Toxoplasma gondii
2024 Case Definition

Clinical Criteria

In the absence of another more likely etiology, a fetus or liveborn child with one or more of the following clinical findings:

• Retinochoroiditis,
• Hydrocephalus, or
• Intracranial calcifications.¹

¹These 3 clinical findings (retinochoroiditis, hydrocephalus, intracranial calcifications) make up the classical triad of congenital toxoplasmosis. Other clinical findings (e.g., ocular [amblyopia, cataract, nystagmus, optic nerve atrophy, strabismus, visual impairment], neurologic [cerebral spinal fluid pleocytosis or elevated protein or eosinophilia or hypoglycorrhachia, developmental delay, hypotonia, macrocephaly or microcephaly, palsies, sensorineural hearing loss, seizures, spasticity], additional signs [anemia, hepatitis, hepatic calcifications, hepatomegaly or splenomegaly or hepatosplenomegaly, myocarditis, preterm birth, rash, sepsis-like illness, thrombocytopenia], fetal ultrasound findings [ascites, echogenic bowel, hepatosplenomegaly, intrahepatic densities/calcifications, intrauterine growth retardation, placenta hyperdensities, placenta increased thickness]) can be seen with congenital toxoplasmosis but are not included in the public health case classification criteria (3).

Laboratory Criteria

Confirmatory Laboratory Evidence:

• Detection of Toxoplasma-specific IgG antibodies AND (Toxoplasma-specific IgM antibodies OR Toxoplasma-specific IgA antibodies)⁴ in blood, confirmed at a reference laboratory,² OR
• Persistence in Toxoplasma-specific IgG antibody titer beyond one year of age in a patient being followed since infancy for possible congenital toxoplasmosis, OR reappearance of Toxoplasma-specific IgG antibodies after period of undetectable levels in a child who recently completed treatment for congenital toxoplasmosis, OR
• Increase in Toxoplasma-specific IgG antibody titer during the first year of life, OR
• Detection of Toxoplasma DNA (by NAAT [e.g., PCR]) performed on any tissue or body fluid (including placental tissue or amniotic fluid from birthing parent), OR
• Visualization of Toxoplasma in any tissue or body fluid (including placental tissue or amniotic fluid from birthing parent), OR
• Detection of Toxoplasma antigen in any tissue by immunohistochemistry (including placental tissue from birthing parent), OR
• Isolation of Toxoplasma whole live parasite from any tissue or body fluid (including placental tissue or amniotic fluid from birthing parent)

Presumptive Laboratory Evidence:

• Detection of Toxoplasma-specific IgG antibodies AND (Toxoplasma-specific IgM antibodies OR Toxoplasma-specific IgA antibodies) in blood, not confirmed at a reference laboratory.²

Supportive Laboratory Evidence

• Detection of Toxoplasma-specific IgG antibodies in blood.⁵

Note: The categorical labels used here to stratify laboratory evidence are intended to support the standardization of case classifications for public health surveillance. The categorical labels should not be used to interpret the utility or validity of any laboratory test methodology.
²In the United States, the toxoplasmosis reference laboratory is the Palo Alto Medical Foundation: Dr. Jack S. Remington Laboratory for Specialty Diagnostics
⁴Detection of Toxoplasma-specific IgM antibodies before 5 days of age or detection of Toxoplasma-specific IgA before 10 days age could represent false-positive results due to the possibility of contamination of the infant’s blood with maternal blood because of materno-fetal blood leak (3). Other possible reasons for false-positive test results (e.g., blood product transfusion or IVIG transfusion) should also be considered (3). If mother had evidence of an acute primary toxoplasmosis infection acquired late in gestation, then initially negative Toxoplasma IgM and IgA results in the newborn at birth could be due to delayed production of those antibodies (3). Antenatal and postnatal treatment can also affect the serologic profile of the infant (3).
⁵Detection of Toxoplasma-specific IgG in the newborn may represent congenital infection or maternal antibodies transferred transplacentally (3).

Epidemiologic Linkage

Fetus or infant delivered to a pregnant person with evidence of Toxoplasma gondii infection or toxoplasmosis acquired or reactivated during current gestation or within 6 months prior to conception.

Suspect

• Meets congenital toxoplasmosis supportive laboratory evidence, OR
• In setting of fetal loss: meets congenital toxoplasmosis epidemiological linkage criteria.

