Investigation on the possibility of spontaneous cure of mice infected with different strains of Trypanosoma cruzi

Seventy Swiss mice chronically infected with different strains of Trypanosoma cruzi, with persistently negative parasitemia on routine blood examination were parasitologically investigated to find out whether spontaneous cure occurred. Duration of infection varied from 90 to 250 days in the initial phase of this investigation. Parasitological tests consisted of daily direct blood examination performed during at least 25 days, followed by xenodiagnosis and subinoculation of blood into newborn mice. Mice that persisted negative were treated with Cyclophosphamide with one dose of 250 mg/kg of body weight and then investigated by direct blood examination, xenodiagnosis and subinoculation. A second dose of 250 mg/kg b. w. was given to the persistently negative mice. With one single exception, all mice showed positive parasitological tests in the different stages of the present investigation and we conclude that spontaneous cure did not occur in this group, which is representative of the chronic infection with different strains of T cruzi.

Effects of vitamin C supplementation on acute phase Chagas disease in experimentally infected mice with Trypanosoma cruzi QM1 strain

The tissue changes that occur in Chagas disease are related to the degree of oxidative stress and antioxidant capacity of affected tissue. Studies with vitamin C supplementation did not develop oxidative damage caused by Chagas disease in the host, but other studies cite the use of peroxiredoxins ascorbate - dependent on T. cruzi to offer protection against immune reaction. Based on these propositions, thirty "Swiss" mice were infected with T. cruzi QM1 strain and treated with two different vitamin C doses in order to study the parasitemia evolution, histopathological changes and lipid peroxidation biomarkers during the acute phase of Chagas disease. The results showed that the parasite clearance was greater in animals fed with vitamin C overdose. There were no significant differences regarding the biomarkers of lipid peroxidation and inflammatory process or the increase of myocardium in animals treated with the recommended dosage. The largest amount of parasite growth towards the end of the acute phase suggests the benefit of high doses of vitamin C for trypomastigotes. The supplementation doesn't influence the production of free radicals or the number of amastigote nests in the acute phase of Chagas disease.

Course of infection and histopathological lesions in mice infected with seventeen Trypanosoma cruzi strains isolated from chronic patients

Mice were infected with blood forms of 17 Trypanosoma cruzi strains recently isolated from chronic patients, which were dassified as of low, medium or high virulence on grounds of the prepatent period, parasitemia and mortality at the acute phase. A total of 212 mice were studied after 3, 6, 9 and 12 months of infection. In the chronic phase, intracellular parasites were detected in 11.0%,27.9%and 54.0,% of mice inoculated, respectively, with the low, medium and high virulent strains (r= 0.98, p < 0.005). Heart fibrosis was also related to virulence, affecting 5.7%, 11.6%and30.8% (r = 0.98, p < 0.001) of the mice inoculated with the above strains; a similar relationship was observed between intensity and frequency of the heart inflammatory reaction and the severity of infection at its early stage. Necrotizing arteritis was detected in 12.2% of the inoculated animals and this lesion was related to the infection duration rather than to strain characteristics. Inflammatory lesions and tissue parasitism were stable within the period of observation, whereas fibrosis was Progressive. The findings suggest that mice may reproduce heart lesions resembling human pathology and that organ damage apparently depends on the parasite virulence.

Trypanosomiasis cruzi: a follow-up study of tissue reacting immunoglobulins in infected purebred pinscher dogs

Antibodies against striated muscle (cardiac and skeletal) were studied in serum samples from 36 purebred prepubertal Pinscher dogs (15 Controls without infection and 21 infected with Trypanosoma cruzi from 7 to 400 days after infection with 1000 trypomastigotes/gram body weight of the Colombiana strain by the intraperitoneal route). Although three different immunohistological pattems of tissue-reacting immunoglobulins were found their presence was not correlated with any peculiar characteristics or with the severity of the disease in each particular dog.

Schistosoma mansoni: immunodepression of hepatic schistosome granuloma formation in mice infected by Trypanosoma cruzi

Infection by Trypanosoma cruzi in mice depresses hepatic granuloma formation around Schistosoma mansoni eggs. This immunodepressive effect occurred in mice with Chagas' disease at the acute and/or chronic phases, granulomas being signijicantly smaller than those in Controls. Data suggest that Chagas ' disease depresses the delayed hypersensitivity immune response directly.

Studies on anti-component 5 antibodies in animals infected with Trypanosoma cruzi

A competitive antibody enzyme immunoassay, using a monoclonal antibody against the species-specific Trypanosoma crnzi antigen 5, was used to investigate the presence of anti-component 5 antibodies in sera of opossums, dogs, rabbits and rats infected with this parasite. The sera from 51 Venezuelan patients with Chagas’disease were also tested. About 90% of the infected subjects showed significant levels of anti-component 5 antibodies. Nevertheless, these antibodies were not detected in the sera of dogs, rats and opossums infected with T. cruzl Some sera from infected rabbits presented significant results but close to the limit ofpositivity ofthe test. These findings suggest that the immune response in animals naturally or experimentally infected with T. cruzi is different from that observed in human Chagas’disease.

Effects of severe protein restriction in levels of parasitemia and in mortality of mice accutely infected with Trypanosoma cruzi

Adult mice were submitted to different degrees of protein restriction for five weeks (4.75, 9.5,14.25 and 19% of protein in isocaloric diets with normal content of mineral and vitamins), being subsequently infected with two strains of Trypanosoma cruzi: 10(5) trypomastigotes of Y strain or 14(5) trypomastigotes of CL strain. The same diet was maintained for all animals and the infection wasfollowed up by evaluation of blood parasites, mortality and intensity of lesions in the heart and skeleton muscle. Only severe protein restriction (4.75%) induced decrease in resistance to the infection with both the Y and CL strains of T. cruzi, which resulted in higher parasitemia and mortality. The inflammatory lesions in heart and skeleton muscle were less extensive in groups with severe protein restriction despite the increased number of parasite in muscle cells. Depression of immune mechanisms could be responsiblefor the reduced resistance and reduced inflammatory reaction after T. cruzi infection in severely protein restricted animals.

