Aims: To describe the outcome of four years' nationwide neonatal screening for congenital toxoplasmosis in liveborn newborns. Methods: Congenital toxoplasmosis was diagnosed if specific Toxoplasma gondii IgM antibodies were detected in eluate from the PKU Guthrie filter paper card from a child. Infants diagnosed with congenital toxoplasmosis were examined for intracranial and retinal lesions and treated for three months with sulphadiazine, pyrimethamine, and folinic acid continuously. Results: Eluates from PKU-cards from 262 912 newborns were analysed. The birth prevalence of congenital toxoplasma infection was 2.1 per 10 000 liveborns. Congenital toxoplasmosis was suspected in 96 infants and confirmed in 55. Forty seven children were examined for intracranial and retinal lesions soon after birth; 12 had clinical signs at this first examination. Of these, 5 had intracranial calcifications, 2 had retinochoroidal lesions, 4 had intracranial calcifications and retinochoroidal lesions, and 1 had hydrocephalus, intracranial calcifications, and retinochoroidal lesions. Ninety four eyes were examined soon after birth; there were central retinochoroidal lesions in 9. Two children had macular lesion of both eyes, five had macular lesions of one eye. At 1 year of age, 10/68 eyes had central lesions, and at 3 years of age, 5/32 had central lesions. Thus new retinochoroidal lesions developed in three eyes in the observation period. Conclusions: Neonatal screening is feasible for diagnosing children with congenital toxoplasmosis at birth in low endemic areas. Retinochoroiditis with macular lesion was diagnosed in 9.6% of the eyes at birth and in 15.6% of the eyes examined at 3 years of age.
Pre- and neonatal screening for congenital toxoplasmosis rests upon the assumption that treatment is beneficial on either acute symptoms or in preventing later reactivation. Postpartum treatment of congenital toxoplasmosis with sulfadiazine and pyrimethamine has remained almost unchanged for 50 years. More recently, sulfadiazine has been substituted by sulfadoxine, which has a much longer half-life and provides a basis for a dose schedule with higher compliance. Newer drugs with potential effects against Toxoplasma gondii, such as azithromycin, atovaquone and clindamycin, require further evaluation in animal models and human studies. No randomized controlled trials have ever been conducted. The available studies are either observational studies of groups of referred patients or observational studies with historical controls accrued over many years, often decades. Pre- and neonatal screening for congenital toxoplasmosis is performed on more than two million pregnant women every year in Europe, North and South America at the estimated cost of more than 500 million annually. The benefit needs to be documented by a prospective, placebo-controlled randomized study, which needs to be organized and financed by the countries performing nationwide, universal screening programs.
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
Differentiation between the specific immunoglobulin G (IgG) response to Toxoplasma gondii by a mother and her newborn child is helpful in the diagnosis of congenital infection with T. gondii in newborns without T. gondii-specific IgM and/or IgA antibodies at birth. Previous methods include immunoblotting and complexing T. gondii antigen with the sera from the mother and child and comparing the bands after electrophoresis. We developed a two-dimensional immunoblotting (2DIB) method with T. gondii RH strain tachyzoite antigen and validated the method with sera from 11 children identified through the neonatal screening program for congenital toxoplasmosis in Denmark. The children were identified by using Toxoplasma-specific IgM antibodies at the screening test, but the presence of T. gondii-specific IgM and/or IgA antibodies could not be confirmed at the subsequent serum sample tested. The children were monitored for at least 12 months, and in seven of eight patients monitored for 12 months the results of the 2DIB-predicted congenital infection were confirmed by the presence of persistent Toxoplasma-specific IgG antibodies. 2DIB is a sensitive technique that allows early differentiation between passively transferred maternal T. gondii-specific IgG antibodies and antibodies synthesized by the newborn child.Primary infection with Toxoplasma gondii during pregnancy may result in congenital infection of the fetus. The majority of congenitally infected newborns do not show clinical signs at birth but may later develop retinochoroiditis and reduced vision that can be prevented by early treatment (7). Diagnosis of congenital infection with T. gondii is difficult at birth if T. gondii-specific immunoglobulin M (IgM) and/or IgA antibodies are not present because present diagnostics methods can distinguish between maternal and fetal IgG only with difficulty.Congenital toxoplasmosis is treated for up to 12 months continuously with sulfadiazine and pyrimethamine, which may cause side effects, and it is therefore important that the diagnosis of congenital toxoplasmosis is firmly established before treatment is started.The detection of T. gondii-specific nucleic acid by PCR is possible in amniotic fluid if a primary T. gondii infection is diagnosed during pregnancy, but in countries without prenatal screening programs or with neonatal screening programs PCRbased diagnosis is not appropriate.Neonatal screening for congenital toxoplasmosis is performed in New England, Denmark, and parts of Brazil by analyzing the blood samples obtained on filter paper (Guthrie cards) on day 5 postpartum (5, 6, 9). Detection of T. gondiispecific IgM antibodies eluted from the filter paper is followed by a request of a blood sample from both the mother and infant for confirmatory testing. Approximately 15 to 20% of these sera have been found to be negative for Toxoplasmaspecific IgM (3,8).Previous studies have shown that transferred maternal and neonate-synthesized T. gondii-specific IgG antibodies can be differentiated by immunoblotting or immunoco...
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