Toxoplasmosis, Congenital

Congenital toxoplasmosis is caused by transplacental acquisition of Toxoplasma gondii. Signs, if present, are prematurity, intrauterine growth restriction, jaundice, hepatosplenomegaly, myocarditis, pneumonitis, rash, chorioretinitis, hydrocephalus, intracranial calcifications, microcephaly, and seizures. Diagnosis is by serology. Treatment is with pyrimethamine, sulfadiazine, and leucovorin.

Toxoplasma gondii, a parasite found worldwide, causes congenital infection in about 1/10,000 to 80/10,000 births.

Etiology

With rare exception, congenital toxoplasmosis is due to a primary maternal infection during pregnancy. Infection with T. gondii occurs primarily from ingestion of inadequately cooked meat containing cysts, or ingestion of oocysts derived from cat feces. The rate of transmission to the fetus is higher in women infected later during pregnancy. However, those infected earlier in gestation generally have more severe disease. Overall, 30 to 40% of women infected during pregnancy will have a congenitally infected child.

Symptoms and Signs

Pregnant women infected with T. gondii generally do not have clinical manifestations. Similarly, infected neonates are usually asymptomatic at birth, but manifestations may include prematurity, intrauterine growth restriction, jaundice, hepatosplenomegaly, myocarditis, pneumonitis, and various rashes. Neurologic involvement, often prominent, includes chorioretinitis, hydrocephalus, intracranial calcifications, microcephaly, and seizures.

Diagnosis

Serology is important in diagnosing maternal and congenital infection; there are numerous tests, some of which are performed only in reference laboratories. The most reliable are the Sabin-Feldman dye test, the indirect fluorescent antibody (IFA) test, and the direct agglutination assay. Acute maternal infection is suggested by seroconversion or a  4-fold rise between acute and convalescent IgG titers. However, maternal IgG antibodies may be detectable in the infant through the 1st year. PCR analysis of fetal blood and amniotic fluid may prove a better method. Tests to isolate the organism include inoculation into mice and tissue culture.

In suspected congenital toxoplasmosis, serologic tests, MRI or CT imaging of the brain, CSF analysis, and a thorough eye examination by an ophthalmologist should be performed. CSF abnormalities include xanthochromia, pleocytosis, and increased protein concentration. The placenta is inspected for characteristic signs of T. gondii infection. Nonspecific laboratory findings include thrombocytopenia, lymphocytosis, monocytosis, eosinophilia, and elevated transaminases.

Prognosis and Treatment

Some have a fulminant course with early death, whereas others have long-term neurologic sequelae. Occasionally, neurologic manifestations (eg, chorioretinitis, mental retardation, deafness, seizures) develop years later in children who appeared normal at birth. Consequently, children with congenital toxoplasmosis should be closely monitored beyond the neonatal period.

Limited data suggest that treatment of infected women during pregnancy may be beneficial to the fetus.  Spiramycin (available in the US from the FDA) has been used to prevent maternofetal transmission.  Pyrimethamine and sulfonamides have been used later in gestation to treat the infected fetus.

Treatment of symptomatic and asymptomatic neonates may improve outcome. Therefore, treatment with Pyrimethamine (initial loading dose of 2 mg/kg po once/day for 2 days followed by 1 mg/kg po once/day, maximum 25 mg, sulfadiazine (42.5 to 50 mg/kg po bid, maximum 4 g), and leucovorin (10 mg po 3 times/wk) is recommended. After the initial 6 mo of treatment, sulfadiazine and leucovorin are continued as previously but the pyrimethamine is administered less frequently (only on Mon-Wed-Fri).  All treatment should be monitored by an expert.  The use of corticosteroids is controversial and should be determined case by case.

Prevention

Pregnant women should avoid contact with cat litter boxes and other areas contaminated with cat feces. Meat should be thoroughly cooked before consumption, and hands should be washed after handling raw meat or unwashed produce. Women at risk for primary infection should be screened during pregnancy. Those infected during the 1st or 2nd trimester should be counseled regarding available treatments.

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