Inquérito sôbre a doença de Chagas no hospital da Santa Casa de Misericórdia de Belo Horizonte (Minas Gerais, Brasil)

São relatados os resultados de um inquérito sôbre doença de Chagas realizado na Santa Casa de Misericórdia de Belo Horizonte (Minas Gerais, Brasil), com a finalidade de verificar a incidência desta moléstia e especialmente de sua forma cardíaca crônica entre os doentes ali internados. Foram examinados 181 pacientes adultos não selecionados, adotando-se os seguintes métodos: a) exame clínico geral e exame minucioso do aparelho circulatório; b) eletrocardiograma; c) reação de fixação do complemento para a doença de Chagas (antígeno de cultura do Schizotrypanum cruzi); d) reação de Wassermann; e) xenodiagnóstico e radiografia dos pacientes com reação de fixação do complemento (Guerreiro & Machado) positiva e de portadores de outras cardiopatias. Dos 181 pacientes examinados, 37 (20,44%) tinham provas de laboratório positivas para foença de Chagas. 49 (27,07%) eram portadores de cardiopatias, com as seguintes etiologias: doença de Chagas (18 casos); arteriosclerose (13 casos); hipertensão arterial (12 casos); sífilis (casos); febre reumática (3 casos); cardiopatia congênita (1 caso); cor pulmonale crônico (1 caso). De 34 pacientes com doença de Chagas, 18 (52,95%) apresentavam evidências eletrocardiográficas de comportamento miocárdico. As alterações eletrocardiográficas mais freqüentes foram: bloqueio do ramo direito, extra-sístoles ventriculares, alterações de QRS (isoladas ou associadas a alterações de T), bloqueios auriculo-ventriculares. Estes achados são semelhantes aos já descritos na cardiopatia chagásica crônica por Laranja e cols. (13,26). As alterações eletrocardiográficas mais frequentes no grupo de pacientes com provas de laboratório negativas para doença de Chagas foram: curvas de hipertrofia ventricular esquerda (strain) alteralçoes primárias de T e extra-sístoles vemtriculares. A idade de 50,0% dos pacientes com miocardite chagásica crônica não ultrapassou os 30 enquanto que 83,33% dos pacientes portafores de outras cardiopatias eram maiores de 30 anos. A reação de fixação do complemento (antígeno de cultura do Schizotrypanum cruzi), devido à sua especificidade e sensibilidade, mostrou ser muito util para o diagnóstico de laboratório da doença de Chagas em sua fase crônica. O xenodiagnóstico foi positivo em 8 casos (25,8%) de 31 pacientes com reação de Guerreiro & Machado positiva. Foi discutidoo problema da etiologia do megaesôfago e do megacolon, admitindo os Autores que adoença de Chagas possivelmente desempenhe, em determinadas zonas, papel significativo no desenvolvimento destas afecções. Foi brevemente relatada a distribuição geográfica dos triatomídeos no Estado de Minas Gerais. Os principais vetores são Panstrongylus megistus, Triatoma infestans e Triatoma sordida, se bem que outras 12 espécies ocorrem neste Estado. Estes triatomídeos existem em 204 (64,55%) dos 316 municípios do Estado de Minas. Vetores infetados foram encontrados em 143 municípios (70,09%). Foram assinaladas as áreas infetadas mais importantes. Os Autores salientaram a importância médica da doença de Chagas, acreditando ser esta infecção um dos mais importantes fatores de cardiopatia em amplas zonas rurais do Estado de Minas Gerais.

Chagas' disease: selective affinity and cytotoxicity of Trypanosoma cruzi-immune lymphocytes to parasympathetic ganglion cells

The megaesophagus and megacolon endemic in South America are related , to Chagas' disease. These mega conditions are found in patients with chronic Chagas's infection, when the parasite is not demonstrable in the lesions. These are characterized by depopulation of parasympathetic ganglion cells, dilation and hypertrophy of the viscera. In the experiments described here we deminstrate a selective affinity and adherence of Trypanosoma cruzi-immune lymphocytes to myenteric, parasympathetic ganglion cells, leading to neuronolysis. None of these features are observed when non-immune lymphocytes from control rabbits are used, or when the immune lymphocytes are allowed to react with CNS neurons. This demonstration is an indication of the high degree of specificity of the destruction of parasympathetic neurons in Chagas' disease. We postulate that the T. cruzi-immune lymphocyte rejection of parasympathetic neurons, but not of CNS neurons, might be related to recognition of a cross-reacting antigenic determinant secreted only by the target neurons. In favor of this interpretation is the observation of lymphocytic infiltrates and parasympathetic ganglion cell destruction in chronic Chagas' infection in the absence of encephalitis.

