Surto de varicela entre imigrantes venezuelanos alojados em abrigos e ocupações no estado de Roraima, 2019: um estudo descritivo

Objective: To describe the chickenpox outbreak among Venezuelan immigrants in shelters and occupations in the municipalities of Pacaraima and Boa Vista, Roraima, Brazil, and the control measures implemented. Methods: Descriptive case series study, that happened between november 21 and december 13, 2019, using secondary database from the investigation of the outbreak, made available by the General Coordination of the National Immunization Program. Descriptive analysis was performed, using simple and relative frequency measures, and calculating measures of central tendency and dispersion. Results: Of the 9,591 immigrants, 38 active cases and 1,500 susceptible to chickenpox were detected. Among the active cases, 23 were female and the most affected age group those under 9 years old (17 cases). Conclusion: The identification of susceptible people in the investigation led to the adoption of immunization actions that controlled the transmission, preventing serious cases, deaths, and the overload of the local health care network.Objetivo: Descrever o surto de varicela entre imigrantes venezuelanos em abrigos e ocupações nos municípios de Pacaraima e Boa Vista, Roraima, Brasil, e as medidas de controle implementadas. Métodos: Estudo descritivo de tipo ‘série de casos’, realizado entre 21 de novembro e 13 de dezembro de 2019, sobre banco de dados secundários da investigação do surto disponibilizado pela Coordenação-Geral do Programa Nacional de Imunizações. Na análise descritiva, utilizou-se medidas de frequência simples e relativa e foram calculadas medidas de tendência central e dispersão. Resultados: Dos 9.591 imigrantes, detectaram-se 38 casos ativos e 1.500 suscetíveis à varicela. Dos casos ativos, 23 eram do sexo feminino e a faixa etária mais acometida foi a de menores de 9 anos (17 casos). Conclusão: Identificou-se pessoas suscetíveis à varicela na investigação; foram adotadas ações de imunização que controlaram a transmissão, evitando casos graves, óbitos e sobrecarga da rede de assistência à saúde local

Coorte retrospectiva de crianças e adolescentes hospitalizados por COVID-19 no Brasil do início da pandemia a 1º de agosto de 2020

Objectives: To characterize the study population, estimating the in-hospital lethality rate by state and analysing associated factors with COVID-19-related deaths. Methods: a retrospective cohort study was carried out of hospitalised children and adolescents diagnosed with COVID-19, confirmed by RT-PCR, whose outcome was death by COVID-19 or recovery, from 2020 March 1 to August 1. The data source was the Influenza Epidemiological Surveillance Information System (SIVEP-Gripe in Brazilian acronym), where patients with Severe Acute Respiratory Syndrome (SARS) are notified. Children were defined as those between the ages of 0 and 11, and adolescents those between 12 and 18. A bi and multivariate analysis were performed using Poisson Regression with robust variance, with adjusted Relative Risk as the final association measure. Results: A total of 4,930 cases were analysed; 2,553 (51.8%) were males, 2,335 (47.4%) were brown-skinned. The Federative Unit of Roraima presented the highest in-hospital case-fatality rate, with 68.8% (n=11/16). Multivariate analysis showed that belonging to the age group adolescent (RR = 1.59; 95% CI 1.12 - 2.25; p=0.009), SARS-critical patient (RR = 4.56; 95% CI 2, 77 - 7.51; p<0.001) and presenting immunological disorders (RR = 2.24; 95% CI 1.58 - 3.17; p<0.001) as comorbidities, were associated factors with death by COVID-19. Conclusion: it was observed that adolescents, SARS-critical patients, and presence of immunological disorders were important factors associated with death. Active surveillance and differentiated care are recommended for patients with chronic diseases and special immunological conditions.Objetivos: Caracterizar a população do estudo, estimar a taxa de letalidade intra-hospitalar por estado e analisar fatores associados aos óbitos por COVID-19. Métodos: Foi realizado estudo de coorte retrospectiva de crianças e adolescentes hospitalizados com diagnóstico de COVID-19, confirmados por RT-PCR, tendo como desfecho óbito por COVID-19 ou recuperado, entre 1º de março a 1º de agosto de 2020. A fonte de dados foi Sistema de Informação de Vigilância Epidemiológica da Gripe (SIVEP-Gripe), onde são notificados pacientes internados com Síndrome Respiratória Aguda Grave (SRAG). Considerou-se crianças aqueles com idade entre 0 e 11 anos completos e adolescentes aqueles com idade entre 12 e 18 anos completos. Realizou-se análise bi e multivariável por meio de Regressão de Poisson com variância robusta, sendo utilizado como medida de associação final o Risco Relativo ajustado (RRa). Resultados: Dos 4.930 casos analisados, 2.553 (51,8%) eram do sexo masculino. A raça/cor autodeclarada parda foi a mais frequente com 2.335 (47,4%). A Unidade Federativa de Roraima apresentou a maior taxa de letalidade intra-hospitalar com 68,8% (n=11/16). Análise multivariada mostrou que pertencer ao grupo etário adolescente (RR= 1,59; IC95% 1,12 – 2,25; p=0,009), ter sido classificado como SRAG-crítico (RR= 4,56; IC95% 2,77 – 7,51; p<0,001) e apresentar imunopatia (RR= 2,24; IC95% 1,58 – 3,17; p<0,001) como comorbidade se configuraram como fatores associados ao óbito pela COVID-19. Conclusão: Observou-se que ser adolescente, ter classificação de SRAG-crítico e imunopatia como comorbidade foram importantes fatores associados ao óbito. Recomenda-se vigilância ativa e cuidados diferenciados a portadores de doenças crónicas e condições imunológicas especiais

