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An. bras. dermatol ; 93(6): 890-892, Nov.-Dec. 2018. graf
Article in English | LILACS | ID: biblio-973633


Abstract: Chagas disease is an endemic zoonosis caused by a protozoan agent called Trypanosoma cruzi. It is mainly transmitted by a hematophagous vector, and less frequently by blood transfusion, transplacental and solid organ transplant. In most cases, primary infection is not diagnosed and the disease progresses to a chronic phase. Immunosuppressed patients are a vulnerable population that may present an acute, atypical and severe reactivation of the chronic form of this disease. We hereby report a case of a female patient, who received a renal transplant with immunosuppressive treatment, who was diagnosed with a chagasic hypodermitis secondary to an acute reactivation of a chronic phase of this disease. We describe the clinical features, epidemiological and histopathological findings, treatment and course.

Humans , Female , Middle Aged , Kidney Transplantation/adverse effects , Chagas Disease/etiology , Dermatitis/etiology , Recurrence , Acute Disease , Immunocompromised Host , Chagas Disease/immunology , Dermatitis/immunology
Rev. Soc. Bras. Med. Trop ; 51(5): 665-669, Sept.-Oct. 2018. graf
Article in English | LILACS | ID: biblio-1041484


Abstract INTRODUCTION: Serological cross-reactivity between leishmaniasis and Chagas disease, especially at low titers, leads to difficulties of the seroepidemiological interpretation. METHODS: We have studied the ability of urea as a chaotrope to select high-avidity antibodies in IgG ELISA, thus reducing low-avidity IgG cross-reactivity in serologically positive samples in both assays. RESULTS: Using 0.5M urea for diluting the sample efficiently defined leishmaniasis or double infections in high-avidity IgG ELISA and eliminated false-positive results. CONCLUSIONS: The use of a chaotropic diluting agent is useful for improving the specificity of Chagas disease and leishmaniasis immunoassays.

Humans , Urea/pharmacology , Immunoglobulin G/blood , Antibodies, Protozoan/blood , Leishmaniasis/immunology , Chagas Disease/immunology , Cross Reactions/immunology , Antibody Affinity/immunology , Urea/chemistry , Brazil/epidemiology , Enzyme-Linked Immunosorbent Assay , Biomarkers/chemistry , Leishmaniasis/complications , Leishmaniasis/diagnosis , Leishmaniasis/epidemiology , Population Surveillance , Sensitivity and Specificity , Chagas Disease/complications , Chagas Disease/diagnosis , Chagas Disease/epidemiology
Rev. Soc. Bras. Med. Trop ; 51(5): 660-664, Sept.-Oct. 2018. tab, graf
Article in English | LILACS | ID: biblio-1041481


Abstract INTRODUCTION: We evaluated clinical and epidemiological characteristics of Trypanosoma cruzi infection in Sergipe. METHODS: In this cross-sectional study, we collected serum samples to identify serological markers of Chagas disease. A questionnaire was used, and electrocardiogram, echocardiogram, chest radiography, and contrast radiography of esophagus and colon were performed. RESULTS: T. cruzi infection seroprevalence was 12.1%, mean age of subjects was 55 years, 90% had an elementary school education, 78.6% were agriculture workers, and 60.5% had electrocardiographic abnormalities. CONCLUSIONS: A high prevalence of T. cruzi infection was observed in mostly elderly individuals.

Humans , Male , Female , Adult , Trypanosoma cruzi/immunology , Antibodies, Protozoan/blood , Chagas Disease/epidemiology , Endemic Diseases , Socioeconomic Factors , Brazil/epidemiology , Enzyme-Linked Immunosorbent Assay , Seroepidemiologic Studies , Prevalence , Cross-Sectional Studies , Chagas Disease/diagnosis , Chagas Disease/immunology , Fluorescent Antibody Technique, Indirect , Middle Aged
Arq. bras. cardiol ; 110(4): 348-353, Apr. 2018. tab, graf
Article in English | LILACS | ID: biblio-888059


