Prevention of electrocardiographic and histopathologic alterations in the murine model of Chagas' disease by preinoculation of an attenuated Trypanosoma cruzi strain

Abstract

SUMMARYThe effects of infection with Trypanosoma cruzi on the electrocardiographic tracings of mice were studied in 4.groups of animals: (1) normal; (2) infected with a pathogenic T. cruzi strain (TS COB); (3) immunized with 3 intraperitoneal inocula of 10 6 attenuated T. cruzi epimastigotes (TCC) and (4) immunized-infected, which sequentially received the treatments of groups 3 and 2. Infection and protection were confirmed by xenodiagnosis and histopathology. Isolated alterations such as extrasystolia, 1 st degree atrioventricular block, arrhythmia and ST elevation were observed in normal as well as infected mice. However, tracings taken repeatedly on each mouse over a 293 day period revealed a set of alterations which were more frequently seen in infected (14/22) than in normal (4/27) animals (p = 0.00048). These alterations consisted of supraventricular tachycardia, sinus bradycardia and persisting, first degree AV blocks, often associated to pacemaker changes. Inoculation of attenuated T. cruzi (group 3) did not increase these alterations (2/27 mice) but significantly prevented their development after challenge with the pathogenic strain (1/19 versus 14/22 mice, p = 0.000095). Thus, preimmunization reduced not only parasitemia but also a pathogenic consequence of T. cruzi infection. This evidence is relevant for immunoprevention studies against Chagas* disease.

A study of experimental reinfection by Trypanosoma cruzi in dogs.

“…They also confirm that the second strain of T. cruzi may infect host without reproducing a characteristic acute phase. [34][35][36][37] The results of the xenodiagnoses observed in the dogs during the course of first infections and subsequent reinfections resemble those observed in humans. 38 The repeated examinations throughout the chronic phase show that the parasitemia profiles encountered may vary among individuals.…”

Weekly electrocardiographic pattern in mice infected with two different Trypanosoma cruzi strains

“…The electrocardiographic study gives important information about aspects of cardiac function and is a useful tool to measure the severity of the cardiopathy as well as the possible prognosis of the disease [8]. The mice model for Chagas' disease was previously described by Laguens et al [9] from a pathological, immunological and electrocardiographic point of view.…”

Protective immunity against Trypanosoma cruzi

“…1). The TCC-primed group displayed a significant reduction in electrocardiographic alterations (Cuneo et al 1989). Pathology of heart and skeletal muscle, tissue parasite load and inflammation, mortality and parasitemia were also reduced in T. cruzi-infected mice previously immunised with DNA vaccines containing the trans-sialidase family genes ASP-1, ASP-2, or TSA-1 (Garg & Tarleton 2002, Vasconcelos et al 2004).…”

“…Some studies have adopted more sensitive determinations of parasitemia, including hemoculture (Machado et al 2006), xenodiagnosis (Basombrío et al 1986, Basso et al 2007, histopathological studies , Basombrío et al 1986, Machado et al 2006, Hoft et al 2007) and electrocardiographic measurements (Cuneo et al 1989). However, perhaps the most stringent method of demonstrating the absence of infection or "sterile immunity" after inoculation is serological testing.…”