RESUMO
Venezuelan equine encephalitis virus (VEEV) is a disease typically confined to South and Central America, whereby human disease is characterised by a transient systemic infection and occasionally severe encephalitis, which is associated with lethality. Using an established mouse model of VEEV infection, the encephalitic aspects of the disease were analysed to identify biomarkers associated with inflammation. Sequential sampling of lethally challenged mice (infected subcutaneously) confirmed a rapid onset systemic infection with subsequent spread to the brain within 24 h of the challenge. Changes in inflammatory biomarkers (TNF-α, CCL-2, and CCL-5) and CD45+ cell counts were found to correlate strongly to pathology (R>0.9) and present previously unproven biomarkers for disease severity in the model, more so than viral titre. The greatest level of pathology was observed within the olfactory bulb and midbrain/thalamus. The virus was distributed throughout the brain/encephalon, often in areas not associated with pathology. The principal component analysis identified five principal factors across two independent experiments, with the first two describing almost half of the data: (1) confirmation of a systemic Th1-biased inflammatory response to VEEV infection, and (2) a clear correlation between specific inflammation of the brain and clinical signs of disease. Targeting strongly associated biomarkers of deleterious inflammation may ameliorate or even eliminate the encephalitic syndrome of this disease.
Assuntos
Vírus da Encefalite Equina Venezuelana , Encefalomielite Equina Venezuelana , Humanos , Cavalos , Camundongos , Animais , Fator de Necrose Tumoral alfa , Vírus da Encefalite Equina Venezuelana/fisiologia , Encéfalo , Inflamação/patologia , Quimiocinas , LeucócitosRESUMO
Plasmids expressing the V antigen of Yersinia pestis or the E2 glycoprotein of Venezuelan Equine Encephalitis (VEE) virus were used to vaccinate mice by intra-dermal or intra-muscular injection, or by particle-mediated bombardment using the Helios gene gun. After two immunizations, groups of mice which had received 4 microg doses of plasmid DNA using the gene gun had IgG levels which were higher than in other groups manually immunised with 12-fold more plasmid DNA. The immunoglobulin isotype profile was predominantly IgG1 following inoculation with either plasmid. Our results indicate that gene gun mediated vaccination can be used to increase the magnitude of the immune response to both bacterial and viral antigens expressed by plasmid DNA.
Assuntos
Antígenos de Bactérias/imunologia , Vacinas Bacterianas/administração & dosagem , Biolística/métodos , Vírus da Encefalite Equina Venezuelana/imunologia , Vacinas de DNA/administração & dosagem , Proteínas do Envelope Viral/imunologia , Vacinas Virais/administração & dosagem , Yersinia pestis/imunologia , Animais , Antígenos de Bactérias/genética , Vacinas Bacterianas/genética , Vacinas Bacterianas/imunologia , Pré-Escolar , DNA/administração & dosagem , DNA/genética , Vírus da Encefalite Equina Venezuelana/genética , Feminino , Ouro , Humanos , Injeções Intradérmicas , Injeções Intramusculares , Camundongos , Camundongos Endogâmicos BALB C , Plasmídeos/administração & dosagem , Plasmídeos/genética , Proteínas Citotóxicas Formadoras de Poros , Vacinas de DNA/genética , Vacinas de DNA/imunologia , Proteínas do Envelope Viral/genética , Vacinas Virais/genética , Vacinas Virais/imunologia , Yersinia pestis/genéticaRESUMO
Guaymi Indian children have recently been identified as a population group who are at risk for vitamin A deficiency with numerous cases of xerophthalmia with ocular perforation being reported. A four-day parasitological and nutritional clinic based survey was conducted with 335 Guaymi women and children in the towns of San Felix and Alto Caballero to identify the prevalence of parasitic infections and factors associated with malnutrition. A subsample of 79 children, under 19 years of age, from independent families was constructed for the current analysis. The results of the study indicated that 20% of the children had a plasma vitamin A concentration less than 20 micrograms/dl. Significant associations were identified between ascariasis, age, a food diversity score and vitamin A concentrations. Other indicators of nutritional status were also negatively associated with intestinal parasitic infections, and a modernization index, using multivariate regression analysis. In conclusion, this study identified several factors associated with poor nutritional status that can be used by health officers to identify Guaymi children at risk for malnutrition.
Assuntos
Indígenas Centro-Americanos , Enteropatias Parasitárias/epidemiologia , Deficiência de Vitamina A/epidemiologia , Adolescente , Carotenoides/sangue , Criança , Pré-Escolar , Características Culturais , Registros de Dieta , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estado Nutricional , Panamá/epidemiologia , Prevalência , Fatores Socioeconômicos , Vitamina A/sangue , Deficiência de Vitamina A/prevenção & controle , Xeroftalmia/prevenção & controleRESUMO
Guaymi Indian children have recenthy beem identified as a population group who are risk for vitamin A deficiency with numerous cases of xerophthalmia with ocular perforation being reported. A fourday parasitological and nutritional clinic based survey was conducted with 335 Guaymi women and children in the towns of San Félix and Alto Caballero to identify the prevalence of parasitic infections and factors associated with malnutrition. A subsample of 79 children, under 19 years of age, from independent families was constructed for the curret analysis. The results of the study indicated that 20% of the children had a plasma vitamin A concentration less than 20 *g/dl. Significant associations were identified between ascariasis, age, a food diversity score and vitamin A concentrations. Other indicators of nutritional status were also negatively associated with intestinal parasitic infections, and a modernization index, using multivariate regression analysis. In conclusion, this study identified several factors associated with poor nutritional status that can be used by health officers to identify Guaymi children at risk for malnutrition