**2.1 First ingredient: the parasite**

The role of *T. cruzi* in the chronic phase has been previously underestimated due to the fact that its presence was believed to be scarce and unrelated to the inflammatory infiltrate present at this stage. Nowadays, the involvement of the parasite in the chronic phase has been well documented. Using dissimilar methods, different authors demonstrated either the persistence of *T. cruzi* or parasite antigens in mice (Younées-Chennoufi, et al., 1988), the parasite DNA sequence amplified by the polymerase chain reaction (PCR) (Jones, et al., 1993, Schijman, et al., 2004), *T. cruzi* antigens from inflammatory lesions in human chagasic cardiomyopathy (Higuchi, Brito et al. 1993), or the immunohistochemical finding of the parasite in endomyocardial biopsies with PCR confirmation (Añez, Carrasco et al. 1999). This would suggest a direct role for the parasite in the perpetuation of myocardial inflammation. In other words, the antigen stimulation would persist throughout the chronic stage, even though the parasites are not morphologically detectable by light microscopy (Andrade 1992).

The role of parasitemia is more controversial. High parasitemia correlated with severity of disease in one report (Basquiera, et al., 2003), but showed no association in another (Castro C., et al., 2005).

Interestingly, it has been observed that immunosuppression reactivates rather than ameliorates the disease, as seen in patients receiving immunosuppressive therapy to prevent transplant rejection and in AIDS patients. Accordingly, many experimental models where strains of genetically manipulated mice lacking various immune functions showed increased susceptibility to develop the disease (Tarleton & Zhang, 1999).