Abstract Background: Vimentin is a main structural protein of the cell, a component of intermediate cell filaments and immersed in cytoplasm. Vimentin is mimicked by some bacterial proteins and anti-vimentin antibodies occur in autoimmune cardiac disease, as rheumatic fever. In this work we studied vimentin distribution on LLC-MK2 cells infected with T. cruzi and anti-vimentin antibodies in sera from several clinical pictures of Chagas' disease or American Trypanosomiasis, in order to elucidate any vimentin involvement in the humoral response of this pathology. Objective: We standardized an indirect immunofluorescence assay (IFI) to determine sub cellular expression in either parasites and host cells, and ELISA to evaluate anti-vimentin antibodies in sera fron chagasic patients. Methods: We analyzed the distribution of vimentin in culture cells using indirect fluorescent assays, using as external controls anti-T. cruzi sera, derived from chronic infected patients for identification of the parasites in the same model. After infection and growth of T.cruzi amastigotes, those cells express larger amounts of vimentin, with heavy staining of cytoplasm outside the parasitophorous vacuole and some particle shadowing patterns, suggesting that vimentin are associated with cell cytoplasm. Anti-vimentin antibodies were present in most American trypanosomiasis samples, but notably, they are much more present in acute (76, 9%) or clinical defined syndromes, especially cardiac disease (87, 9%). Paradoxically, they were relatively infrequent in asymptomatic (25%) infected patients, which had a clearly positive serological reaction to parasite antigens, but had low frequency of anti-vimentin antibodies, similar to controls (2,5%). Conclusion: Our current data revealed that anti-vimentin antibodies induced during T. cruzi infection could be a marker of active disease in the host and its levels could also justify drug therapy in American Trypanosomiasis chronic infection, as a large group of asymptomatic patients would be submitted to treatment with frequent adverse reactions of the available drugs. Anti-vimentin antibodies could be a marker of cardiac muscle cell damage, appearing in American Trypanosomiasis patients during active muscle cell damage.

Resumo Fundamento: A Vimentina é uma proteína estrutural importante da célula, um componente dos filamentos celulares intermediários e imersa no citoplasma. Algumas proteínas bacterianas imitam a Vimentina e anticorpos anti-vimentina ocorrem em doenças cardíacas auto-imunes, como a febre reumática. Neste trabalho, estudamos a distribuição de vimentina em células LLC-MK2 infectadas com T. Cruzi e anticorpos anti-vimentina em soros de várias imagens clínicas da doença de Chagas ou tripanossomíases americanas, a fim de elucidar qualquer implicação da vimentina na resposta humoral desta patologia. Objetivo: padronizamos um teste de imunofluorescência indireta (IFI) para determinar a expressão subcelular em parasitas e células hospedeiras, e ELISA para testar anticorpos anti-vimentina em soros de pacientes chagásicos. Métodos: analisamos a distribuição de vimentina em células de cultura usando ensaios fluorescentes indiretos, utilizando como controles externos soros anti-T. Cruzi, derivados de pacientes com infecção crônica para a identificação de parasitas no mesmo modelo. Após a infecção e o crescimento de amastigotas de T. Cruzi, essas células expressam grandes quantidades de vimentina, com forte coloração do citoplasma fora da vacuola parasitófora e alguns padrões de sombreamento das partículas, sugerindo que a vimentina está associada ao citoplasma da célula. Os anticorpos anti-vimentina estavam presentes na maioria das amostras americanas de tripanossomíases, mas estão notavelmente mais presentes em síndromes agudas ou clinicamente definidas (76,9%), especialmente em doenças cardíacas (87,9%). Paradoxalmente, eram relativamente infrequentes em pacientes infectados assintomáticos (25%), que apresentavam uma reação sorológica claramente positiva aos antígenos parasitas, mas apresentavam baixa frequência de anticorpos anti-vimentina, semelhante aos controles (2,5%). Conclusão: Nossos dados atuais revelaram que os anticorpos anti-vimentina induzidos durante a infecção por T. Cruzi poderiam ser um marcador de doença ativa no hospedeiro e seus níveis também poderiam justificar o tratamento farmacológico em infecção crônica com tripanossomíase americana, uma vez que um grande grupo de pacientes assintomáticos seria submetido a tratamento com reações adversas frequentes aos medicamentos disponíveis. Os anticorpos anti-vimentina poderiam ser um marcador de danos nas células do músculo cardíaco, que aparece em pacientes com tripanossomíase americana durante o dano das células musculares ativas.

