The TcI and TcII Trypanosoma cruzi experimental infections induce distinct immune responses and cardiac fibrosis in dogs

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.

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.

Chronic interstitial pneumonitis in dogs naturally infected with Leishmania (Leishmania) chagasi: a histopathological and morphometric study

Eighteen mongrel dogs of unknown age and naturally infected with Leishmania (Leishmania) chagasi, were obtained from the City Hall of Belo Horizonte, Brazil. Four dogs were used as control. Lung samples were obtained and immediately fixed in formalin. The histopathological picture of all lung tissue sections was a chronic and diffuse interstitial pneumonitis. The thickened inter-alveolar septa were characterized by the cellular exudate (mostly macrophages, lymphocytes and plasmocytes) associated with collagen deposition. Morphometric analysis showed greater septal thickness in the infected animals than in controls. In fact, the morphometric study of collagen stained with ammoniac silver confirmed a larger deposition of collagen in the infected animals. The parasitologic method was carried out during the study of the lesions on the slides. However, we did not observe any correlation between the histopathologic and morphometric data and the clinical status of the animals. We conclude that the pulmonary lesions observed in all naturally infected dogs were correlated with the disease and that the morphometric method used was satisfactory for the analysis of septal thickness and of increased collagen deposition, confirming the presence of fibrosis

Quantitative analysis of cardiac lesions in chronic canine chagasic cardiomyopathy

Lesions observed in chronic chagasic cardiopathy frequently produce electrocardiographic alterations and affect cardiac function. Through a computerized morphometrical analysis we quantified the areas occupied by cardiac muscle, connective and adipose tissues in the right atrium of dogs experimentally infected with Trypanosoma cruzi. All of the infected dogs showed chronic myocarditis with variable reduction levels of cardiac muscle, fibrosis and adipose tissue replacement. In the atrial myocardium of dogs infected with Be78 and Be62 cardiac muscle represented 34 and 50 percent, fibrosis 28 and 32 percent and adipose tissue 38 and 18 percent, respectively. The fibrosis observed was both diffuse and focal and mostly intrafascicular, either partially or completely interrupting the path of muscle bundles. Such histological alterations probably contributed to the appearance of electrocardiographic disturbances verified in 10 out 11 dogs which are also common in human chronic chagasic cardiopathy. Fibrosis was the most important microscopic occurrence found since it produces rearrangements of collagen fibers in relation to myocardiocytes which causes changes in anatomical physiognomy and mechanical behavior of the myocardium. These abnormalities can contribute to the appearance of cardiac malfunction, arrythmias and congestive cardiac insufficiency as observed in two of the analyzed dogs. Strain Be78 caused destruction of atrial cardiac muscle higher than that induced by strain Be62

Histopathology and immunocytochemical study of type 3 e and type 4 complement receptors in the liver and spleen of dogs naturally and experimentally infected with Leishmania (Leishmania) chagasi

Os objetivos deste trabalho visaram uma analise comparativa das alteracoes histopatologicas e da expressao de CR3 e CR4 no figado e baco de caes natural e experimentalmente infectados com L. chagasi. As lesoes histopatologicas fundamentais observadas principalmente nos caes naturalmente infectados foram: os granulomas epitelioides hepaticos, a hiperplasia e a hipertrofia das celulas de Kupffer, dos foliculos de Malpighi e das celulas monucleadas da polpa vermelha do baco. Os cortes de figado e baco corados pela tecnica de imunocitoquimica mostraram a presenca dos antigenos CD11b,cCD18 nos animais controles e infectados, sem diferencas qualitativas e quantitativas no figado...

Estudo quantitativo e qualitativo dos plexos de Auerbach e Meissner do esôfago de cäes inoculados com o Trypanosoma cruzi / A quantitative and qualitative study of the Auerbach and Meissner plexus in dogs inoculated with Trypanosoma cruzi

A quantitative and qualitative study was conducted on the Auerbach and Meissner plexuses of the esophagus of four chagasic dogs sacrificed during the acute phase of infection. Ganglionitis and periganglionitis of the Auerbach plexus ranged from mild to moderate and induced significant neuronal lesions, especially in two animals. The ganglions of the Meissner plexus were observed in small number which did not permit any analysis. Mild or moderate myositis was observed mainly in the lower third of the esophagus and was rarely associated with amastigote nests. Ganglion and neuron counts did not demonstrate denervation. Although the formation of megaesophagus was not induced in any dog, lesions of the Auerbach plexus and myocells of the esophagus were observed during the acute phase of chagasic infection. To our knowledge, this is the first systematic quantitative and qualitative study of the Auerbach and Meissner plexuses of the esophagus in experimental trypanosomiasis cruzi.

