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 reproducibility 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 Word Health Organization (1984). Furthermore the animal is easily obtained and easy to handle and maintain in experimental laboratory conditions.     

The epidemiological significance of Chagas' disease in women.

Little is known about the risks associated with Trypanosoma cruzi infection in non-pregnant and pregnant women. From a limited number of studies it appears that in rural areas, parasite rates and rates of serological positivity are similar in both sexes. Abnormal ECG tracings are consistently more frequent in men suggesting that immunity to T. cruzi may be different in females. Complications arising from Chagas' disease in pregnancy are only infrequently reported. Evidence for increased risk of abortion or prematurity is inconclusive except in cases of congenital infection. Most cases of congenital Chagas' disease have been reported from non-endemic areas and there is a suggestion that parasitemic episodes during pregnancy may influence pregnancy outcome. Preliminary evidence indicates that chronic infection can result in in-utero sensitization via passively acquired maternal antibodies. The review concludes that maternal T. cruzi infection carries risks for the child and these warrant systematic research because of their public health significance.     

Suppression of cell-mediated immunity in experimental Chagas' disease.

The effect of acute infection with the Tulahuén strain of Trypanosoma cruzi on the cellular immune response in Swiss mice was studied. Mice were immunized with either Freund's complete adjuvant or oxazolone, a skin sensitizing agent, and subsequently skin-tested with either BCG protoplasm or oxazolone to detect delayed hypersensitivity. Depression of the response to these antigens was observed in infected mice during the stage of marked parasitemia. Mice which were responsive to oxazolone before infection lost their ability to respond as the infection progressed. When immunized with live attenuated T. cruzi before infection with virulent organisms, mice developed a greater than normal sensitivity to oxazolone and survived infection. These experiments do not conclude whether immunosuppression due to infection with T. cruzi is directed toward induction or expression of the cell-mediated immune response to the antigens employed.     

Ultrastructure of murine cardiac ganglia in experimental Chagas' disease.

Albino mice, infected with Trypanosoma cruzi (Tulahuen strain) were sacrificed on days 7, 9, 12, 14, 16, 18, 21, 32 and 39 following infection. Transmission electron microscopic examination of the cardiac ganglia revealed no ultrastructural change at day 7. At day 9 there was peri- and intraganglionic monocytic infiltration but parasites were absent. Between days 12 and 16 there was intense monocytic infiltration, with intra-ganglionic presence of parasites within fibroblasts, monocytes and macrophages. None were seen within capsular cells, endothelial cells, Schwann cells, satellite cells and ganglion cells. The Schwann cells and satellite cells, however, showed phagocytic activity. Satellite cells were also reactive with proliferative pseudopodia which encircled neuronal processes. By day 18, parasites were absent in the ganglia. But monocytes were still present up to day 39, some of them still engulfing satellite cell and neuronal processes. Satellite cells continued to be reactive and Schwann cells phagocytic. Ganglion cells remained normal throughout the experiment. The results suggest that infection of Schwann cells, satellite cells and ganglion cells may depend upon the tissue tropism of the strain of the parasite used and its concentration in the inoculum. The results are consistent with the view that any parasympathetic dysfunction in experimental Chaga's disease in the mouse may be of a transient nature.     

Chagas' disease and AIDS

Chagas' disease caused by Trypanosoma cruzi is an opportunistic infection in the setting of HIV/AIDS. Some individuals with HIV and chronic T. cruzi infection may experience a reactivation, which is most commonly manifested by meningoencephalitis. A reactivation myocarditis is the second most common manifestation. These presentations may be difficult to distinguish from toxoplasmosis in individuals with HIV/AIDS. The overlap of HIV and Trypanosoma cruzi infection occurs not only in endemic areas but also in non-endemic areas of North America and Europe where the diagnosis may be even more difficult. The pathological features, diagnosis and the role of cytokines in the pathogenesis of the disease are discussed.     

Tropical diseases encountered in Canada: 1. Chagas' disease.

Chagas'' disease, or South American trypanosomiasis, is an endemic South American disease now being seen in Canada in both acute and chronic forms. It is characterized by an initial parasitemia that elicits a brisk immune response. Evidence is mounting that the debilitating chronic form, which is characterized by cardiac and visceral organ failure, results from antigenic cross-reactivity between the parasite and the human host, which generates an aberrant, destructive, cell-mediated immune response. Diagnosis, treatment and potential areas for investigation are discussed.     

Isotype determination of anti-Trypanosoma cruzi antibody in murine Chagas' disease.

Isotypic analysis of anti-parasite humoral responses of C57B1/6 and C3H (He) mice surviving acute Trypanosoma cruzi infection showed that both mouse strains demonstrate IgG1, IgG2a, IgG2b, and IgM enzyme-linked immunosorbent assay titers from days 21 to 300 of infection. Using the western blot technique to determine the antigen specificity of the isotypic responses, 100-day infected C3H mice showed strong IgG1, IgG2a, and IgG2b responses to many antigens, whereas C57B1/6 mice showed weak responses to fewer antigens. Isotype western blots showed that reactivity to the T. cruzi antigen of 75-77 kDa is present in the humoral response of day 21-infected mice that will survive and missing in those that will not survive. In general, surviving immunized C3H mice respond with IgG1, IgG2a, and IgG2b reactions to the 75-77-kDa and other antigens, whereas resistant B6 mice concentrate their anti-T. cruzi response in the IgG2b isotype to the 75-77-kDa antigen. Perhaps induction of ineffective antibody responses to nonprotective antigens is beneficial to the parasite and detrimental to the host.