Humans , Animals , Trypanosoma cruzi/immunology , Vimentin/immunology , Antibodies, Protozoan/immunology , Chagas Disease/immunology , Antigens, Protozoan/immunology , Reference Values , Enzyme-Linked Immunosorbent Assay/methods , Antibodies, Protozoan/analysis , Cells, Cultured , Analysis of Variance , Statistics, Nonparametric , Fluorescent Antibody Technique, Indirect/methods , Macaca mulatta , Antigens, Protozoan/analysis
Clinics ; 72(11): 652-660, Nov. 2017. tab, graf
Article in English | LILACS | ID: biblio-890691


OBJECTIVES: The impact of Chagas disease (CD) in HIV-infected patients is relevant throughout the world. In fact, the characterization of the adaptive immune response in the context of co-infection is important for predicting the need for interventions in areas in which HIV and Chagas disease co-exist. METHODS: We described and compared the frequency of cytokine-producing T cells stimulated with soluble antigen of Trypanosoma cruzi (T. cruzi) using a cytometric assay for the following groups: individuals with chronic Chagas disease (CHR, n=10), those with Chagas disease and HIV infection (CO, n=11), those with only HIV (HIV, n=14) and healthy individuals (C, n=15). RESULTS: We found 1) a constitutively lower frequency of IL-2+ and IFN-γ+ T cells in the CHR group compared with the HIV, CO and healthy groups; 2) a suppressive activity of soluble T. cruzi antigen, which down-regulated IL-2+CD4+ and IFN-γ+CD4+ phenotypes, notably in the healthy group; 3) a down-regulation of inflammatory cytokines on CD8+ T cells in the indeterminate form of Chagas disease; and 4) a significant increase in IL-10+CD8+ cells distinguishing the indeterminate form from the cardiac/digestive form of Chagas disease, even in the presence of HIV infection. CONCLUSIONS: Taken together, our data suggest the presence of an immunoregulatory response in chronic Chagas disease, which seems to be driven by T. cruzi antigens. Our findings provide new insights into immunotherapeutic strategies for people living with HIV/AIDS and Chagas disease.

Humans , Male , Female , Adult , CD4-Positive T-Lymphocytes/immunology , HIV Infections/immunology , Cytokines/biosynthesis , Chagas Disease/immunology , CD8-Positive T-Lymphocytes/immunology , Adaptive Immunity/immunology , HIV Infections/complications , Chronic Disease , Chagas Disease/complications , Coinfection/immunology , Flow Cytometry
Rev. Soc. Bras. Med. Trop ; 49(6): 721-727, Dec. 2016. tab, graf
Article in English | LILACS | ID: biblio-829672


Abstract INTRODUCTION: Geographical, epidemiological, and environmental differences associated with therapeutic response to Chagas etiological treatment have been previously discussed. This study describes high seroconversion rates 72 months after benznidazole treatment in patients under 16 years from a project implemented by Doctors without Borders in Guatemala. METHODS: An enzyme-linked immunosorbent assay was used to detect Trypanosoma cruzi IgG antibodies in capillary blood samples from patients 72 months after treatment. Fisher's exact test was used to establish association between characteristics, such as sex, age, and origin of patients, and final seroconversion. Kappa index determined concordance between laboratory tests. The level of significance was set to 5%. RESULTS: Ninety-eight patients, aged 6 months to 16 years, were available for follow-up. Sex and origin were not associated with seroconversion. Individuals older than 13 were more prone to maintain a positive result 72 months after treatment, although results were not highly significant. Laboratory tests presented elevated Kappa concordance (95% CI) = 0.8290 (0.4955-1), as well as high (97%) seroconversion rates. CONCLUSIONS: The high seroconversion rate found in this study emphasizes the importance of access to diagnosis, treatment, and follow-up of individuals affected by Chagas disease. Moreover, it contradicts the idea that it is not possible to achieve a cure with the currently available drugs. This study strongly supports expanding programs for patients infected with T. cruzi in endemic and non-endemic countries.

Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Trypanocidal Agents/therapeutic use , Trypanosoma cruzi/immunology , Antibodies, Protozoan/blood , Chagas Disease/drug therapy , Nitroimidazoles/therapeutic use , Enzyme-Linked Immunosorbent Assay , Chronic Disease , Treatment Outcome , Chagas Disease/immunology , Seroconversion , Guatemala
Rev. bras. parasitol. vet ; 25(1): 90-98, Jan.-Mar. 2016. tab, graf
Article in English | LILACS | ID: lil-777532