Morbidade da doença de Chagas: I - Estudo de casos procedentes de vários estados do Brasil, observados no Rio de Janeiro

Um estudo da morbidade através de exames clínicos, eletrocardiográficos, radiológicos, sorológicos, xenodiagnósticos e outros exames laboratoriais seriados, foi feito em 510 pacientes com sorologia positiva para doença de Chagas, procedentes de vários Estados do Brasil e observados no Rio de Janeiro a partir de 1960. Os pacientes foram classificados, de acordo com a forma clínica, em assintomáticos (forma indeterminada), cardíacos, portadores de "megas" ou com formas clínicas associadas. Foi observada uma prevalência de cardiopatia em 52,1% dos pacientes, de "megas" em 14,3% e de associação entre cardiopatia e "megas" em 10,7% e entre megaesôfago e megacolon em 10,9% dos casos. A forma indeterminada (assintomática) foi observada em 39% dos pacientes. A proporção de casos de cardiopatia aumentou progressivamente da 1ª a 5ª décadas de vida, enquanto a dos "megas" continuou aumentando até a 7ª década. Entretanto, em número de casos o pico de ambas as formas ocorreu na 4ª década. Não houve diferenças significativas de formas clínicas com relação ao sexo, apesar de uma discreta predominância de cardiopatia no sexo masculino e de "megas" no sexo feminino. Com relação à raça, entre os pacientes classificados como brancos, pretos e mestiços, não foi possível determinar a significância entre as diversas formas clínicas, por desconhecimento da constituição do universo da procedência de cada paciente. Embora o reduzido número de casos não possa ser considerado como representativo da prevalência das fomas clínicas nas regiões de origem dos pacientes, tomando-se os quatro Estados representados com maior número de casos, verificou-se que as proporções de cardiopatia e "megas" foram respectivamente de 65,7 e 20,1% nos casos procedentes da Bahia, de 55,7 e 14,7% nos de Minas Gerais, de 50,9 e 15% nos de Pernambuco e de 23,3 e 0% nos procedentes da Paraíba. O reduzido número de casos procedentes dos demais Estados não permitiu qualquer inferência de proporção entre as formas...

Characterization of T cell clones from chagasic patients: predominance of CD8 surface phenotype in clones from patients with pathology

Human Chagas' disease, caused by the protozoan Trypanosoma cruzi, is associated with pathological processes whose mechanisms are not known. To address this question, T cell lines were developed from chronic chagasic patients peripheral blood mononuclear cells (PBMC) and cloned. These T cell clones (TCC) were analyzed phenotypically with monoclonal antibodies by the use of a fluorescence microscope. The surface phenotype of the TCC from the asymptomatic patient were predominantly CD4 positive (86%). On the contrary, the surface phenotype CD8 was predominant in the TCC from the patients suffering from cardiomegaly with right bundle branch block (83%), bradycardia with megacolon (75 %) and bradycardia (75%). Future studies will be developed in order to identify the antigens eliciting these T cell subpopulations.

Clinical forms of Trypanosoma cruzi infected individuals in the chronic phase of Chagas disease in Puebla, Mexico

In Mexico, despite the relatively high seroprevalence of Trypanosoma cruzi infection in humans in some areas, reported morbidity of Chagas disease is not clear. We determined clinical stage in 71 individuals seropositive to T. cruzi in the state of Puebla, Mexico, an area endemic for Chagas disease with a reported seroprevalence of 7.7%. Diagnosis of Chagas disease was made by two standardized serological tests (ELISA, IHA). Individuals were stratified according to clinical studies. All patients were submitted to EKG, barium swallow, and barium enema. Groups were identified as indeterminate form (IF) asymptomatic individuals without evidence of abnormalities (n = 34 cases); those with gastrointestinal alterations (12 patients) including symptoms of abnormal relaxation of the lower esophageal sphincter and absent peristalsis in the esophageal body, grade I megaesophagus, and/or megacolon; patients with clinical manifestations and documented changes of chronic Chagas heart disease who were subdivided as follows: mild (8 patients) - mild electrocardiographic changes of ventricular repolarization, sinus bradychardia); moderate (6 patients) - left bundle branch block, right bundle branch block associated with left anterior fascicular block); severe (8 patients) - signs of cardiomegaly, dilated cardiomyopathy); and the associated form (3 cases) that included presence of both cardiomyopathy and megaesophagus. These data highlight the importance of accurate evaluation of the prevalence and clinical course of Chagas disease in endemic and non-endemic areas of Mexico.

