Antiparasitic treatment with itraconazole and amiodarone in 2 dogs with severe, symptomatic Chagas cardiomyopathy.

Chagas cardiomyopathy, caused by the protozoal parasite Trypanosoma cruzi, is characterized by arrhythmias, myocardial damage, heart failure, and sudden death. We describe 2 dogs with severe, symptomatic Chagas cardiomyopathy characterized by myocardial dysfunction and electrocardiographic abnormalities that were managed with a combination of cardiac medications and antiparasitic treatment with itraconazole and amiodarone. Both dogs died suddenly within 6 months of diagnosis. These cases highlight the need for early detection of Chagas disease in dogs and continued research to develop effective antiparasitic treatment protocols.

Histologic comparison in two Doberman pinschers with a dilated cardiomyopathy phenotype.

Idiopathic dilated cardiomyopathy (DCM) is a common acquired cardiac disease in large breed dogs with a high prevalence in Doberman pinschers. It is characterized histologically by attenuated wavy fibers and fatty infiltration with degeneration. The phenotypic appearance of DCM includes ventricular dilation with systolic dysfunction and ventricular arrhythmias. These changes can be caused by other etiologies, including infectious, toxic, metabolic, and nutritional deficiencies. Chagas disease is the result of an infection with the protozoal parasite, Trypanosoma cruzi, transmitted by an insect vector. Histopathology of the myocardium is characterized by inflammation, fibrosis, and pseudocysts containing T. cruzi amastigotes. Differentiating idiopathic DCM from infectious myocarditis can be challenging when the clinical presentation and diagnostic test results are similar in affected dogs. We present thoracic radiographs, echocardiography, and post-mortem histopathology images obtained from two Doberman pinschers with similar signalment, clinical presentation, and electrocardiographic and echocardiographic appearance but with different appearing radiographs and different etiologies for their heart disease, one with idiopathic DCM and one with myocarditis attributed to Chagas disease, to highlight the value of considering alternative etiologies for DCM to guide additional clinical evaluation and owner counseling.

Histopathological study in cardiac tissue of rodents infected with Trypanosoma cruzi, captured in suburbs of Mérida, México / Estudio histopatológico de tejido cardiaco de roedores infectados con Trypanosoma cruzi capturados en barrios suburbanos de Mérida, México

Introduction: Trypanosoma cruzi is the causal agent of the American trypanosomiasis, an endemic disease in México. The commensal rodents Mus musculus and Rattus rattus are reservoirs of this parasite, which invades cardiac fibers and develops parasite nests causing various lesions. Histopathological studies in naturally infected rodents are scarce. Objective: To describe the types and frequencies of microscopic lesions in cardiac tissue of M. musculus and R. rattus infected with T. cruzi captured in Mérida, México. Materials and methods: The rodents were captured in suburban environments of Mérida. Cardiac tissue was extracted and processed by the paraffin inclusion technique and hematoxylin and eosin stained. The observation was made with a conventional microscope and all the lesions, as well as their degree, were identified. Results: Eight tissue samples of M. musculus and seven of R. rattus were studied. Parasite nests were found in 7/15, specifically 3/8 in M. musculus and 4/7 in R. rattus. The inflammatory infiltrate was the most frequent lesion. Other lesions were: Degeneration of cardiac fibers (8/15), congestion of blood vessels (6/15), and necrosis (5/15). Discussion: The lesions we observed have been described in experimental animal models and in humans with American trypanosomiasis. The inflammatory infiltrate has been identified as the most significant lesion in humans and reservoirs in the chronic stage of the disease. Conclusion: The lesions we described are associated with T. cruzi infection, which confirms that the rodents studied are reservoirs of this parasite.