Abstract The aim of this survey was to determine the seropositivity and risk factors forLeishmania spp. and Trypanosoma cruzi in dogs in the State of Paraíba, Northeastern Brazil. A total of 1,043 dogs were tested, and the serological diagnoses of Chagas disease (CD) and canine visceral leishmaniasis (CVL) was performed by the indirect fluorescent antibody test (IFAT). Animals that tested seropositive for both diseases (by IFAT) were further subjected to ELISA. Of the 1,043 dogs 81 (7.8%; 95% CI = 6.1-9.4%) tested seropositive for Leishmania spp., while 83 were seropositive for T. cruzi (7.9%; 95% CI = 6.3-9.6%). Simultaneous serological reactions were detected in 49 animals (4.6%; 95% CI= 3.6-6.2%). Semi-domiciled housing (OR = 2.044), free housing (OR = 4.151), and soil (OR = 3.425) and soil/cement (OR = 3.065) environmental conditions were identified as risk factors for CVL seropositivity. The risk factors identified for CD seropositivity were semi-domiciled (OR = 2.353) or free housing (OR = 3.454), and contact with bovine (OR = 2.015). This study revealed the presence of dogs in the Paraíba State seropositive for CVL and CD, suggesting the need for revisiting and intensification of disease control measures through constant monitoring of the canine population.

Resumo O objetivo do presente trabalho foi determinar a soropositividade paraLeishmania spp. e Trypanosoma cruzi em cães do Estado da Paraíba, Nordeste do Brasil, bem como identificar fatores de risco. Foram utilizados 1.043 cães e, para o diagnóstico sorológico de doença de Chagas (DC) e leishmaniose visceral canina (LVC), foi utilizada a reação de imunofluorescência indireta (RIFI). Animais positivos para ambas as doenças (pela RIFI) foram submetidos ao ELISA. Dos 1.043 cães investigados, 81 foram soropositivos para Leishmania spp., resultando em prevalência de 7,8% (IC 95% = 6,1-9,4%) e, para T. cruzi, 83 (7,9%; IC 95% = 6,3-9,6%) animais foram soropositivos. Quarenta e nove animais (4,6%; IC 95% = 3,6-6,2%) apresentaram sororeatividade mista. Criação semidomiciliar (OR = 2,044), criação solta (OR = 4,151), ambiente de terra (OR = 3,425) e ambiente de terra/cimento (OR = 3,065) foram apontados como fatores de risco para LVC, e criação semidomiciliar (OR = 2,353), criação solta (OR = 3,454) e contato com bovinos (OR = 2,015) para DC. Conclui-se que LVC e DC estão presentes em cães do Estado da Paraíba, o que sugere revisão e intensificação das medidas de controle através do constante monitoramento da população canina.

Animals , Dogs , Trypanosoma cruzi/immunology , Chagas Disease/veterinary , Dog Diseases/diagnosis , Leishmania/immunology , Leishmaniasis, Visceral/veterinary , Brazil , Risk Factors , Chagas Disease/diagnosis , Chagas Disease/immunology , Dog Diseases/immunology , Leishmaniasis, Visceral/diagnosis , Leishmaniasis, Visceral/immunology
Recife; s.n; 2016. 196 p. ilus, tab, c30 cm.
Thesis in Portuguese | LILACS | ID: biblio-871413


O diagnóstico da doença de Chagas crônica (DCC) baseia-se em metodologias que usam em sua fase sólida antígenos brutos, semipurificados ou recombinantes, podendo resultar em baixa sensibilidade ou reação cruzada. Uma forma para resolver este problema é o uso de quimeras formadas por epítopos conservados e repetitivos de diferentes estruturas parasitárias em uma única molécula. O nosso objetivo foi caracterizar e avaliar o uso de quimeras em imunoensaios para o diagnóstico da DCC. As quimeras, IBMP-8.1, IBMP-8.2, IBMP-8.3 e IBMP-8.4 foram purificadas por meio de cromatografia e sua pureza avaliada por SDS-PAGE. Ensaios de dicroísmo circular (DC) e espalhamento dinâmico da luz (EDL) foram usados para avaliação do raio hidrodinâmico das quimeras, avaliação de sua estabilidade e escolha do sistema tampão que oferecesse o menor estado de agregação molecular. Ensaios sorológicos para detecção de anticorpos anti-Trypanosoma cruzi através de ELISA foram realizados utilizando um painel de 857 amostras positivas para a DCC e 689 negativas. Para avaliação de reação cruzada foram usadas 1079 amostras de diversas doenças endêmicas no país. A purificação foi eficiente uma vez que o SDS-PAGE indicou ausência de degradação das quimeras. As análises de DC e EDL mostraram que as quatro quimeras apresentaram menor tendência de agregação em tampão carbonato pH 9,6, sendo, assim, este o sistema para a sensibilização das placas. Os ensaios sorológicos revelaram valores elevados de sensibilidade (Sen) e especificidade (Esp) para a molécula IBMP-8.4 (Sen-99,3 por cento; Esp-100 por cento). O desempenho para as demais moléculas foi satisfatório, ficando os valores de Sen e Esp acima de 94 por cento. As moléculas IBMP-8.1, IBMP-8.2, IBMP-8.3 e IBMP-8.4 apresentaram respectivamente 0,46 por cento, 0,85 por cento, 0,46 por cento e 0,37 por cento de reação cruzada. Os resultados apontam que as quimeras atingiram os critérios de proficiência do Ministério da Saúde podendo, dessa forma, ser utilizados em ensaios diagnósticos para a DCC.

