Influence of treatment with immunosuppressive drugs in mice chronically infected with Trypanosoma cruzi

Abstract

Latent Trypanosoma cruzi infection may be reactivated in immunosuppressed individuals, with unusual clinical patterns, such as meningoencephalitis, pseudo neoplastic lesions in the central nervous system, and myocarditis with numerous parasites in the heart muscle. To investigate this problem 68 Swiss mice chronically infected with different strains of T. cruzi were treated with different combinations of immunosuppressive drugs (azathioprine, cyclosporine and betamethasone), in such a way as to imitate the situation during post transplantation treatment. Mortality varied from 6 to 25% in treated mice. There were no deaths in untreated controls. Normal mice have been submitted to the same schedules of immunosuppression as controls of treatment and no deaths were registered during treatment. Chronically infected mice showed significant elevation of total number of leukocytes and lymphocytes in comparison with intact controls; a significant decrease in blood leukocytes and lymphocytes occurred post-treatment in two of the treated experimental groups. Exacerbation of myocarditis and myositis and a high incidence of brain lesions, with focal necrosis, granulomatous lesions and glial proliferation even in the absence of parasites were present in immunosuppressed mice but not in infected controls. Although differing in some aspects from Chagas' disease in immunosuppressed humans, the murine model did show some features that resembled it, especially the peculiar pattern of central nervous system involvement.

Hydroxymethylnitrofurazone treatment in indeterminate form of chronic Chagas disease: Reduced intensity of tissue parasitism and inflammation—A histopathological study

“…Histopathological analysis of hearts from patients with chronic Chagas cardiomyopathy reveals a diffuse infiltrating inflammatory, hypertrophy, fibrosis and myocarditis with scarce tissue parasitism . In the previous literature, the immunosuppression during the chronic phase of Chagas disease (Y strain) caused development of myocardial lesions in mice . In our study, 100% of the infected animals were found to have cardiac hypertrophy and inflammatory infiltrates that were statistically different from the NEG group.…”

“…[71][72][73] In the previous literature, the immunosuppression during the chronic phase of Chagas disease (Y strain) caused development of myocardial lesions in mice. 69 In our study, 100% of the infected animals were found to have cardiac hypertrophy and inflammatory infiltrates that were statistically different from the NEG group. Amastigote nests were found in 55.5% of cardiac tissue for the POS group and 50% for the BZN group.…”

“…The immunosuppression can be reactivated and induced by drugs for animals and humans with a T. cruzi infection, after transplantation or even in association with autoimmune diseases, such as AIDS . According to Pereira et al, dexamethasone can be used to induce reactivation of disease in animals, and Andrade et al reported 6%‐25% of deaths after immunosuppression of animals.…”

Current advances in drug discovery for Chagas disease

“…The World Health Organization (WHO) estimates that 8 million people are infected with T. cruzi and more than 10,000 die every year on account of the infection [11]. Furthermore, an increase in the number of HIV-positive patients and indiscriminate use of corticosteroids, has led to the reactivation of asymptomatic Chagas disease indicating that T. cruzi is also an opportunist parasite [12,13].…”

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

“…However, this methodology is not extensively used in every laboratory. Table 1, Table 2 and Table 3 indicate the studies that have reported the effect of BZN in indeterminate/chronic infections and the experiments for chronic infections in several T. cruzi strains ( Table 1 17 -19,22 , Table 2 17,18,[21][22][23] , Table 3 18, [24][25][26][27][28][29] ).…”