Main Cardiac Histopathologic Alterations in the Acute Phase of Trypanosoma cruzi Infection in a Murine Model.

Symptoms in the acute phase of Chagas disease are usually mild and nonspecific. However, after several years, severe complications like dilated heart failure and even death may arise in the chronic phase. Due to the lack of specific symptoms in the acute phase, the aim of this work was to describe and analyze the cardiac histopathology during this phase in a CD1 mouse model by assessing parasitism, fibrotic damage, and the presence and composition of a cellular infiltrate, to determine its involvement in the pathogenesis of lesions in the cardiac tissue. Our results indicate that the acute phase lasts about 62 days post-infection (dpi). A significant increase in parasitemia was observed since 15 dpi, reaching a maximum at 33 dpi (4.1 × 106). The presence of amastigote nests was observed at 15-62 dpi, with a maximum count of 27 nests at 35 dpi. An infiltrate consisting primarily of macrophages and neutrophils was found in the cardiac tissue within the first 30 days, but the abundance of lymphocytes showed an 8 ≥ fold increase at 40-62 dpi. Unifocal interstitial fibrosis was identified after 9 dpi, which subsequently showed a 16 ≥ fold increase at 40-60 dpi, along with a 50% mortality rate in the model under study. The increased area of fibrotic lesions revealed progression in the extent of fibrosis, mainly at 50-62 dpi. The presence of perivasculitis and thrombus circulation disorders was seen in the last days (62 dpi); finally, cases of myocytolysis were observed at 50 and 62 dpi. These histopathological alterations, combined with collagen deposition, seem to lead to the development of interstitial fibrosis and damage to the cardiac tissue during the acute phase of infection. This study provides a more complete understanding of the patterns of histopathological abnormalities involved in the acute phase, which could help the development of new therapies to aid the preclinical tests of drugs for their application in Chagas disease.

Trypanosoma cruzi: A review of biological and methodological factors in Mexican strains.

Trypanosoma cruzi, responsible for Chagas disease, is a serious public health problem in Latin America with eight million people infected in the world. Clinical manifestations observed in humans due to T. cruzi infection are largely associated with the wide biological and genetic heterogeneity of the parasite. This review presents an overview of the parasitological aspects of various strains of T. cruzi isolated mainly in Mexico, as well as an analysis of the methodological processes used to determine their virulence that could be influencing their biological characterization. We emphasize the importance of using uniform protocols to study T. cruzi virulence, taking into account factors related to: strain (i.e. developmental stage, lineage, biological origin, genetic variability), animal model used (i.e. role of hormones, host immune response, age) and methodology (i.e. inoculum size, inoculation route, and laboratory conditions used during strain maintenance). These uniform protocols will then allow proposing elements for understanding clinical evolution and management of the disease, for providing adequate treatment, and for developing tools for future vaccines against Chagas disease.