Long term objectives are to reduce morbidity and mortality due to congenital Toxoplasma gondii infection through improved use of antimicrobial agents.
Specific aims are to develop optimal methods to treta congenital toxoplasmosis. To develop optimal strategies to manage human congenital Toxoplasma infection, a serologic screening program to diagnose Toxoplasma infection acquired during pregnancy will be evaluated. Congenitally infected infants identified in this program (and through collaborative arrangements) will be studied prospectively to determine feasibility, safety, adn efficacy of treatment. Treatment for clinically normal infants or those with mild involvement will be either one year of pyrimethamine and trisulfapyrimidines or this regimen for six months followed by these medications in alternating months with spiramycin. Infants with severe neurologic or ocular involvement at birth will receive treatment for one year iwth pyrimethamine and trisulfapyrimidines. Their pyrimethamine treatment will be administered in one of two dosage regimens: either one milligram per kilogram daily for two or for six months followed by the same dosage administered three times per week for a total of one year of therapy. Growth and development, general clinical, neurologic, ophthalmologic, audiologic and hematologic status at near birth and one, three, five, ten, fifteen and twenty years of age will be evaluated in a uniform manner. Outcome for treated children will also be compared with outcome of historical, untreated controls. Early evaluations will provide information concerning response to therapy of acute signs and symptoms du to Toxoplasma infection, immediate information about toxicity of medications, and preliminary indications of potential general, neurologic, audiologic, intellectual adn ophthalmologic function. The later evaluations will assess incidence of recrudescent chorioretinitis and ultimate general, ophthalmologic, audiologic status and intellectual performance. Pharmacokinetics of pyrimethamine and folinic acid will be studied, as currently there are no such data to guide therapy. This information is greatly needed, as at present therapy is totally empiric and potentially toxic. Immunologic functions of children in the study, which are of potential importance in containing Toxoplasma infection, also will be evaluated. These studies will attempt to determine how to best provide medical care to children afflicted with congenital toxoplasmosis.
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