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Traumatic brain injury is a global health crisis, causing significant death and disability worldwide. Neuroinflammation that follows traumatic brain injury has serious consequences for neuronal survival and cognitive impairments, with astrocytes involved in this response. Following traumatic brain injury, astrocytes rapidly become reactive, and astrogliosis propagates from the injury core to distant brain regions. Homeostatic astroglial proteins are downregulated near the traumatic brain injury core, while pro-inflammatory astroglial genes are overexpressed. This altered gene expression is considered a pathological remodeling of astrocytes that produces serious consequences for neuronal survival and cognitive recovery. In addition, glial scar formed by reactive astrocytes is initially necessary to limit immune cell infiltration, but in the long term impedes axonal reconnection and functional recovery. Current therapeutic strategies for traumatic brain injury are focused on preventing acute complications. Statins, cannabinoids, progesterone, beta-blockers, and cerebrolysin demonstrate neuroprotective benefits but most of them have not been studied in the context of astrocytes. In this review, we discuss the cell signaling pathways activated in reactive astrocytes following traumatic brain injury and we discuss some of the potential new strategies aimed to modulate astroglial responses in traumatic brain injury, especially using cell-targeted strategies with miRNAs or lncRNA, viral vectors, and repurposed drugs.
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Astrocytes provide metabolic support to neurons, maintain ionic and water homeostasis, and uptake and recycle neurotransmitters. After exposure to the prototypical PAMP lipopolysaccharide (LPS), reactive astrocytes increase the expression of pro-inflammatory genes, facilitating neurodegeneration. In this study, we analyzed the expression of homeostatic genes in astrocytes exposed to LPS and identified the epigenetic factors contributing to the suppression of homeostatic genes in reactive astrocytes. Primary astrocytic cultures were acutely exposed to LPS and allowed to recover for 24, 72 h, and 7 days. As expected, LPS exposure induced reactive astrogliosis and increased the expression of pro-inflammatory IL-1B and IL-6. Interestingly, the acute exposure resulted in persistent hypermethylation of astroglial DNA. Similar hypermethylation was observed in highly reactive astrocytes from the traumatic brain injury (TBI) penumbra in vivo. Hypermethylation was accompanied by decreased expression of homeostatic genes including LDHA and Scl16a1 (MCT1) both involved in the lactate shuttle to neurons; glutamine synthase (GS) responsible for glutamate processing; Kcnj10 (Kir4.1) important for K+ homeostasis, and the water channel aquaporin-4 (Aqp4). Furthermore, the master regulator of DNA methylation, MAFG-1, as well as DNA methyl transferases DNMT1 and DNMT3a were overexpressed. The downregulation of homeostatic genes correlated with increased methylation of CpG islands in their promoters, as assessed by methylation-sensitive PCR and increased DNMT3a binding to the GS promoter. Treatment with decitabine, a DNMT inhibitor, prevented the LPS- and the HMGB-1-induced downregulation of homeostatic genes. Decitabine treatment also prevented the neurotoxic effects of these astrocytes in primary cortical cultures. In summary, our findings reveal that the pathological remodeling of reactive astrocytes encompasses not only the pro-inflammatory response but, significantly, also entails a long-term suppression of homeostatic gene expression with methylation of crucial CpG islands within their promoters.
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Astrócitos , Metilação de DNA , Regulação para Baixo , Homeostase , Astrócitos/metabolismo , Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Metilação de DNA/efeitos dos fármacos , Animais , Homeostase/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Células Cultivadas , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/genética , Ratos , Camundongos Endogâmicos C57BLRESUMO
Epilepsy, a chronic neurological disorder characterized by recurrent seizures, affects millions of individuals worldwide. Despite extensive research, the underlying mechanisms leading to epileptogenesis, the process by which a normal brain develops epilepsy, remain elusive. We, here, explored the immune system and spleen responses triggered by pilocarpine-induced status epilepticus (SE) focusing on their role in the epileptogenesis that follows SE. Initial examination of spleen histopathology revealed transient disorganization of white pulp, in animals subjected to SE. This disorganization, attributed to immune activation, peaked at 1-day post-SE (1DPSE) but returned to control levels at 3DPSE. Alterations in peripheral blood lymphocyte populations, demonstrated a decrease following SE, accompanied by a reduction in CD3+ T-lymphocytes. Further investigations uncovered an increased abundance of T-lymphocytes in the piriform cortex and choroid plexus at 3DPSE, suggesting a specific mobilization toward the Central Nervous System. Notably, splenectomy mitigated brain reactive astrogliosis, neuroinflammation, and macrophage infiltration post-SE, particularly in the hippocampus and piriform cortex. Additionally, splenectomized animals exhibited reduced lymphatic follicle size in the deep cervical lymph nodes. Most significantly, splenectomy correlated with improved neuronal survival, substantiated by decreased neuronal loss and reduced degenerating neurons in the piriform cortex and hippocampal CA2-3 post-SE. Overall, these findings underscore the pivotal role of the spleen in orchestrating immune responses and neuroinflammation following pilocarpine-induced SE, implicating the peripheral immune system as a potential therapeutic target for mitigating neuronal degeneration in epilepsy.
