The pathogenesis of chronic Chagas disease still is an unresolved and controversial issue. Parasite persistence and autoimmune responses cannot explain the spectrum of chronic Chagas disease. However, a modified neurogenic hypothesis, concerning the timing and mechanisms responsible for the cardiac parasympathetic damage and for the activation of the sympathetic nervous system and of other neurohormonal systems, unifies cardiac remodelling and neurohormonal activation to explain most of the events of the natural history of Chagas disease.
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