Toxoplasma gondii - Toxoplasmosis | Choose the Right Test

Toxoplasmosis, which results from infection with Toxoplasma gondii, causes more deaths in the United States than any other foodborne illness. Although toxoplasmosis is usually asymptomatic or mild (presenting with flu-like symptoms) in immunocompetent individuals, it may be serious in individuals with compromised immune systems, in pregnant individuals, and in infants infected congenitally. T. gondii is usually transmitted by the consumption of undercooked meat or accidental ingestion of cat feces (eg, while cleaning a litter box). Human-to-human transmission can occur congenitally from mother to fetus or, in rare instances, from blood transfusion or organ transplantation. Laboratory testing includes serology and molecular tests, and confirmatory testing generally must be performed by a specialized reference lab.

Quick Answers for Clinicians

How should positive Toxoplasma gondii immunoglobulin M antibody tests be interpreted?

Assays for immunoglobulin M (IgM) antibodies to Toxoplasma gondii lack specificity, which can result in false-positive serologic results, complicating the diagnosis of toxoplasmosis. Two specific situations suggest the possibility of false-positive results:

Positive IgM and negative IgG: This result is highly suspect but is possible soon after infection, before IgG antibodies have had a chance to form. A second specimen should be collected 2 weeks after the first specimen and both specimens should be tested (the first specimen should be retested).
Positive IgM and positive IgG: A second specimen should be collected and both specimens should be submitted to a reference lab that uses a different method from that used for the first test for detecting IgM antibodies.

Does the diagnosis of toxoplasmosis require specialized testing?

Results of Toxoplasma gondii serology assays may be difficult to interpret correctly, and some tests (eg, immunoglobulin A [IgA] antibodies to T. gondii) are not commercially available. Initial serologic tests for both IgG and IgM antibodies are available through many labs, but clinicians should consider seeking confirmation testing through the Palo Alto Medical Foundation Toxoplasma Serology Laboratory, the reference laboratory for the CDC and U.S. Food and Drug Administration (FDA). Specialized testing at this laboratory includes IgA serology testing, IgE serology testing, IgG dye testing, IgG avidity testing, and differential agglutination testing.

Is universal screening for toxoplasmosis recommended for pregnant individuals in the United States?

No. Prenatal screening for toxoplasmosis presents many challenges, including low seroprevalence, a lack of standardization among diagnostic serologic tests, a low incidence of acute infection, and a high testing cost. Therefore, prenatal screening for toxoplasmosis in the United States should be limited to pregnant individuals who have HIV or are immunosuppressed.

Indications for Testing

Testing for toxoplasmosis should be considered in the following vulnerable groups:

Pregnant individuals who are either immunocompromised or immunosuppressed, or who have symptoms of acute toxoplasmosis (ie, flu-like symptoms and blurred vision or photophobia)
Immunocompromised individuals with symptoms of acute toxoplasmosis or reactivated disease (specifically, focal encephalitis that causes confusion, headache, motor weakness, and/or seizures)
Neonates whose mothers experienced acute T. gondii infection during pregnancy

Laboratory Testing

Serology

Serology, using either indirect fluorescent antibody (IFA) tests or enzyme immunoassays (EIAs) such as enzyme-linked immunosorbent assays (ELISAs), is the most common diagnostic testing for toxoplasmosis. Both immunoglobulin G (IgG) antibodies, which indicate a past infection, and IgM antibodies, which indicate a more recent infection, may be assessed. Interpretation of IgM results may be complicated because IgM antibodies lack specificity and may be detected up to 18 months after infection.

If initial testing is not conclusive, additional testing (eg, IgA serology testing, IgE serology testing, IgG dye testing, IgG avidity testing, and differential agglutination testing) should be pursued at a specialized reference lab.

Serologic Test Interpretation for Patients >1 Yr of Age
Test Results		Possible Interpretations	Next Steps
IgG	IgM	Possible Interpretations	Next Steps
Negative	Negative	No infection	None
Negative	Positive	Possible acute infection False-positive IgM	Retest for both IgG and IgM antibodies on both the original and a second specimen If the result is the same, infection is unlikely
Negative	Equivocal	Possible early acute infection False-positive IgM	Retest for both IgG and IgM antibodies on a second specimen If the result is the same, infection is unlikely
Positive	Negative	Infected for ≥6 mos	None for the general population If patient is pregnant and gestation is ≥18 weeks, additional testing should be pursued^a
Positive	Positive	Possible infection in previous 12 mos False-positive IgM	Send specimen to specialized reference lab for further testing If patient is pregnant, perform IgG avidity test^a
Positive	Equivocal	Infected for >1 yr False-positive IgM	Retest for IgM on a second specimen If result is the same, send both specimens to specialized reference lab for additional testing
Equivocal	Negative	Indeterminate	Retest for IgG on either the same specimen or a second specimen
Equivocal	Positive	Possible acute infection	Retest for IgG and IgM on second specimen If the results are the same or if IgG is positive, send both specimens to specialized reference lab for additional testing
Equivocal	Equivocal	Indeterminate	Retest for IgG and IgM on second specimen
^aFor more information, see the Toxoplasmosis Serologic Testing for Pregnant Individuals algorithm. Source: CDC; Montoya, 2008

Pregnant Individuals

If a pregnant individual tests positive for both IgG and IgM antibodies, an IgG avidity test should be performed to help differentiate between acute and past infection. If performed within the first 12-16 weeks of pregnancy, the results should be interpreted as follows:

High IgG avidity rules out T. gondii infection acquired during pregnancy.
Low IgG avidity does not rule out T. gondii infection acquired during pregnancy, but does not necessarily indicate recent infection.

If a pregnant patient with suspected toxoplasmosis has low IgG titers, a second sample may be tested 2-3 weeks later. An increase in antibody titer suggests acute infection.

If initial testing is not conclusive, samples should be sent to a specialized reference lab for further assessment. For more information about interpreting serologic tests during pregnancy, see the Toxoplasmosis Serologic Testing for Pregnant Individuals algorithm.

Neonates

When congenital toxoplasmosis is suspected in neonates, IgA antibody levels should be assessed, in addition to IgM levels, because IgA antibody testing is more sensitive than IgM antibody testing in infants. Because there are no FDA-approved commercial assays for IgA antibodies, testing should be performed at a specialized reference lab.

Immunocompromised Individuals

Serologic testing is not always reliable in immunocompromised individuals; therefore, test results should be considered in the context of clinical presentation and other testing performed (eg, polymerase chain reaction [PCR]). In patients with AIDS, for example, IgG antibodies are occasionally negative, and IgM antibodies are usually negative.

Nucleic Acid Detection

PCR testing of amniotic fluid may be useful in diagnosing congenital T. gondii infection.

PCR testing may also be useful in immunocompromised patients to assist in diagnosis, alongside serology and clinical presentation. However, a negative result does not rule out infection. In patients with HIV, PCR testing of cerebrospinal fluid (CSF) may be considered to diagnose toxoplasmic encephalitis, which is caused by reactivated T. gondii infection, although the utility of this test is limited by low sensitivity.

Immunohistochemistry

Immunohistochemistry (IHC) may also be used to diagnose T. gondii infection, although the use of IHC is limited because it may be difficult to obtain an appropriate specimen.