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Doenças Neuroinflamatórias , Pilocarpina , Baço , Estado Epiléptico , Animais , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/patologia , Baço/imunologia , Baço/patologia , Masculino , Doenças Neuroinflamatórias/patologia , Doenças Neuroinflamatórias/induzido quimicamente , Doenças Neuroinflamatórias/imunologia , Esplenectomia , Ratos Sprague-Dawley , Hipocampo/patologia , Modelos Animais de Doenças , Linfócitos T/imunologia , Córtex Piriforme/patologia , Neurônios/patologiaRESUMO
Astrocytes are the main homeostatic cells in the central nervous system (CNS) and they have an essential role in preserving neuronal physiology. After brain injury, astrocytes become reactive, and that involves a profound change in the astroglial gene expression program as well as intense cytoskeleton remodeling that has been classically shown by the up-regulation of glial fibrillary acidic protein (GFAP), a pan-reactive gene over-expressed in reactive astrocytes, independently of the type of injury. Using the stab wound rodent model of penetrating traumatic injury in the cortex, we here studied the reactive astroglial morphology and reactive microgliosis in detail at 1, 3, 7, 14, and 28 days post-injury (dpi). By combining immunohistochemistry, morphometrical parameters, and Sholl analysis, we segmented the astroglial cell population into clusters of reactive astrocytes that were localized in the core, penumbra, and distal regions of the stab wound. Specifically, highly reactive clusters with more complex morphology, increased C3, decreased aquaporin-4 (AQP4), and glutamine synthetase (GS) expression, were enriched at 7 dpi when behavioral alterations, microgliosis, and neuronal alterations in injured mice were most significant. While pro-inflammatory gain of function with peripheral lipopolysaccharide (LPS) administration immediately after a stab wound expanded these highly reactive astroglial clusters, the treatment with the NF-κB inhibitor sulfasalazine reduced the abundance of this highly reactive cluster. Increased neuronal loss and exacerbated reactive microgliosis at 7 dpi were associated with the expansion of the highly reactive astroglial cluster. We conclude that highly reactive astrocytes found in stab wound injury, but expanded in pro-inflammatory conditions, are a population of astrocytes that become engaged in pathological remodeling with a pro-inflammatory gain of function and loss of homeostatic capacity. Controlling this astroglial population may be a tempting strategy to reduce neuronal loss and neuroinflammation in the injured brain.
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Among the emerging and reemerging arboviral diseases, Zika, dengue and chikungunya deserve special attention due to their wide geographical distribution and clinical severity. The three arboviruses are transmitted by the same vector and can present similar clinical syndromes, bringing challenges to their identification and register. Demographic characteristics and individual and contextual social factors have been associated with the three arboviral diseases. However, little is known about such associations among adolescents, whose relationships with the social environment are different from those of adult populations, implying potentially different places, types, and degrees of exposure to the vector, particularly in the school context. This study aims to identify sociodemographic and environmental risk factors for the occurrence of Zika, dengue, and chikungunya in a cohort of adolescents from the Study of Cardiovascular Risks in Adolescents-ERICA-in the cities of Rio de Janeiro/RJ and Fortaleza/CE, from January 2015 to March 2019. Cases were defined as adolescents with laboratory or clinical-epidemiological diagnosis of Zika, dengue, or chikungunya, notified and registered in the Information System for Notifiable Diseases (SINAN). The cases were identified by linkage between the databases of the ERICA cohort and of SINAN. Multilevel Cox regression was employed to estimate hazard ratios (HR) as measures of association and respective 95% confidence intervals (95%CI). In comparison with adolescents living in lower socioeconomic conditions, the risk of becoming ill due to any of the three studied arboviral diseases was lower among those living in better socioeconomic conditions (HR = 0.43; 95%CI: 0.19-0.99; p = 0.047) and in the adolescents who attended school in the afternoon period (HR = 0.17; 95%CI: 0.06-0.47; p<0.001). When compared to areas whose Building Infestation Index (BII) for Aedes aegypti was considered satisfactory, a BII in the school region classified as "alert" and "risk" was associated with a higher risk of arboviral diseases (HR = 1.62, 95%CI: 0.98-2.70; p = 0.062; HR = 3.72, 95%CI: 1.27-10.9; p = 0.017, respectively). These findings indicate that living in less favored socioeconomic conditions, attending school in the morning, and having a high BII for Ae. aegypti in school's region can contribute to an increased risk of infection by Zika, dengue, or chikungunya in adolescents. The identification of residential or school areas based on those variables can contribute to the implementation of control measures in population groups and priority locations.
