ABSTRACT
Visceral leishmaniasis (VL) is a potentially fatal disease, in which the treatment based on chemotherapy is considered toxic. The cure of disease is associated with the life-long Th1-type immunity against the infection. The Th1-related cytokines production by peripheral blood mononuclear cells (PBMCs) seems to be crucial for host control of parasite load and clinical cure. In the current study, we used five proteins (IgE-dependent histamine-releasing factor [HRF], LiHyD, LiHyV, LiHyT and LiHyp6) recently shown to be antigenic and/or immunogenic in the canine VL, aiming to evaluate the antigen-specific antibody levels and cytokine production in PBMCs culture supernatants collected from VL patients before and after anti-VL treatment. In the results, when PBMCs were exposed to rHRF, rLiHyD and rLiHyT, higher IFN-γ and lower IL-10 levels were observed in all patients that were treated and clinically cured. Analysis of specific antibody subclasses was in line with in vitro cellular response, since a higher IgG2 production was found in the treated and cured patients, when compared to the IgG1 subclass levels. In addition, evaluating the diagnostic efficacy of the recombinant molecules, the rHRF, rLiHyD and rLiHyT proteins showed the best results in the serology assays to identify all VL patients, as well as these antigens were not recognized by antibodies in sera from non-infected subjects or those with leishmaniasis-related diseases. Our results corroborate the view that clinical cure of VL is associated with a sustained Th1-related response, and indicate the potential use of rHRF, rLiHyD and rLiHyT as immune biomarkers of VL treatment.
Subject(s)
Antibodies, Protozoan/blood , Biomarkers, Pharmacological/blood , Leishmania infantum/physiology , Leishmaniasis, Visceral/diagnosis , Leukocytes, Mononuclear/immunology , Th1 Cells/immunology , Adult , Animals , Antigens, Protozoan/genetics , Antigens, Protozoan/immunology , Cells, Cultured , Disease Progression , Dogs , Female , Humans , Interferon-gamma/metabolism , Interleukin-10/metabolism , Leishmaniasis, Visceral/therapy , Leukocytes, Mononuclear/parasitology , Lymphocyte Activation , Male , Middle Aged , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Young AdultABSTRACT
Serological methods used to diagnose visceral leishmaniasis (VL) are considered minimally invasive, but they present problems related with their sensitivity and/or specificity. In this study, a subtractive selection using the phage display technology against antibodies from healthy subjects living in endemic and non-endemic areas of disease, as well as from Chagas disease patients and those developing active VL, was developed. The aim of this study was to select bacteriophage-fused epitopes to be used in the serodiagnosis of human VL. Eight phage clones were selected after the bio-panning rounds, and their reactivity was evaluated in a phage-ELISA assay against a human serological panel. A wild-type clone and the recombinant K39-based immunochromatographic test were used as controls. In the results, it was shown that all clones showed an excellent performance to serologically identify VL patients, demonstrating the feasibility of the isolated phages for developing a specific and sensitive serodiagnosis of human VL.
Subject(s)
Antigens, Protozoan/immunology , Cell Surface Display Techniques/methods , Enzyme-Linked Immunosorbent Assay/methods , Leishmania infantum/immunology , Leishmaniasis, Visceral/diagnosis , Protozoan Proteins/immunology , Adult , Antibodies, Protozoan/immunology , Chagas Disease/immunology , Epitopes/immunology , Female , Humans , Male , Middle Aged , Sensitivity and Specificity , Serologic Tests/methods , Young AdultABSTRACT
OBJECTIVES: Recent clinical data suggest that severe kala-azar (or visceral leishmaniasis) is an exaggerated innate immune response mediated by inflammatory cytokines, leading to a systemic inflammatory syndrome similar to what is observed in malaria, sepsis and other diseases. We tested this hypothesis by measuring serum cytokines in individuals with kala-azar. METHODS: We compared patients with severe kala-azar (i.e. hemorrhagic manifestations, n = 38) with patients without evidence of hemorrhage (n = 96). We conducted a detailed clinical and laboratory evaluation, measuring serum IL-1beta, IL-6, IL-8, IL-10, IL-12, interferon-gamma, and TNF-alpha, and markers of disseminated intravascular coagulation (DIC). RESULTS: Infants had higher levels of inflammatory cytokines, while HIV-infected patients had lower concentrations of IL-10 and interferon-gamma. Higher levels of IL-6, interferon-gamma, and IL-8 were found among deceased patients. IL-8 and interferon-gamma were independently associated with bleeding. Several cytokines were associated with different signs of severe clinical and laboratory manifestations, including DIC. IL-6 was highly positively and independently associated with IL-1beta, IL-8, IL-10, and negatively associated with TNF-alpha. IL-1beta and TNF-alpha were also highly independently associated with disease severity. CONCLUSION: In its severe form, kala-azar, a neglected tropical disease, initiates a systemic inflammatory response that leads to DIC and other manifestations. Children may have higher risk of death due to the more intense cytokine release. The data supports the notion that IL-6 is the central cytokine that is associated with lethal disease, but interferon-gamma, IL1beta, IL-8, and TNF-alpha are also involved with disease severity. Inhibition of IL-6 is a potential target of adjuvant therapy for severe or pediatric forms of this disease.
