Toxoplasmosis is a zoonosis caused by the parasite Toxoplasma gondii, an obligate intracellular parasite which infects both birds and mammals, including felines. Infection may cause no obvious symptoms in adults, but may be serious in pregnant women. Serology testing is the primary diagnostic method; acute and convalescent antibody testing is recommended to confirm the presence of disease.
Quick Answers for Clinicians
Diagnosis
Indications for Testing
- Suspected exposure in pregnant female
- Undiagnosed flulike illness in immunocompromised patient
Laboratory Testing
- Serology
- Primary diagnostic method; recommend paired acute and convalescent antibody testing to confirm presence of disease
- Pregnancy
- IgG, IgM antibodies in pregnant women – caution should be exercised in use of IgM antibody levels due to lack of specificity in prenatal screening
- Positive results in pregnant patients must be confirmed positive by a reference laboratory that specializes in toxoplasmosis
- CDC recommends the Toxoplasma Serology Laboratory at Palo Alto Medical Foundation
- If positive at reference lab, testing should be evaluated by amniocentesis and polymerase chain reaction (PCR) testing for Toxoplasma gondii
- See the Toxoplasmosis Serologic Testing Algorithm for test result interpretation or the CDC's toxoplasmosis information page for serology result interpretation
- As suggested by the CDC, any equivocal or positive result should be retested using a different test (eg, Sabin-Feldman IgG dye test, IgM enzyme-linked immunosorbent assay [ELISA], IgA ELISA, IgG ELISA, differential agglutination, avidity)
- IgG, IgM antibodies in pregnant women – caution should be exercised in use of IgM antibody levels due to lack of specificity in prenatal screening
- Suspected congenital toxoplasmosis – IgG and IgA by enzyme immunoassay (EIA)
- IgA more sensitive than IgM in congenitally infected infants
- No commercial test in the U.S. is cleared by the Food and Drug Administration (FDA) for in vitro diagnostic use in infants
- Specimens from neonates suspected of having congenital toxoplasmosis should be sent for testing by the Toxoplasma Serology Laboratory
- Neonate – PCR on amniotic fluid
- Immunocompromised – PCR
- Serological determination of active central nervous system (CNS) toxoplasmosis in immunocompromised patients is not possible at this time
- Toxoplasma-specific IgG antibody levels in AIDS patients are often low to moderate and occasionally undetectable
- Tests for IgM antibodies are generally negative
- Cerebrospinal fluid (CSF) exam
- Not frequently performed because of increased CNS pressure
- Elevated protein, variable glucose, mildly elevated white blood cell count with mononuclear predominance
- PCR for T. gondii may establish meningitis/encephalitis
Histology
- Definitive diagnosis may require biopsy and pathologist examination
- Useful immunohistochemical stain may include T. gondii stain
- For detailed descriptions, refer to ARUP’s Immunohistochemistry Stain Offerings
Imaging Studies
Computed tomography (CT)/magnetic resonance imaging (MRI) of the brain in patients presenting with encephalitis
Differential Diagnosis
- Flu-like presentation
- CNS disease
- Malignancy
- Primary CNS lymphoma
- Primary brain tumor
- Metastasis
- Viral/bacterial meningitis
- Encephalitis
- Demyelinating disease – multiple sclerosis
- Vasculitis
- Multifocal infarct
- Arteriovenous malformation
- Malignancy
- Congenital disease
- Cytomegalovirus
- Herpes simplex virus
- Rubella
- Treponema pallidum
- Parvovirus B19
- Listeria monocytogenes
- Lymphocytic choriomeningitis
- Varicella-zoster virus
Background
Epidemiology
- Incidence
- 15-29% of U.S. population is seropositive for toxoplasmosis
- Hot, arid climates have a low incidence of toxoplasmosis
- Transmission
- Usually oral
- May occur via blood transfusion, organ transplant, or transplacentally from mother to infant
Risk Factors
- Immunocompromised status, including AIDS
- Ingestion of raw or undercooked meat
Clinical Presentation
- Nonimmunocompromised
- Usually mild or asymptomatic disease in adults
- Constitutional – prolonged fever, headache, lymph node enlargement, myalgias
- Gastrointestinal – hepatomegaly, hepatitis
- Pregnant females
- Most experience minimal symptoms
- If immunocompromised, reactivation may occur – presents risk to fetus (rare vertical transmission)
- Congenital
- Risk of infection varies with gestational age
- Symptoms range from asymptomatic to death
- In infected neonates – chorioretinitis, encephalomyelitis, developmental delay, seizures, diffuse intracranial calcifications
- Triad of chorioretinitis, hydrocephalus, brain calcification – highly suggestive of toxoplasmosis
- Immunocompromised
- Symptoms generally more severe
- HIV patients – most common presentation is encephalitis (altered mental status, headache, fever, focal neurologic deficits)
ARUP Laboratory Tests
First-line test for identifying visceral T. gondii infection
CDC suggests equivocal or positive results should be retested using a different assay from another reference laboratory specializing in toxoplasmosis testing (IgG dye test, IgM enzyme-linked immunosorbent assay [ELISA], reflex to avidity and/or other tests)
This test should not be used for blood donor screening, associated reentry protocols, or for screening human cell, tissues and cellular and tissue-based products (HCT/P)
Semi-Quantitative Chemiluminescent Immunoassay
Confirm toxoplasmosis infection in immunocompromised hosts as well as fetuses and newborns
May be used to confirm equivocal antibody testing
Qualitative Polymerase Chain Reaction
Limited utility for routine clinical use
Serology has low sensitivity for detecting central nervous system (CNS) toxoplasmosis
Qualitative Enzyme-Linked Immunosorbent Assay
Detect presence of IgM antibodies to T. gondii
For male patients or nonpregnant female patients with equivocal or positive results, polymerase chain reaction (PCR) may also be useful if a specimen can be collected from an affected body site
Semi-Quantitative Chemiluminescent Immunoassay
Detect prior exposure to T. gondii
This test should not be used for blood donor screening, associated reentry protocols, or for screening human cell, tissues and cellular and tissue-based products (HCT/P)
Semi-quantitative Chemiluminescent Immunoassay
Use only in neonates for cases of suspected congenital toxoplasmosis
Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Not recommended for diagnosing congenital infections in newborns; tests should be selected individually to target the most likely infectious agents
May be used in pregnant women to assess past exposure or immunization to Toxoplasma, rubella, cytomegalovirus (CMV), and herpes simplex virus (HSV)
Semi-Quantitative Chemiluminescent Immunoassay
Not recommended for diagnosing congenital infections in newborns; tests should be selected individually to target the most likely infectious agents
Semi-Quantitative Chemiluminescent Immunoassay/Semi-Quantitative Enzyme-Linked Immunosorbent Assay
Aid in histological diagnosis of T. gondii
Stained and returned to client pathologist; consultation available if needed
Immunohistochemistry
Medical Experts
Couturier

Hillyard

References
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Neu N, Duchon J, Zachariah P. TORCH infections. Clin Perinatol. 2015;42(1):77-103.
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CDC - Parasites - Toxoplasmosis (Toxoplasma infection)
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Parasites - toxoplasmosis (Toxoplasma infection). [Last updated: Apr 2017; Accessed: Sep 2017]