A serological test to determine strains associated with ocular toxoplasmosis

Massachusetts Institute Of Technology, Cambridge MA

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Abstract

? DESCRIPTION (provided by applicant): The obligate intracellular parasite Toxoplasma gondii can infect the fetus and cause congenital toxoplasmosis. Infection of the fetus during the first trimester can result in abortion or severe birth defects such as mental retardation and blindness while neonates infected during the second and third trimester are usually born without clinical symptoms. However, a large number of them will develop ocular toxoplasmosis (OT) later in life. Besides congenital infections, acute Toxoplasma infections can also lead to eye disease and ocular toxoplasmosis is recognized as the most common etiology of posterior uveitis in the United States and in the world. At the moment it is unknown why some infected people will develop ocular disease while others will stay disease free but the specific Toxoplasma strain they are infected is known to play an important role. If it was known what strain a person was infected with the treatment could be matched to the specifics of the infection; for example serotyping could identify patients infected with atypical strains that have not yet developed OT allowing changes in their management (e.g. more frequent eye exams or even prophylactic treatment). It has been shown that OT patients infected with atypical strains have a higher chance of recurrences and therefore long term treatment might be recommended to patients infected with atypical strains. Furthermore, once an association between Toxoplasma strain and disease phenotype is established experiments can be designed to determine what the molecular basis is for the increased virulence of that strain which might ultimately lead to novel therapies. Novel therapies are urgently needed against ocular toxoplasmosis because the current drugs are poorly tolerated and seem to be ineffective. The aim of this project is to develop a serological test that can correctly determine what strain a patient is infected with. Thi serological test will then be used to correlate parasite genotype with disease outcome. Finally, the assays proposed in this project could tell us if the Toxoplasma proteins that determine strain-specific differences in virulence in mice also determine strain- specific differences in virulence in humans. This information would be extremely useful because it could lead to new drug treatments with the aim of preventing blindness caused by toxoplasmosis.