Trypanosoma cruzi: acute and long-term infection in the vertebrate host can modify the response to benznidazole.
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.
Caldas
Sérgio
S
Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Minas Gerais, Brazil.
Santos
Fabiane M
FM
de Lana
Marta
M
Diniz
Lívia F
LF
Machado-Coelho
George L L
GL
Veloso
Vanja M
VM
Bahia
Maria T
MT
D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy / Q000469:parasitology*; D003520:Cyclophosphamide / Q000494:pharmacology; D004285:Dogs; D004351:Drug Resistance / Q000502:physiology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D009593:Nitroimidazoles / Q000494:pharmacology*; D018512:Parasitemia / Q000188:drug therapy / Q000469:parasitology; D012692:Serial Passage; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
D007166:Immunosuppressive Agents; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; D003520:Cyclophosphamide; C009999:benzonidazole