Doença de Chagas: caracterização de formas clínicas e estratificação do risco de morte no Oeste do Estado do Rio Grande do Norte

O perfil clínico com classificação das formas clínicas e a gravidade da doença de Chagas foram avaliados em indivíduos sororreativos para o Trypanosoma cruzi procedentes da mesorregião Oeste Potiguar. Neste estudo transversal foram incluídos 186 indivíduos adultos, entre 23 a 78 anos de idade. Todos os indivíduos foram submetidos à avaliação clínica, aplicado um questionário clínicoepidemiológico e realizados eletrocardiograma de repouso, ecocardiograma transtorácico, radiografia simples de tórax e contrastadas de esôfago e cólon. O Holter foi realizado em 98 pacientes e aplicado escores de risco de acidente vascular encefálico isquêmico e morte. A forma clínica indeterminada foi detectada em 51,6% (96/186) dos pacientes, a cardíaca em 32,2% (60/186), a digestiva em 8,1% (15/186) e a cardiodigestiva em 8,1% (15/186). Dos pacientes com a forma clínica digestiva, 7,0% (13/186) apresentaram diferentes grupos de megaesôfago (I a IV) e 12,9% (24/186) apresentaram megacólon de grau 1 a 3. Destes, 29,2% (7/24) com ambos os órgãos afetados. As alterações eletrocardiográficas foram observadas em 48,9% (91/186) dos pacientes e a arritmia ventricular complexa presente em 41,8% (41/98). Desses pacientes, 10,2% (19/186) apresentaram cardiomegalia, o aneurisma apical foi diagnosticado em 10,8% (20/186) e, as alterações da contratilidade miocárdica segmentar do ventrículo esquerdo em 33,9% (63/186). Em 7,5% (14/186) dos pacientes foi detectada insuficiência cardíaca com classes funcionais que variam de I a IV. A classificação da insuficiência cardíaca por estádios demonstrou que 36,4% (24/66), 30,3% (20/66), 15,2% (10/66), 13,6% (9/66) e 4,5% (3/66) dos pacientes apresentaram estágios A, B1, B2, C e D, respectivamente. O escore de estratificação de risco de acidente vascular encefálico isquêmico identificou 80,6% (150/186) dos pacientes em baixo risco, 15,6% (29/186) em moderado e 3,8% (7/186) em alto risco. O escore de risco de morte foi aplicado em 84 pacientes e 69,0% (58/84) mostraram baixo risco, 25,0% (21/84) intermediário e 6,0% (5/84) alto risco. Os resultados demonstraram a existência das principais formas clínicas da doença de Chagas em diferentes estágios de evolução, inclusive o registro da forma digestiva isolada; observou-se que um quarto dos pacientes com a forma indeterminada deveria ser considerado cardiopatas subclínicos ou pelo menos, pacientes de maior potencial evolutivo para outras formas clínicas ou fase pré- clínica, e confirmou-se a existência de correlação positiva entre o escore de risco de morte e seus principais determinantes, insuficiência cardíaca, morte súbita e acidente vascular encefálico isquêmico, oferecendo mais um elemento para a tomada de condutas frente ao chagásico cardiopata

Trypanosoma cruzi III causing the indeterminate form of Chagas disease in a semi-arid region of Brazil

Objective: Trypanosoma cruzi is subdivided into six discrete typing units (DTUs), TcI–TcVI. The precise identification of each can contribute to tracking wild DTUs that invade the domiciliary environment. Methods: Twenty T. cruzi stocks isolated from 16 chagasic patients, two Panstrongylus lutzi, one Galea spixii, and one Euphractus sexcinctus, from different localities in the State of Rio Grande do Norte, Brazil, were characterized by genotyping the 3′ region of the 24Sα rRNA gene, the mitochondrial cytochrome oxidase subunit 2 gene, and the spliced leader intergenic region. Results: TcIII was identified in 18.7% (3/16) of patients from different municipalities, as well as in P. lutzi, G. spixii, and E. sexcinctus, indicating the connection between the sylvatic and domestic cycles in this Brazilian semi-arid region. TcI and TcII were also detected, in 37.5% (6/16) and 43.8% (7/16) of patients, respectively. These DTUs were associated with cardiac, digestive, and indeterminate clinical forms, while TcIII was identified only in patients with the indeterminate form. Conclusions: The occurrence of these DTUs reveals important phylogenetic diversity in T. cruzi isolates from humans. TcIII is reported for the first time in northeastern Brazil. These findings appear to indicate an overlap between the sylvatic and domestic transmission cycles of the parasite in this region