Animals , Chronic Disease , Chagas Disease/diagnosis , Chagas Disease/immunology , Trypanosoma cruzi/immunology , Antigen-Antibody Reactions , Antigens, Protozoan/analysis , Chimera , Enzyme-Linked Immunosorbent Assay/methods , Predictive Value of Tests , Sensitivity and Specificity , Serologic Tests
Salvador; s.n; 2016. 116 p. ilus, tab.
Thesis in Portuguese | LILACS | ID: biblio-1001009


INTRODUÇÃO: A cardiomiopatia chagásica crônica (CCC), doença de elevada morbimortalidade, associada à grave disfunção ventricular e a arritmias cardíacas, caracteriza-se histologicamente por intensa reação inflamatória multifocal, com pronunciada fibrose miocárdica. Diante da ausência de uma terapia eficaz para os pacientes com as formas mais graves da doença, torna-se crucial a descoberta de biomarcadores que possam identificar pacientes em estágios mais precoces, sob risco mais elevado para a progressão da doença. Neste contexto, surge a syndecan-4, uma glicoproteína transmembrana associada à inflamação e fibrose, cujos níveis estão aumentados em indivíduos com insuficiência cardíaca. OBJETIVO: Neste trabalho, avaliamos o padrão de expressão da syndecan-4 no tecido cardíaco de camundongos e de indivíduos com cardiomiopatia chagásica e a possível correlação entre a concentração sérica de syndecan-4 com grau de fibrose miocárdica e com fração de ejeção do ventrículo esquerdo em indivíduos com doença de Chagas...

INTRODUCTION: The hallmark of chronic Chagas cardiomyopathy (CCC) is the presence of a multifocal inflammatory reaction, which leads to myocardial fibrosis, often followed by ventricular dysfunction and arrhythmias. Syndecan-4 is a transmembrane glycoprotein associated with inflammation and fibrosis. Syndecan-4 levels are increased in subjects with heart failure and it has been proposed as a biomarker to predict cardiovascular events. The expression of syndecan-4 is increased in the hearts of mice chronically infected with Trypanosoma cruzi, suggesting a role of this protein in the pathogenesis of CCC. OBJETIVE: Here we aimed to evaluate the pattern of expression of syndecan-4 in heart tissue of mice and subjects with Chagas cardiomyopathy, and to correlate with the degree of inflammation and fibrosis, as well as to determine the correlation of syndecan-4 serum concentration with the degree of myocardial fibrosis and with left ventricular ejection fraction in subjects with Chagas disease...

Chagas Disease/complications , Chagas Disease/diagnosis , Chagas Disease/immunology , Chagas Disease/microbiology , Chagas Disease/pathology , Chagas Disease/transmission
Braz. j. phys. ther. (Impr.) ; 19(3): 211-217, May-Jun/2015. tab, graf
Article in English | LILACS | ID: lil-751376


Background: Hippotherapy uses horseback riding movements for therapeutic purposes. In addition to the horse's movement, the choice of equipment and types of floor are also useful in the intervention. The quantification of dynamic parameters that define the interaction of the surface of contact between horse and rider provides insight into how the type of floor surface variations act upon the subject's postural control. Objective: To test whether different types of surfaces promote changes in the amplitude (ACOP) and velocity (VCOP) of the center of pressure (COP) displacement during the rider's contact with the saddle on the horse's back. Method: Twenty two healthy adult male subjects with experience in riding were evaluated. The penetration resistances of asphalt, sand and grass surfaces were measured. The COP data were collected on the three surfaces using a pressure measurement mat. Results: ACOP values were higher in sand, followed by grass and asphalt, with significant differences between sand and asphalt (anteroposterior, p=0.042; mediolateral, p=0.019). The ACOP and VCOP values were higher in the anteroposterior than in the mediolateral direction on all surfaces (ACOP, p=0.001; VCOP, p=0.006). The VCOP did not differ between the surfaces. Conclusion: Postural control, measured by the COP displacement, undergoes variations in its amplitude as a result of the type of floor surface. Therefore, these results reinforce the importance of the choice of floor surface when defining the strategy to be used during hippotherapy intervention. .

