Treatment of infants with congenital toxoplasmosis: tolerability and plasma concentrations of sulfadiazine and pyrimethamine

Abstract

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.

Trypanosoma cruzi high infectivity in vitro is related to cardiac lesions during long-term infection in Beagledogs

“…As expected IgG isotype levels were higher during the chronic phase. While IgA antibodies may aim in congenital Chagas disease diagnosis achievement, as used in acute toxoplasmosis diagnosis (Signorell et al 2006, Schmidt et al 2006.…”

Diagnosis, Treatment, and Prevention of Congenital Toxoplasmosis in the United States

“…13 However, data from Denmark have shown that the medication was not well tolerated in only 14% (4 of 29) of treated infants. 207 The main adverse effect was neutropenia, reported to occur more often with higher doses of P/S and especially when folinic acid was not administered. 13 Moreover, seizures have been reported with cases of pyrimethamine overdose resulting from prescription dosing errors.…”

Actividad anti-Toxoplasma de extractos metanólicos de frutos y hojas de Sambucus nigra (Caprifoliaceae)

“…On the other hand, these drugs have side effects such as neutropenia, severe drop of platelet count, thrombocytopenia, leucopenia, elevation in serum creatinine and serum liver enzymes, haematological abnormalities and hypersensitivity reactions (Bosch-Driessen et al, 2002;Silveira et al, 2002;Schmidt et al, 2006). For many centuries, herbal remedies and plant extracts have been used as treatments for ailments from headaches to parasite infections (Jones, 1996).…”