The current situation regarding specific
chemotherapy for
Chagas disease (
American trypanosomiasis), and new developments in this field, are reviewed. Despite previous controversy on the autoimmune origin of
Chagas disease pathology, available knowledge supports the notion that this condition should be treated as a parasitic, not an
autoimmune, disease. Currently available drugs (
nitrofurans and
nitroimidazoles) are active in acute or short-term
chronic infections, but have very low
antiparasitic activity against the prevalent chronic form of the disease, and toxic side-effects are frequently encountered. The
nitroimidazole benznidazole has also shown significant activity in the treatment of reactivated
Trypanosoma cruzi infections in patients with
acquired immune deficiency syndrome and in other immunosuppressed patients with underlying chronic
Chagas disease. Although the etiological agent, T. (Schizotrypanum) cruzi, requires specific endogenous
sterols for cell viability and proliferation, the currently available antifungal
sterol biosynthesis inhibitors are not powerful enough to induce parasitological cures of human or experimental
infections. However, new
triazole antifungal compounds, which are potent inhibitors of the
sterol C14alpha demethylase of the parasite and have special pharmacokinetic properties, are capable of inducing parasitological cures in murine models of both acute and chronic
Chagas disease. They are currently the most advanced candidates for clinical trials in patients with
Chagas disease. Other potential chemotherapeutic agents against T. cruzi currently in development include antiproliferative
lysophospholipid analogs (already in clinical trials as the first oral treatment for
visceral leishmaniasis),
cysteine proteinase (
cruzipain) inhibitors, and compounds that interfere with
purine salvage and
inositol metabolism.