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Aedes , Infecções por Arbovirus , Febre de Chikungunya , Dengue , Infecção por Zika virus , Zika virus , Adulto , Animais , Humanos , Adolescente , Febre de Chikungunya/epidemiologia , Brasil/epidemiologia , Dengue/epidemiologia , Mosquitos Vetores , Infecção por Zika virus/epidemiologiaRESUMO
This article aims to analyse the magnitude and profile of legal demands for public health goods and services, also verifying the presence of legal demands for neglected tropical diseases (NTDs) in the State of Piauí between 2000-2020. Cross-sectional descriptive study based on the databases of the Court of Justice of Piauí on lawsuits demanding from the Direct Public Administration, goods and health services. A total of 6,658 lawsuits were initially identified. After eligibility analysis, 1,384 cases (20.8%) were analysed, with an increase in demand from 2017. We highlight the characteristics: origin in the capital Teresina (614; 44.4%), 40 to 59 years of age (372; 26.9%), female (761; 55.0%), farmers (123; 8.9%), public legal assistance (1,063; 76.8%), upheld (594; 42.9%). Five (5; 0.4%) lawsuits for NTDs, one visceral leishmaniasis requesting transportation, with granting, four for leprosy (two medicines, one granted, other extinguished without resolution of the merit, one consultation and one exam granted). The judicialization of the right to health is expressive and growing in the State of Piauí. The low demand related to NTDs may translate into limited access not only to health care, but also to the judiciary.
O objetivo deste artigo é analisar a magnitude e o perfil das demandas judiciais por bens e serviços de saúde pública, verificando também a presença de demandas judiciais para doenças tropicais negligenciadas (DTNs) no Estado do Piauí entre 2000-2020. Estudo transversal descritivo a partir de bases de dados do Tribunal de Justiça do Piauí acerca de processos judiciais demandando bens e serviços de saúde à administração pública direta. Foram identificados inicialmente um total de 6.658 processos judiciais. Após análise de elegibilidade, 1.384 processos (20,8%) foram analisados, verificando-se aumento da demanda a partir de 2017. Ressalta-se as características: origem na capital Teresina (614; 44,4%), 40 a 59 anos de idade (372; 26,9%), sexo feminino (761; 55,0%), agricultores (123; 8,9%), assistência jurídica pública (1.063; 76,8%), julgados procedentes (594; 42,9%). Cinco (5; 0,4%) demandas judiciais para DTNs, uma leishmaniose visceral solicitando transporte, procedente; quatro para hanseníase (dois medicamentos, um concedido, outro extinto sem resolução do mérito, uma consulta e um exame, ambos concedidos). A judicialização do direito à saúde é expressiva e crescente no estado do Piauí. A baixa demanda relacionada a DTNs pode traduzir limitação de acesso não apenas à saúde, mas ao Poder Judiciário.
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Acessibilidade aos Serviços de Saúde , Direito à Saúde , Feminino , Humanos , Brasil , Estudos Transversais , Preparações FarmacêuticasRESUMO
BACKGROUND: To analyze the epidemiology, surveillance, and control strategies for trachoma in the state of Ceará, northeast Brazil, from 2007 to 2021. METHODS: This ecological study was based on secondary data from the Information System on Notifiable Diseases of the Secretary of Health of the state of Ceará. Data from school and home surveys for trachoma detection obtained during the study period were analyzed, the percentage of positivity was estimated, and sociodemographic and clinico-epidemiological factors were investigated. RESULTS: The coverage of trachoma surveillance and control actions in Ceará municipalities increased from 12.5% in 2007 to 55.9% in 2019, but with an average restriction of 8.0% during the COVID-19 pandemic. The estimated trachoma positivity (mean overall positivity) was less than 5.0% (2.76%, 95% CI 1.2-5.2), with a higher proportion of cases in the 5-9-year age group (45.0%, 95% CI 44.6-45.4), in females (53.2%, 95% CI 52.8-53.6), and rural areas (52.6%, 95% CI 52.2-53.0). Positivity above 10.0% was observed in the Litoral Leste/Jaguaribe and Sertão Central regions, with a higher occurrence of the follicular inflammatory clinical form (98.1%, 95% CI 98.0-98.2). CONCLUSIONS: Trachoma remains in the state of Ceará and is likely underreported. Despite recent advances, the fragility of health surveillance activities compromises the recognition of the actual magnitude and distribution of trachoma in the state. Accurate information is fundamental for planning, monitoring, and evaluating surveillance and disease control.
