Immunopathological Mechanisms Underlying Cardiac Damage in Chagas Disease.

In Chagas disease, the mechanisms involved in cardiac damage are an active field of study. The factors underlying the evolution of lesions following infection by Trypanosoma cruzi and, in some cases, the persistence of its antigens and the host response, with the ensuing development of clinically observable cardiac damage, are analyzed in this review.

Response to Infection by Trypanosoma cruzi in a Murine Model.

Cardiopathy is a common, irreversible manifestation of the chronic phase of Chagas disease; however, there is controversy as to how the causes for progression from the acute to the chronic phase are defined. In this work, the presence of the parasite is correlated with the occurrence of cell infiltration and fibrosis in cardiac tissues, as well as IgG detection and disease progression in a murine model. Fifty CD1 mice were infected intraperitoneally with Trypanosoma cruzi, while 30 control were administered with saline solution. Parasitemia levels were determined, and IgG titers were quantified by ELISA. At different times, randomly selected mice were euthanized, and the heart was recovered. Cardiac tissue slides were stained with HE and Masson trichrome stain. A significant increase in parasitemia levels was observed after 15 days post-infection (dpi), with a maximum of 4.1 × 106 parasites on 33 dpi, ending on 43 dpi; amastigote nests were observed on 15-62 dpi. Histological analysis revealed lymphocytic infiltration and fibrotic lesions from 8 dpi until the end of the study, on 100 dpi. The presence of plasma cells in the myocardium observed on 40-60 dpi, accompanied by seropositivity to ELISA on 40-100 dpi, was regarded as the hallmark of the transition phase. Meanwhile, the chronic phase, characterized by the absence of amastigotes, presence of cell infiltration, fibrotic lesions, and seropositivity, started on 62 dpi. A strong correlation between parasitemia and the presence of amastigote nests was found (r 2 = 0.930), while correlation between the presence of fibrosis and of amastigote nests was weak (r 2 = 0.306), and that between fibrosis and lymphocyte infiltration on 100 dpi was strong (r 2 = 0.899). The murine model is suitable to study Chagas disease, since it can reproduce the chronic and acute phases of the human disease. The acute phase was determined to occur on 1-60 dpi, while the chronic phase starts on 62 dpi, and fibrotic damage is a consequence of the continuous inflammatory infiltration; on the other hand, fibrosis was determined to start on the acute phase, being more apparent in the chronic phase, when Chagas disease-related cardiopathy is induced.

[Identification of immunodominant components of an isolate of Trypanosoma cruzi by immunoblot and its standardization for diagnostic purposes]. / Identificación de componentes inmunodominantes de un aislado de Trypanosoma cruzi por inmunoblot y su estandarización con fines diagnósticos.

INTRODUCTION: Conventional serology was used for the detection of Trypanosoma cruzi infection, with diverse sensitivity and specificity results. Due to the number of samples with doubtful results, it is necessary to develop additional confirmation tests such as the immunoblot. OBJECTIVE: The aim of this study was identify major immunogenic proteins of T. cruzi isolate and establish criteria for immunoblot positivity with diagnostic purposes. METHODS: Immunoblot initial standardization was performed, determining optimal concentrations of antigen, serum, and second antibody. Thirty-five positive and thirty negative sera were assayed to evaluate different criteria of positivity and determine which provides greater sensitivity and specificity. RESULTS: Immunoblot of T. cruzi positive sera shared a rich pattern of components with molecular weights between 10-250 kDa. Twelve components had a recognition rate higher than 50%, of which the polypeptides of 27, 32, 34, and 38 kDa were close to 100%. Of the positivity criteria evaluated, the recognition of the components of 27 and 32 kDa provided sensitivity and specificity of 100%. DISCUSSION: The Immunoblot is suitable for confirmation of infection by T. cruzi, so it is strongly recommended for confirmation and discrimination of discordant cases.

In vitro antiparasitic activity of new thiosemicarbazones in strains of Trypanosoma cruzi.

In this study thiosemicarbazones derivatives of 5-[(trifluoromethyl)phenylthio]-2-furaldehyde were synthesized and evaluated in terms of their efficiency in challenging the growth of epimastigote forms of Trypanosoma cruzi, the etiological agent of Chagas' disease. A number of compounds were synthesized from 5-bromo-2-furfuraldehyde using nucleophilic aromatic substitution, with a series of trifluoromethyl thiolates, followed by condensation reactions with thiosemicarbazide. Their molecular structures were determined by (1)H, (13)C and (19)F NMR, MS and IR spectroscopy. When tested with T. cruzi, they showed a stronger reaction, similar to nifurtimox and benznidazole, with the 5-[nitro-4-(trifluoromethyl)phenyltio]-2-furaldehyde thiosemicarbazone (compound 4) showing the highest antiparasitic activity. This improved activity may be explained due to the nitro group present in the molecule, which potentiates its activity. The thiosemicarbazone derivatives in this study showed no apoptosis in platelets or monocytes, nor did they induce platelet activation. The trypanocidal activity of these substances represents a good starting point for a medicinal chemistry program aimed at therapy for Chagas' disease.

Insecticide and community interventions to control Triatoma dimidiata in localities of the State of Veracruz, Mexico

Three different interventions to control Triatoma dimidiata in the State of Veracruz were implemented: X-1 = whole dwelling spraying, X-2 = middle wall spraying, X-3 = household cleaning. Cyfluthrin was sprayed 3 times with 8 month intervals. After each spraying, insects were collected and sent to the laboratory to be recorded and to determine genus and species of the adult triatomine bugs, and nymphs were counted. Trypanosoma cruzi presence was determined. With X-1, the infestation, colonization, and natural infection indexes were reduced to 0 percent in the 3 localities, with respect to t0. With X-2, the infestation index was reduced to 10 percent at t3 in 3 localities; the colonization index was reduced to 0 percent in only 1 locality at t3, and the natural infection index was reduced to 0 percent at t3. With X-3 the 3 indexes were not effectively reduced but they decreased with respect to the baseline study. Insecticide application to the whole dwelling is a more efficient intervention than its application to only the lower half of the walls and to the cleaning of houses.