Efficacy of atovaquone and sulfadiazine in the treatment of mice infected with Toxoplasma gondii strains isolated in Brazil.
The efficacy of atovaquone and sulfadiazine was examined alone or in combination for the treatment of mice infected with six Brazilian Toxoplasma gondii strains previously genotyped using the PCR-RFLP assays of the SAG2 gene, in addition to RH strain. Swiss mice were infected intraperitoneally with 10(2) tachyzoites from each strain of T. gondii and treated with 6.25, 12.5, 25 and 50 mg/Kg/day of atovaquone or 40, 80, 160 and 320 mg/Kg/day of sulfadiazine. In a second experiment, mice were treated with the association of previously determined doses of each drug. Treatment started 48 hours post-infection, and lasted 10 days. The susceptibility of T. gondii to atovaquone and to sulfadiazine was different according to the parasite strain. It was observed strains that are susceptible to atovaquone, and strains that are resistant to it. Type I strains were more susceptible to the activity of sulfadiazine and more resistant to atovaquone. Yet type III strains were susceptible to atovaquone and to sulfadiazine. Association of atovaquone and sulfadiazine presented a synergic effect in the treatment of mice infected with RH type I strain and an additive effect in the treatment of mice infected with one type I strain and with two type III strains.
Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Belo Horizonte, Minas Gerais, Brasil.
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Alves
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D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology / Q000627:therapeutic use; D053626:Atovaquone; D003049:Coccidiostats / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D005260:Female; D005838:Genotype; D051379:Mice; D009285:Naphthoquinones / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D013411:Sulfadiazine / Q000494:pharmacology / Q000627:therapeutic use*; D014122:Toxoplasma / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D014124:Toxoplasmosis, Animal / Q000188:drug therapy*; D016896:Treatment Outcome
D000981:Antiprotozoal Agents; D003049:Coccidiostats; D004338:Drug Combinations; D009285:Naphthoquinones; D013411:Sulfadiazine; D053626:Atovaquone