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COVID-19 , Tracoma , Feminino , Humanos , COVID-19/epidemiologia , Tracoma/diagnóstico , Tracoma/epidemiologia , Tracoma/prevenção & controle , Brasil/epidemiologia , Pandemias , PrevalênciaRESUMO
BACKGROUND: To analyze the temporal evolution of research on Neglected Tropical Diseases (NTDs) published by the Journal of the Brazilian Society of Tropical Medicine (JBSTM). METHODS: We performed an analysis of the scientific production in JBSTM on NTDs using an advanced search, which included authors' descriptors, title, and abstract, and by combining specific terms for each NTDs from 1991 to 2021. Data related to authors, countries of origin, institutions, and descriptors, were evaluated and analyzed over time. Bibliographic networks were constructed using VOSviewer 1.6.16. RESULTS: The JBSTM published 4,268 scientific papers during this period. Of these 1,849 (43.3%) were related to NTDs. The number of publications on NTDs increased by approximately 2.4-fold, from 352 (total 724) during 1991-2000 to 841 (total 2,128) during 2011-2021, despite the proportional reduction (48.6% versus 39.5%). The most common singular NTDs subject of publications included Chagas disease (31.4%; 581/1,849), leishmaniasis (25.5%, 411/1,849), dengue (9.4%, 174/1,849), schistosomiasis (9.0%; 166/1,849), and leprosy (6.5%, 120/1,849), with authorship mostly from Brazil's South and Southeast regions. CONCLUSIONS: Despite the proportional reduction in publications, JBSTM remains an important vehicle for disseminating research on NTDs during this period. There is a need to strengthen the research and subsequent publications on specific NTDs. Institutions working and publishing on NTDs in the country were concentrated in the South and Southeast regions, requiring additional investments in institutions in other regions of the country.
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Doença de Chagas , Hanseníase , Esquistossomose , Medicina Tropical , Humanos , Brasil , Doenças NegligenciadasRESUMO
BACKGROUND: Some authors claim that the clinical methods often employed to assess chronic venous leg ulcers (CVLU) are based on subjective interpretation. The treatments based on a subjective characterization could become a trial-and-error therapy, resulting in longer evolutions and high recurrence rates. PURPOSE: The aim of this work was to compare numeric parameters from acute and chronic venous leg ulcers to identify potential objective nonhealing parameters. METHODS: The study was performed with hospital outpatients from 2016 to 2019. Cohorts were established according to the ulcer evolution time. Data collected related to ulcer characteristics included exudate pH, lactate and glucose concentrations, temperatures, microbiology findings, and imaging study results. RESULTS: Approximately 83% of the examined ulcers were chronic. Seventy-one percent of CVLUs and 59% of the acute ulcers had a pH ≥8. A high variability was found for the concentration of glucose and lactate in exudates of both acute and chronic ulcers. Variations of temperatures of normal skin (ΔT1) and periulcer zone (ΔT2) in reference to the wound bed temperature with values above 1 could indicate the presence of an inflammatory process and be used as a new potential marker of inflammation. All the acute ulcers and 88% of CVLUs showed <80% of granulation tissue in the imaging study. Finally, more than 105 organisms per gram of tissuewere found in 100% of the analyzed samples. CONCLUSIONS: Whereas there were not significant differences among the clinical measured parameters between acute and chronic ulcers, further research on the use of objective measurable parameters is needed to establish cutoff points to differentiate the "chronic state" of an ulcer as a "nonhealing state" regardless of the evolution time. Also, the use of these easily obtainable and low-cost nonhealing parameters would be a new approach to accurately monitor this pathology.