Introducción. Trypanosoma cruzi es el agente causal de la tripanosomiasis americana, enfermedad endémica en México. Los roedores Mus musculus y Rattus rattus son reservorios del parásito, el cual invade las fibras cardiacas y desarrolla nidos parasitarios produciendo diversas lesiones. Los estudios histopatológicos en roedores naturalmente infectados son escasos. Objetivo. Describir los tipos y las frecuencias de las lesiones microscópicas en muestras de tejido cardiaco de M. musculus y R. rattus infectados con T. cruzi capturados en Mérida, México. Materiales y métodos. Los roedores se capturaron en los barrios suburbanos de Mérida. Se extrajo el tejido cardiaco y se procesó por la técnica de inclusión en parafina y tinción con hematoxilina y eosina. Su examen se hizo con un microscópico convencional y se determinaron todas las lesiones y su grado de afección. Resultados. Se trabajaron ocho muestras de tejido de M. musculus y siete de R. rattus. Se encontraron nidos parasitarios en siete del total de las muestras: en 3 de las 8 de M. musculus y en 4 de las 7 de R. rattus. Se observaron infiltrados inflamatorios en todas las muestras. Otras lesiones fueron la degeneración de las fibras cardiacas (8/15), la congestión de los vasos sanguíneos (6/15) y la necrosis (5/15). Discusión. Las lesiones observadas están descritas en los modelos animales experimentales y en los  humanos con tripanosomiasis americana. Los infiltrados inflamatorios se han descrito como la lesión más significativa en los humanos y en los reservorios en la etapa crónica de la enfermedad. Conclusión. Las lesiones observadas están asociadas con la infección con T. cruzi, lo cual confirma que los roedores estudiados son reservorios de este parásito.

Estudio histopatológico de tejido cardiaco de roedores infectados con Trypanosoma cruzi capturados en barrios suburbanos de Mérida, México / Histopathological study in cardiac tissue of rodents infected with Trypanosoma cruzi, captured in suburbs of Mérida, México

Resumen Introducción. Trypanosoma cruzi es el agente causal de la tripanosomiasis americana, enfermedad endémica en México. Los roedores Mus musculus y Rattus rattus son reservorios del parásito, el cual invade las fibras cardiacas y desarrolla nidos parasitarios produciendo diversas lesiones. Los estudios histopatológicos en roedores naturalmente infectados son escasos. Objetivo. Describir los tipos y las frecuencias de las lesiones microscópicas en muestras de tejido cardiaco de M. musculus y R. rattus infectados con T. cruzi capturados en Mérida, México. Materiales y métodos. Los roedores se capturaron en los barrios suburbanos de Mérida. Se extrajo el tejido cardiaco y se procesó por la técnica de inclusión en parafina y tinción con hematoxilina y eosina. Su examen se hizo con un microscópico convencional y se determinaron todas las lesiones y su grado de afección. Resultados. Se trabajaron ocho muestras de tejido de M. musculus y siete de R. rattus. Se encontraron nidos parasitarios en siete del total de las muestras: en 3 de las 8 de M. musculus y en 4 de las 7 de R. rattus. Se observaron infiltrados inflamatorios en todas las muestras. Otras lesiones fueron la degeneración de las fibras cardiacas (8/15), la congestión de los vasos sanguíneos (6/15) y la necrosis (5/15). Discusión. Las lesiones observadas están descritas en los modelos animales experimentales y en los humanos con tripanosomiasis americana. Los infiltrados inflamatorios se han descrito como la lesión más significativa en los humanos y en los reservorios en la etapa crónica de la enfermedad. Conclusión. Las lesiones observadas están asociadas con la infección con T. cruzi, lo cual confirma que los roedores estudiados son reservorios de este parásito.

Abstract Introduction: Trypanosoma cruzi is the causal agent of the American trypanosomiasis, an endemic disease in México. The commensal rodents Mus musculus and Rattus rattus are reservoirs of this parasite, which invades cardiac fibers and develops parasite nests causing various lesions. Histopathological studies in naturally infected rodents are scarce. Objective: To describe the types and frequencies of microscopic lesions in cardiac tissue of M. musculus and R. rattus infected with T. cruzi captured in Mérida, México. Materials and methods: The rodents were captured in suburban environments of Mérida. Cardiac tissue was extracted and processed by the paraffin inclusion technique and hematoxylin and eosin stained. The observation was made with a conventional microscope and all the lesions, as well as their degree, were identified. Results: Eight tissue samples of M. musculus and seven of R. rattus were studied. Parasite nests were found in 7/15, specifically 3/8 in M. musculus and 4/7 in R. rattus. The inflammatory infiltrate was the most frequent lesion. Other lesions were: Degeneration of cardiac fibers (8/15), congestion of blood vessels (6/15), and necrosis (5/15). Discussion: The lesions we observed have been described in experimental animal models and in humans with American trypanosomiasis. The inflammatory infiltrate has been identified as the most significant lesion in humans and reservoirs in the chronic stage of the disease. Conclusion: The lesions we described are associated with T. cruzi infection, which confirms that the rodents studied are reservoirs of this parasite.