Pre-Columbian Chagas disease in Brazil: Trypanosoma cruzi I in the archaeological remains of a human in Peruaçu Valley, Minas Gerais, Brazil

We evaluated the presence and distribution of Trypanosoma cruzi DNA in a mummy presenting with megacolon that was dated as approximately 560 ± 40 years old. The mummy was from the Peruaçu Valley in the state of Minas Gerais, Brazil. All samples were positive for T. cruzi minicircle DNA, demonstrating the presence and broad dissemination of the parasite in this body. From one sample, a mini-exon gene fragment was recovered and characterized by sequencing and was found to belong to the T. cruzi I genotype. This finding suggests that T. cruzi I infected humans during the pre-Columbian times and that, in addition to T. cruzi infection, Chagas disease in Brazil most likely preceded European colonization.

Paleoparasitology of Chagas disease: a review

One hundred years since the discovery of Chagas disease associated with Trypanosoma cruzi infection, growing attention has focused on understanding the evolution in parasite-human host interaction. This interest has featured studies and results from paleoparasitology, not only the description of lesions in mummified bodies, but also the recovery of genetic material from the parasite and the possibility of analyzing such material over time. The present study reviews the evidence of Chagas disease in organic remains excavated from archeological sites and discusses two findings in greater detail, both with lesions suggestive of chagasic megacolon and confirmed by molecular biology techniques. One of these sites is located in the United States, on the border between Texas and Mexico and the other in state of Minas Gerais, in the Brazilian cerrado (savannah). Dated prior to contact with Europeans, these results confirm that Chagas disease affected prehistoric human groups in other regions outside the Andean altiplanos and other transmission areas on the Pacific Coast, previously considered the origin of T. cruzi infection in the human host.

Chronic phase of Chagas disease: why should it be treated? A comprehensive review

The pathogenesis and evolutive pattern of Chagas disease suggests that the chronic phase should be more widely treated in order to (i) eliminate Trypanosoma cruzi and prevent new inflammatory foci and the extension of tissue lesions, (ii) promote tissue regeneration to prevent fibrosis, (iii) reverse existing fibrosis, (iv) prevent cardiomyopathy, megaoesophagus and megacolon and (v) reduce or eliminate cardiac block and arrhythmia. All cases of the indeterminate chronic form of Chagas disease without contraindications due to other concomitant diseases or pregnancy should be treated and not only cases involving children or recently infected cases. Patients with chronic Chagas cardiomyopathy grade II of the New York Heart Association classification should be treated with specific chemotherapy and grade III can be treated according to medical-patient decisions. We are proposing the following new strategies for chemotherapeutic treatment of the chronic phase of Chagas disease: (i) repeated short-term treatments for 30 consecutive days and interval of 30-60 days for six months to one year and (ii) combinations of drugs with different mechanisms of action, such as benznidazole + nifurtimox, benznidazole or nifurtimox + allopurinol or triazole antifungal agents, inhibition of sterol synthesis.

Myenteric plexus is differentially affected by infection with distinct Trypanosoma cruzi strains in Beagle dogs

Chagasic megaoesophagus and megacolon are characterised by motor abnormalities related to enteric nervous system lesions and their development seems to be related to geographic distribution of distinct Trypanosoma cruzi subpopulations. Beagle dogs were infected with Y or Berenice-78 (Be-78) T. cruzi strains and necropsied during the acute or chronic phase of experimental disease for post mortem histopathological evaluation of the oesophagus and colon. Both strains infected the oesophagus and colon and caused an inflammatory response during the acute phase. In the chronic phase, inflammatory process was observed exclusively in the Be-78 infected animals, possibly due to a parasitism persistent only in this group. Myenteric denervation occurred during the acute phase of infection for both strains, but persisted chronically only in Be-78 infected animals. Glial cell involvement occurred earlier in animals infected with the Y strain, while animals infected with the Be-78 strain showed reduced glial fibrillary acidic protein immunoreactive area of enteric glial cells in the chronic phase. These results suggest that although both strains cause lesions in the digestive tract, the Y strain is associated with early control of the lesion, while the Be-78 strain results in progressive gut lesions in this model.

