Lesões coriorretinianas em mães de crianças com toxoplasmose congênita no national collaborative Chicago-based, toxoplasmosis study / Chorioretinal lesions in mothers of children with congenital toxoplasmosis in the national collaborative Chicago-based, congenital toxoplasmosis study

Aims: To determine whether mothers of children with congenital toxoplasmosis have chorioretinal lesions consistent with toxoplasmosis. Methods: Prospective cohort study. Ophthalmologists in our study have examined 173 children with congenital toxoplasmosis in a hospital outpatient setting. These children were referred to us by their primary care physicians. One hundred and thirty mothers of these children had retina examinations of both eyes at least once. Main outcome measure was lesion(s) consistent with ocular toxoplasmosis. Results: Of 130 mothers examined between 1991-2005, 10 (7.7%, 95% Confidence Interval 3.8%, 13.7%) had chorioretinal lesions which likely represent resolved toxoplasmic chorioretinitis. Most of these were small peripheral chorioretinal lesions. None reactivated between 1991-2005. Conclusions: Chorioretinal lesions consistent with quiescent ocular toxoplasmosis occur in mothers of children with congenital toxoplasmosis in the United States.

Host genetic and epigenetic factors in toxoplasmosis

Analysing human genetic variation provides a powerful tool in understanding risk factors for disease. Toxoplasma gondii acquired by the mother can be transmitted to the fetus. Infants with the most severe clinical signs in brain and eye are those infected early in pregnancy when fetal immunity is least well developed. Genetic analysis could provide unique insight into events in utero that are otherwise difficult to determine. We tested the hypothesis that propensity for T. gondii to cause eye disease is associated with genes previously implicated in congenital or juvenile onset ocular disease. Using mother-child pairs from Europe (EMSCOT) and child/parent trios from North America (NCCCTS), we demonstrated that ocular and brain disease in congenital toxoplasmosis associate with polymorphisms in ABCA4 encoding ATP-binding cassette transporter, subfamily A, member 4 previously associated with juvenile onset retinal dystrophies including Stargardt's disease. Polymorphisms at COL2A1 encoding type II collagen, previously associated with Stickler syndrome, associated only with ocular disease in congenital toxoplasmosis. Experimental studies showed that both ABCA4 and COL2A1 show isoform-specific epigenetic modifications consistent with imprinting, which provided an explanation for the patterns of inheritance observed. These genetic and epigenetic risk factors provide unique insight into molecular pathways in the pathogenesis of disease.

Why prevent, diagnose and treat congenital toxoplasmosis?

Evidence that prevention, diagnosis and treatment of toxoplasmosis is beneficial developed as follows: anti-parasitic agents abrogate Toxoplasma gondiitachyzoite growth, preventing destruction of infected, cultured, mammalian cells and cure active infections in experimental animals, including primates. They treat active infections in persons who are immune-compromised, limit destruction of retina by replicating parasites and thereby treat ocular toxoplasmosis and treat active infection in the fetus and infant. Outcomes of untreated congenital toxoplasmosis include adverse ocular and neurologic sequelae described in different countries and decades. Better outcomes are associated with treatment of infected infants throughout their first year of life. Shorter intervals between diagnosis and treatment in utero improve outcomes. A French approach for diagnosis and treatment of congenital toxoplasmosis in the fetus and infant can prevent toxoplasmosis and limit adverse sequelae. In addition, new data demonstrate that this French approach results in favorable outcomes with some early gestation infections. A standardized approach to diagnosis and treatment during gestation has not yet been applied generally in the USA. Nonetheless, a small, similar experience confirms that this French approach is feasible, safe, and results in favorable outcomes in the National Collaborative Chicago-based Congenital Toxoplasmosis Study cohort. Prompt diagnosis, prevention and treatment reduce adverse sequelae of congenital toxoplasmosis.