In situ hybridization assay for the diagnosis of chagas myocarditis and orchitis in a rhesus macaque (Macaca mulatta): A case report.

We present the first documented case of Trypanosoma cruzi-induced orchitis in a rhesus macaque. Additionally, we describe an in situ hybridization-based assay to confirm T. cruzi infection in formalin-fixed tissues.

Efficacy of Recombinase Polymerase Amplification to Diagnose Trypanosoma cruzi Infection in Dogs with Cardiac Alterations from an Endemic Area of Mexico.

Chagas disease is a lingering Public Health problem in Latin America with ∼5.7 million people infected with Trypanosoma cruzi. Transmission is still taking place in most countries of the Americas, including the United States. Dogs are frequently infected with T. cruzi and its high infection prevalence is associated with increased risk of Chagas disease in humans. The city of Mérida in the Yucatan peninsula is endemic for Chagas disease and canines are frequently infected with T. cruzi. The objective of this study was to evaluate the performance of a qualitative point of care (POC) molecular test (RPA-LF, recombinase polymerase amplification-lateral flow) developed in our laboratory for identifying infected dogs. We used retrospective samples of dogs that came for consultation because of cardiac alterations and proved to be infected with T. cruzi as determined by enzyme-linked immunosorbent assay (ELISA), Western blot, and quantitative PCR (qPCR). The analytical sensitivity indicated that RPA-LF amplified T. cruzi DNA in samples containing almost equal to one to two parasites per reaction. Serial twofold dilutions of T. cruzi epimastigotes showed that the test had 95% (19/20) repeatability at concentrations of two parasites per reaction. The test showed no cross reactivity with human DNA or other protozoan parasites (Trypanosoma rangeli, Leishmania spp., and Plasmodium spp.). RPA-LF had the capacity to amplify all discrete typing units (DTUs I-VI) of T. cruzi that circulate in domestic or extradomestic environments. The RPA-LF had 93.2% (95% confidence interval 87.2-98.1) sensitivity and excellent agreement with qPCR used as gold standard (Cohen's Kappa test = 0.963). ELISA was positive in 96.6% (85/88) of dogs, which together with the molecular tests confirmed the frequent contact with infected triatomine bugs in the city of Mérida. These preliminary results on the diagnostic efficacy of the RPA-LF deserve further large-scale field testing of this POC test for T. cruzi infection in endemic areas.

Chagas disease in 2 geriatric rhesus macaques (Macaca mulatta) housed in the Pacific Northwest.

Chagas disease (American trypanosomiasis) is caused by the protozoan parasite Trypanosoma cruzi. It is endemic in Latin America but also is found in the southern United States, particularly Texas and along the Gulf Coast. Typical clinical manifestations of Chagas disease are not well-characterized in rhesus macaques, but conduction abnormalities, myocarditis, and encephalitis and megaesophagus have been described. Here we report 2 cases of Chagas disease in rhesus macaques housed in the northwestern United States. The first case involved a geriatric male macaque with cardiomegaly, diagnosed as dilated cardiomyopathy on ultrasonographic examination. Postmortem findings included myocarditis as well as ganglioneuritis in the esophagus, stomach, and colon. The second case affected a geriatric female macaque experimentally infected with SIV. She was euthanized for a protocol-related time point. Microscopic examination revealed chronic myocarditis with amastigotes present in the cardiomyocytes, ganglioneuritis, and opportunistic infections attributed to her immunocompromised status. Banked serum samples from both macaques had positive titers for T. cruzi. T. cruzi DNA was amplified by conventional PCR from multiple tissues from both animals. Review of their histories revealed that both animals had been obtained from facilities in South Texas more than 12 y earlier. Given the long period of clinical latency, Chagas disease may be more prevalent in rhesus macaques than typically has been reported. T. cruzi infection should be considered for animals with unexplained cardiac or gastrointestinal pathology and that originated from areas known to have a high risk for disease transmission.