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Úlcera , Úlcera Varicosa , Humanos , Cicatrização , Úlcera Varicosa/complicações , Úlcera Varicosa/terapia , Ácido Láctico/uso terapêutico , Glucose/uso terapêuticoRESUMO
To characterize the magnitude of hospital admissions and costs of patients with neglected tropical diseases, their time trends, and spatial patterns in Piauí, in the Northeast Region of Brazil, in 2001-2018. Ecological study of mixed designs, with calculation of relative risk (RR), time-trend analysis by Poisson regression, and inflection points, using data from neglected tropical diseases Hospital Admission Authorizations available in the Hospital Information System of the Brazilian Unified National Health System (SIH/SUS). Data showed 49,832 hospital admissions due to neglected tropical diseases in the period (rate: 86.70/100,000 inhabitants; 95%CI: 83.47; 89.93); of these, dengue (78.2%), leishmaniasis (8.6%), and leprosy (6.4%). The total cost was BRL 34,481,815.43, 42.8% of which referred to medium complexity cases. Higher risks of hospitalization occurred among people ≥ 60 years (RR = 1.8; 95%CI: 1.5; 2.2), mixed race/color (RR = 1.7; 95%CI: 1.1; 2.4), residents of municipalities presenting medium social vulnerability (RR = 1.5; 95% CI: 1.3; 1.6), and population size (RR = 1.6; 95%CI: 1.4; 1.9). The time trend showed a reduction in hospital admissions due to neglected tropical diseases, 2003-2018 (annual percent change - APC: -10.3; 95%CI: -14.7; -5.6). The spatial pattern showed clusters with higher rates of hospital admission in border municipalities located south of the Mid-north macroregion, north of the Semiarid macroregion, and south of the Cerrados macroregion. Piauí remains with high hospital admission rates and costs for neglected tropical diseases. Despite the reduction in time trends, knowledge burden, population groups, and municipalities at greater risk and vulnerability reinforce the importance of monitoring and strengthening control actions to maintain the reduction of the burden and costs of hospital admission due to neglected tropical diseases in the state.
Caracterizar a magnitude das internações hospitalares e custos por doenças tropicais negligenciadas, suas tendências temporais e padrões espaciais no Piauí, Nordeste do Brasil, 2001-2018. Estudo ecológico misto, com cálculo de risco relativo (RR) e análise de tendência temporal por regressão de Poisson, pontos de inflexão, utilizando-se dados de Autorizações de Internações Hospitalares por doenças tropicais negligenciadas via Sistema de Informações Hospitalares do Sistema Único de Saúde (SIH/SUS). Verificaram-se 49.832 internações hospitalares por doenças tropicais negligenciadas (taxa: 86,70/100 mil habitantes; IC95%: 83,47; 89,93) no período, principalmente dengue (78,2%), leishmanioses (8,6%) e hanseníase (6,4%). O custo total foi de R$ 34.481.815,43, sendo 42,8% de média complexidade. Maiores riscos de hospitalizações ocorreram em: pessoas ≥ 60 anos (RR = 1,8; IC95%:1,5; 2,2), etnia/cor parda (RR = 1,7; IC95%: 1,1; 2,4), residentes em municípios de média vulnerabilidade social (RR = 1,5; IC95%: 1,3; 1,6) e porte populacional (RR = 1,6; IC95%: 1,4; 1,9). A tendência temporal foi de redução nas taxas de internações hospitalares por doenças tropicais negligenciadas, 2003-2018 (variação percentual anual - APC: -10,3; IC95%: -14,7; -5,6). O padrão espacial apresentou aglomerados com maiores taxas de internações hospitalares nos municípios limítrofes ao sul da macrorregião Meio-norte, norte do Semiárido e sul dos Cerrados. O Piauí persiste com elevadas taxas de hospitalizações e custos por doenças tropicais negligenciadas. Apesar da redução nas tendências temporais, o conhecimento de sua carga, seus grupos populacionais e municípios de maior risco e vulnerabilidade reforçam a importância do monitoramento e fortalecimento das ações de controle para manutenção na redução da carga e custos de internações hospitalares por doenças tropicais negligenciadas no estado.
