New insights into genetic diversity, and its influence on parasite biology and clinical outcomes.

Chagas disease, caused by , remains a serious public health problem worldwide. The parasite was subdivided into six distinct genetic groups, called "discrete typing units" (DTUs), from TcI to TcVI. Several studies have indicated that the heterogeneity of species directly affects the diversity of clinical manifestations of Chagas disease, control, diagnosis performance, and susceptibility to treatment. Thus, this review aims to describe how genetic diversity influences the biology of the parasite and/or clinical parameters in humans. Regarding the geographic dispersion of , evident differences were observed in the distribution of DTUs in distinct areas. For example, TcII is the main DTU detected in Brazilian patients from the central and southeastern regions, where there are also registers of TcVI as a secondary DTU. An important aspect observed in previous studies is that the genetic variability of can impact parasite infectivity, reproduction, and differentiation in the vectors. It has been proposed that DTU influences the host immune response and affects disease progression. Genetic aspects of the parasite play an important role in determining which host tissues will be infected, thus heavily influencing Chagas disease's pathogenesis. Several teams have investigated the correlation between DTU and the reactivation of Chagas disease. In agreement with these data, it is reasonable to suppose that the immunological condition of the patient, whether or not associated with the reactivation of the infection and the parasite strain, may have an important role in the pathogenesis of Chagas disease. In this context, understanding the genetics of and its biological and clinical implications will provide new knowledge that may contribute to additional strategies in the diagnosis and clinical outcome follow-up of patients with Chagas disease, in addition to the reactivation of immunocompromised patients infected with .