Mrs. M. is diagnosed with acute toxoplasmosis. Her doctor provides counselling for her and her husband. She's prescribed spiramycin to prevent further transmission to the fetus. An amniocentesis is scheduled to determine whether or not the baby has been infected.

Making the case
Toxoplasmosis is caused by the protozoan Toxoplasma gondii. It's one of the world's most common parasitic infections. On average, one-third of Canadians carry this bug, and in some regions of Europe and South America, prevalence rates can reach as high as 90%. Fortunately, in healthy adults, the parasite is rapidly controlled by the host immune system, and most infected individuals experience only subclinical or mild disease. The protozoan forms tissue cysts throughout the body, however, which can remain latent for years.

Fetus at risk
The parasite can be transmitted to the developing fetus when infection is acquired during pregnancy. In utero complications include hydrocephalus, intracranial calcification, retinochoroiditis and psychomotor retardation. Stillbirth or spontaneous abortion may also result.

It's worth mentioning that there's an inverse relationship between the rate and timing of transmission to the fetus and the severity of disease manifestations. For instance, transmission across the placenta is rare if the mother is infected shortly before or in the few weeks following conception, but the fetus has a much greater risk of developing serious complications. Conversely, the parasite has a higher chance of crossing the placenta when acquired later in pregnancy, but complications are much less common. Infants infected during the third trimester are typically born without any signs or symptoms. These children are at high risk, though, for developing complications later in life and should be treated and monitored closely. Women who are already infected with T. gondii before they become pregnant rarely, if ever, transmit the parasite to the fetus.

Reactivated infection
Toxoplasmosis is a serious opportunistic infection in immunocompromised individuals, causing ocular toxoplasmosis, encephalitis and other central nervous system disorders that can be fatal.

T. gondii is one of many protozoans capable of establishing long-term, chronic, asymptomatic infection. If an infected individual becomes immunosuppressed, then tissue cysts - in the brain, heart and skeletal muscle - can release parasites that cause clinical symptoms.

Sources of transmission
The most common route to infection is eating raw or undercooked meat containing tissue cysts. They can be found in various meats due to the parasite's versatility in host distribution, including beef, lamb and goat, but generally not poultry. Another possible source of infection is oocysts that are shed in the feces of both domestic and wild cats. These contaminate water, sand boxes and vegetable gardens.

Red flags
Acute infection with T. gondii is completely asymptomatic in most immunocompetent individuals, including pregnant women.

In 10% of cases, however, it presents as a short, self-limiting illness with nonspecific symptoms, such as lymphadeno­pathy (cervical or occipital), fever, malaise or fatigue. On the very rare occasion, a severe disseminated disease can occur in normal hosts causing hepatitis, myocarditis, polymyositis or pneumonitis.

Diagnostic tests
Because infection is usually asymptomatic, screening is important for pregnant women. Initial screening usually consists of detection of T. gondii-specific IgM and IgG antibodies in serum. Long-established infections are generally not a threat to the fetus, but distinguishing between recent and more distantly acquired infection can be challenging.

Isolated IgM antibodies (IgM+, IgG-) are usually indicative of infection within the last few weeks, whereas isolated IgG (IgM-, IgG+) suggests an exposure more than 3 months earlier. Unfortunately, IgM antibodies can persist at low levels for prolonged periods in some people, and double-positive tests (IgM+, IgG+) are difficult to interpret. In this case, additional investigations are often required. The IgG avidity assay is most commonly used for this purpose, as the development of high avidity antibodies typically takes several months to occur. A high avidity index argues strongly against the possibility of a recent infection and can prevent unnecessary treatment, follow-up and worry.

If the mother was infected at or during pregnancy, molecular tools can provide a definitive diagnosis of fetal toxoplasmosis in utero. Polymerase chain reaction (PCR) of amniotic fluid is the method of choice and is usually performed in combination with ultrasound imaging of the fetus.

Treatment
In recent infections in pregnancy, spiramycin is usually given to reduce the chances of transmission to the fetus. If fetal infection is confirmed, treat the mother with alternating regimens of pyrimethamine/sulfadiazine/folinic acid and spiramycin. However, take note that pyrimethamine is not recommended in the first 16 weeks of pregnancy due to possible teratogenicity.

Congenitally infected infants must be prescribed pyrimethamine/sulfadiazine/folinic acid for the first 6-12 months of life to limit the risk of late complications. For specific dosing and duration recommendations, see Montoya and Liesenfeld (Lancet 2004;363[9425]: 1965-76).

Normally, in immunocompetent non-pregnant individuals don't need treatment. For symptomatic disease, though, a combination of pyrimethamine and a sulfonamide such as sulfadiazine is usually prescribed. Add folinic acid supplements to prevent bone marrow suppression. Trimethoprim-sulfamethoxazole is sometimes used as long-term suppression or prophylaxis in immunocompromised people and to treat recurrent chorioretinitis and AIDS-associated Toxoplasma encephalitis. For those who can't tolerate sulfona­mide, either clindamycin or atovaquone can be substituted.