Chagas disease: morbidity profile in an endemic area of Northeastern Brazil

Abstract: INTRODUCTION : This study evaluated the clinical forms and manifestation severities of Chagas disease among serologically reactive individuals from Western Rio Grande do Norte (Northeastern Brazil). METHODS : This cross-sectional study included 186 adults who were evaluated using electrocardiography, echocardiography, chest radiography, and contrast radiography of the esophagus and colon. A clinical-epidemiological questionnaire was also used. RESULTS : The indeterminate, cardiac, digestive, and cardiodigestive clinical forms of Chagas disease were diagnosed in 51.6% (96/186), 32.2% (60/186), 8.1% (15/186) and 8.1% (15/186) of the participants, respectively. Heart failure (functional classes I-IV) was detected in 7.5% (14/186) of the participants, and 36.4% (24/66), 30.3% (20/66), 15.2% (10/66), 13.6% (9/66), and 4.5% (3/66) of the patients were at stage A, B1, B2, C, and D, respectively. Dilated cardiomyopathy and electrocardiographic changes were detected in 10.2% (19/186) and 48.1% (91/186) of the participants, respectively. Apical aneurysm was diagnosed in 10.8% (20/186) of the participants, and other changes in the segmental myocardial contractility of the left ventricle were diagnosed in 33.9% (63/186) of the participants. Megaesophagus (groups I-IV) was observed in 7% (13/186) of the participants, megacolon (grades 1-3) was detected in12.9% (24/186) of the participants, and both organs were affected in 29.2% (7/24) of the megacolon cases. CONCLUSIONS : We detected various clinical forms of Chagas disease (including the digestive form). Our findings indicate that clinical symptoms alone may not be sufficient to exclude or confirm cardiac and/or digestive damage, and the number of patients with symptomatic clinical forms may be underestimated

Innate immune receptors over expression correlate with chronic chagasic cardiomyopathy and digestive damage in patients.

Chronic chagasic cardiomyopathy (CCC) is observed in 30% to 50% of the individuals infected by Trypanosoma cruzi and heart failure is the important cause of death among patients in the chronic phase of Chagas disease. Although some studies have elucidated the role of adaptive immune responses involving T and B lymphocytes in cardiac pathogenesis, the role of innate immunity receptors such as Toll-like receptors (TLRs) and Nod-like receptors (NLRs) in CCC pathophysiology has not yet been determined. In this study, we evaluated the association among innate immune receptors (TLR1-9 and nucleotide-binding domain-like receptor protein 3/NLRP3), its adapter molecules (Myd88, TRIF, ASC and caspase-1) and cytokines (IL-1β, IL-6, IL-12, IL-18, IL-23, TNF-α, and IFN-β) with clinical manifestation, digestive and cardiac function in patients with different clinical forms of chronic Chagas disease. The TLR8 mRNA expression levels were enhanced in the peripheral blood mononuclear cells (PBMC) from digestive and cardiodigestive patients compared to indeterminate and cardiac patients. Furthermore, mRNA expression of IFN-β (cytokine produced after TLR8 activation) was higher in digestive and cardiodigestive patients when compared to indeterminate. Moreover, there was a positive correlation between TLR8 and IFN-β mRNA expression with sigmoid and rectum size. Cardiac and cardiodigestive patients presented higher TLR2, IL-12 and TNF-α mRNA expression than indeterminate and digestive patients. Moreover, cardiac patients also expressed higher levels of NLRP3, ASC and IL-1β mRNAs than indeterminate patients. In addition, we showed a negative correlation among TLR2, IL-1β, IL-12 and TNF-α levels with left ventricular ejection fraction, and positive correlation between NLRP3 with cardiothoracic index, and TLR2, IL-1β and IL-12 with left ventricular mass index. Together, our data suggest that high expression of innate immune receptors in cardiac and digestive patients may induce an enhancement of cytokine expression and participate of cardiac and digestive dysfunction

Innate immune receptors over expression correlate with chronic chagasic cardiomyopathy and digestive damage in patients