Metallothionein-1 and nitric oxide expression are inversely correlated in a murine model of Chagas disease

Chagas disease, caused by Trypanosoma cruzi, represents an endemic among Latin America countries. The participation of free radicals, especially nitric oxide (NO), has been demonstrated in the pathophysiology of seropositive individuals with T. cruzi. In Chagas disease, increased NO contributes to the development of cardiomyopathy and megacolon. Metallothioneins (MTs) are efficient free radicals scavengers of NO in vitro and in vivo. Here, we developed a murine model of the chronic phase of Chagas disease using endemic T. cruzi RyCH1 in BALB/c mice, which were divided into four groups: infected non-treated (Inf), infected N-monomethyl-L-arginine treated (Inf L-NAME), non-infected L-NAME treated and non-infected vehicle-treated. We determined blood parasitaemia and NO levels, the extent of parasite nests in tissues and liver MT-I expression levels. It was observed that NO levels were increasing in Inf mice in a time-dependent manner. Inf L-NAME mice had fewer T. cruzi nests in cardiac and skeletal muscle with decreased blood NO levels at day 135 post infection. This affect was negatively correlated with an increase of MT-I expression (r = -0.8462, p < 0.0001). In conclusion, we determined that in Chagas disease, an unknown inhibitory mechanism reduces MT-I expression, allowing augmented NO levels.

Síndrome de chilaiditi associada a megaduodeno e megacólon transverso

Chilaiditi syndrome is a rare abnormality, uncommon in children, whith an incidence increasing with the age, ranging from 0.025% to 0.28% in the general population usually affecting males. The patients are usually asymptomatics and the syndrome is incidently discover through radiologic exams. However, abdominal pain and distention, nauseas, vomits and changes in intestinal habits, and even intestinal obstruction can occur. The authors report a case of a patient with Chilaiditi's syndrome associated to megastomach, megaduodenum and megacolon.

Megacólon chagásico associado a pneumatose cística difusa do delgado e úlcera péptica duodenal

Diffuse intestinal pneumatosis appears as gaseous cysts in the intestinal wall in the submucosal layer or, more frequently, sub-serous layer. It affects more the jejunum than the ileum, can be diffuse and may extend into the colon. It's diagnosis is established during a small bowel transit examination, necropsy examination or during surgical exploration of the peritoneal cavity.

Intrinsic denervation of the colon is associated with a decrease of some colonic preneoplastic markers in rats treated with a chemical carcinogen

Denervation of the colon is protective against the colon cancer; however, the mechanisms involved are unknown. We tested the hypothesis that the denervated colonic mucosa could be less responsive to the action of the chemical carcinogen dimethylhydrazine (DMH). Three groups of 32 male Wistar rats were treated as follows: group 1 (G1) had the colon denervated with 0.3 mL 1.5 mM benzyldimethyltetradecylammonium (benzalkonium chloride, BAC); G2 received a single ip injection of 125 mg/kg DMH; G3 was treated with BAC + the same dose and route of DMH. A control group (Sham, N = 32) did not receive any treatment. Each group was subdivided into four groups according to the sacrifice time (1, 2, 6, and 12 weeks after DMH). Crypt fission index, ß-catenin accumulated crypts, aberrant crypt foci, and cell proliferation were evaluated and analyzed by ANOVA and the Student t-test. G3 animals presented a small number of aberrant crypt foci and low crypt fission index compared to G2 animals after 2 and 12 weeks, respectively. From the second week on, the index of ß-catenin crypt in G3 animals increased slower than in G2 animals. From the 12th week on, G2 animals presented a significant increase in cell proliferation when compared to the other groups. Colonic denervation plays an anticarcinogenic role from early stages of colon cancer development. This finding can be of importance for the study of the role of the enteric nervous system in the carcinogenic process.