Benznidazole

Chronic chagasic cardiomyopathy affects 20% of Chagas' disease patients. At present, Chagas' disease chemotherapy uses nitrofurans, benznidazole (Rochagan®, Rodanil®, Roche) or nifurtimox (Lampit®, Bayer). Treatment during acute and recent chronic phases in childhood effects 71.5% and 57.6%, respectively, of parasitological cure. However, in clinical trials during the late chronic phase, only 5.9% of parasitological cure were achieved. This review focuses on the benefit from aetiological treatment to avoid, stop or revert myocarditis. Divergent data gathered from clinical practice are not convincing to support prescription of aetiological treatment as routine for indeterminate and cardiac chronic patients.

Inflammatory cytokines and microbe-borne immunostimulators have emerged as triggers of depressive
behavior. Behavioral alterations affect patients chronically infected by the parasite Trypanosoma cruzi. We
have previously shown that C3H/He mice present acute phase-restricted meningoencephalitis with persistent
central nervous system (CNS) parasitism, whereas C57BL/6 mice are resistant to T. cruzi-induced CNS inflammation. In the present study, we investigated whether depression is a long-term consequence of acute CNS inflammation and a contribution of the parasite strain that infects the host. C3H/He and C57BL/6 mice were infected with the Colombian (type I) and Y (type II) T. cruzi strains. Forced-swim and tail-suspension tests were used to assess depressive-like behavior. Independent of the mouse lineage, the Colombian-infected mice showed significant increases in immobility times during the acute and chronic phases of infection. Therefore, T. cruzi-induced depression is independent of active or prior CNS inflammation. Furthermore, chronic depressive-like behavior was triggered only by the type I
Colombian T. cruzi strain. Acute and chronic T. cruzi infection increased indoleamine 2,3-dioxygenase
(IDO) expression in the CNS. Treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine
abrogated the T. cruzi-induced depressive-like behavior. Moreover, treatment with the parasiticide drug
benznidazole abrogated depression. Chronic T. cruzi infection of C57BL/6 mice increased tumor necrosis
factor (TNF) expression systemically but not in the CNS. Importantly, TNF modulators (anti-TNF and pentoxifylline)
reduced immobility. Therefore, direct or indirect parasite-induced immune dysregulation may contribute to chronic depressive disorder in T. cruzi infection, which opens a new therapeutic pathway to be explored.