NEW INSIGHTS IN CHAGAS' DISEASE TREATMENT

Chagas' disease, caused by the kinetoplastid protozoon Trypanosoma cruzi, remains the highest parasitic disease burden in the American continent and is now spreading to nonendemic countries due to international migrations. Specific therapy for this complex condition remains unsatisfactory due to limited efficacy and common side effects of currently available drugs (nifurtimox and benznidazole), as well as controversies regarding the pathogenesis of the disease in the chronic stage. In contrast to long-held views on the autoimmune origin of the pathological manifestations of the chronic stage of the disease, recent studies have concluded that the persistence of parasites is the key factor leading to the sustained inflammatory responses underlying the characteristic lesions of chronic Chagas' disease, and that this condition should be treated as an infectious and not an autoimmune disease. Among the most promising approaches to new treatments are ergosterol biosynthesis inhibitors, such as posaconazole and ravuconazole, which are poised to enter clinical trials in Chagas' disease in the short term; the antiarrhythmic drug amiodarone, which was recently shown to also have potent activity against T cruzi; inhibitors of cruzipain, the main cysteine protease of T. cruzi; and combination therapies such as nifurtimox or benznidazole with posaconazole, ravuconazole or amiodarone hydrochloride.