Animals , Male , Blood Transfusion/veterinary , Chagas Disease/veterinary , Immunocompromised Host , Macaca nemestrina/parasitology , Monkey Diseases/parasitology , Trypanosoma cruzi/isolation & purification , Antibodies, Protozoan/blood , Biomarkers/blood , Blood Transfusion/adverse effects , Chagas Disease/blood , Chagas Disease/immunology , Chagas Disease/transmission , Dose Fractionation, Radiation , Genetic Therapy , Models, Animal , Macaca nemestrina/blood , Macaca nemestrina/immunology , Monkey Diseases/blood , Monkey Diseases/immunology , Stem Cell Transplantation , Trypanosoma cruzi/immunology
Mem. Inst. Oswaldo Cruz ; 110(3): 445-451, 05/2015. graf
Article in English | LILACS | ID: lil-745966


Prevention of Trypanosoma cruzi infection in mammals likely depends on either prevention of the invading trypomastigotes from infecting host cells or the rapid recognition and killing of the newly infected cells by T. cruzi-specific T cells. We show here that multiple rounds of infection and cure (by drug therapy) fails to protect mice from reinfection, despite the generation of potent T cell responses. This disappointing result is similar to that obtained with many other vaccine protocols used in attempts to protect animals from T. cruzi infection. We have previously shown that immune recognition of T. cruzi infection is significantly delayed both at the systemic level and at the level of the infected host cell. The systemic delay appears to be the result of a stealth infection process that fails to trigger substantial innate recognition mechanisms while the delay at the cellular level is related to the immunodominance of highly variable gene family proteins, in particular those of the trans-sialidase family. Here we discuss how these previous studies and the new findings herein impact our thoughts on the potential of prophylactic vaccination to serve a productive role in the prevention of T. cruzi infection and Chagas disease.

Animals , Female , Mice , Chagas Disease/immunology , Protozoan Vaccines/immunology , Trypanosoma cruzi/immunology , Antibodies, Protozoan/immunology , Antigens, Protozoan/immunology , Chagas Disease/parasitology , Chagas Disease/prevention & control
Mem. Inst. Oswaldo Cruz ; 110(3): 414-421, 05/2015. tab, graf
Article in English | LILACS | ID: lil-745978


The aim of this review is to describe the contributions of the knowledge of T-cell responses to the understanding of the physiopathology and the responsiveness to etiological treatment during the chronic phase of Chagas disease. T-helper (Th)1 and interleukin (IL)-10 Trypanosoma cruzi-specific T-cells have been linked to the asymptomatic phase or to severe clinical forms of the disease, respectively or vice versa, depending on the T. cruzi antigen source, the patient’s location and the performed immunological assays. Parasite-specific T-cell responses are modulated after benznidazole (BZ) treatment in chronically T. cruzi-infected subjects in association with a significant decrease in T. cruzi-specific antibodies. Accumulating evidence has indicated that treatment efficacy during experimental infection with T. cruzi results from the combined action of BZ and the activation of appropriate immune responses in the host. However, strong support of this interaction in T. cruzi-infected humans remains lacking. Overall, the quality of T-cell responses might be a key factor in not only disease evolution, but also chemotherapy responsiveness. Immunological parameters are potential indicators of treatment response regardless of achievement of cure. Providing tools to monitor and provide early predictions of treatment success will allow the development of new therapeutic options.

Humans , Chagas Disease/immunology , Nitroimidazoles/therapeutic use , T-Lymphocytes/immunology , Trypanocidal Agents/therapeutic use , Trypanosoma cruzi/immunology , Antigens, Protozoan/immunology , Chronic Disease , Chagas Disease/drug therapy , T-Lymphocytes/drug effects , Trypanosoma cruzi/drug effects
Mem. Inst. Oswaldo Cruz ; 109(8): 1005-1013, 12/2014. graf
Article in English | LILACS | ID: lil-732612


Trypanosoma cruzi infection may be caused by different strains with distinct discrete typing units (DTUs) that can result in variable clinical forms of chronic Chagas disease. The present study evaluates the immune response and cardiac lesions in dogs experimentally infected with different T. cruzi strains with distinct DTUs, namely, the Colombian (Col) and Y strains of TcI and TcII DTU, respectively. During infection with the Col strain, increased levels of alanine aminotransferase, erythrocytes, haematocrit and haemoglobin were observed. In addition, CD8+ T-lymphocytes isolated from the peripheral blood produced higher levels of interleukin (IL)-4. The latter suggests that during the acute phase, infection with the Col strain may remain unnoticed by circulating mononuclear cells. In the chronic phase, a significant increase in the number of inflammatory cells was detected in the right atrium. Conversely, infection with the Y strain led to leucopoenia, thrombopoenia, inversion of the ratio of CD4+/CD8+ T-lymphocytes and alterations in monocyte number. The Y strain stimulated the production of interferon-γ by CD4+ and CD8+ T-lymphocytes and IL-4 by CD8+ T-cells. In the chronic phase, significant heart inflammation and fibrosis were observed, demonstrating that strains of different DTUs interact differently with the host.

