Trypanosoma cruzi: Acute and long-term infection in the vertebrate host can modify the response to benznidazole

• Published in: Experimental parasitology Vol. 118; no. 3; pp. 315 - 323
• Main Authors: Caldas, Sérgio, Santos, Fabiane M., Lana, Marta de, Diniz, Lívia F., Machado-Coelho, George L.L., Veloso, Vanja M., Bahia, Maria T.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01-03-2008; Elsevier
• Subjects: acute course; animal disease models; Animals; benznidazole; Biological and medical sciences; Chagas disease; Chagas Disease - drug therapy; Chagas Disease - parasitology; Chemotherapy; chronic diseases; Cure control; cyclophosphamide; Cyclophosphamide - pharmacology; Dogs; Drug resistance; Drug Resistance - physiology; Female; Fundamental and applied biological sciences. Psychology; Humans; immunosuppression (physiological); Immunosuppressive Agents - pharmacology; infection; Life cycle. Host-agent relationship. Pathogenesis; Mice; nifurtimox; nitroimidazoles; Nitroimidazoles - pharmacology; parasitemia; Parasitemia - drug therapy; Parasitemia - parasitology; Protozoa; Serial Passage; Trypanocidal Agents - pharmacology; trypanocides; Trypanosoma cruzi; Trypanosoma cruzi - drug effects; virulence; Chemotherapy; Cure control; Chagas disease; Bz; Nf; Drug resistance; Trypanosoma cruzi; Kinetoplastida; Infection; Protozoa; Vertebrata; Benznidazole; Acute; Parasite; Host; Long term
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2007.08.016

We analyzed the influence of Trypanosoma cruzi maintenance in different hosts (dog and mouse) on its susceptibility to benznidazole treatment. Five T. cruzi stocks were isolated from dogs inoculated with Be-62 or Be-78 strain (both sensitive to benznidazole) 2–10 years ago, and the benznidazole sensitivity was then determined using the mouse as experimental model. The different T. cruzi stocks obtained from long-term infected dogs showed 50–90% drug resistance right after isolation. However, maintenance of these T. cruzi stocks in mice, by successive blood passages (2.5 years), led to either a decrease or stability of the drug resistance pattern and an increase in parasite virulence. We also demonstrated the effectiveness of the induction of parasitemia reactivation by cyclophosphamide immunosuppression in the evaluation of the response to the specific drug treatment.