Caracterizar la magnitud de las internaciones hospitalarias y los costos por las enfermedades tropicales desatendidas, sus tendencias temporales y patrones espaciales en Piauí, Nordeste de Brasil, 2001-2018. Estudio ecológico mixto, con cálculo de riesgo relativo (RR), y análisis de tendencia temporal por regresión de Poisson, puntos de inflexión, utilizando datos de Autorizaciones de Internaciones Hospitalarias por enfermedades tropicales desatendidas a través del Sistema de Informaciones Hospitalarias del Sistema Único de Salud (SIH/SUS). Se verificó 49.832 internaciones hospitalarias por enfermedades tropicales desatendidas (tasa: 86,70/100.000 habitantes; IC95%: 83,47; 89,93) en el periodo, las más frecuentes dengue (78,2 %), leishmaniasis (8,6%) y lepra (6,4%). El costo total fue de BRL 34.481.815,43, siendo 42,8 %, fueron de mediana complejidad. Los mayores riesgos de hospitalización se dieron en: personas ≥ 60 años (RR = 1,8; IC95%: 1,5; 2,2), etnia/color pardo (RR = 1,7; IC95%: 1,1; 2,4), residentes en municipios de vulnerabilidad social media (RR = 1,5; IC95%: 1,3; 1,6) y tamaño de la población (RR = 1,6; IC95%: 1,4; 1,9). La tendencia temporal fue de reducción en las tasas de internaciones hospitalarias por enfermedades tropicales desatendidas, 2003-2018 (cambio porcentual anual - APC: -10,3; IC95%: -14,7; -5,6). El patrón espacial presentó conglomerados con mayores tasas de internaciones hospitalarias en los municipios limítrofes al sur de la macrorregión del Medio-norte, el norte del Semiárido, y sur de los Cerrados. El Piauí persiste con elevadas tasas de hospitalizaciones y costos por enfermedades tropicales desatendidas. A pesar de la reducción de las tendencias temporales, el conocimiento de su carga, los grupos poblacionales y los municipios de mayor riesgo y vulnerabilidad refuerzan la importancia del monitoreo y fortalecimiento de las acciones de control para mantenimiento en la reducción de la carga y los costos de internaciones hospitalarias por enfermedades tropicales desatendidas en el estado.
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Hanseníase , Brasil/epidemiologia , Cidades , Hospitalização , Hospitais , Humanos , Hanseníase/epidemiologia , Doenças Negligenciadas/epidemiologiaRESUMO
OBJECTIVE: To characterize databases of the courts of justice of Brazil as a potential tool for research in Collective Health, in its interface with the legal sciences. METHODS: Cross-sectional study of quantitative and descriptive nature, focusing on analysis of strategic management and judicial systems. RESULTS: Databases used by the Common Justice in the Federation Units to systematize judicial processes were identified and analyzed. A total of 123 databases were found in the courts of justice per state, with emphasis on the South and Northeast regions, in contrast to the North region, which has a smaller number of systems. This large number of judicial systems limits access to legal operators, and hinders the collection of evidence by health researchers and, consequently, impacts the strategic management of the Executive Branch. There were limitations from design to transparent and democratic data extraction by the users themselves, as well as restricted integration between bases. CONCLUSIONS: Although advances have been made in recent years by the courts of justice to unify these databases, the multiplicity of information systems used in the Common State Justice complicates the management of knowledge, limits the development of research, even when carried out by lawyers or researchers in the legal area, as well as generates slow data extraction for public management. It is recognized the need for additional efforts for standardization, as well as for improvement of these databases, expanding access, transparency and integration with a view to a transdisciplinary look between the field of Law and Collective Health.
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Saúde Pública , Justiça Social , Brasil , Estudos Transversais , HumanosRESUMO
Objective: To identify nationwide temporal trends and spatial patterns of gastric cancer-related mortality in Brazil. Methods: An ecological study was performed using death certificates registered from 2000 to 2019 in which gastric cancer was recorded as any cause of death (an underlying or associated cause). Trends over time were assessed using joinpoint regression models. Spatial and spatiotemporal clusters were identified by Kulldorff's space-time scan statistics to identify high-risk areas. Results: In 276 897/22 663 091 (1.22%) death certificates gastric cancer was recorded as any cause of death. Age-adjusted gastric cancer-related mortality increased significantly over time (annual percentage change [APC]: 0.7, 95% confidence interval [CI]: 0.5 to 0.8). The increase in mortality was more pronounced in the less-developed North and Northeast Regions (North Region, APC: 3.1, 95% CI: 2.7 to 3.5; Northeast Region, APC: 3.1, 95% CI: 2.5 to 3.7). Eight spatiotemporally associated high-risk clusters of gastric cancer-related mortality were identified in the North, South, Northeast and Central-West Regions, as well as a major cluster covering a wide geographical range in the South and Southeast Regions of Brazil during the first years of the study period (2000 to 2009). Conclusions: More recently, during 2010 to 2019, clusters of gastric cancer have been identified in the Northeast Region. The nationwide increase in mortality in this analysis of 20 years of data highlights the persistently high burden of gastric cancer in Brazil, especially in socioeconomically disadvantaged regions. The identification of these areas where the population is at high risk for gastric cancer-related mortality emphasizes the need to develop effective and intersectoral control measures.
