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.     

Morbidity in Chagas' disease. IV. Longitudinal study of 10 years in Pains and Iguatama, Minas Gerais, Brazil

An evolutive study of the "case-control" type was carried out in an endemic area of Chagas' disease in Minas Gerais State, Brazil, using two cross-section evaluations with an interval of ten years between them (1974-1984). Patients were paired for sex and age. In the first cross-section study 264 pairs one with a positive serology and the other with a negative serology for T. cruzi antibodies were included. In the second evaluation, ten years later, 235 patients among those with previous positive serology and 216 with negative serology were located, but only 110 pairs could be recomposed and reexamined (clinical examination, ECG and Rx of the heart and esophagus). The incidence of chagasic cardiopathy in the cases with positive serology but previously assymptomatic was 38.3% during the ten year period. On the other hand there was a deterioration in 24% of the patients with chagasic cardiopathy since the first examination. Considering all clinical forms of the disease in 34.5% of the patients the clinical situation deteriorated, in 57.3% there was no change and in 8.2% the situation improved. The general mortality in the period was 23% in the chagasic group and 10.6% in the control group, but the lethality by cardiopathy was 17% in chagasic group and only 23.3% in the control group. The mortality was twice as high in males than in females, mainly in the age group from 30 to 59 years.     

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.     

Morbidity in Chagas' disease. III. Longitudinal study of 6 years, in Virgem da Lapa, MG, Brazil

In a clinical, radiological and electrocardiographical, follow-up study of the "case control" type performed in Virgem da Lapa, Minas Gerais State, Brazil, 124 chagasic patients were followed during six years. The results of the patients, the majority in the indeterminate form, did not register any change, in 32.2% there was a progress in the disease and in 5.6% the electrocardiogram returned to normal. These results when compared to that achieved by the control group, composed of pairs of non chagasic persons with the same age and sex, was shown to be 27.4% higher than among patients with positive serology. This factor represents the excess risk or exclusively chagasic component in the development of the disease. No differences were observed by sex related to the development of the disease. It was more premature and seven times more frequent however when related to the cardiopathy than to the megaesophagus. Both conditions occurring mainly in slight or moderate degree. In 192 chagasic patients and 188 non chagasic persons observed in that area in the same period, the mortality was 3.6 times higher among the chagasic patients with a letality due to cardiopathy of 8.9% without difference between sexes but more premature among the males. Sudden death was more frequent than that one caused by cardiac insufficiency. The prognostic was good for the patients with indeterminate and digestive forms and reserved for patients with the highest degree of cardiopathy.     

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.