicted to cause structural perturbations in the protein. The multivariate statistical analysis revealed that carriers of NAT2*5/*5 slow acetylator genotype presented a higher risk of developing anti-tuberculosis DIH, on a clinical basis, when compared to the compound heterozygotes presenting NAT2*5 and any other slow acetylator haplotype [aOR 4.97, 95% confidence interval (CI) 1.47-16.82, p = 0.01]. CONCLUSION These findings suggest that patients with TB diagnosis who present the NAT2*5B/*5B genotype should be properly identified and more carefully monitored until treatment outcome in order to prevent the occurrence of anti-tuberculosis DIH.

ABSTRACT Background: An outbreak of acute hepatitis of unknown etiology in children was recently reported worldwide. We aimed to describe the burden of hospitalizations due to hepatitis of unknown etiology in children/adolescents in Brazilian public hospitals. Methods: We retrieved a database of all hospitalizations in the Brazilian Unified Health System (SUS) from January/2019 to February/2022 using the “microdatasus” R package. Hepatitis of unknown etiology was defined by the following International Classification of Diseases [ICD-10] codes: B19, B19.0, B19.9, K72.0, K72.9, K75, K75.9, R94.5, or R93.2. The incidence rates (95% confidence interval, IC) per 1,000 all-cause hospitalizations in different age strata [< 6 years; 6–11 years and 12–17 years] were estimated. Results: A total of 94,198 hospitalizations due to hepatic or infectious diseases with potential liver injury were analyzed. Of them, 1,535 children/adolescents [48.2% male sex, 41.6% aged < 6 years] were hospitalized with hepatitis with unknown etiology. The top ICD-10 codes were B19.9 [unspecified viral hepatitis without hepatic coma; 39.9% (n = 612)], K72.9 [hepatic failure, unspecified; 29.8% (n = 457)], and K72.0 [hepatic failure, not elsewhere classified; 14.5% (n = 223)]. A total of 8.5% (n = 131) of individuals required liver transplantation and 7.0% (n = 107) died during the hospital-stay. In 2021, the incidence rates (95% CI) of hospitalizations for hepatitis with unknown etiology were 7.80 (7.63–7.98), 17.96 (17.46–18.48) and 13.28 (12.95–13.62) per 1,000 all-cause hospitalizations in subjects aged < 6 years, 6–11 years and 12–17 years-old, respectively. Similarly, the incidence rates of hospitalization due to hepatitis with unknown etiology per 1,000 all-cause hospitalizations (CI95%) in January-February/2022 were 7.52 (7.11–7.94), 16.82 (15.68–18.03), and 13.96 (13.10–14.85) for children/adolescents with age < 6 years, 6–11 years, and 12–17 years, respectively. Conclusions: A non-negligible number of hospitalizations due to hepatitis with unknown etiology in children/adolescents was observed in the last years in Brazil. Up to 15% of those cases needed liver transplantation or died.

SUMMARY OBJECTIVE: This study aims to analyze the risk factors for in-hospital mortality in a cohort of patients admitted to a newly adapted intensive care unit in a public hospital in Rio de Janeiro. METHODS: This was an observational, retrospective, and descriptive study. Data were obtained from electronic medical records. Coronavirus disease 2019 (COVID-19) was diagnosed by detecting viral ribonucleic acid using reverse transcription polymerase chain reaction. Factors associated with the risk/protection from death were determined using the odds ratio and adjusted odds ratio. RESULTS: Fifty-one patients were admitted to the hospital. The median age of the patients was 63 years, 60% were male patients, and 54% were white patients. Sixty-seven percent of the patients were diagnosed with COVID-19. Sepsis at admission increased the chance of in-hospital death by 21 times (adjusted odds ratio=21.06 [0.79–555.2]; p=0.06). The strongest risk factor for death was the development of septic shock during hospitalization (adjusted odds ratio=98.56 [2.75–352.5]; p=0.01), and one in four patients had multidrug-resistant bacteria. Mechanical ventilation, vasopressors, neuromuscular blockers, and sedatives were also the risk factors for in-hospital mortality. The in-hospital mortality rate was 41%, and the mortality rate of patients on mechanical ventilation was 60%. The diagnosis of COVID-19 was not statistically related to the adverse outcomes. CONCLUSIONS: In this cohort, the strongest risk factor for in-hospital death was the development of nosocomial septic shock. Healthcare-associated infections have a significant impact on mortality rates. Therefore, to have a better outcome, it is important to consider not only the availability of beds but also the way healthcare is delivered.

