The aim was to study the tolerability and plasma concentrations of
pyrimethamine and
sulfadiazine in children treated for
congenital toxoplasmosis. Infants were diagnosed through the Danish Toxoplasma Neonatal Screening Programme, based on detection of toxoplasma-specific
IgM- and/or
IgA-
antibodies on 3 mm blood spots collected from
phenylketonuria [PKU cards (Guthrie cards)]. Toxoplasma-infected children received 3 months' continuous treatment with 50-100 mg/kg per day
sulfadiazine in two separate administrations and 1 mg/kg per day
pyrimethamine after a 1-day loading dose of 2 mg/kg, and
folinic acid 7.5 mg was administered twice weekly. Blood cell counts and
body weight were recorded during follow-up. The plasma concentrations of
pyrimethamine and
sulfadiazine were analysed in a subgroup of seven children, using high performance liquid chromatography with ultraviolet and mass spectrometric detection. Of 48 infants, 41 completed the treatment without change in schedule. Six infants had neutrophil counts below 0.5x10(9)/l, and one infant had an elevated
bilirubin value. Twenty-nine children were tested by a series of neutrophil counts during treatment. The neutrophil count was <or=0.5x10(9)/l or lower in 4/29 (13.8%). None of the children had anaemia or
thrombocytopenia. The drugs did not affect
weight gain. Mean plasma
drug concentrations varied between 1.3 microg/ml and 2.2 microg/ml for
pyrimethamine and between 60 microg/ml and 86 microg/ml for
sulfadiazine. Treatment efficacy is still a concern, since progression of eye lesions was observed in three eyes during the follow-up period. We concluded that the treatment was well tolerated in 86% (25/29) of the children. The drugs did not affect their
weight gain. Drugs given in the recommended doses led to concentrations within expected therapeutic limits.