Subject(s)
Cytokines/blood , HIV Seropositivity/immunology , Hemorrhage/immunology , Inflammation Mediators/blood , Leishmaniasis, Visceral/immunology , Adolescent , Adult , Brazil/epidemiology , Child , Child, Preschool , Female , HIV Seropositivity/blood , HIV Seropositivity/drug therapy , Hemorrhage/blood , Hemorrhage/drug therapy , Humans , Infant , Inflammation Mediators/immunology , Interferon-gamma/blood , Interleukin-10/blood , Interleukin-12/blood , Interleukin-1beta/blood , Interleukin-6/blood , Interleukin-8/blood , Leishmaniasis, Visceral/blood , Leishmaniasis, Visceral/drug therapy , Male , Severity of Illness Index , Tumor Necrosis Factor-alpha/bloodABSTRACT
OBJECTIVES: To present a detailed investigation of risk factors, symptoms, and laboratory and imaging tests that may be useful to establish the clinical laboratory diagnosis of visceral larva migrans (VLM) in children, demonstrating the importance of diagnosis and treatment to prevent complications in the eyes, liver, and other organs. SOURCES: Literature review using the MEDLINE and LILACS (1952-2009) databases, selecting the most recent and representative articles on the topic. SUMMARY OF THE FINDINGS: VLM is an infectious disease with non-specific clinical presentation, whose transmission is related to contact with dogs, especially puppies, and which may progress to late systemic complications in vital organs such as the eyes and the central nervous system. IgG (ELISA) anti-T. canis can be used to establish the laboratory diagnosis. Higher cutoff points suggest recent illness and lower cutoff points demonstrate mild infection or infection in remission. Therapeutic response may be assessed by means of eosinophil blood cell count. The present article provides the pediatrician with updated information regarding VLM, a disease of high prevalence worldwide and in Brazil. CONCLUSIONS: The diagnosis of VLM depends mainly on the presence of dogs in the child's household, associated with ELISA (IgG anti-T. canis), using excretory-secretory antigens of Toxocara canis. Prospective studies are warranted to assess the best drug therapy. Prevention is the most important strategy because of the high prevalence of T. canis in urban areas.
Subject(s)
Larva Migrans, Visceral , Toxocara canis , Animals , Child, Preschool , Dogs , Humans , Larva Migrans, Visceral/diagnosis , Larva Migrans, Visceral/immunology , Larva Migrans, Visceral/therapy , Larva Migrans, Visceral/transmission , Risk FactorsABSTRACT
OBJETIVOS: Apresentar investigação detalhada de fatores de risco, sintomatologia, exames laboratoriais e de imagem que possam contribuir para o diagnóstico clínico-laboratorial da larva migrans visceral (LMV) em crianças e mostrar a importância do diagnóstico e do tratamento para evitar complicações oculares, hepáticas e em outros órgãos. FONTES DOS DADOS: Revisão de literatura utilizando os bancos de dados MEDLINE e LILACS (1952-2009), selecionando os artigos mais atuais e representativos do tema. SÍNTESE DOS DADOS: LMV é uma doença infecciosa de apresentação clínica inespecífica cuja transmissão está relacionada ao contato com cães, principalmente filhotes, podendo evoluir com complicações sistêmicas tardias em órgãos vitais como o olho e sistema nervoso central. Para diagnóstico laboratorial, pode ser utilizado IgG (ELISA) anti-Toxocara canis, cujos pontos de corte mais elevados sugerem doença recente e, os mais baixos, infecção leve ou em resolução. A resposta terapêutica pode ser avaliada por meio da contagem de eosinófilos no sangue. Esse artigo atualiza o pediatra em relação à LMV, doença de alta prevalência no mundo e no Brasil. CONCLUSÕES: O diagnóstico de LMV depende principalmente da epidemiologia da presença de cães no domicílio da criança, associada ao ELISA (IgG para T. canis), utilizando antígenos Toxocara de excreção e secreção. São necessários estudos prospectivos para avaliar a melhor droga na terapêutica. A prevenção é a estratégia mais importante devido à alta prevalência de T. canis na região urbana.
