In vivo activity of the bis-triazole D0870 against drug-susceptible and drug-resistant strains of the protozoan parasite Trypanosoma cruzi.

We report the in vivo activity of the bis-triazole derivative D0870 against a variety of strains of Trypanosoma cruzi, the causative agent of Chagas' disease, including nitroimidazole/nitrofuran-resistant strains. In both acute and chronic murine models of the disease, treatment with D0870 at < or = 10 mg/kg on alternate days for a total of 20 doses provided 60-100% protection against death, regardless of the drug sensitivity of the infecting strain. In the acute model we obtained 70-100% parasitological cure in seven of the nine strains tested, including one intermediate and two highly drug-resistant strains. D0870 was able to cure 30-45% of animals chronically infected with various strains, including those harbouring the Colombiana strain, among which no cures were obtained with benznidazole. We also found that the anti-T. cruzi activity of D0870 is largely retained even if the hosts are immunosuppressed.

[1]  D. Loebenberg,et al.  Activities of the Triazole Derivative SCH 56592 (Posaconazole) against Drug-Resistant Strains of the Protozoan ParasiteTrypanosoma (Schizotrypanum) cruzi in Immunocompetent and Immunosuppressed Murine Hosts , 2000, Antimicrobial Agents and Chemotherapy.

[2]  Tropical disease research , 2000, Releve epidemiologique hebdomadaire.

[3]  J. Ramirez,et al.  Myocardial parasite persistence in chronic chagasic patients. , 1999, The American journal of tropical medicine and hygiene.

[4]  J. Urbina Chemotherapy of Chagas’ disease: the how and the why , 1999, Journal of Molecular Medicine.

[5]  L. Kirchhoff Chagas'Disease (American Trypanosomiasis): a Tropical Disease Now Emerging in the United States , 1999 .

[6]  P. Wincker,et al.  Antiproliferative Effects and Mechanism of Action of SCH 56592 against Trypanosoma (Schizotrypanum)cruzi: In Vitro and In Vivo Studies , 1998, Antimicrobial Agents and Chemotherapy.

[7]  P. Wincker,et al.  Cure of Short- and Long-Term Experimental Chagas' Disease Using D0870 , 1996, Science.

[8]  O. Martins-Filho,et al.  Flow cytometry, a new approach to detect anti-live trypomastigote antibodies and monitor the efficacy of specific treatment in human Chagas' disease , 1995, Clinical and diagnostic laboratory immunology.

[9]  L. Filardi,et al.  Susceptibility and natural resistance of Trypanosoma cruzi strains to drugs used clinically in Chagas disease. , 1987, Transactions of the Royal Society of Tropical Medicine and Hygiene.