Chagas disease, induced by Trypanosoma cruzi, is a common cause of infectious myocarditis. Recent clinical treatment trials and vaccine studies indicate that chagasic immunopathology is directed against the parasite and not self-antigens. Therefore, vaccines may have the potential to protect against disease progression. Certain combinations of mouse and parasite strains produce significant histopathology and can be used for safety analyses of new vaccination strategies. The goals of this study were to determine: (1) if the development of Chagasic cardiomyopathy in the murine model could be identified by ECG; and (2) whether these potential Chagasic ECG changes would correlate with histopathologic findings. Groups of BALB/c, C57BL/6, and C3H mice were infected with different parasite strains (Tulahuén, Brazil or Sylvio-X10/4) and evaluated weekly by ECG. Selected tissues from subsets of mice were harvested periodically for blinded histologic evaluation. Significantly increased proportions of BALB/c mice infected with Brazil and Tulahuén strain parasites displayed prolonged QT intervals. Prolonged mean QT intervals detected in infected BALB/c mice significantly correlated with chagasic histopathologic changes. These results indicate that ECG can be used as a non-invasive method to screen for immune-mediated damage resulting in Chagasic cardiomyopathy in the murine model.
Chagas disease, caused by infection with the parasite Trypanosoma cruzi, is the most common cause of infectious myocarditis. More than 11 million people are infected worldwide with this protozoan parasite (CDC, 2007). Currently, there are no highly effective treatments once an individual has proceeded past acute infection, and vaccine work is still in the research stage.
Human infection begins after being inoculated with T. cruzi parasites, usually via the fecal matter of triatomine insects (`kissing bugs') through an insult to the dermis or via mucosal membranes, such as the eye. The acute phase of infection is characterized by mild clinical symptoms (fever and malaise) in spite of high parasitemia. Patients usually recover from this acute illness and enter the latent (or indeterminate) stage of the infection with low-level parasite persistence which can last from 10 to > 40 yr. An estimated 30% of infected individuals develop the symptomatic chronic stage of infection, which is characterized by myocarditis or megacolon (CDC, 2007). Recent studies report progress of drug intervention during chronic infection, but are more often successful in reducing progression towards disease when given during acute infection (Braga et al., 2000; Lauria-Pires et al., 2000; Cancado, 2002; Andrade et al., 2004; Garcia et al., 2005; Viotti et al., 2006). However, with detection of acute infection being low, treatment is often not given.
Previous studies have indicated that infection of certain mouse strains with specific parasite strains can induce significant histological changes in both skeletal muscle and cardiac tissue (Postan et al., 1986; Postan et al., 1987...
