Evaluation of the rabbit as a model for Chagas disease - II: histopathologic studies of the heart, digestive tract and skeletal muscle

Silva, Arnaldo Moreira da; Ramírez, Laura; Vargas, Marlene; Chapadeiro, E; Brener, Z.

doi:10.1590/s0074-02761996000200015

Cited by 12 publications

(14 citation statements)

References 8 publications

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“…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). …”

Section: 1 Introductionmentioning

confidence: 99%

Advances in Imaging of Animal Models of Chagas Disease

Jelicks¹,

Tanowitz²

2011

Advances in Parasitology

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Since serial studies of patients are limited, researchers interested in Chagas disease have relied on animal models of Trypanosoma cruzi infection to explore many aspects of this important human disease. These studies have been important for evaluation of the immunology, pathology, physiology and other aspects of pathogenesis. While larger animals have been employed, mice have remained the most favoured animal model, as they recapitulate many aspects of the human disease, are easy to manipulate genetically and are amenable to study by small animal imaging technologies. Further, developments in non-invasive imaging technologies have permitted the study of the same animal over an extended period of time by multiple imaging modalities, thus permitting the study of the transition from acute infection through the chronic stage and during therapeutic regimens.

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Section: 1 Introductionmentioning

confidence: 99%

Advances in Imaging of Animal Models of Chagas Disease

Jelicks¹,

Tanowitz²

2011

Advances in Parasitology

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“…2 The presence of T. cruzi trypomastigotes in histologic preparations has been difficult to demonstrate, although the presence of T. cruzi amastigotes has been demonstrated histologically in several tissues. [3][4][5][6][7][8][9] In patients with chronic cardiomyopathy, inflammatory infiltrates and granular staining (representing either T. cruzi antigens and nucleic acids) have been reported using several techniques. [10][11][12] In the present study, all parasite mammalian forms (amastigotes, trypomastigotes, and granular staining) were detected in a mouse model that mimics human chronic chagasic cardiomyopathy.…”

Section: Introductionmentioning

confidence: 99%

“…2,[10][11][12][13][14][15][16] Animal models of Chagas disease using dogs, rabbits and mice have studied cardiac or central nervous system (CNS) pathology in both the acute and chronic phases. [4][5][6][7][8][9]13 Mouse models have presented the advantage of producing varying degrees of chronic cardiomyopathy dependent on the strain of mouse and the strain of T. cruzi parasites. 13,[17][18][19][20] DBA/2 mice develop severe chronic chagasic cardiomyopathy which is similar to severe chronic Chagas disease in humans, thus being a valuable tool for the study of immune responses at different time points.…”

Section: Introductionmentioning

confidence: 99%

Mouse model for Chagas disease: immunohistochemical distribution of different stages of Trypanosoma cruzi in tissues throughout infection.

Guarner¹,

Bartlett²,

Zaki³

et al. 2001

The American Journal of Tropical Medicine and Hygiene

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Abstract. Different stages of Trypanosoma cruzi are seen during mammalian infection. Histologic sections of infected hearts have shown amastigotes and, when using immunohistochemistry (IHC), parasite antigens; however, demonstration of trypomastigotes in these tissues has proven elusive. Using a mouse strain that develops chagasic cardiomyopathy (histologically similar to human infection) 70 days after injecting T. cruzi-Brazil strain, we studied the distribution of parasite stages and the extent of inflammation. All organs had varying amounts of mononuclear inflammation by day 10, which peaked between day 20 and day 30, and decreased by day 50. Amastigotes were detected in myocytes, histiocytes, acinar pancreatic cells, astrocytes and ependymal cells by day 10, and the number of amastigotes peaked on day 30. Immunohistochemistry demonstrated trypomastigotes in sinusoids, vessels and interstitial tissues of several organs between day 15 and 50. Abundant parasite antigens (granular staining) were detected in connective tissues throughout the infection. The burden of amastigotes and trypomastigotes during the acute phase seems to correlate with the degree of inflammation and granular staining in the chronic stage.

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“…The rat has been used in the past, but early observations concluded that it is somewhat resistant to T. cruzi infection, developing a mild and slow pathology 57 . Rabbits proved to be capable of developing some of the chronic alterations such as focal myocarditis with a fibrous nature, but did not show more severe forms of chronic myocarditis or severe histological lesions in digestive track and skeletal muscles found in typical infections 58 . .…”

Section: Animal Modelsmentioning

confidence: 91%

Current and Future Chemotherapy for Chagas Disease

Gaspar¹,

Moraes²,

Freitas‐Junior³

et al. 2015

CMC

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American trypanosomiasis, commonly called Chagas disease, is one of the most neglected illnesses in the world and remains one of the most prevalent chronic infectious diseases of Latin America with thousands of new cases every year. The only treatments available have been introduced five decades ago. They have serious, undesirable side effects and disputed benefits in the chronic stage of the disease -a characteristic and debilitating cardiomyopathy and/or megavisceras. Several laboratories have therefore focused their efforts in finding better drugs. Although recent years have brought new clinical trials, these are few and lack diversity in terms of drug mechanism of action, thus resulting in a weak drug discovery pipeline. This fragility has been recently exposed by the failure of two candidates, posaconazole and E1224, to sterilely cure patients in phase 2 clinical trials. Such setbacks highlight the need for continuous, novel and high quality drug discovery and development efforts to discover better and safer treatments.In this article we will review past and current findings on drug discovery for Trypanosoma cruzi made by academic research groups, industry and other research organizations over the last half century. 2We will also analyze the current research landscape that is now better placed than ever to deliver alternative treatments for Chagas disease in the near future.

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Evaluation of the rabbit as a model for Chagas disease - II: histopathologic studies of the heart, digestive tract and skeletal muscle

Cited by 12 publications

References 8 publications

Advances in Imaging of Animal Models of Chagas Disease

Advances in Imaging of Animal Models of Chagas Disease

Mouse model for Chagas disease: immunohistochemical distribution of different stages of Trypanosoma cruzi in tissues throughout infection.

Current and Future Chemotherapy for Chagas Disease

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