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

Effect of medicinal plants on the parasitemia of Trypanosoma cruzi and on the biodistribution of sodium pertechnetate (Na99mTcO4)

Artemisia vulgaris (AV) is an antihelmintic and antimalarial drug; Aloe vera(babosa) acts as antidiabetic, laxative and anti-inflammatory;Benznidazole (BZ) is a trypanocidal of Trypanosoma cruzi (TC). Technetium-99m (99mTc) has been used in nuclear medicine to obtain diagnostic images. This study evaluated the plant effects in TC parasitemia and on the biodistribution of 99mTc in mice. Twenty mice were infected by TC. At the peak of parasitemia, 5 mice received babosa; 5 received AV and 5 received BZ. The parasitemia was determined at 0, 2, 4 and 6 h of drugs administration. Five infected mice without drugs, 5 mice without TC and the group treated with AV, received 99mTc. The radioactivity was calculated. Infected mice that received babosa reduced significantly (p<0.05) the TC parasitemia. The percentage of activity per gram (%ATI/g) decreased significantly on the AV group. These results indicate that babosa possibly is an anti-TC drug and AV reduces the %ATI/g probably due to its biological effects

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

Triatomine and Trypanosoma cruzi discrete typing units distribution in a semi-arid area of northeastern Brazil

Federal University of Rio Grande do Norte. Graduate Program in Parasitic Biology. Natal, RN, Brazil.Federal University of Rio Grande do Norte. Graduate Program in Pharmaceutical Sciences. Natal, RN, Brazil.Federal University of Rio Grande do Norte. Pharmacy Undergraduate Course. Natal, RN, Brazil.State Secretariat of Public Health of Rio Grande do Norte. Natal, RN, Brazil.Fundação Oswaldo Cruz. René Rachou Institute. Triatomine Research Group. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. René Rachou Institute. Triatomine Research Group. Belo Horizonte, MG, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Geoprocessamento. Ananindeua, PA, Brasil.Federal University of Rio Grande do Norte. Graduate Program in Pharmaceutical Sciences. Natal, RN, Brazil / Federal University of Rio Grande do Norte. Graduate Program in Health Sciences. Natal, RN, Brazil.Federal University of Rio Grande do Norte. Graduate Program in Parasitic Biology. Natal, RN, Brazil / Federal University of Rio Grande do Norte. Graduate Program in Pharmaceutical Sciences. Natal, RN, Brazil.The occurrence of triatomine species, their bloodmeal sources and the discrete typing units (DTUs) of Trypanosoma cruzi isolated from them were determined in different municipalities of the state of Rio Grande do Norte, Brazil. Triatomine captures were carried out in the rural areas of 23 municipalities. The genotyping of T. cruzi isolates was performed using the mitochondrial cytochrome c oxidase subunit 2 (coii) gene, the D7 region of the 24Sα rDNA, and the spliced leader intergenic region (SL-IR). Five triatomine species were captured, and the most frequent was Triatoma brasiliensis (84.3%; 916/1086), which was found in 16 of the 23 municipalities surveyed, and infested all types of environment investigated. The TcI DTU was found in all mesoregions surveyed in 51.5% (17/33) of the culture-positive samples. In contrast, TcII (9.1%; 3/33) was detected in the Central mesoregion, while TcIII (27.3%; 9/33) was found in all mesoregions. The geographic distribution and spatial overlap of different DTUs was inferred using the superposition of the radius of occurrence of isolates and using ecological niche distribution modelling. Triatoma brasiliensis was found infected in all mesoregions and with all three T. cruzi DTUs, including mixed infections. With regard to bloodmeal sources, the DNA of rodents was found in triatomines infected with either TcI or TcIII, while that of domestic animals and humans was associated with both single and mixed infections. Our findings demonstrate that different DTUs of T. cruzi are widely dispersed among triatomines in our study area. The association of T. brasiliensis with several different mammalian hosts, as well as overlapping areas with different DTUs, suggests that this triatomine species may have an important role as a vector in both anthropic and sylvatic environments

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

Genome-wide screening and identification of new Trypanosoma cruzi antigens with potential application for chronic Chagas disease diagnosis.

The protozoan Trypanosoma cruzi is the etiologic agent of Chagas disease, an infection that afflicts approximately 8 million people in Latin America. Diagnosis of chronic Chagas disease is currently based on serological tests because this condition is usually characterized by high anti-T. cruzi IgG titers and low parasitemia. The antigens used in these assays may have low specificity due to cross reactivity with antigens from related parasite infections, such as leishmaniasis, and low sensitivity caused by the high polymorphism among T. cruzi strains. Therefore, the identification of new T. cruzi-specific antigens that are conserved among the various parasite discrete typing units (DTUs) is still required. In the present study, we have explored the hybrid nature of the T. cruzi CL Brener strain using a broad genome screening approach to select new T. cruzi antigens that are conserved among the different parasite DTUs and that are absent in other trypanosomatid species. Peptide arrays containing the conserved antigens with the highest epitope prediction scores were synthesized, and the reactivity of the peptides were tested by immunoblot using sera from C57BL/6 mice chronically infected with T. cruzi strains from the TcI, TcII or TcVI DTU. The two T. cruzi proteins that contained the most promising peptides were expressed as recombinant proteins and tested in ELISA experiments with sera from chagasic patients with distinct clinical manifestations: those infected with T. cruzi from different DTUs and those with cutaneous or visceral leishmaniasis. These proteins, named rTc_11623.20 and rTc_N_10421.310, exhibited 94.83 and 89.66% sensitivity, 98.2 and 94.6% specificity, respectively, and a pool of these 2 proteins exhibited 96.55% sensitivity and 98.18% specificity. This work led to the identification of two new antigens with great potential application in the diagnosis of chronic Chagas disease

Clinical data of chronic chagasic patients from the Northeast of Brazil included in this investigation.

<p>Clinical data of chronic chagasic patients from the Northeast of Brazil included in this investigation.</p