The etiologic agent of Chagas Disease is the Trypanosoma cruzi, transmitted through blood-sucking insect vectors of the Triatominae subfamily, representing one of the most serious public health concerns in Latin America. There are geographic variations in the prevalence of clinical forms and morbidity of Chagas disease, likely due to genetic variation of the T. cruzi and the host genetic and environmental features. Increasing evidence has supported that inflammatory cytokines and chemokines are responsible for the generation of the inflammatory infiltrate and tissue damage. Moreover, genetic polymorphisms, protein expression levels, and genomic imbalances are associated with disease progression. This paper discusses these key aspects. Large surveys were carried out in Brazil and served as baseline for definition of the control measures adopted. However, Chagas disease is still active, and aspects such as host-parasite interactions, genetic mechanisms of cellular interaction, genetic variability, and tropism need further investigations in the attempt to eradicate the disease. 1. Chagas Disease 1.1. Epidemiology and Clinical Outcomes Chagas disease, also called American trypanosomiasis, remains an epidemiologic challenge more than one hundred years after its discovery by Carlos Chagas [1]. It is estimated that 12–14 million people are infected with Trypanosoma cruzi in Latin America where the disease is endemic, and 75–90 million are exposed to infection [1, 2]. Less frequently, infection occurs through blood transfusion, vertical transmission (from infected mother to child), or organ donation [3]. In 2008, it was estimated that more than 10 thousand people were killed by Chagas disease [3]. In Brazil, the infection has already afflicted about 2.5 million individuals [4] despite the success of control measures responsible of elimination of domestic and peridomestic colonies of vector and monitoring of blood banks, which reduced incidence by approximately 70% in the Southern Cone countries. Due to the intense population migration and mobility, Chagas disease has spread in North America and Europe and is now global [5, 6]. Chagas disease is characterized by a wide spectrum of clinical outcomes, ranging from absence of symptoms to severe disease. Clinical course includes acute and chronic phases, separated by an indefinite period when patients are relatively asymptomatic. The acute phase is usually subclinical with deep parasitemia. In the indeterminate phase, patients have positive serologic and/or parasitological tests but are asymptomatic without
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