Correlation between presence of Trypanosoma cruzi DNA in heart tissue of baboons and cynomolgus monkeys, and lymphocytic myocarditis.

Trypanosoma cruzi, the causative agent of Chagas' disease, preferentially infects cardiac and digestive tissues. Baboons living in Texas (Papio hamadryas) and cynomolgus monkeys (Macaca fascicularis) have been reported to be infected naturally with T. cruzi. In this study, we retrospectively reviewed cases of animals that were diagnosed with lymphocytic myocarditis and used a polymerase chain reaction (PCR)-based method (S36/S35 primer set) to amplify T. cruzi DNA from archived frozen and formalin-fixed paraffin-embedded (FFPE) cardiac tissues. We show that the PCR method is applicable in archived frozen and FFPE tissues and the sensitivity is in the femtogram range. A positive correlation between PCR positivity and lymphocytic myocarditis in both baboons and cynomolgus monkeys is shown. We also show epicarditis as a common finding in animals infected with T. cruzi.

Immunopathologic characterization of naturally acquired Trypanosoma cruzi infection and cardiac sequalae in cynomolgus macaques (Macaca fascicularis).

Trypanosoma cruzi, the causative agent of Chagas disease, is endemic in south Texas due to the abundant vector and wild small mammalian reservoir populations. This situation predisposes nonhuman primate colonies exposed to outdoor housing to infection from ingestion or bite of triatomid insects. Using a T. cruzi-specific real-time PCR and Trypanosome spp.-specific ELISA, we revealed a prevalence rate of 8.5% in a colony of outdoor-housed cynomolgus macaques. By using a discriminating kinetoplastid minicircle PCR, we eliminated the possibility of mixed prevalence with nonpathogenic trypanosomes and showed the ELISA results were specific for T. cruzi. In this study, we found an inverse relationship between antibody titers and circulating parasite load. Also, 23% of T. cruzi IgG ELISA-positive macaques were negative by real-time PCR. Furthermore, in a subset of infected macaques, cardiac tissue was infiltrated by inflammatory mononuclear cells and contained T. cruzi genomic and kinetoplast DNA despite lacking microscopic evidence of discrete parasite stages. In addition, 19% of the infected macaques had titers for cardiac troponin I autoantibody, which could contribute to autoimmune myocarditis or interfere with circulating troponin I measurements. These findings indicate the possibility of T. cruzi to interfere with the assessment of cardiac safety signals in preclinical toxicology and safety pharmacology studies and the necessity for prestudy screening for T. cruzi in outdoor-housed nonhuman primates from endemic areas.

Bradyarrhythmias and pacemaker therapy in dogs with Chagas disease.

BACKGROUND: Chagas disease (Trypanosomiasis) is a cause of myocarditis in the southern United States causing cardiac conduction abnormalities, arrhythmias, and heart failure. OBJECTIVES: To report clinical findings and outcome in Chagas positive (CP) dogs requiring pacemaker implantation for bradyarrhythmias. ANIMALS: One hundred and forty-four client-owned dogs requiring pacemaker implantation. METHODS: Retrospective case series. Information regarding history, physical exam, laboratory and diagnostic imaging findings, treatment, and survival were obtained from medical records, with additional follow-up information obtained by contacting referring veterinarians and owners. RESULTS: Of the 144 dogs requiring pacemaker implantation from January 2001 to May 2010, 83 (57.6%) had a Chagas titer performed and 9 (10%) were CP. Concurrent ventricular arrhythmias (odds ratio 1.61, P = .005) or atrioventricular (AV) block (odds ratio 4.18, P < .001) increased the likelihood that a Chagas titer was submitted. Median age for CP dogs was 6.2 years (range, 0.3-10); 7 were male. Bradyarrhythmias included high-grade 2nd or 3rd degree AV block (n = 8) and sinus bradycardia with 1st degree AV block (n = 1); 5 had concurrent ventricular arrhythmias. A positive Chagas titer had a negative impact on survival (hazard ratio 4.04; 95% CI 1.36-12.1, P = .012) with a reported median survival time of 365 days (interquartile range, 84-973 days). CONCLUSIONS AND CLINICAL IMPORTANCE: Bradyarrhythmias can result in clinical signs requiring pacemaker implantation in CP dogs, and although the diagnosis negatively impacts survival, pacemaker therapy is a viable treatment option.