Cardiac plexus of dogs experimentally infected with Trypanosoma cruzi: inflammatory lesions and quantitative studies

Qualitative and quantitative aspects of the superficial and profound cardiac plexus of dogs experimentally infected with Be-62 and Be-78 strains of Trypanosoma cruzi were studied. Animals were autopsied in the acute phase ofinfection. The inflammatory process, lesions and number of parasites were more intense and frequent in animals infected with the Be-78 strain than in those infected with Be-62. espite this, no statistically significant differences could be found between the number of neuron bodies in the ganglia of infected and control dogs.

An attempt at reversebility and increase of the virulence of axemic strains of Entamoeba hitolytica

Neste trabalho procuramos verificar se a interacao "in vitro" com bacterias e fragmentos de figado de hamster normal, modificaria o comportamento patogenico de cepas axenicas de E. histolytica avirulentas (ICB-32 e ICB-RPS); virulentas, porem atenuadas (ICB-CSP e HM1) e de media virulencia (ICB-462). Todas as tentativas de tornar virulentas, restabelecer ou aumentar a virulencia das cepas axenicas de E. histolytica utilizadas fracassaram.

Experimental Chagas' disease in dogs

This paper describes the development of experimental Chagas' disease in 64 out-bred young dogs. Twenty-nine animals were inoculated with the Be-62 and 35 with Be-78 Trypanosoma cruzi strains. Twenty-six were infected with blood trypomastigotes by different inoculation routes and 38 with metacyclic trypomastigotes from the vector via the conjunctival route. Twenty of the 26 dogs infected with blood trypomastigotes were autopsied during the acute phase. Eleven died spontaneously and nine were sacrificed. Six remained alive until they died suddenly (two) or were autopsied (four). Twelve of the 38 dogs infected with metacyclic trypomastigotes evolved naturally to the chronic phase and remained alive for 24-48 months. The parasitemia, clinical aspects and serology (IgM and IgG) as well as electrocardiogram, hemogram and heart anatomo-histopathologic patterns of acute and chronic cardiac forms of Chagas' disease as seen in human infections, were reproduced. The most important finding is the reproductibility of diffuse fibrosing chronic chagasic cardiopathy in all dogs infected with Be-78 T. cruzi strain autopsied between the 90th and 864th days of infection. Thus, the dog can be considered as a suitable experimental model to study Chagas' disease according to the requisites of the World Health Organization (1984). Futhermore the animal is easily obtained and easy to handle and maintain in experimental laboratory conditions

Estudo, ao microscópio óptico e eletrônico, do rim de cäes natural e experimentalmente infectados com Leishmania (Leishmania) chagasi / Optical and electron microscopic study of the kidney of dogs naturally and experimentally infected with Leishmania (Leishmania) chagasi

Os autores estudaram os rins de 4 cäes infectados con Leishmania (Leishmania) chagasi. Dois animais (um macho e uma fêmea) naturalmente infectados foram sacrificados 18 meses após sua permanencia no laboratório. Dois machos foram inoculados por via endovenosa, com 1x10***6 promastigotas da cepa MHO/BR/70/BH46 e sacrificados após 18 meses e 2 anos, respectivamente. Em todos os animais os rins estavam lesados. As alteraçöes encontradas foram: (1) glomerulonefrite mesangioproliferativa focal ou difusa, com pronunciada hipertrofia e hiperplasia das células mesangiais e com alargamneto da matriz; (2) espessamento da membrana basal com depósitos eletrodensos; (3) nefrite intersticial intertubular crônica com exsudaçäo plasmocitária intensa. (4) degeneraçäo albuminosa dos túbulos renais. Baseados nos achados os autores discutem os prováveis mecanismos patogenéticos

Fase crônica cardíaca fibrosante da tripanossomíase cruzi experimental no cäo / Fibrosing cardiac chronic phase in experimental Chagas' disease in dogs

Os autores documentan a cardiopatia difusa fibrosante, com todos os sintomas clínicos e dados de autópsia pertinente a insuficiência cardíaca congestiva, em um dos 21 cäes infectados com a cepa Colombiana (cinco morreram na fase aguda e quatro continuam vivos) e cinco, dos 13 infectados com a cepa Berenice-78 (oito morrerm na fase aguda), num período de oito anos de observaçäo. Em vista destes resultados, os autores sugerem que o cäo possa vir a ser um modelo experimental, adequado par o estudo da história da doença de Chagas, preenchendo os requisitos estabelecidos pelo Comitê Assessor de Doença de Chagas do Programa Especial de Pesquisa e Treinamento em Doenças Tropicais da Organizaçäo Mundial de Saúde

