Abstract
Chagas disease develops upon infection with the protozoan parasite Trypanosoma cruzi and undergoes an acute phase characterized by massive parasite replication and the presence of parasites in the blood. This condition is known as acute phase parasitemia. This initial stage may result in a cure, in the development of the chronic stages of the disease or in the death of the infected host. Despite intensive investigation related to the characterization of the acute and chronic phases of the disease, the cause-effect relationship of acute phase parasitemia to the outcome of the disease is still poorly understood. In this study, we artificially generated a heterogeneously controlled mouse population by intercrossing F1 mice obtained from a parental breeding of highly susceptible A/J with highly resistant C57BL/6 mouse strains. This F2 population was infected and used to assess the correlation of acute phase parasitemia with the longevity of the animals. We used nonparametric statistical analyses and found a significant association between parasitemia and mortality. If males and females were evaluated separately, we found that the former were more susceptible to death, although parasitemia was similar in males and females. In females, we found a strong negative correlation between parasitemia and longevity. In males, however, additional factors independent of parasitemia may favor mouse mortality during the development of the disease. The correlations of acute phase parasitemia with mortality reported in this study may facilitate an appropriate prognostic approach to the disease in humans. Moreover, these results illustrate the complexity of the mammalian genetic traits that regulate host resistance during Chagas disease.
Highlights
Chagas disease is a parasitic infection caused by the protozoan parasite Trypanosoma cruzi that causes strong morbidity effects in immunocompetent individuals
In studies addressing the susceptibility to the Y strain of T. cruzi, it has been shown that mice from the A/J inbred strain succumb to infection, whereas C57BL/6 mice survive to the acute phase when infected with low inoculum (,1000 forms) [22,23]
Under the conditions used in this study, we found that A/J mice infected with T. cruzi succumbed to infection during the acute phase, whereas all C57BL/6 infected mice survived during the same observation period (Fig. 1A)
Summary
Chagas disease is a parasitic infection caused by the protozoan parasite Trypanosoma cruzi that causes strong morbidity effects in immunocompetent individuals. It is well accepted that the genetic characteristics of both the parasite and the host are important in determining the outcome of infection [11,13,14,15,16] In this scenario, the reduction of the complexity of these interactions is essential to facilitate the experimental assessment of the factors influencing the course of Chagas disease. We addressed the correlation between parasitemia induced during the acute phase of infection and mortality during the course of infection in a mouse model of Chagas disease To address this question, we artificially generated a F2 mouse population by intercrossing F1 mice obtained from a parental breeding of the highly susceptible A/J strain with the highly resistant C57BL/6 strain. The results of this study serve to elucidate a controversial issue underlying this disease: the statistical correlation of acute phase parasitemia with mortality during the outcome of Chagas disease
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