Reinfections and Trypanosoma cruzi strains can determine the prognosis of the chronic chagasic cardiopathy in mice

Abstract

Chronic Chagas' disease represents the result of the interaction between the host and the parasite, producing different clinical features: from a mild disease to a severe heart failure. In the present investigation, we analyzed whether Trypanosoma cruzi strain and/or reinfections in the acute stage, determine changes in the chronic phase (135 days postinfection, d.p.i) that could explain the diverse evolution of cardiac lesions. After infection of albino Swiss mice (n = 170) with 50 blood trypomastigote of the T. cruzi, strain Tulahuen (n = 80) and the isolate SGO-Z12 (n = 90), respectively, and reinfections at 10 and 20 d.p.i. Parasitemia, survival, electrocardiography, affinity and density of cardiac beta-receptors and histopathology of the heart were studied. Parasitemias in reinfected mice were significantly higher than those in single-infected mice. Survival of SGO-Z12-infected group was significantly higher than the other groups (p < 0.01). All Tulahuen-reinfected mice and 55-67% of the infected and SGO-Z12-reinfected groups presented some electrocardiographic abnormality (p < 0.01). Hearts from single-infected mice presented fibber disorganization and necrosis; reinfected groups also exhibited fibber fragmentation and a diminished affinity and a higher beta-adrenergic receptors' density than the other groups (p < 0.05). Therefore, parasite strain and reinfections determine different cardiac damage, and either (or both) of these factors are involved in the severity of the clinical picture and the prognosis of the chronic cardiac disease.

Chagas Cardiomyopathy in the Context of the Chronic Disease Transition

“…Many experts also believe that intense exposure to infected vectors and repeated T. cruzi reinfection contributed to accelerated progression of cardiomyopathy and high rates of severe disease in the decades before the Southern Cone Initiative began in 1991, and that vector control has led to an amelioration of Chagas cardiomyopathy since then [32], [33], [34]. Although this hypothesis is difficult to test in human populations, animal models provide supporting evidence that repeated infection worsens the long-term prognosis of Chagas heart disease [35]. We observed that patients who had lived in a house with earthen floor and walls were more likely to have severe Chagas cardiomyopathy; this finding may reflect poor housing conditions acting as a proxy for more intense vector exposure and reinfection risk.…”

Current concepts in immunoregulation and pathology of human Chagas disease

“…Parasite load, time of infection and exposure to reinfection are extremely hard to ascertain while studying human populations. Using animal models, it has been possible to demonstrate that these factors affect protection and pathology following T. cruzi infection [12][13][14]. It has been shown, in experimental as well as human T. cruzi infection, that parasites isolated from different organs are genetically distinct, suggesting that the genetic variability of the parasite strains may influence disease outcome [15,16].…”

Epidemiological modeling of Trypanosoma cruzi: Low stercorarian transmission and failure of host adaptive immunity explain the frequency of mixed infections in humans

“…It has been repeatedly proposed that infected people living in endemic areas suffer from frequent reinfections, and that such reinfections increase the strength of cardiomyopathy in humans [28, 29, 32], just as they do in mice [20–22, 30, 31]. Although those epidemiological studies were based on sound statistical comparisons between individuals with different levels of exposure to vectors, none of them provided estimates of the actual level of vector-human contacts and its associated number of reinfection events per person.…”

“…Several authors proposed a role of reinfections in pathogeny. Although parasitaemia is lower in the reinfections compared to the primary infection in animal models [20, 22, 23], reinfections may aggravate chronic disease in mice [20–22, 30, 31] and they may be associated to chronic cardiac damage in humans [28, 29, 32]. To determine the frequency of reinfections and the ability of the human immune system to prevent them is thus essential to our understanding of the disease dynamics.…”