OBJECTIVES: To present a detailed investigation of risk factors, symptoms, and laboratory and imaging tests that may be useful to establish the clinical laboratory diagnosis of visceral larva migrans (VLM) in children, demonstrating the importance of diagnosis and treatment to prevent complications in the eyes, liver, and other organs. SOURCES: Literature review using the MEDLINE and LILACS (1952-2009) databases, selecting the most recent and representative articles on the topic. SUMMARY OF THE FINDINGS: VLM is an infectious disease with non-specific clinical presentation, whose transmission is related to contact with dogs, especially puppies, and which may progress to late systemic complications in vital organs such as the eyes and the central nervous system. IgG (ELISA) anti-T. canis can be used to establish the laboratory diagnosis. Higher cutoff points suggest recent illness and lower cutoff points demonstrate mild infection or infection in remission. Therapeutic response may be assessed by means of eosinophil blood cell count. The present article provides the pediatrician with updated information regarding VLM, a disease of high prevalence worldwide and in Brazil. CONCLUSIONS: The diagnosis of VLM depends mainly on the presence of dogs in the child's household, associated with ELISA (IgG anti-T. canis), using excretory-secretory antigens of Toxocara canis. Prospective studies are warranted to assess the best drug therapy. Prevention is the most important strategy because of the high prevalence of T. canis in urban areas.
Subject(s)
Animals , Child, Preschool , Dogs , Humans , Larva Migrans, Visceral , Toxocara canis , Larva Migrans, Visceral/diagnosis , Larva Migrans, Visceral/immunology , Larva Migrans, Visceral/therapy , Larva Migrans, Visceral/transmission , Risk FactorsABSTRACT
Resumo Objetivos: identificar fatores associados a níveis elevados de pressão arterial em crianças. Métodos: estudo transversal da pressão arterial de 672 crianças entre 2 e 11 anos de idade em duas instituições de ensino de Belo Horizonte, entre setembro e dezembro de 2001. A pressão arterial foi mensurada seguindo os parâmetros estabelecidos pelo relatório do Update on the 1987 Task Force Report on High Blood Pressure in Children and Adolescents. As seguintes variáveis foram estudadas: idade, sexo, cor da pele, índice de qualidade de vida urbana, estatura e índice de massa corporal. Para a comparação das médias, foi utilizada a análise de variância, e para a comparação de proporções, o teste qui-quadrado. As variáveis associadas a níveis mais elevados de pressão arterial foram incluídas em análise de regressão linear múltipla. Resultados: na análise univariada, níveis mais elevados de pressão arterial sistólica e diastólica estiveram associados com crianças de cor branca, crianças da região com alto índice de qualidade de vida urbana e com elevado índice de massa corporal. Na análise multivariada, apenas o índice de massa corporal, o índice de qualidade de vida urbana e a estatura mantiveram-se associados com níveis elevados de pressão sistólica. Em relação aos níveis mais elevados de pressão arterial diastólica, apenas as variáveis índice de qualidade de vida urbana e idade foram mantidas no modelo após o ajustamento. Conclusão: o sobrepeso e a obesidade estiveram associados com níveis mais elevados de pressão arterial sistólica. Outros fatores, não identificados, foram parcialmente associados a níveis mais elevados de pressão arterial de crianças do estabelecimento privado do ensino.