RESUMO Objetivo: Avaliar o desempenho diagnóstico do teste Xpert MTB/RIF - teste molecular rápido para tuberculose, comparando-o com o da pesquisa de BAAR e da cultura, em amostras de LBA de pacientes com suspeita clínica de tuberculose pulmonar (TBP) que apresentam baciloscopia de escarro negativa ou produzem amostras com quantidade insuficiente de escarro. Métodos: Estudo retrospectivo de 140 casos suspeitos de TBP em pacientes que apresentaram baciloscopia negativa ou produziram amostras de escarro insuficientes e foram avaliados em um hospital-escola terciário na cidade do Rio de Janeiro (RJ). Todos os pacientes foram submetidos à fibrobroncoscopia com LBA. Os espécimes de LBA foram avaliados por meio da realização de pesquisa de BAAR, cultura para micobactérias e teste Xpert MTB/RIF. Resultados: Entre os 140 pacientes, resultados de todos os três exames microbiológicos estavam disponíveis para 73 (52,1%), dos quais 22 apresentaram cultura positiva, 17, pesquisa de BAAR positiva, e 20, teste Xpert MTB/RIF positivo. A sensibilidade, especificidade, valor preditivo positivo, valor preditivo negativo e precisão global da pesquisa de BAAR foram de 68,1%, 96,1%, 88,2%, 87,5% e 87,6%, respectivamente, contra 81,8%, 96,1%, 90,0%, 92,4% e 91,8%, respectivamente, do teste Xpert MTB/RIF. A concordância entre a pesquisa de BAAR e a cultura foi de 82,3% (kappa = 0,46; p < 0,0001), enquanto a concordância entre o teste Xpert MTB/RIF e a cultura foi de 91,8% (kappa = 0,8; p < 0,0001). Conclusões: Em amostras de LBA, o teste Xpert MTB/RIF tem melhor desempenho do que os métodos tradicionais, fornecendo uma alternativa confiável à análise do escarro em casos suspeitos de TBP. No entanto, a taxa de resultados discordantes merece uma reflexão cuidadosa.

ABSTRACT Objective: To assess the diagnostic performance of the Xpert MTB/RIF assay, a rapid molecular test for tuberculosis, comparing it with that of AFB staining and culture, in BAL fluid (BALF) samples from patients with clinically suspected pulmonary tuberculosis (PTB) who are sputum smear-negative or produce sputum samples of insufficient quantity. Methods: This was a retrospective study of 140 cases of suspected PTB in patients who were smear-negative or produced insufficient sputum samples and were evaluated at a tertiary teaching hospital in the city of Rio de Janeiro, Brazil. All of the patients underwent fiberoptic bronchoscopy with BAL. The BALF specimens were evaluated by AFB staining, mycobacterial culture, and the Xpert MTB/RIF assay. Results: Among the 140 patients, results for all three microbiological examinations were available for 73 (52.1%), of whom 22 tested positive on culture, 17 tested positive on AFB staining, and 20 tested positive on the Xpert MTB/RIF assay. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy for AFB staining were 68.1%, 96.1%, 88.2%, 87.5%, and 87.6%, respectively, compared with 81.8%, 96.1%, 90.0%, 92.4%, and 91.8%, respectively, for the Xpert MTB/RIF assay. The agreement between AFB staining and culture was 82.3% (kappa = 0.46; p < 0.0001), whereas that between the Xpert MTB/RIF assay and culture was 91.8% (kappa = 0.8; p < 0.0001). Conclusions: In BALF samples, the Xpert MTB/RIF assay performs better than do traditional methods, providing a reliable alternative to sputum analysis in suspected cases of PTB. However, the rate of discordant results merits careful consideration.

Resumo: Os Grupos Funcionais de Alimentação (GFA) são utilizados para determinar a dinâmica da comunidade de macroinvertebrados bentônicos e como uma ferramenta de biomonitoramento. Os principais objetivos deste estudo foram: avaliar os efeitos de variáveis de riacho na abundância e riqueza de GFAs e os atributos do ecossistema (razão GFA) como uma ferramenta para avaliar as condições ecológicas dos córregos da Mata Atlântica. Foram amostrados 146 locais com diferentes condições de impacto no Rio de Janeiro, Brasil. A riqueza foi significativamente diferente com as condições de impacto entre todos os GFA. Os modelos de efeito misto mostraram que os GFA diferiam em suas respostas às variáveis abióticas quanto à abundância e riqueza. Além disso, eles diferem nas áreas impactadas quando comparados as áreas intermediária e de referência. A razão de GFA encontrou diferenças significativas ao longo do gradiente de impacto. A análise da razão de GFA evidenciou-se uma ferramenta rápida e barata, com potencial para ser utilizada no monitoramento de ecossistemas aquáticos no bioma Mata Atlântica. No entanto, mais estudos serão necessários para calibrar o método especificamente para a região da Mata Atlântica.