Role of Δ1-Pyrroline-5-Carboxylate Dehydrogenase Supports Mitochondrial Metabolism and Host-Cell Invasion ofTrypanosoma cruzi

Proline is crucial for energizing critical events throughout the life cycle of Trypanosoma cruzi, the etiological agent of Chagas disease. The proline breakdown pathway consists of two oxidation steps, both of which producereducing equivalents as follows: the conversion of proline to Δ1-pyrroline-5-carboxylate (P5C), and the subsequent conversion of P5C to glutamate. We have identified and characterized the Δ1-pyrroline-5-carboxylate dehydrogenase from T. cruzi (TcP5CDH) and report here on how this enzyme contributes to a central metabolic pathway in this parasite. Size-exclusionchromatography, two-dimensional gel electrophoresis, and small angle x-ray scattering analysis of TcP5CDH revealed an oligomericstate composed of two subunits of six protomers. TcP5CDH was found to complement a yeast strain deficient in PUT2 activity,confirming the enzyme's functional role; and the biochemical parameters (Km, kcat, and kcat/Km) of the recombinant TcP5CDH were determined, exhibiting values comparable with those from T. cruzi lysates. In addition, TcP5CDH exhibited mitochondrial staining during the main stages of the T. cruzi life cycle. mRNA and enzymatic activity levels indicated the up-regulation (6-fold change) of TcP5CDH during the infectivestages of the parasite. The participation of P5C as an energy source was also demonstrated. Overall, we propose that thisenzymatic step is crucial for the viability of both replicative and infective forms of T. cruzi

NR4A orphan nuclear receptor family members, NR4A2 and NR4A3, regulate neutrophil number and survival.

Neutrophil lifespan is plastic and highly responsive to factors that regulate cellular survival. Defects in neutrophil number and survival are common to both hematologic disorders and chronic inflammatory diseases. At sites of inflammation, neutrophils respond to multiple signals that activate protein kinase A (PKA) signaling, which positively regulates neutrophil survival. The aim of this study was to define transcriptional responses to PKA activation and to delineate the roles of these factors in neutrophil function and survival. In human neutrophil gene array studies, we show that PKA activation upregulates a significant number of apoptosis related genes, the most highly regulated of these being NR4A2 and NR4A3 Direct PKA activation by the site-selective PKA agonist pair N6/8-AHA and treatment with endogenous activators of PKA, including adenosine and PGE2, results in a profound delay of neutrophil apoptosis and concomitant upregulation of NR4A2/3 in a PKA dependent manner. NR4A3 expression is also increased at sites of neutrophilic inflammation in a human model of intradermal inflammation. PKA activation also promotes survival of murine neutrophil progenitor cells, and siRNA to NR4A2 decreases neutrophil production in this model. Antisense knockdown of NR4A2 and NR4A3 homologues in zebrafish larvae significantly reduces absolute neutrophil number without affecting cellular migration. In summary, we show that NR4A2 and NR4A3 are components of a downstream transcriptional response to PKA activation in the neutrophil, and that they positively regulate neutrophil survival and homeostasis

The Immunomodulatory Effects of Thalidomide on Human Immunodeficiency Virus-Infected Children

The safety and immune effects of low-dose thalidomide treatment (3 mg/kg/day for 28 days) were evaluated in a study involving 8 South African human immunodeficiency virus (HIV)-infected children. The children were 7-69 months old and in disease stages A1-C3. Thalidomide therapy did not affect virus load, even though none of the children was receiving antiretroviral therapy. Thalidomide stimulated CD8+ T cells in peripheral blood, which increased expression of the activation markers CD38 and human leukocyte antigen DR and of the memory cell marker CD45RO. The frequency of HIV gag-specific CD8+ T cells in peripheral blood increased in 3 of 4 children who were evaluated during treatment with thalidomide. Clinical adverse events were mild. In this study, thalidomide was found to be safe and well tolerated and caused significant immunomodulation at a low dose. This is the first report describing use of an oral drug that may enhance HIV-specific CD8+ T cell function in HIV-infected childre

Expression of the developmental Sonic hedgehog (Shh) signalling pathway is up-regulated in chronic lung fibrosis and the Shh receptor patched 1 is present in circulating T lymphocytes

During pulmonary development, Sonic hedgehog (Shh) and transforming growth factor beta1 (TGF-beta1) signalling both contribute to branching morphogenesis. In interstitial lung disease, the complex alveolar structure of the lung is disrupted and remodelled, which leads to fibrosis, loss of respiratory surface, morbidity, and mortality. It is well documented that TGF-beta1 is involved in fibrosis. However, little is known about Shh signalling in damaged epithelia. This study examined whether or not components of the Shh signalling pathway, as well as TGF-beta1, are expressed in human fibrotic lung disease (cryptogenic fibrosing alveolitis and bronchiectasis) and in murine experimental models of fibrotic and non-fibrotic chronic pulmonary inflammation. Using immunohistochemistry, it was observed that Shh, like TGF-beta1, is up-regulated in epithelial cells at sites of fibrotic disease but not non-fibrotic inflammation. The Shh receptor patched was detected in infiltrating mononuclear cells and alveolar macrophages, as well as normal resting peripheral blood T lymphocytes. Neither Shh nor patched is expressed by hyperproliferative goblet cells in inflammatory epithelium. This study demonstrates that patched is present in human peripheral CD4 and CD8 lymphocytes at both protein and mRNA levels. Taken together, these results suggest that components of the highly conserved Shh signalling pathway may play a role in the remodelling of damaged pulmonary epithelium and that damaged epithelium and cells of the immune system may communicate via this pathway