A clinical-parasitological monotherapy cure in the treatment of experimental infection by a highly virulent strain of Toxoplasma gondii.
Toxoplasmic encephalitis in patients with the acquired immunodeficiency syndrome (AIDS) is treated classically with pyrimethamine plus sulfadiazine. Unfortunately, up to 40% of these patients are unable to complete the course of therapy because of adverse reactions to sulfonamides. This study considers the possible usefulness of monotherapies in the treatment of acute toxoplasmosis, producing parasitological cures 2-3 months after the date of infection. With this therapy, the main adverse effects are suppressed. Groups of mice infected with the RH strain of Toxoplasma gondii were treated with pyrimethamine alone, sulfadiazine alone, and pyrimethamine plus sulfadiazine for 7 d. Treatment with pyrimethamine plus sulfadiazine produced clinical cures in 100% of the infected mice 1 month after infection. Treatment with pyrimethamine gave a 60% survival rate (clinical cure) at 1 month postinfection. Finally, treatment with sulfadiazine produced a 60% survival rate at 1 month postinfection. Although the antitoxoplasmic regimen with pyrimethamine plus sulfadiazine has proven to be effective in intensive treatment of toxoplasmic encephalitis, relapses occur in more than 80% of cases after cessation of antitoxoplasmic therapy, making secondary prophylaxis mandatory. In this study the efficacy of treatment was also evaluated in terms of parasitological cure. None of the three therapies showed parasitological cure after 1 month of treatment. When the intervals were extended to a 3-month observation, monotherapy with pyrimethamine and sulfadiazine alone produced a parasitological cure.
de Diego
J A
JA
Department of Preventive Medicine and Public Health, Autonomous University, School of Medicine, Madrid, Spain.
Penin
P
P
Arribas
J R
JR
Vázquez
E
E
Vázquez
J J
JJ
D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001921:Brain / Q000469:parasitology; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D051379:Mice; D011739:Pyrimethamine / Q000008:administration & dosage / Q000627:therapeutic use*; D012008:Recurrence; D013411:Sulfadiazine / Q000008:administration & dosage / Q000627:therapeutic use*; D014122:Toxoplasma / Q000187:drug effects* / Q000302:isolation & purification / Q000472:pathogenicity; D014124:Toxoplasmosis, Animal / Q000188:drug therapy* / Q000469:parasitology; D016781:Toxoplasmosis, Cerebral / Q000188:drug therapy* / Q000469:parasitology; D014774:Virulence
D000981:Antiprotozoal Agents; D013411:Sulfadiazine; D011739:Pyrimethamine