Abstract: Benthic macroinvertebrates Functional Feeding Group (FFG) have been used to determine aquatic assemblage dynamics and as a biomonitoring tool. The main goals of this study were to assess the effects of stream variables on the abundance and richness of FFGs and evaluate ecosystem attributes (FFG ratios) as a tool to assess ecological conditions of Atlantic Rainforest streams. We sampled 146 sites with different impairment conditions in Rio de Janeiro, Brazil. Richness was significantly different among impairment conditions for all FFGs. Mixed-effect models show that aquatic macroinvertebrate FFGs differed in their responses to abiotic variables for abundance and richness. Also, they were reduced in the impaired sites when compared to intermediate and reference sites. The FFG ratio indicated significant differences along the impairment gradient. The FFG ratio analysis was shown to be a fast and cheap tool that can be used for monitoring aquatic ecosystems in the Atlantic Forest biome. However, further studies are required to calibrate the method specifically for the Atlantic Forest region.

RESUMO A Covid-19 é uma ameaça global que atrai pesquisadores de todas as áreas a fim de conhecer a história natural da doença e seus parâmetros epidemiológicos. O desenvolvimento tecnológico de vacinas, testes para diagnóstico e alvos terapêuticos tem mobilizado grande quantidade de recursos em curto tempo. A Avaliação de Tecnologias em Saúde (ATS), baseada em uma análise sistemática das propriedades, efeitos e/ou impactos das tecnologias em Saúde através de métodos e instrumentos validados internacionalmente para avaliar a qualidade e rigor metodológico dos estudos que demonstrem eficácia, efetividade e segurança, está sofrendo pressões, sem precedentes, devido à pandemia. Este artigo traz uma reflexão sobre a autorização emergencial do uso de tratamentos e testes diagnósticos que conflita com os preceitos da ATS. Apresentaremos também uma avaliação das tecnologias não farmacológicas de contenção da doença e seus impactos na economia doméstica e internacional, bem como as intervenções judiciais que impactam as decisões dos gestores no contexto excepcional da pandemia de Covid-19.

ABSTRACT Covid-19 is a global threat that attracts researchers from all areas to understand the natural history of the disease and its epidemiological parameters. The technological development of vaccines, diagnostic tests, and therapeutic targets has mobilized many resources in a short time. Health technology assessment (HTA), based on a systematic analysis of the properties, effects and/or impacts of health technologies through internationally-validated methods and instruments to assess the quality and methodological rigor of studies that demonstrate effectiveness, efficacy, and safety, is under unprecedented pressure due to the pandemic. This article also reflects on the emergency authorization of the use of treatments and diagnostic tests that conflict with HTA precepts. We will also evaluate non-pharmacological technologies of containment of the disease and their impacts on the domestic and international economy, as well as the judicial interventions that impact the decisions of managers in the exceptional context of the covid-19 pandemic.

BACKGROUND Dengue is an arthropod-borne viral disease with a majority of asymptomatic individuals and clinical manifestations varying from mild fever to severe and potentially lethal forms. An increasing number of genetic studies have outlined the association between host genetic variations and dengue severity. Genes associated to viral recognition and entry, as well as those encoding mediators of the immune response against infection are strong candidates for association studies. OBJECTIVES The aim of this study was to investigate the association between MBL2, CLEC5A, ITGB3 and CCR5 genes and dengue severity in children. METHODS A matched case-control study was conducted and 19 single nucleotide polymorphisms (SNPs) were investigated. FINDINGS No associations were observed in single SNP analysis. However, when MBL2 SNPs were combined in haplotypes, the allele rs7095891G/rs1800450C/ rs1800451C/rs4935047A/rs930509G/rs2120131G/rs2099902C was significantly associated to risk of severe dengue under α = 0.05 (aOR = 4.02; p = 0.02). A second haplotype carrying rs4935047G and rs7095891G alleles was also associated to risk (aOR = 1.91; p = 0.04). MAIN CONCLUSIONS This is the first study to demonstrate the association between MBL2 haplotypes and dengue severity in Brazilians including adjustment for genetic ancestry. These results reinforce the role of mannose binding lectin in immune response to DENV.