Cardiomyopathy prognosis after benznidazole treatment in chronic canine Chagas' disease.

OBJECTIVES: To evaluate the effects of benznidazole on Chagas' disease cardiac prognosis using an experimental dog model of infection. METHODS: A total of 28 dogs were divided into three groups: 10 were infected with Trypanosoma cruzi and treated benznidazole during the chronic phase, 10 were infected but untreated, and 8 were non-infected/healthy. The trypanocidal efficacy was measured by parasite kDNA detection in blood and cardiac tissue samples. The effects of benznidazole in ameliorating the cardiac systolic function were evaluated by echodopplercardiogram. RESULTS: The benznidazole initially induced a potent suppression of parasitaemia in treated animals. However, 12 months post-treatment, the parasite kDNA detections were similar between infected groups. In the baseline echocardiographic parameters there was no variation among all animals. Similarly, 1 month post-treatment there was no significant difference among healthy and infected animals with regard to systolic function. At 12 months post-treatment, an increase in cardiac chamber size related to cardiomegaly was detected among treated and untreated animals, but not in the healthy controls. Interestingly, in spite of both groups of infected animals developing a decrease in their systolic cardiac function, this decline was slightly less in the treated animals. We also evaluated levels of tumour necrosis factor-α and interleukin-10 in peripheral blood mononuclear cell culture supernatant. Cytokine profiles were similar between infected animal groups and correlated with alterations in cardiac function. CONCLUSIONS: The temporary suppression of the T. cruzi infection induced by benznidazole treatment was efficient in reducing systolic cardiac function alterations, but not in preventing the development of cardiomyopathy.

Low doses of simvastatin therapy ameliorate cardiac inflammatory remodeling in Trypanosoma cruzi-infected dogs.

Chagas cardiomyopathy remodeling is based on the presence of Trypanosoma cruzi in heart tissue and on the complex inflammatory response leading to a myocardium fibrosis and alterations in conductive and functional heart parameters. This study aims to evaluate Simvastatin on the inflammatory response and heart functionality using dogs infected with Y strain of T. cruzi. Animals were treated daily with Simvastatin (20 mg) for 6 months and submitted to clinical and immunopathological evaluations. Simvastatin reduced heart expression and serum levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) but not interleukin-10 (IL-10), possibly favoring blood parasitism but reducing inflammation and fibrosis in the left ventricle and right atrium. Simvastatin also ameliorated ejection fraction, diastolic diameter, and mass index of the left ventricle 6 months after infection. This study suggests that more investigation should be performed on the use of statins as a prophylactic therapy against cardiac remodeling because of their effects on modifying immune response and benefiting functional parameters in dogs with T. cruzi-induced ventricular dysfunctions.

Cardiac function in dogs with chronic Chagas cardiomyopathy undergoing autologous stem cell transplantation into the coronary arteries.

This study assessed the effects of a single intracoronary injection of autologous stem cells on the cardiac function of dogs with Chagas cardiomyopathy. Bone-marrow-derived stem cells were delivered into the right and left coronary arteries of 5 mature dogs with mildly compromised cardiac function due to chronic Chagas cardiomyopathy. Blood pressure and electrocardiographic and echocardiographic parameters were recorded at monthly intervals for 6 mo in the 3 dogs that survived. Although no changes were observed in the electrocardiogram and blood pressure, there was a significant increase in peak velocity of aortic flow 3 mo after stem cell transplantation. Pre-ejection period, isovolumic relaxation time, and the Tei index of myocardial performance were reduced significantly 4 mo after the procedure. All significant changes persisted to the end of the study. The results suggest that the transplantation of autologous bone-marrow-derived stem cells into the coronary arteries of dogs with Chagas cardiomyopathy may have a beneficial effect but the small number of dogs studied was a limitation.