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BACKGROUND: We analyzed the trends and spatial patterns of schistosomiasis-related mortality in Northeast Brazil in 2000-2019. METHODS: A mixed population-based ecological study was conducted, using information on the underlying or associated causes of death. We used Joinpoint regression analysis to calculate the trends. The spatial analysis included rates, spatial moving averages, and standardized mortality rates. The spatial dependence analysis was based on Getis-Ord's G and Gi* indices (Gi star) and local Moran's index to check for autocorrelation. RESULTS: A total of 5,814,268 deaths were recorded, of which 9,276 (0.16%) were schistosomiasis-related; 51.0% (n=4,732, adjusted rate 0.90/100,000 inhabitants [95% confidence interval (CI) 0.88-0.93]) were males; 40.0% (n=3,715, adjusted rate 7.40/100.000 inhabitants [95%CI: 7.16-7.64]) were ≥70 years old; 54.8% (n=5,087, crude rate 0.80/100,000 inhabitants) were of mixed/Pardo-Brazilian ethnicity; and 77.9% (n=7,229, adjusted rate 0.86/100,000 inhabitants [95%CI: 0.84-0.88]) lived outside state capitals. The highest proportion of deaths was in the state of Pernambuco (53.9%, n=4,996, adjusted rate 2.72/100,000 inhabitants [95%CI: 2.64-2.79]). Increasing mortality rate was verified in the state of Sergipe. On the coast of the state of Rio Grande do Norte and Bahia, there was spatial dependence of spatio-temporal risk patterns with clusters. Throughout the study period, we found positive spatial autocorrelation and cluster formation. CONCLUSIONS: In Northeast Brazil, schistosomiasis persists with a high mortality rate, especially in the coastal region, with heterogeneous spatial and temporal patterns. To eliminate schistosomiasis by 2030, it is necessary to strengthen the financing and management of the unified health system (SUS).
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Esquistossomose , Idoso , Brasil/epidemiologia , Meio Ambiente , Feminino , Humanos , Masculino , Análise de Regressão , Análise EspacialRESUMO
OBJETIVE: To analyze temporal trends and spatial patterns of mortality due to neglected tropical diseases (NTDs) in Piauí, Brazil, 2001-2018. METHODS: This was a mixed ecological study, with risk ratio (RR) calculation, spatiotemporal trend analysis, Poisson joinpoint regression, using data from the Mortality Information System. RESULTS: There were 2,609 deaths due to NTDs in the period (4.60/100,000 inhabitants), 55.2% were due to Chagas' disease. There was a higher risk of death in male (RR=1.76; 95%CI 1.25;2.46), being aged ≥60 years (RR=40.71; 95%CI 10.01;165.53), municipalities with medium vulnerability social (RR=1.76; 95%CI 1.09;2.84), smaller population size (RR=1.99; 95%CI 1.28;3.10) and the Cerrados macro-region (RR=4.51; 95%CI 2.51;8.11). There was an upward trend in mortality rates from 2001-2008 and a falling trend from 2009-2018. CONCLUSION: Mortality due to NTDs in Piauí remains high, particularly due to Chagas' disease, among groups with greater vulnerability, with concentration of higher rates in the southwest of the Semiarid macro-region and the northeast and south of the Cerrados macro-region.
Assuntos
Doença de Chagas , Doenças Negligenciadas , Brasil/epidemiologia , Doença de Chagas/epidemiologia , Humanos , Masculino , Doenças Negligenciadas/epidemiologia , Razão de Chances , Análise Espaço-TemporalRESUMO
OBJECTIVE: To analyze the temporal trend and spatial patterns of schistosomiasis-related morbidity in Northeast Brazil, 2001-2017. METHODS: Ecological study, of time series and spatial analysis, based on case notifications and hospital admission data, as provided by the Ministry of Health. RESULTS: Of a total of 15,574,392 parasitological stool examinations, 941,961 (6.0%) were positive, mainly on the coastline of Pernambuco, Alagoas and Sergipe states. There was a reduction from 7.4% (2002) to 3.9% (2017) of positive samples and in the temporal trend of the detection rate (APC-11.6*; Confidence Interval 95%-13.9 to -9.1). There was a total of 5879 hospital admissions, with 40.4% in Pernambuco state. The hospitalization rate reduced from 0.82 (2001) to 0.02 (2017) per 100,000 inhabitants. CONCLUSION: Despite the reduction in case detection and hospitalizations, the persistence of focal areas of the disease in coastal areas is recognized. This reduction may indicate a possible positive impact of control on epidemiological patterns, but also operational issues related to access to healthcare and the development of surveillance and control actions in the Unified Health System.
