**5. Chagas disease**

In humans, Chagas disease progresses through two phases, acute and chronic, with the development of a symptomatic or an asymptomatic form [34]. The initial acute phase evolves within 1–2 weeks after the inoculation, lasts for 4–8 weeks, and is characterized for high levels of blood parasitemia. Affected individuals show moderate and unspecific symptoms such as fever, general discomfort, and hepatosplenomegaly. Sometimes it is possible to observe a cutaneous node (inoculation chagoma) or a unilateral bipalpebral edema (Romaña sign) that indicates the parasite inoculation site [34, 35]. The majority of acute infections are never detected. Only in less than 1% of the cases, encephalitis or myocarditis occurs that can be fatal mainly in children and the elderly [36]. The initial increase in parasitemia is contained by proinflammatory cytokines (IL-12, TNF-α, IFN-γ) and microbicidal substances synthesized by macrophages (reactive oxygen and nitrogen species) and NK cells (perforins). This initial innate immune response is followed by the development of an acquired immune response characterized by a polyclonal lymphocyte activation against the parasite mediated by T CD4+ , CD8+ , and B lymphocytes, which together reduce the parasite load, but do not completely eliminate *T. cruzi*, which still survives in the host tissues, thus initiating the chronic phase [37, 38]. Observations from research conducted before 1990 show that after being in the acute phase for 10–30 years, 30–40% of patients will turn to the symptomatic chronic phase and present digestive and/ or cardiac compromise, while the rest will remain in an indeterminate phase for the rest of their lives [39–41]. Recent studies performed in children and teenagers from endemic areas in Mexico suggest that the time for the outcome of the CCC symptoms is shorter, months in some cases. Therefore, more research is required to clarify this aspect [42, 43].