Caracterização clínica da cardiomiopatia chagásica crônica em cães / Clinical characterization of chronic chagasic cardiomyopathy in dogs

On the American continent, almost 15 million people are affected by Chagas disease, resulting in important economic and social damages. Dogs are considered to be an excellent experimental model to study Chagas' disease; as a result, in this research, the characterization of cardiovascular abnormalities was performed in dogs experimentally infected with Trypanosoma cruzi (the Colombian strain) that were at chronic stage. Thirteen adult female dogs were evaluated by electrocardiographic, echocardiographic, hematological and biochemical analyses in the chronic phase. For the electrocardiographic studies, respiratory sinus arrhythmia was the predominant rhythm during the entire research period (49.55 percent to 67 percent), with a low prevalence of right bundle branch block (0-13 percent) and first-degree atrioventricular block (0-14 percent). The spectral Doppler echocardio-graphy showed E and A mitral wave reversal (0.71±0.17), confirming the diastolic dysfunction present in all dogs. An increase in the enzymes activities was detected in the serum analysis, indicating myocardial injury by the infection. Six dogs died during the follow-up. In this way, the clinical characterization of experimentally infected dogs, as described here, increases the knowledge and allows for recognition of the behavioural modifications present in Chagas' disease in affected dogs.

No continente Americano, aproximadamente 15 milhões de pessoas são afetadas pela doença de Chagas, ocasionando importantes danos econômicos e sociais. O cão é considerado excelente modelo experimental para o estudo dessa enfermidade; assim sendo, foram caracterizadas, neste ensaio, as anormalidades cardiovasculares de 13 cães experimentalmente infectados com a cepa Colombiana do Trypanosoma cruzi, em fase crônica (1997-2004). Ao eletrocardiograma, a arritmia sinusal respiratória foi o ritmo predominante durante todo período experimental (49,55-67 por cento), com baixas prevalências de bloqueio de ramo direito (0-13 por cento) e de bloqueio atrioventricular de primeiro grau (0-14 por cento). A EcoDopplercardiografia espectral revelou inversão das ondas E e A mitral (0.71±0.17), confirmando a disfunção diastólica presente em todos os cães avaliados. O aumento da atividade enzimática sérica foi detectado, indicando agressão miocárdica pela infecção. Seis cães morreram durante o período experimental. Desta forma, a caracterização clínica dos cães experimentalmente infectados trouxe informações importantes, possibilitando reconhecer o comportamento clínico dessa importante infecção, na espécie canina.

Trypanosoma cruzi circulating in the southern region of the State of Mexico (Zumpahuacan) are pathogenic: a dog model.

Here we describe clinical and pathologic evidence of Chagas disease caused in dogs by circulating Trypanosoma cruzi from a newly recognized endemic area in Mexico. We show that the Zumpahuacan isolate, although less virulent than the Sylvio-X10 reference strain that caused acute myocarditis and death, was pathogenic in dogs. Dogs infected with the Zumpahuacan isolate exhibited electrocardiographic alterations, left- and right-ventricle dilation, and hydropericardium. Histologically, diffused perimysial and endomysial lymphoplasmacytic cell infiltration, cardiomyocyte necrosis, and amastigote nests were noted in Zumpahuacan-infected dogs. These findings suggest that the risk of T. cruzi infection and Chagas disease is present in the State of Mexico, and further research is needed to identify the T. cruzi bio-types circulating in southern State of Mexico.

Nonspecific lymphocytic myocarditis in baboons is associated with Trypanosoma cruzi infection.

Non-specific lymphocytic myocarditis (NLM) is frequently observed in baboons within the endemic range of Trypanosoma cruzi. We sought to determine whether T. cruzi infection is a cause of baboon NLM. We evaluated serial histologic sections of cardiac muscle, blood cultures, immunohistochemistry, serology, polymerase chain reaction, and clinical pathology from 31 baboons with NLM to determine whether T. cruzi infection is associated with NLM. Eleven baboons with no evidence of T. cruzi infection by serology and no NLM were used as controls. Seropositivity for T. cruzi was 45% in baboons with NLM compared with a 2-3% colony prevalence. NLM lesion severity was significantly higher in seropositive than seronegative baboons with NLM. NLM was significantly more common in older baboons. No statistical association between NLM and sex, weight, or clinical pathology was found. These results suggest an association between NLM and T. cruzi infection in the baboon.

