Вроджений токсоплазмоз

Congenital toxoplasmosis is almost exclusively due to a primary maternal infection during pregnancy; however, there are exceptions, including reinfection with a new serotype of T. gondii or reactivation of toxoplasmosis in mothers with severe cell-mediated immunodeficiencies. Infection with T. gondii occurs primarily from ingestion of inadequately cooked meat containing cysts or from ingestion of oocysts derived from food or water contaminated with cat feces.

The rate of transmission to the fetus is higher in women infected later during pregnancy. However, fetuses infected earlier in gestation generally have more severe disease. Overall, 30 to 40% of women infected during pregnancy will have a congenitally infected child.

Pregnant women infected with T. gondii generally do not have clinical manifestations, but some may have a mild mononucleosis-like syndrome, regional lymphadenopathy, or occasionally chorioretinitis. Similarly, infected neonates are usually asymptomatic at birth, but manifestations may include

• Prematurity

• Intrauterine growth restriction

• Jaundice

• Hepatosplenomegaly

• Myocarditis

• Pneumonitis

• Various rashes

Neurologic involvement, often prominent, includes chorioretinitis, hydrocephalus, intracranial calcifications, microcephaly, and seizures. The classic triad of findings consists of chorioretinitis, hydrocephalus, and intracranial calcifications. Neurologic and ophthalmologic sequelae may be delayed for years or decades.

• Serial IgG measurement (for maternal infection)

• Amniotic fluid polymerase chain reaction (PCR) testing (for fetal infection)

• Serologic testing, brain imaging, cerebrospinal fluid (CSF) analysis, ophthalmologic evaluation (for neonatal infection), and PCR testing of various body fluids or tissues

Serologic testing is important in diagnosing maternal and congenital infection.

Maternal infection should be suspected if women have one or more of the following:

• A mononucleosis-like syndrome and negative tests for Epstein-Barr virus, HIV, and cytomegalovirus (antibody or PCR)

• Isolated regional adenopathy not due to another cause (eg, HIV)

• Chorioretinitis

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 first year.

For fetal infection, PCR analysis of amniotic fluid is emerging as the diagnostic method of choice. There are numerous other serologic tests, some of which are done only in reference laboratories. The most reliable are the Sabin-Feldman dye test, the indirect immunofluorescent antibody (IFA) test, and the direct agglutination assay. Tests to isolate the organism include inoculation into mice and tissue culture, but these tests are not usually done because they are expensive, not highly sensitive, and can take weeks before yielding results.

For infants with suspected congenital toxoplasmosis, serologic tests, MRI or CT imaging of the brain, CSF analysis, brain stem auditory evoked responses, and a thorough eye examination by an ophthalmologist should be done. CSF abnormalities include xanthochromia, pleocytosis, and increased protein concentration. The placenta is inspected for characteristic signs of T. gondii infection (eg, placentitis). Nonspecific laboratory findings include thrombocytopenia, lymphocytosis, monocytosis, eosinophilia, and elevated transaminases. PCR testing of body fluids, including CSF, and tissues (placenta) can also be done to confirm infection.

Вроджений токсоплазмоз

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By permission of the publisher. From Demmler G: Congenital and perinatal infections. In Atlas of Infectious Diseases: Pediatric Infectious Diseases. Edited by CM Wilfert. Philadelphia, Current Medicine, 1998.

Some states in the US do routine newborn screening to detect specific toxoplasmosis IgM antibody using dried blood.

Some children have a fulminant course with early death, whereas others have long-term neurologic sequelae. Occasionally, neurologic manifestations (eg, chorioretinitis, intellectual disability, 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.

The severity of infection may correlate with parasite burden in amniotic fluid measured by PCR testing (1).

• Sometimes spiramycin for pregnant women

• Pyrimethamine, sulfadiazine, and leucovorin

Limited data suggest that treatment of infected women during pregnancy may be beneficial to the fetus (1). Spiramycin (available in the US with special permission from the U.S. Food and Drug Administration [FDA]) has been used to prevent maternofetal transmission but does not provide treatment to the fetus. A recent retrospective review suggests that the addition of trimethoprim/sulfamethoxazole may increase the effectiveness of transmission prevention (2). 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 is begun with oral pyrimethamine (initial loading dose of 2 mg/kg once a day for 2 days followed by 1 mg/kg once a day, maximum 25 mg) and oral leucovorin (10 mg 3 times a week). Oral sulfadiazine (50 mg/kg 2 times a day, maximum 4 g) is begun after neonatal jaundice has resolved. After the initial 6 months of treatment, sulfadiazine and leucovorin are continued at the same dose, but pyrimethamine is given less frequently (only on Monday, Wednesday, and Friday). This regimen is continued for at least 6 more months. All treatment should be overseen by an expert. The use of corticosteroids is controversial and should be determined case by case but may be considered for active chorioretinitis or if CSF protein is > 1 gm/dL.

Pregnant women should be counseled to avoid contact with cat litter boxes and other areas contaminated with cat feces. Because oocysts require > 24 hours after excretion to become infectious, conscientiously changing the entire litter box on a daily basis while wearing gloves followed by careful handwashing should reduce infection by this route if other members of the household cannot handle litter box chores.

Meat should be thoroughly cooked before consumption by pregnant women. Fruits and vegetables should be washed thoroughly or peeled, and all food preparation should be followed immediately by handwashing.

Women at risk of primary infection (eg, those frequently exposed to cat feces) should be screened during pregnancy. Women infected during the 1st or 2nd trimester should be counseled regarding available treatments.