Summary Objective: to identify factors associated with increased arterial blood pressure in children. Methods: in this cross-sectional study, arterial blood pressure was measured in 672 children between 2 and 11 years of age from two schools in the city of Belo Horizonte, Brazil. After providing informed consent, all children had their blood pressure and anthropometric parameters measured. Blood pressure was measured based on the recommendations of the Update on the 1987 Task Force Report on High Blood Pressure in Children and Adolescents. The following variables were assessed: age, sex, race, urban life quality index, weight, height, and body mass index. Analysis of variance was used for comparison of means and the chi-square was used for comparison of proportions. Variables associated with increased blood pressure were included in a multiple regression model. Results: according to univariate analysis, increased systolic and diastolic blood pressure were associated with high urban life quality index, white race and high body mass index. On multivariate analysis, body mass index, urban life quality index and height remained associated with increased systolic blood pressure; urban life quality index and age were associated with increased diastolic blood pressure. Conclusion: in this study, excess weight and obesity were associated with increased systolic blood pressure. Other unidentified factors were partially associated with increased blood pressure in children from the school with elevated urban life quality index.
ABSTRACT
OBJECTIVE: To identify factors associated with increased arterial blood pressure in children. METHODS: In this cross-sectional study, arterial blood pressure was measured in 672 children between 2 and 11 years of age from two schools in the city of Belo Horizonte, Brazil. After providing informed consent, all children had their blood pressure and anthropometric parameters measured. Blood pressure was measured based on the recommendations of the Update on the 1987 Task Force Report on High Blood Pressure in Children and Adolescents. The following variables were assessed: age, sex, race, urban life quality index, weight, height, and body mass index. Analysis of variance was used for comparison of means and the chi-square was used for comparison of proportions. Variables associated with increased blood pressure were included in a multiple regression model. RESULTS: According to univariate analysis, increased systolic and diastolic blood pressure were associated with high urban life quality index, white race and high body mass index. On multivariate analysis, body mass index, urban life quality index and height remained associated with increased systolic blood pressure; urban life quality index and age were associated with increased diastolic blood pressure. CONCLUSION: In this study, excess weight and obesity were associated with increased systolic blood pressure. Other unidentified factors were partially associated with increased blood pressure in children from the school with elevated urban life quality index.
Subject(s)
Hypertension/etiology , Age Distribution , Analysis of Variance , Black People , Body Mass Index , Brazil/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Hypertension/epidemiology , Male , Risk Factors , Socioeconomic Factors , White PeopleABSTRACT
OBJETIVOS: Identificar fatores associados a níveis elevados de pressão arterial em crianças. MÉTODOS: Estudo transversal da pressão arterial de 672 crianças entre 2 e 11 anos de idade em duas instituições de ensino de Belo Horizonte, entre setembro e dezembro de 2001. A pressão arterial foi mensurada seguindo os parâmetros estabelecidos pelo relatório do Update on the 1987 Task Force Report on High Blood Pressure in Children and Adolescents. As seguintes variáveis foram estudadas: idade, sexo, cor da pele, índice de qualidade de vida urbana, estatura e índice de massa corporal. Para a comparação das médias, foi utilizada a análise de variância, e para a comparação de proporções, o teste qui-quadrado. As variáveis associadas a níveis mais elevados de pressão arterial foram incluídas em análise de regressão linear múltipla. RESULTADOS: Na análise univariada, níveis mais elevados de pressão arterial sistólica e diastólica estiveram associados com crianças de cor branca, crianças da região com alto índice de qualidade de vida urbana e com elevado índice de massa corporal. Na análise multivariada, apenas o índice de massa corporal, o índice de qualidade de vida urbana e a estatura mantiveram-se associados com níveis elevados de pressão sistólica. Em relação aos níveis mais elevados de pressão arterial diastólica, apenas as variáveis índice de qualidade de vida urbana e idade foram mantidas no modelo após o ajustamento. CONCLUSAO: O sobrepeso e a obesidade estiveram associados com níveis mais elevados de pressão arterial sistólica. Outros fatores, não identificados, foram parcialmente associados a níveis mais elevados de pressão arterial de crianças do estabelecimento privado do ensino.
Subject(s)
Child, Preschool , Child , Humans , Male , Female , Hypertension , Black People , Age Distribution , Body Mass Index , Brazil , Cross-Sectional Studies , Risk Factors , Socioeconomic FactorsABSTRACT
Os autores comparam as alteraçöes radiológicas pulmonares observadas nas fases inicial e tardia da infecçäo esquistossomática nas formas aguda toxêmica (46 pacientes), hepatointestinal (70 pacientes) e hepatoesplênica (40 pacientes).