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 of infection. 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. Despite this, no statistically significant differences could be found between the number of neuron bodies in the ganglia of infected and control dogs.

Treatment with benznidazole in association with immunosuppressive drugs in mice chronically infected with Trypanosoma cruzi: investigation into the possible development of neoplasias

Benznidazole is recommended in Brazil for the treatment of Trypanosoma cruzi infection in acute and early chronic phases of Chagas' disease. Observations by others have indicated a higher incidence of neoplasias in immunosuppressed patients, presenting Chagas' disease reactivation, submitted to treatment with benznidazole. In the present study, we investigated whether there is a potentiation in the generation of lymphomas in chronically infected mice, treated with immunosuppressive drugs and benznidazole. For this, 142 Swiss mice chronically infected with the 21 SF strain of T. cruzi and 72 normal Swiss mice were used. Both infected and normal mice were divided into experimental groups and submitted to one of the following treatment regimens: benznidazole alone; immunosuppressive drugs (azathioprine, betamethasone and cyclosporin); a combination of immunosuppressive drugs and benznidazole; and untreated controls. In the infected group treated with benznidazole, one mouse developed a non-Hodgkin's lymphoma. This finding has been interpreted as a spontaneous tumor of mice. The study of the chronically infected mice treated with the combination of immunosuppressive drugs and benznidazole demonstrated an absence of lymphomas or other neoplasias. These findings support the indication of benznidazole, as the drug of choice, for immunosuppressed patients that develop a reactivation of Chagas' disease.

Cytokine serum levels in patients infected by human immunodeficiency virus with and without Trypanosoma cruzi coinfection

This study assessed the number of CD4 T lymphocytes, the parasitemia and serum levels of interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), IL-4 and IL-10 of patients infected by human immunodeficiency virus (HIV) and human immunodeficiency virus/Chagas' disease coinfection. CD4 T lymphocytes were low in the two groups of patients, although significantly lower in patients without Chagas' disease. Serum levels of IFN-gamma, IL-4 and TNF-alpha were significantly higher in patients with HIV/Chagas' disease. IL-4/IFN-gamma ratios were higher in patients with HIV/Chagas' disease, which showed a clear balance in favor of Th2-like cytokines in this group of patients. This Th2 balance was higher in patients with detectable parasitemia. We conclude that, although immunosuppression was observed, with CD4 T lymphocytes bellow 200/µm³, these patients did not display reactivation of T. cruzi infection and that a balance favorable to Th2 was associated with the presence of parasitemia.

Etiological treatment of young women infected with Trypanosoma cruzi, and prevention of congenital transmission

The objective was to detect Trypanosoma cruzi infection in 32 children in Salta, Argentina, born to 16 chronically infected young women who were treated with benznidazole. Tests were performed to assess the efficacy of treatment after 14 years. At the end of the follow up, 87.5% of the women were non-reactive to EIA tests, 62.5% to IHA and 43.8% to IFA. 62.5% of the women were non-reactive according to two or three serological tests. No infected children were detected among the newborns of mothers treated before their pregnancy.

Vitamin C effects in mice experimentally infected with Trypanosoma cruzi QM2 strain

INTRODUCTION: To evaluate the efficacy of vitamin C in reducing the consequences generated by the production of free radicals in the acute and chronic phases of Chagas disease, two different doses of ascorbic acid were administered orally to 60 mice infected by Trypanosoma cruzi QM2 strain. METHODS: The animals were divided into six groups: G1, G2, and G3 for the acute phase study, and G'1, G'2, and G'3 for the chronic stage. The groups G1 and G'1 received 8.6x10-4mg/g of vitamin C daily, whereas G2 and G'2 received 7.14x10-3mg/g daily. The other groups, G3 and G'3, were considered placebos and received 10µL of mineral water. RESULTS: The study of the acute phase showed statistically significant differences between G1 and the other groups at various count days of the parasitemia evolution. The multiplying parasite was slower in G1 until the 11th day, but on the 22nd day it had greater parasitemia than in G2 and G3, and from the 36th day on, parasitemia stabilized at higher levels. However, when the histopathology of acute and chronic phases is considered, one does not note significant differences. CONCLUSIONS: The administration of two different doses of vitamin C was not able to protect mice and to contain the oxidative stress caused by free radicals formed by the metabolism of oxygen (reactive oxygen species) and nitrogen (reactive nitrogen species).

Evolution of sarcoma 180 in mice infected with Trypanosoma cruzi

Mice infected with Trypanosoma cruzi were challenged with 2x10[raised to the power of 6] cells of sarcoma 180 (ascite tumor) by i.p. route, on day seven post infection. Tumor development was followed by evaluation of weight gain, by measurement of ascitic fluid produced and enumeration of tumor cells in ascitic fluid. Infected mice were more resitant to tumor development as demonstrated by reduction in ascites formation and by reduction in the number of tumor cells in ascitic fluid, at different time intervals after tumor challenge. The number of peritoneal cells exsudated after tumor inoculation was greater in infected mice than in controls. This increased resitance of mice infected with T. cruzi to tumor development could be due to the action of macrophages activated by the infection and by the action of endotoxins absorbed from the gut or produced by the own parasite.