Animals , Dogs , Chagas Disease/immunology , Myocardium/pathology , Trypanosoma cruzi/immunology , Alanine Transaminase/blood , /metabolism , /metabolism , Chronic Disease , Chagas Disease/blood , Chagas Disease/pathology , Disease Models, Animal , Erythrocyte Count , Flow Cytometry , Fibrosis/immunology , Fibrosis/parasitology , Hematocrit , Hemoglobins/analysis , /metabolism , Lymphocyte Count , Leukocytes, Mononuclear/chemistry , Myocardium/chemistry , Myocardium/immunology , Phenotype , Trypanosoma cruzi/metabolism
Invest. clín ; 55(3): 227-237, sep. 2014. ilus, tab
Article in Spanish | LILACS | ID: lil-780158


Diversos agentes infecciosos interfieren en la progresión del cáncer. En esta investigación se estudió el efecto de la infección o inmunización con Trypanosoma cruzi (Tc) sobre el desarrollo del melanoma maligno. Se utilizaron 258 ratones machos C57BL/6 divididos en 5 grupos melanoma: melanoma control, melanoma Tc inmunizado, melanoma Tc agudo, melanoma Tc crónico y melanoma Tc infectado; 3 grupos controles: control sano, control Tc agudo, control Tc crónico. 100.000 células de melanoma B16-BL6 fueron inoculados vía intramuscular a los grupos melanoma; 3 ó 20 tripomastigotes/g de peso fueron inoculados vía intraperitoneal a los grupos Tc crónicos o Tc agudos previo a la inoculación del melanoma, respectivamente, el grupo melanoma Tc inmunizado fue inoculado con 30.000 epimastigotes fijados en formol y suspendidos en adyuvante completo de Freund, y el grupo melanoma Tc infectado fue inoculado con células de melanoma obtenidas de ratones melanoma Tc agudo. Se evaluó volumen tumoral, supervivencia, parasitemia e histopatología tumoral. Los grupos melanoma Tc: agudo, crónico y melanoma infectado, respectivamente, mostraron una disminución significativa del desarrollo tumoral y de la supervivencia al ser comparados con los grupos melanoma control e inmunizado. Los estudios histopatológicos mostraron áreas de necrosis asociadas con depósitos de melanina, degeneración citopática tumoral y amastigotes intracelulares contenidos en vacuolas parasitofóricas. En conclusión, Tc inhibe el desarrollo tumoral del melanoma maligno y aumenta la supervivencia de ratones C57BL/6, fenómeno que podría estar relacionado con la capacidad invasiva tumoral del parásito y a la respuesta inmune generada.

Some infectious pathogens have the capacity to affect cancer progression. In the present paper we studied the effect of infection or immunization with Trypanosoma cruzi (Tc) against malignant melanoma development. We worked on 258 C57BL/6 male mice divided in five melanoma groups: control melanoma, melanoma Tc acutely infected, melanoma Tc chronically infected, melanoma Tc immunized and infected melanoma; and three control groups: healthy, Tc acutely infected and Tc chronically infected. 100.000 B16-BL6 melanoma cells were inoculated in the thigh of melanoma groups; 3 or 20 trypomastigotes/g were inoculated intraperitoneally in chronic or acute Tc groups, before the melanoma injection, respectively; melanoma Tc immunized were subcutaneously inoculated with 30.000 formaldehide-fixed epimastigotes diluted in complete Freund´s adjuvant and the infected melanoma group was inoculated with melanoma cells obtained from melanoma Tc acutely infected mice. We evaluated survival, parasitemia, tumor volume and tumor histopathology. Results showed that in mice infected with Tc, the tumor development and survival were significantly lower as compared with control melanoma and melanoma Tc immunized. Histopathologically, the tumor displayed necrosis areas with melanin deposits, cytopathic degeneration and amastigotes in parasitophorous vacuoles. In conclusion, Tc inhibits the development of malignant melanoma, increasing C57BL/6 survival, a phenomena that could be related to the parasite tumoral invasive capacity, its ability to produce melanoma cell lysis and to induce a robust immune response.

