I. EPIDEMIOLOGY. Toxoplasma gondii, an obligate, intracellular protozoan parasite, is an important human pathogen, especially for the fetus, newborn, and immunocompromised patient.

A. Transmission. T. gondii exists in three infectious forms: tachyzoite, tissue cysts containing bradyzoites, and oocysts containing sporozoites. The tachyzoite is the form responsible for symptoms during acute infection, whereas the tissue cyst is responsible for latent infection. The only definitive host of T. gondii is the cat. When infected, cats are usually asymptomatic. Intermediate hosts include all warm-blooded animals and humans. Tissue cysts form in the intermediate host, particularly in brain, eye, and muscle. The cysts are infectious. Cats are infected by ingesting cysts from an infected intermediate host, ultimately shedding oocysts from their intestinal lumen into the environment. Cats can shed up to 10 million oocysts a day for 20 to 24 days following initial infection. Sporulated oocysts remain infective in soil for up to 18 months. Other animals become infected by ingesting the oocysts resulting in tissue cysts containing viable organisms predominately in muscle and brain.

T. gondii infection can be acquired via ingestion of infected oocysts from the environment (contaminated food or water), ingestion of tissue
cysts from raw or undercooked meat (most common in developed world), or via transplacental transmission (congenital infection). Risk factors associated with acute infection in the United States include eating raw ground beef and lamb; eating locally produced, cured, dried, or smoked meat; working with meat; drinking unpasteurized goat’s milk; and having three or more kittens. Raw oysters and clams have also been associated with transmission. Untreated water has been reported to be the source of major outbreaks around the world. The prevalence of T. gondii varies broadly among different countries and geographic areas. The presence of serum antibodies to T. gondii increases with age. 22.5% of people ≥12 years of age in the United States have been infected with T. gondii.

The reported prevalence of T. gondii antibodies in women of childbearing age ranges from 10% 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. Incidence of maternal seroconversion during pregnancy in the United States is estimated at 0.2% to 1%. The rate of mother-to-child transmission in the United States is 50% to 60% for mothers not treated during pregnancy and 25% to 30% for those treated.

B. Incidence. The reported incidence of congenital toxoplasmosis in the United States has decreased during the last 20 years from a high of 20 per 10,000 to 1 per 10,000. In the United States, an estimated 500 to 5,000 infants are born each year with congenital toxoplasmosis.

A. Postnatal infection. 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. The majority of T. gondii infections in immunocompetent hosts are asymptomatic. Possible mild symptoms include lymphadenopathy, malaise, fever, and headache. More severe symptoms such as encephalitis, myocarditis, pneumonia, and hepatitis are less common. Chorioretinitis has also been reported in postnatally acquired cases. In immunocompetent hosts, infection with T. gondii imparts lifelong immunity.

B. Congenital infection. Congenital infection is most commonly secondary to acute maternal infection during pregnancy and less commonly due to reactivation of previous infection in an immunocompromised mother. It should also be considered in women infected within 3 months prior to conception. Parasitemia in the mother leads to placental invasion by the parasite and subsequent passage into the fetal circulation and tissues resulting in fetal infection.

The risk of intrauterine infection increases with gestational age. One analysis demonstrated the risk of transmission to the fetus to be 6% at 13 weeks, 40% at 26 weeks, and 72% at 36 weeks. However, the effects on the fetus are more severe with maternal infection occurring earlier in pregnancy. Sixty-one percent of infants will have clinical manifestations
when seroconversion occurs at 13 weeks’ gestation in contrast to about 9% at 36 weeks. Infection early in pregnancy may result in intrauterine fetal demise and spontaneous abortion. Nearly all infants infected during the third trimester will be asymptomatic accounting for 67% to 80% of prenatally infected infants.

Immunocompetent women with prior toxoplasma infection are protected from transmitting infection to the fetus. Immunocompromised pregnant patients previously infected with T. gondii may transmit infection to the fetus if their immune system is unable to suppress the parasite (i.e., HIV infection, lymphoma, immunosuppressive therapy).

1. Maternal infection is asymptomatic in more than 90% of women. However, symptoms can include fatigue, painless lymphadenopathy, and chorioretinitis.

2. Fetal findings on ultrasound (US) include hydrocephalus, brain, splenic and hepatic calcifications, hepatosplenomegaly, and ascites.

i. Detection and quantification of antibodies in pregnant women can determine if and potentially when infection has occurred. Serology performed earlier in pregnancy (i.e., first trimester) is more helpful in determining if infection was acquired during pregnancy than serology drawn after 18 weeks’ gestation.

ii. Toxoplasma IgG and IgM: Initial testing can be done at a nonreference commercial lab. Negative results or positive IgG and negative IgM (old infection) should be reliable to rule out infection during current pregnancy if done before the third trimester. A positive or equivocal IgM should be confirmed at reference laboratory (Palo Alto Medical Foundation Toxoplasma Serology Laboratory. www.pamf.org/serology.

iii. IgM can be positive 2 weeks after infection and peaks in 1 month. It typically becomes negative within 6 to 9 months but can persist for more than a year. A reference lab can help determine if a patient with a positive IgM acquired infection recently or in the distant past.

b. Confirmatory testing of a positive or equivocal IgM test at a reference laboratory: IgG, IgM, IgA, and IgE A series of IgG tests can help differentiate acute versus remote infection.

i. Toxoplasma IgG avidity test used in conjunction with differential agglutination (AC/HS) test. High avidity antibodies develop at least 12 to 16 weeks after infection. If positive during the first months of pregnancy, they would indicate that infection
occurred prior to conception. AC/HS compares IgG titers for sera against formalin (HS) versus acetone (AC) fixed tachyzoites. AC antigens detect acute IgG antibodies formed only during the acute stage of infection.