What is the recommended method for testing for Toxoplasma (Toxoplasma) gondii infection?

Testing for Toxoplasma gondii Infection

Serologic testing is the primary method for diagnosing Toxoplasma gondii infection, with the specific approach depending on the clinical context—whether screening for congenital infection, evaluating acute infection in pregnancy, or diagnosing CNS toxoplasmosis in immunocompromised patients. 1

General Population and Pregnant Women

Initial Screening

• Test for both Toxoplasma IgG and IgM antibodies simultaneously in all HIV-infected pregnant women and when screening for toxoplasmosis 1
• For pregnant women, use a specialized reference laboratory capable of performing comprehensive serologic panels, as interpretation is often confusing and difficult 1

Acute Infection in Pregnancy

When both IgG and IgM are positive, the following additional tests are essential:

• Toxoplasma IgA antibody testing significantly improves diagnostic accuracy—75.3% of IgA-positive pregnant women have acute infection versus only 4.4% of IgA-negative women 1, 2
• IgG avidity testing is critical: high avidity reliably excludes acute infection acquired within the past 3-4 months (100% positive predictive value for chronic infection) 1, 3
• When both IgA and IgM are positive, 85.9% have acute infection compared to only 19.2% when IgM alone is positive 2

Congenital Toxoplasmosis in Newborns

Serologic Testing

• Test neonatal Toxoplasma IgG in parallel with maternal IgG to allow proper interpretation 1
• Toxoplasma-specific IgM (ISAGA method), IgA, or IgE in neonatal serum within the first 6 months of life confirms congenital infection 1
• IgA may be more sensitive than IgM or IgE for detecting congenital infection, though 20-30% of infected infants will still be missed by IgA or IgM assays in the neonatal period 1
• Persistence of IgG antibody beyond 12 months confirms congenital infection (maternal antibodies should disappear by this time) 1

Timing Considerations for Neonatal Testing

• Repeat positive IgM results at least 5 days after birth to avoid false positives from maternal blood contamination (IgM half-life is 5 days) 1
• Repeat positive IgA results at least 10 days after birth for the same reason (IgA half-life is 10 days) 1
• Repeat testing 2-4 weeks after birth and every 4 weeks until 3 months if maternal infection occurred very late in gestation and initial IgM/IgA are negative (delayed antibody production) 1

PCR Testing in Newborns

Perform Toxoplasma PCR on CSF, peripheral blood, and urine when there is strong suspicion of congenital toxoplasmosis 1

Specific indications for CSF PCR include:

• Infants with positive IgM ISAGA and/or IgA ELISA 1
• Infants born to mothers with confirmed acute infection who had positive amniotic fluid PCR or abnormal fetal ultrasound 1
• Infants born to mothers with confirmed infection in second or third trimester who did not receive antepartum treatment 1

CSF PCR can be deferred in asymptomatic infants whose mothers were diagnosed in first trimester, received spiramycin, had negative amniotic fluid PCR, normal fetal ultrasounds, and the infant has negative IgM ISAGA and IgA ELISA at birth 1

Additional Diagnostic Methods for Newborns

• Parasite isolation by mouse inoculation or tissue culture of CSF, urine, placental tissue, amniotic fluid, or infant blood 1
• Complete evaluation including ophthalmologic, auditory, and neurologic examinations; lumbar puncture; and head imaging (CT or MRI) to detect hydrocephalus or calcifications 1

CNS Toxoplasmosis in Immunocompromised Patients

Presumptive Diagnosis

Base presumptive CNS toxoplasmosis diagnosis on clinical symptoms, positive Toxoplasma IgG serology, and space-occupying lesions on brain imaging 1

Critical Caveat

• Negative serology does not exclude CNS toxoplasmosis—cases have been reported in persons without detectable Toxoplasma-specific IgG antibodies 1
• In HIV patients with brain mass and negative toxoplasma serology, proceed directly to brain biopsy rather than empiric therapy 4

Imaging Findings

• MRI is more sensitive than CT and will confirm basal ganglia lesions in the majority of patients 1
• CT typically shows multiple, bilateral, ring-enhancing lesions in basal ganglia and cerebral corticomedullary junction 1

Definitive Diagnosis

Brain biopsy provides histologic or cytologic confirmation and should be considered when early neurologic deterioration occurs despite empiric treatment or when patients fail to respond after 10-14 days 1

Screening Recommendations by Population

HIV-Infected Individuals

• All HIV-infected pregnant women should undergo serologic testing for Toxoplasma 1
• HIV-infected adolescents without history of previous infection should undergo serologic testing 1
• In the United States, routine screening of HIV-infected children whose mothers don't have toxoplasmosis is not recommended due to low prevalence 1
• In regions with high Toxoplasma incidence, consider serologic testing for HIV-infected children aged >12 months 1

Reference Laboratory Testing

Use specialized reference laboratories (such as Palo Alto Medical Foundation Toxoplasma Serology Laboratory) that can perform comprehensive panels including IgG dye test, IgM ISAGA, IgA ELISA, IgE testing, and AC/HS differential agglutination test—most of these are not available in non-reference laboratories 1