Development of chronic cardiomyopathy in canine Chagas disease correlates with high IFN-gamma, TNF-alpha, and low IL-10 production during the acute infection phase.

When infected with Trypanosoma cruzi, Beagle dogs develop symptoms similar to those of Chagas disease in human beings, and could be an important experimental model for a better understanding of the immunopathogenic mechanisms involved in chronic chagasic infection. This study evaluates IL-10, IFN-gamma and TNF-alpha production in the sera, culture supernatant, heart and cervical lymph nodes and their correlation with cardiomegaly, cardiac inflammation and fibrosis in Beagle dogs infected with T. cruzi. Pathological analysis showed severe splenomegaly, lymphadenopathy and myocarditis in all infected dogs during the acute phase of the disease, with cardiomegaly, inflammation and fibrosis observed in 83% of the animals infected by T. cruzi during the chronic phase. The data indicate that infected animals producing IL-10 in the heart during the chronic phase and showing high IL-10 production in the culture supernatant and serum during the acute phase had lower cardiac alterations (myocarditis, fibrosis and cardiomegaly) than those with high IFN-gamma and TNF-alpha levels. These animals produced low IL-10 levels in the culture supernatant and serum during the acute phase and did not produce IL-10 in the heart during the chronic phase of the disease. Our findings showed that Beagle dogs are a good model for studying the immunopathogenic mechanism of Chagas disease, since they reproduce the clinical and immunological findings described in chagasic patients. The data suggest that the development of the chronic cardiac form of the disease is related to a strong Th1 response during the acute phase of the disease, while the development of the indeterminate form results from a blend of Th1 and Th2 responses soon after infection, suggesting that the acute phase immune response is important for the genesis of chronic cardiac lesions.

Distribution and characterization of canine Chagas disease in Texas.

Although acute and chronic cases of canine Chagas disease have been reported from multiple areas in the southern region of the United States, little data are available on current disease occurrence patterns in endemic areas. Therefore, a study to assess frequency, geographic distribution, signalment, and clinical spectrum of Chagas disease in domestic dogs from Texas was conducted. Serology, histopathology, and clinical case records from multiple institutions for the time period 1993-2007 were analyzed. A total of 537 serologically and/or histopathologically confirmed cases were documented. Cases were reported from 48 of 254 counties within Texas, covering all major geographic regions. Forty-eight dog breeds were represented among the cases, primarily in the sporting and working groups. In histopathologically confirmed cases, acute death occurred in 42%, approximately half of which were <1 year of age. Nearly all cases with histopathology data reported myocarditis (97.9%) and observation of Trypanosoma cruzi organisms (81.7%). Predominant clinical observations included enlarged heart, lethargy, anorexia, ascites, cardiac conduction disturbances, and respiratory difficulties. An increasing rate of serologic test submissions was noted over the study period, with an overall positive test prevalence of 20.3%. The study results provide strong evidence that an active canine Chagas disease transmission cycle is present throughout all ecoregions of Texas, affecting a broad range of dog breeds and age groups.

Disfunção ventricular esquerda em hamsters com doença de Chagas tratados com etanercept / Left ventricular dysfunction in hamsters with Chagas disease and treated with etanercept

Objetivo: a doença afeta mais de 10 milhões de pessoas na América Latina. Leva a cardiomiopatia dilatada inflamatória em 30% dos pacientes como conseqüência tardia da infecção pelo protozoário Trypanosoma cruzi, com pior prognóstico que as outras cardiomiopatias dilatadas. estudos prévios mostram aumento dos níveis circulantes do fator de necrose tumoral-alfa (TNF-x) em pacientes com cardiomiopatia chagásica crônica. Assim, o objetivo do presente trabalho foi avaliar efeito do bloqueio do TNF-x com Etanercept na função ventricular esquerda em hamsters sírios cronicamente infectados pelo T. cruzi...