Submitted by Sandra Infurna ([email protected]) on 2019-01-30T10:27:25Z No. of bitstreams: 1 adelaideV_Motta_etal_IOC_2018.pdf: 4348852 bytes, checksum: 2a6663ea033f9812085adebf92dec5ce (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-01-30T10:46:20Z (GMT) No. of bitstreams: 1 adelaideV_Motta_etal_IOC_2018.pdf: 4348852 bytes, checksum: 2a6663ea033f9812085adebf92dec5ce (MD5)Made available in DSpace on 2019-01-30T10:46:20Z (GMT). No. of bitstreams: 1 adelaideV_Motta_etal_IOC_2018.pdf: 4348852 bytes, checksum: 2a6663ea033f9812085adebf92dec5ce (MD5) Previous issue date: 2018Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brasil / Universidade Federal do Rio Grande do Norte. Departamento de Microbiologia e Parasitologia. Natal, RN, Brasil / Universidade Potiguar. Escola de Saúde. Natal, RN, Brasil.Universidade Federal do Rio Grande do Norte. Departamento de Microbiologia e Parasitologia. Natal, RN, Brasil.Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brasil.Universidade do Estado do Rio Grande do Norte. Departamento de Ciências Biomédicas. Mossoró, RN, Brasil.Instituto Internacional de Neurociências Edmond e Lilly Safra. Macaíba, RN, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ. Brasil.Universidade Federal do Rio Grande do Norte. Departamento de Análises Clínicas e Toxicológicas. Natal, RN, Brasil.Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brasil.Universidade Federal do Rio Grande do Norte. Departamento de Microbiologia e Parasitologia. Natal, RN, Brasil.Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, BrasilChronic chagasic cardiomyopathy (CCC) is observed in 30% to 50% of the individuals infected by Trypanosoma cruzi and heart failure is the important cause of death among patients in the chronic phase of Chagas disease. Although some studies have elucidated the role of adaptive immune responses involving T and B lymphocytes in cardiac pathogenesis, the role of innate immunity receptors such as Toll-like receptors (TLRs) and Nod-like receptors (NLRs) in CCC pathophysiology has not yet been determined. In this study, we evaluated the association among innate immune receptors (TLR1-9 and nucleotide-binding domain-like receptor protein 3/NLRP3), its adapter molecules (Myd88, TRIF, ASC and caspase- 1) and cytokines (IL-1β, IL-6, IL-12, IL-18, IL-23, TNF-α, and IFN-β) with clinical manifestation, digestive and cardiac function in patients with different clinical forms of chronic Chagas disease. The TLR8 mRNA expression levels were enhanced in the peripheral blood mononuclear cells (PBMC) from digestive and cardiodigestive patients compared to indeterminate and cardiac patients. Furthermore, mRNA expression of IFN-β (cytokine produced after TLR8 activation) was higher in digestive and cardiodigestive patients when compared to indeterminate. Moreover, there was a positive correlation between TLR8 and IFN-β mRNA expression with sigmoid and rectum size. Cardiac and cardiodigestive patients presented higher TLR2, IL-12 and TNF-α mRNA expression than indeterminate and digestive patients. Moreover, cardiac patients also expressed higher levels of NLRP3, ASC and IL-1β mRNAs than indeterminate patients. In addition, we showed a negative correlation among TLR2, IL-1β, IL-12 and TNF-α levels with left ventricular ejection fraction, and positive correlation between NLRP3 with cardiothoracic index, and TLR2, IL-1β and IL-12 with left ventricular mass index. Together, our data suggest that high expression of innate immune.receptors in cardiac and digestive patients may induce an enhancement of cytokine expression and participate of cardiac and digestive dysfunction

Inflammation Enhances the Risks of Stroke and Death in Chronic Chagas Disease Patients

