Specific treatment of Chagas disease: current status and new developments.
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.
Urbina
J A
JA
Biological Chemistry Laboratory, Center for Biochemistry and Biophysics, Venezuelan Institute for Scientific Research, Caracas, Venezuela. jaurbina@ivic.ve
D014355:Chagas Disease / Q000188:drug therapy*; D015853:Cysteine Proteinase Inhibitors / Q000627:therapeutic use; D006801:Humans; D011799:Quinazolines / Q000627:therapeutic use; D014230:Triazoles / Q000627:therapeutic use; D005466:Fluorocarbons
D015853:Cysteine Proteinase Inhibitors; D011799:Quinazolines; D014230:Triazoles; C058219:ICI 195739; C105227:TAK 187; D005466:Fluorocarbons; C112424:albaconazole