Animals , Male , Mice , Chagas Disease/immunology , Melanoma/immunology , Melanoma/mortality , Skin Neoplasms/immunology , Skin Neoplasms/mortality , Chagas Disease/complications , Melanoma/complications , Survival Rate , Skin Neoplasms/complications
Mem. Inst. Oswaldo Cruz ; 109(4): 459-465, 03/07/2014. graf
Article in English | LILACS | ID: lil-716311


Nitric oxide (NO) participates in neuronal lesions in the digestive form of Chagas disease and the proximity of parasitised glial cells and neurons in damaged myenteric ganglia is a frequent finding. Glial cells have crucial roles in many neuropathological situations and are potential sources of NO. Here, we investigate peripheral glial cell response to Trypanosoma cruzi infection to clarify the role of these cells in the neuronal lesion pathogenesis of Chagas disease. We used primary glial cell cultures from superior cervical ganglion to investigate cell activation and NO production after T. cruzi infection or lipopolysaccharide (LPS) exposure in comparison to peritoneal macrophages. T. cruzi infection was greater in glial cells, despite similar levels of NO production in both cell types. Glial cells responded similarly to T. cruzi and LPS, but were less responsive to LPS than macrophages were. Our observations contribute to the understanding of Chagas disease pathogenesis, as based on the high susceptibility of autonomic glial cells to T. cruzi infection with subsequent NO production. Moreover, our findings will facilitate future research into the immune responses and activation mechanisms of peripheral glial cells, which are important for understanding the paradoxical responses of this cell type in neuronal lesions and neuroprotection.

Animals , Chagas Disease/immunology , Lipopolysaccharides/pharmacology , Macrophages, Peritoneal/parasitology , Neuroglia/parasitology , Nitric Oxide/biosynthesis , Trypanosoma cruzi/immunology , Chagas Disease/etiology , Fluorescent Antibody Technique , Mice, Inbred BALB C , Macrophages, Peritoneal/drug effects , Macrophages, Peritoneal/immunology , Neuroglia/drug effects , Neuroglia/immunology
Rev. peru. med. exp. salud publica ; 31(2): 278-281, abr.-jun. 2014. tab
Article in Spanish | LILACS, LIPECS | ID: lil-719505


Con el objetivo de evaluar la especificidad de la leishmanina en pacientes con enfermedad de Chagas, sin antecedente clínico de leishmaniosis, actual o antigua. Una muestra de 102 personas infectadas por Trypanosoma cruzi (14 casos agudos con diagnóstico parasitológico y 88 casos crónicos a través de la demostración de anticuerpos IgG por ELISA e inmunofluorescencia indirecta (IFI) fueron evaluados con leishmanina, antígeno soluble que contenia Leishmania (Viannia) peruviana a la concentración de 25-30 ug/mL. Solo cinco personas presentaron reacción de hipersensibilidad cutánea a la aplicación del antígeno a las 48-72 h. La leishmanina evaluada fue negativa en 97 personas infectadas con T. cruzi, con lo cual se alcanzó una especificidad del 95,1%. En conclusión, la prueba intradérmica de Montenegro es una herramienta diagnóstica simple y eficaz, que además podría ser utilizada para discriminar infecciones por Leishmania o T. cruzi, en áreas geográficas del Perú donde ambos parásitos están presentes.

In order to assess the specificity of the leishmanin skin test in Chagas disease patients without clinical history of leishmaniasis, present or former. A sample of 102 persons infected with Trypanosoma cruzi (14 acute cases with parasitological diagnosis and 88 chronic cases) through the demonstration of IgG antibodies by ELISA and indirect immunofluorescence (IIF) were evaluated with leishmanin soluble antigen which contained Leishmania (Viannia) peruviana concentration of 25-30 ug/mL. Only five people showed cutaneous hypersensitivity reaction to the application of the antigen between hours 48 and 72. The Leishmanin skin test evaluated was negative in 97 people infected with T. cruzi, thus specificity of 95.1% was achieved. In conclusion, the intradermal Montenegro test is a simple and effective diagnostic tool that also could be used to discriminate infections by Leishmania or T. cruzi, in Peruvian geographic areas where both parasites are present.

Humans , Male , Female , Adolescent , Adult , Young Adult , Chagas Disease/diagnosis , Antibodies, Protozoan/analysis , Chagas Disease/immunology , Peru , Sensitivity and Specificity , Skin Tests/methods , Trypanosoma cruzi/immunology