Congenital Toxoplasmosis
Lucila Marquez
Debra Palazzi
I. EPIDEMIOLOGY.
Toxoplasma gondii—an obligate, intracellular protozoan parasite— is an important human pathogen, especially for the fetus, newborn, and immunocompromised patient.
Transmission
The cat, the only definitive host, is usually asymptomatic. During acute infection, millions of oocysts are shed daily in the stool for 2 weeks or longer. Oocysts may remain viable in the soil for over 1 year in some climates. Other animals become infected by ingesting the oocysts resulting in tissue cysts containing viable organisms, predominately in muscle and brain.
Toxoplasma can be acquired through food, water, or soil contaminated with oocysts or through ingestion of cysts in undercooked meat. The meat products most often implicated include pork and lamb. Food products that have been implicated include mussels, produce such as raspberries, and unpasteurized milk.
Congenital infection can occur through transplacental transmission.
The prevalence of Toxoplasma antibody increases with age and varies by geographic location and population. Data from one area or population may not accurately be generalized to other areas or populations. Based on data from the National Health and Nutrition Examination Survey (NHANES), the seroprevalence in persons ages 12 to 49 in the United States is 15.8%. The reported prevalence of T. gondii antibodies in women of childbearing age ranges from 4% to 80% worldwide. Women without antibodies are at risk for acute toxoplasmosis during pregnancy.
Seroconversion during pregnancy also varies by geographic location. Rates range from 1.5% in France, a high prevalence country, to 0.17% in Norway, a low prevalence country. The National Collaborative Perinatal Project (National Institutes of Health) estimated the rate at 1.1 in 1,000 in the United States.
The reported incidence of congenital toxoplasmosis in the United States has decreased during the last 20 years, from a high of 20 in 10,000 to 1 in 10,000. In the United States, an estimated 500 to 5,000 infants are born each year with congenital toxoplasmosis.
II. PATHOPHYSIOLOGY
Normal children and adults are susceptible to acute infection if they lack specific antibody to the organism. Both humoral and cell-mediated immunity are important in the control of infection. Transmission usually occurs by direct ingestion
of oocysts or ingestion of the cysts in undercooked meat. After acute parasitemia, the organism forms tissue cysts, which probably persist for life in multiple organs including muscle and brain. Usually, these are of little consequence to the normal host, but progressive, localized, or reactivated disease may occur.
Human congenital infection
Placental pathology suggests that parasites from the maternal circulation invade and multiply within placental cells before reaching the fetal circulation. This delay in transmission from the placenta to the fetus, called the prenatal incubation period, ranges from under 4 weeks to over 16 weeks.
The risk of congenital infection increases with gestational age, occurring in 6% of infants whose mothers seroconvert at 13 weeks’ gestation and 72% at 36 weeks. The fetal disease severity, however, is inversely proportional to gestational age; 61% of infants will have clinical manifestations when seroconversion occurs at 13 weeks’ gestation in contrast to 9% at 36 weeks. Without prenatal therapy, most fetuses infected in the first trimester die in utero or in the neonatal period or have severe central nervous system (CNS) and ophthalmologic disease. Conversely, most fetuses infected in the second trimester, and almost all infants infected in the third trimester have mild or subclinical disease in the newborn period. Therefore, the period of highest risk for severe congenital disease is thought to be between 10 and 24 weeks.
Congenital infection due to serologic relapse in chronic maternal infection is extremely rare. Maternal immune dysfunction, including human immunodeficiency virus (HIV) infection, should be suspected if this occurs.
III. MATERNAL/FETAL INFECTION
Clinical manifestations
Maternal infection is asymptomatic in more than 90% of women. However, symptoms can include fatigue, painless lymphadenopathy, and chorioretinitis.
Fetal findings on ultrasound include hydrocephalus, brain and hepatic calcifications, hepatosplenomegaly, and ascites.
Diagnosis
Recommended maternal tests
Screening: Serum immunoglobulin G (IgG) and immunoglobulin M (IgM)
After infection, IgG is detectable in 1 to 2 weeks, peaks in 3 to 6 months, and persists at low titers for life. The Sabin-Feldman dye test is the most reliable IgG assay but available in only a few reference labs. Direct agglutination tests are accurate. Immunofluorescent assay (IFA) test and enzyme-linked immunosorbent assay (ELISA) are not consistently reliable. Indirect hemagglutination should not be used for screening pregnant women.
IgM appears within 2 weeks after infection, peaks at 1 month, and usually declines to undetectable levels within 6 to 9 months. However, IgM may persist for more than 1 year after initial infection and, thus, does not necessarily indicate an acute infection.
It is recommended that a Toxoplasma reference laboratory confirm all positive or equivocal IgM test results. The serologic tests discussed here are available as panels and are performed by the Toxoplasma Serology Laboratory at Palo Alto, California (available at: http://www.pamf.org/serology).
Confirmatory: IgG; IgM; immunoglobulin A (IgA); immunoglobulin E (IgE). A series of IgG tests can help differentiate acute vs. remote infection.
Avidity testing (IgG) may differentiate acute vs. remote infection. IgG antibodies produced early in infection have low avidity, but avidity increases over time. The presence of high-avidity antibodies indicates that infection occurred 12 to 16 weeks prior; thus, testing is useful in early pregnancy. The test has limitations, however, as slow maturation of this high-avidity response has been reported in pregnant women. This test is not commercially available in the United States.
Differential agglutination detects rising IgG titers. Rising titers indicate acute infection.
Differential agglutination test AC/HS compares IgG titers for sera against formalin (HS) vs. acetone (AC)-fixed tachyzoites. The AC preparation is recognized by antibodies early in infection.
Fetal testing
Ultrasound is recommended monthly in women suspected of having acute infection.
Amniotic fluid polymerase chain reaction (PCR) is recommended to diagnose fetal infection in cases where there is serologic evidence of acute infection, ultrasound evidence of fetal damage, or severe maternal immunocompromise. High parasite DNA levels can be found in cases in which infection occurred earlier in gestation or sequelae are more severe. A negative amniotic fluid PCR does not rule out fetal infection as the accuracy range is wide and parasite transmission from the mother to the fetus may be delayed. PCR sensitivity for the B1 gene is high (>90%) when maternal infection occurs between 17 to 21 weeks’ gestation, and is lower (29%—68%) before 17 weeks and after 21 weeks. In suspected or probable cases, antenatal maternal therapy to prevent or treat fetal infection should extend until delivery, even with a negative PCR result.
Treatment
Medications. Treatment should be instituted for mothers with acute infections and immunocompromised mothers with evidence of distant infection. In some studies, treatment has reduced fetal infection by 50%. Prompt treatment may prevent irreversible in utero retinal and brain damage.
Spiramycin (prophylaxis) can prevent placental transmission of Toxoplasma
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