Trypanosoma cruzi: experimental Chagas' disease in Rhesus monkeys. II. Ultraestructural and cytochemical studies of peroxidase and acid phosphatase activities

Abstract

Ultrastructural and cytochemical studies of peroxidase and acid phosphatase were performed in skin, lymph node and heart muscle tissue of rhesus monkeys with experimental Chagas' disease. At the site of inoculation there was a proliferative reaction with the presence of immature macrophages revealed by peroxidase technique. At the lymph node a diffuse inflammatory exudate with mononuclear cells, fibroblasts and immature activated macrophages reproduces the human pattern of acute Chagas' disease inflammatory lesions. The heart muscle cells present different degrees of degenerative alterations and a striking increase in the number of lysosomal profiles that exhibit acid hydrolase reaction product. A strong inflammatory reaction was present due to lymphocytic infiltrate or due to eosinophil granulocytes associated to ruptured cells. The present study provides some experimental evidences that the monkey model could be used as a reliable model to characterize histopathological alterations of the human disease.

Chronic Chagas’ Disease in Rhesus Monkeys (Macaca Mulatta): Evaluation of Parasitemia, Serology, Electrocardiography, Echocardiography, and Radiology

“…16,[51][52][53] Rhesus monkeys acutely infected with the Colombian strain also showed aggressive cardiomyopathy. 13,14 In addition, the histopathologic analysis of the chronically infected monkeys that were killed (monkeys 42 and 68) confirms the presence of mild myocarditis in absence of significant ECG abnormalities (Carvalho CME and others, unpublished data). Interestingly, we have shown that rhesus monkeys chronically infected with the Colombian strain developed electrocardiographic alterations similar to those observed in chronic chagasic patients.…”

“…A strong inflammatory reaction with lymphocytic infiltrate and eosinophils associated with ruptured cells was present. 13,14 Considering that approximately one-third of T. cruziinfected humans develop severe chronic disease with irreversible damage to the heart and/or gastrointestinal tract with dilation and disorders of nerve conduction, it is crucial to understand the mechanisms leading to these organ-specific pathologies. 15 Because these alterations are observed 10-20 years after the acute phase, we have examined long-lasting (15-19 years) T. cruzi experimental infection in seven male rhesus monkeys that were initially evaluating for the clinical, parasitologic, serologic, and hematologic aspects of the chronic infection.…”

Advances in Imaging of Animal Models of Chagas Disease

“…Non-human primates have also been explored as models for Chagas disease (Bonecini-Almeida Mda et al, 1990; de Almeida et al, 1992; de Meirelles Mde et al, 1990; Milei et al, 1982). Early studies revealed that ECG changes in infected monkeys were correlated with specific anatomic lesions (Milei et al, 1982).…”

“…Interestingly, similar arguments have recently appeared in the literature questioning the relevance of the mouse model of cerebral malaria to human cerebral malaria (Taylor-Robinson, 2010). Thus, several studies have employed T. cruzi -infected larger animals such as rabbits, rats, guinea pigs, dogs and subhuman primates (Barbabosa-Pliego et al, 2009; Bonecini-Almeida Mda et al, 1990; Chandrasekar et al, 1998; Chen et al, 1996; Cruz-Chan et al, 2009; da Silva et al, 1996; de Almeida et al, 1992; de Meirelles Mde et al, 1990; Figueiredo et al, 1986; Guedes et al, 2002, 2009; Junqueira Junior et al, 1992; Labrador-Hernandez et al, 2008; Milei et al, 1982; Morris et al, 1991; Perez et al, 2009; Ramirez and Brener, 1987; Teixeira et al, 1983; Zabalgoitia et al, 2004). …”

Response to different benznidazole doses in animal models of chronic phase Chagas disease: a critical review

“…As well as smaller mammals such as rabbits and rats 36,37 , larger animal models including dogs and non-human primates [38][39][40][41][42][43][44][45][46][47][48][49][50] are also used for experimental studies, mainly in Chagas disease, due to these mammals' capacity to host parasites. Dogs and non-human primates (baboons, macaques, and capuchin monkeys) have been important experimental models to study the pathogenesis of Chagas disease, mainly in regard to the immunopathogenic mechanisms involved in the chronic phase of T. cruzi infection 38,[42][43][44][45][46][47][48][49][50] . Electrocardiography alterations 39,40,47,49 have been reported in studies of dogs and nonhuman primates infected with several T. cruzi strains as well in studies using BZN chemotherapy in dogs who received the same regimen as humans (7mg/kg), corroborating with the outcomes of other clinical trials 42 .…”