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Malaria, leishmaniasis and trypanosomiasis are arthropod-borne, parasitic diseases that constitute a major global health problem. They are generally found in developing countries, where lack of access to preventive tools and treatment hinders their management. Because these parasites share an increased demand on glucose consumption with most cancer cells, six compounds used in anti-tumoral research were selected to be tested as antiparasitic agents in in vitro models of Leishmania infantum, Trypanosoma brucei, T. cruzi, and Plasmodium falciparum: dichloroacetic acid (DCA), 3-bromopyruvic acid (3BP), 2-deoxy-D-glucose (2DG), lonidamine (LND), metformin (MET), and sirolimus (SIR). No parasite-killing activity was found in L. infantum promastigotes, whereas DCA and 3BP reduced the burden of intra-macrophagic amastigotes. For T. brucei all selected compounds, but 2DG, decreased parasite survival. DCA, 2DG, LND and MET showed parasite-killing activity in T. cruzi. Finally, anti-plasmodial activity was found for DCA, 2DG, LND, MET and SIR. These results reinforce the hypothesis that drugs with proven efficacy in the treatment of cancer by interfering with ATP production, proliferation, and survival cell strategies might be useful in treating threatening parasitic diseases and provide new opportunities for their repurposing., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

CD8(+) T cells have emerged as crucial players in the control of a number of protozoan pathogens, including Trypanosoma cruzi, the agent of human Chagas disease. The recent identification of the dominant targets of T. cruzi-specific T cells has allowed investigators to follow the generation of and document the functionality of T cell responses in both mice and humans. Although slow to develop in the early stages of the infection, T. cruzi-specific CD8(+) T cells reach prodigious levels and remain highly functional throughout chronic infections in mice. Following drug-induced cure during either the acute or chronic stage, these immunodominant T cells persist as stable, antigen-independent memory populations. T. cruzi-specific CD8(+) T cells in humans are less-well-studied but appear to lose functionality and decline in numbers in these decades-long infections. Changes in the frequency of parasite-specific T cell upon therapeutic treatment in humans may provide a new metric for determining treatment efficacy.

Background: It has been demonstrated that the beta-adrenergic signal transduction system is altered somewhere along its pathway in Trypanosoma cruzi infected hearts and we think that these alterations would differ according to the infection phase and the parasite strain. Their study would be important for the understanding of the disease's pathophysiology., Methods: In the present work we studied important components of this system in mice hearts infected with T. cruzi, Tulahuen strain and with SGO-Z12 isolate, obtained from a patient of an endemic area, in the acute phase of the infection, determining: the plasma catecholamines levels, the beta-receptors density and affinity as well as their function, the cardiac concentration of cAMP and the cardiac contractility as the physiologic response to the initial stimulus., Results: Plasma catecholamines levels were diminished in both infected groups when compared to the uninfected one (P < 0.01). The receptor's affinity was also diminished (P < 0.05) while their density was augmented only in the SGO-Z12 infected one (P < 0.01). The cAMP levels were higher in both infected groups (P < 0.01), the basal contractile force however increased only in the Tulahuen infected one (P < 0.01) while the response to catecholamines remained unchanged. The hearts infected with the SGO Z12 isolate presented an inferior response to epinephrine (P < 0.05) than the ventricles infected with the Tulahuen strain., Conclusions: This model represents an important approach to understand the biochemical, physiological and molecular changes in the cardiac beta-adrenergic signalling that clearly begin in the acute phase of Chagas' disease and reveal a clear differentiation in the alterations produced by different parasite strains.

Background: Chagas' disease, which is caused by Trypanosoma cruzi, affects 20 million people. The electrocardiographic alterations are usually the first evidence of disease progression. In this work, we evaluated if two different T. cruzi strains presented electrocardiographic and heart histopathological alterations that could be characteristic and only achieved to the parasite strain. The moment when the electric alterations began was also studied., Methods: Albino mice (n=100) were inoculated with 50 (n=50) and 500 (n=50) trypomastigotes of T. cruzi, for Tulahuen strain and SGO-Z12 isolate, respectively. Electrocardiograms were obtained before infection and once a week from 7 to 147 days post infection (d.p.i). Dipolar and unipolar leads were analyzed. Hearts were removed by necropsy on 14, 90 and 147 d.p.i. Each heart was cut horizontally into 5-mum sections and they were stained with Hematoxilin-Eosine., Results: At 147 d.p.i., 30% of Tul-infected mice were found alive, while in the SGO-Z12 infected group, 75% were alive at the same moment. The Tul-infected group showed more intraventricular blockage alterations than the other groups from 49 to 70 d.p.i, (p<0.01). No structural cardiac alterations were detected in SGO-Z12-infected mice at 7 d.p.i., while the Tul-infected group showed mononuclear cell infiltrates. At 147 d.p.i., fiber disorganization and cell infiltration were observed in the SGO-Z12 and Tul-infected groups., Conclusions: We demonstrated that T. cruzi Tulahuen strain and SGO-Z12 isolate determined different electrocardiographic alterations which were characteristic for each stage of the experimental Chagas' disease. These results highlight the importance of the T. cruzi strain in the severity of the cardiopathy.