Envolvimento renal na associaçäo Salmonella-Schistosoma mansoni / Renal involvement in the association of Salmonelosis with Schistosoma mansoni

Vinte pacientes com a associaçäo Salmonella-S. mansoni (Grupo 1) e 20 com esquistossomose mansoni hepatesplênica (Grupo 2) foram selecionados para o estudo. Submeteram-se os pacientes dos Grupos 1 e 2 a exame clínico minucioso e a uma série de exames complementares, com destaque para as provas de funçäo renal. Em 10 pacientes do Grupo 1 e 20 do Grupo 2, realizou-se, ainda, estudo histológico do rim à microscopia óptica, de fluorescência e eletrônica. As alteraçöes renais foral mais freqüentes nos pacientes do Grupo 1. Após o tratamento dos pacientes do Grupo 1, com antibióticos e/ou esquistossomicidas, observou-se regressäo das alteraçöes renais sob o ponto de vista clínico, laboratorial e imunopatológico. Os autores concluem pela existência de duas nefropatias distintas: a nefropatia esquistossomótica e a encontrada em pacientes com a associaçäo Salmonella-S. mansoni

Alteraçöes quantitativas das células neuroendócrinas no megacólon chagásico / Quantitative changes in the neuroendocrine cells of chagasic megacolon

Utilizando-se técnicas histoquímicas pela prata (Masson-Fontana e Sevier-Munger) estudaram-se a distribuiçäo e o número de células enterocromafins (EC) e do conjunto EC mais células argirófilas (ARG) em peças cirúrgicas de megassigmóide chagásico. Observou-se que tanto nos "megas" (n = 16) como nos controles (n = 8), a posiçäo das células EC e ARG na mucosa foi predominantemente basal, com distribuiçäo irregular, principalmente das EC. A análise histológica revelou aparente aumento numérico das EC e do conjunto EC mais ARG. Todavia, contagens sistematizadas mostraram que somente o conjunto dessas células apresentou aumento estatisticamente significativo (P<0,01). Realizou-se tambéjm o estudo morfométrico da mucosa e das musculares que revelou espessamento significativo (P<0,01) dessas camadas em relaçäo aos casos controles

Involvement of the autonomic nervous system in Chagas heart disease

The autonomic nervous system and especially the intracardiac autonomic nervous system is involved in Chagas' disease. Ganglionitis and periganglionitis were noted in three groups ofpatients dying with Chagas'disease: 1) Those in heart failure; 2) Those dying a sudden, non violent death and; 3) Those dying as a consequence ofaccidents or homicide. Hearts in the threegroups also revealed myocarditis and scattered involvement of intramyocardial ganglion cells as well as lesions of myelinic and unmyelinic fibers ascribable to Chagas'disease. In mice with experimentally induced Chagas' disease weobserved more intensive neuronal lesions of the cardiac ganglia in the acute phase of infection. Perhaps neuronal loss has a role in the pathogenesis of Chagas cardiomyopathy. However based on our own experience and on other data from the literature we conclude that the loss of neurones is not the main factor responsible for the manifestations exhibited by chronic chagasic patients. On the other hand the neuronal lesions may have played a role in the sudden death ofone group of patients with Chagas'disease but is difficult to explain the group of patients who did not die sudderly but instead progressed to cardiac failure.

O sistema nervoso autônomo e especialmente o sistema nervoso autônomo intracardiaco são lesados na doença de Chagas. Ganglionite e periganglionite foram observadas em 1) chagásicos com insuficiência cardíaca; 2} em tripanossomóticos, assintomáticos ou paucissintomáticos, em vida, falecidos subitamente em conseqüência da doença de Chagas e 3) nos chagásicos, também assintomáticos, e que faleceram devido a acidentes ou homicídios. Em todos os três grupos os corações mostraram miocardite e lesões das células ganglionares intramiocárdicas bem como das fibras nervosas mielínicas e amielínicas. Em camundongos com infecção chagásica experimental, observamos que na fase aguda da doença as lesões são mais graves e intensas. A denervação talvez desempenhe algum papel na patogênese da cardiopatia chagásica. Entretanto, baseados em nossa experiência pessoal e em outros dados da literatura concluímos que a perda de neurônios não é o principal nem o fator exclusivo pelas manifestações apresentadas pelos pacientes chagásicos crônicos. Por outro lado, as lesões dos neurônios talvez possam ter algum papel no mecanismo da morte súbita do chagásico mas é difícil explicar porque tripanossomóticos, com lesões similares, não faleceram subitamente.