Submitted by sandra infurna ([email protected]) on 2016-06-19T18:59:10Z No. of bitstreams: 1 mariaadelaide_matta_etal_IOC_2016.pdf: 749988 bytes, checksum: 989d8777a371bcd276efecde9a5d4214 (MD5)Approved for entry into archive by sandra infurna ([email protected]) on 2016-06-19T19:21:52Z (GMT) No. of bitstreams: 1 mariaadelaide_matta_etal_IOC_2016.pdf: 749988 bytes, checksum: 989d8777a371bcd276efecde9a5d4214 (MD5)Made available in DSpace on 2016-06-19T19:21:52Z (GMT). No. of bitstreams: 1 mariaadelaide_matta_etal_IOC_2016.pdf: 749988 bytes, checksum: 989d8777a371bcd276efecde9a5d4214 (MD5) Previous issue date: 2016Made available in DSpace on 2016-07-08T12:21:49Z (GMT). No. of bitstreams: 3 mariaadelaide_matta_etal_IOC_2016.pdf.txt: 58546 bytes, checksum: d1a8f1e931ab9591fce414aa980fdaa1 (MD5) mariaadelaide_matta_etal_IOC_2016.pdf: 749988 bytes, checksum: 989d8777a371bcd276efecde9a5d4214 (MD5) license.txt: 2991 bytes, checksum: 5a560609d32a3863062d77ff32785d58 (MD5) Previous issue date: 2016Universidade Federal do Rio Grande do Norte. Departamento de Microbiologia e Parasiologia. Natal, RN, BrasilUniversidade do Estado do Rio Grande do Norte. Departamento de Ciências Biomédicas. Mossoró, RN, Brasil.Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brasil.Universidade Federal do Rio Grande do Norte. Departamento de Microbiologia e Parasiologia. Natal, RN, Brasil / Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brasil.Universidade Federal do Rio Grande do Norte. Departamento de Microbiologia e Parasiologia. Natal, RN, BrasilUniversidade Federal de Ouro Preto. Escola de Medicina. Ouro Preto, MG, Brasil.Univrsidade de São Paulo. Escola de Medicina de Ribeirão Preto. Ribeirão Preto, SP, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório deUltraestrutura Celular. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio Grande do Norte. Departmaneto de Análises Clínicas e Toxicológicas. Natal, RN, Brasil.Universidade Federal de Minas Gerais. Departamento de Parasitologia. Belo Horizonte, MG, Brasil.Ischemic strokes have been implicated as a cause of death in Chagas disease patients. Inflammation has been recognized as a key component in all ischemic processes, including the intravascular events triggered by vessel interruption, brain damage and repair. In this study, we evaluated the association between inflammatory markers and the death risk (DR) and stroke risk (SR) of patients with different clinical forms of chronic Chagas disease. The mRNA expression levels of cytokines, transcription factors expressed in the adaptive immune response (Th1, Th2, Th9, Th17, Th22 and regulatory T cell), and iNOS were analyzed by realtime PCR in peripheral blood mononuclear cells of chagasic patients who exhibited the indeterminate, cardiac, digestive and cardiodigestive clinical forms of the disease, and the levels of these transcripts were correlated with the DR and SR. Cardiac patients exhibited lowermRNA expression levels of GATA-3, FoxP3, AHR, IL-4, IL-9, IL-10 and IL-22 but exhibited higher expression of IFN-γ and TNF-α compared with indeterminate patients. Digestive patients showed similar levels of GATA-3, IL-4 and IL-10 than indeterminate patients. Cardiodigestive patients exhibited higher levels of TNF-α compared with indeterminate and digestive patients. Furthermore, we demonstrated that patients with high DR and SR exhibited lower GATA-3, FoxP3, and IL-10 expression and higher IFN-γ, TNF-α and iNOS mRNA expression than patients with low DR and SR. A negative correlation was observed between Foxp3 and IL-10 mRNA expression and the DR and SR. Moreover, TNF-α and iNOS expression was positively correlated with DR and SR. Our data suggest that an inflammatory imbalance in chronic Chagas disease patients is associated with a high DR and SR. This study provides a better understanding of the stroke pathobiology in the general population and might aid the development of therapeutic strategies for controlling the morbidity and mortality of Chagas disease

Naturally Leishmania infantum-infected dogs display an overall impairment of chemokine and chemokine receptor expression during visceral leishmaniasis.

Dogs are the primary reservoir for Leishmania parasites. The immune response induced by Leishmania infantum infection in these animals has not been completely elucidated, and few studies have investigated the relationship between the expression levels of chemokines and chemokine receptors and the clinical status of dogs with canine visceral leishmaniasis (CVL). The aim of this study was to correlate the clinical status of naturally L. infantuminfected dogs (from rural areas of Mossoró city, State of Rio Grande do Norte, Brazil) with the expression levels of chemokines (ccl1, ccl2, ccl3, ccl4, ccl5, ccl17, ccl20, ccl24, ccl26, cxcl9, cxcl10) and chemokine receptors (cxcr3, ccr3, ccr4, ccr5, ccr6, ccr8) in the liver and spleen determined using real-time PCR. Twenty-one dogs were clinically evaluated and classified as asymptomatic (n = 11) or symptomatic (n = 10). Splenomegaly, weight loss and onychogryphosis were the most pronounced symptoms. In the liver, the mRNA expression levels of ccl1, ccl17, ccl26, ccr3, ccr4, ccr5, ccr6, and ccr8 were lower in symptomatic animals than in asymptomatic animals. Compared with uninfected animals, symptomatic dogs had lower expression levels of almost all molecules analyzed. Moreover, high clinical scores were negatively correlated with ccr5 and ccr6 expression and positively correlated with cxcl10 expression. We conclude that the impairment of the expression of chemokines and chemokine receptors results in deficient leukocyte migration and hampers the immune response, leading to the development of disease