RESUMO
OBJECTIVE: Chagas disease (CD) globalization facilitated the co-infection with Human Immunodeficiency Virus (HIV) in endemic and non-endemic areas. Considering the underestimation of Trypanosoma cruzi (T. cruzi)-HIV co-infection and the risk of life-threatening Chagas Disease Reactivation (CDR), this study aimed to analyze the major co-infection clinical characteristics and its mortality rates. METHODS: This is a cross-sectional retrospective multicenter study of patients with CD confirmed by two serological or one parasitological tests, and HIV infection confirmed by immunoblot. CDR was diagnosed by direct microscopy with detection of trypomastigote forms in the blood or other biological fluids and/or amastigote forms in inflammatory lesions. RESULTS: Out of 241 patients with co-infection, 86.7% were from Brazil, 47.5% had <200 CD4+ T cells/µL and median viral load was 17,000 copies/µL. Sixty CDR cases were observed. Death was more frequent in patients with reactivation and was mainly caused by CDR. Other causes of death unrelated to CDR were the manifestation of opportunistic infections in those with Acquired Immunodeficiency Syndrome. The time between the co-infection diagnosis to death was shorter in patients with CDR. Lower CD4+ cells count at co-infection diagnosis was independently associated with reactivation. Similarly, lower CD4+ cells numbers at co-infection diagnosis and male sex were associated with higher lethality in CDR. Additionally, CD4+ cells were lower in meningoencephalitis than in myocarditis and milder forms. CONCLUSION: This study showed major features on T. cruzi-HIV co-infection and highlighted the prognostic role of CD4+ cells for reactivation and mortality. Since lethality was high in meningoencephalitis and all untreated patients died shortly after the diagnosis, early diagnosis, immediate antiparasitic treatment, patient follow-up and epidemiological surveillance are essentials in T. cruzi/HIV co-infection and CDR managements.
Assuntos
Doença de Chagas/mortalidade , Coinfecção/mortalidade , Atenção à Saúde , Infecções por HIV/mortalidade , Terapia de Imunossupressão , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/mortalidade , Adulto , Brasil/epidemiologia , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos , Doença de Chagas/parasitologia , Coinfecção/parasitologia , Estudos Transversais , Gerenciamento de Dados , Feminino , Infecções por HIV/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Trypanosoma cruzi , Carga ViralRESUMO
Synaptic alterations concomitant with neuroinflammation have been described in patients and experimental models of autism spectrum disorder (ASD). However, the role of microglia and astroglia in relation to synaptic changes is poorly understood. Male Wistar rats prenatally exposed to valproic acid (VPA, 450 mg/kg, i.p.) or saline (control) at embryonic day 10.5 were used to study synapses, microglia, and astroglia in the prefrontal cortex (PFC) at postnatal days 3 and 35 (PND3 and PND35). Primary cultures of cortical neurons, microglia, and astroglia isolated from control and VPA animals were used to study each cell type individually, neuron-microglia and microglia-astroglia crosstalk. In the PFC of VPA rats, synaptic changes characterized by an increase in the number of excitatory synapses were evidenced at PND3 and persisted until PND35. At PND3, microglia and astroglia from VPA animals were morphologically similar to those of age-matched controls, whereas at PND35, reactive microgliosis and astrogliosis were observed in the PFC of VPA animals. Cortical neurons isolated from VPA rats mimicked in vitro the synaptic pattern seen in vivo. Cortical microglia and astroglia isolated from VPA animals exhibited reactive morphology, increased pro-inflammatory cytokines, and a compromised miRNA processing machinery. Microglia from VPA animals also showed resistance to a phagocytic challenge. In the presence of neurons from VPA animals, microglia isolated from VPA rats revealed a non-reactive morphology and promoted neurite outgrowth, while microglia from control animals displayed a reactive profile and promoted dendritic retraction. In microglia-astroglia co-cultures, microglia from VPA animals displayed a reactive profile and exacerbated astrocyte reactivity. Our study indicates that cortical microglia from VPA animals are insensitive or adapted to neuronal cues expressed by neurons from VPA animals. Further, long-term in vivo microgliosis could be the result of altered microglia-astroglia crosstalk in VPA animals. Thus, our study highlights cortical microglia-astroglia communication as a new mechanism implicated in neuroinflammation in ASD; consequently, we propose that this crosstalk is a potential target for interventions in this disorder.