Probable

• Meets congenital toxoplasmosis presumptive laboratory criteria AND (congenital toxoplasmosis epidemiologic linkage criteria OR congenital toxoplasmosis clinical criteria), OR
• Meets congenital toxoplasmosis clinical criteria AND congenital toxoplasmosis epidemiologic linkage criteria.

Confirmed

• Meets congenital toxoplasmosis confirmatory laboratory evidence.

Case Classification Comments

• The diagnosis of congenital toxoplasmosis after infancy is confounded by the small possibility of the child acquiring a toxoplasmosis infection postnatally (4).
• Clinical and laboratory evidence of congenital toxoplasmosis may evolve and take time to manifest throughout the infancy period.

Clinical Criteria

In the absence of another more likely etiology, a person with new onset of one or more of the following clinical signs or symptoms:

• Fever,
• Lymphadenopathy,
• Muscle ache,
• Joint ache,
• Fatigue,
• Headache,
• Pharyngitis,
• Hepatosplenomegaly,
• Diffuse non-pruritic maculopapular rash,
• Pneumonitis,
• Myocarditis,
• Pericarditis,
• Polymyositis,
• Hepatitis,
• Retinochoroiditis without evidence of a scar, or
• Encephalitis

Laboratory Criteria

Confirmatory Laboratory Evidence:

• Detection of Toxoplasma-specific IgM antibodies in blood, confirmed at a reference laboratory,² with laboratory evidence of acute pattern of infection,³ OR
• Detection of Toxoplasma DNA (by NAAT [e.g., PCR]) performed on any tissue or body fluid, OR
• Visualization of Toxoplasma in any tissue or body fluid, OR
• Detection of Toxoplasma antigen in any tissue by immunohistochemistry, OR
• Isolation of Toxoplasma whole live parasite from any tissue or body fluid, OR
• A fourfold or greater increase in Toxoplasma-specific IgG antibody titer in paired sera samples collected at least three weeks apart, OR
• Evidence of Toxoplasma-specific IgG antibody seroconversion over two sequential samples collected up to 12 weeks apart, or during current pregnancy for pregnant persons.

Presumptive Laboratory Evidence:

• Detection of Toxoplasma-specific IgG antibodies in blood.

Supportive Laboratory Evidence:

• Detection of Toxoplasma-specific IgM antibodies in blood, not confirmed at a reference laboratory.²

Note: The categorical labels used here to stratify laboratory evidence are intended to support the standardization of case classifications for public health surveillance. The categorical labels should not be used to interpret the utility or validity of any laboratory test methodology.
²In the United States, the toxoplasmosis reference laboratory is the Palo Alto Medical Foundation: Dr. Jack S. Remington Laboratory for Specialty Diagnostics
³This determination is made by the reference laboratory based on the results of additional Toxoplasma testing such as AC/HS differential agglutination, avidity, IgA and IgE.

Epidemiologic Linkage

Evidence of a shared exposure that is associated with at least one probable or confirmed case of active toxoplasmosis-primary infection.

Suspect

• Meets toxoplasmosis epidemiologic linkage criteria AND toxoplasmosis clinical criteria, OR
• Meets toxoplasmosis supportive laboratory evidence.

Probable

• Meets toxoplasmosis epidemiologic linkage criteria AND toxoplasmosis supportive laboratory evidence AND toxoplasmosis clinical criteria.

Confirmed

• Meets toxoplasmosis confirmatory laboratory evidence, OR
• Meets toxoplasmosis presumptive laboratory evidence.

Clinical Criteria

In the absence of another more likely etiology, a person with new onset of one or more of the following clinical signs or symptoms:

• Fever,
• Lymphadenopathy,
• Muscle ache,
• Joint ache,
• Fatigue,
• Headache,
• Pharyngitis,
• Hepatosplenomegaly,
• Diffuse non-pruritic maculopapular rash,
• Pneumonitis,
• Myocarditis,
• Pericarditis,
• Polymyositis,
• Hepatitis,
• Retinochoroiditis without evidence of a scar, or
• Encephalitis

Laboratory Criteria

Confirmatory Laboratory Evidence:

• Detection of Toxoplasma-specific IgM antibodies in blood, confirmed at a reference laboratory,² with laboratory evidence of acute pattern of infection,³ OR
• Detection of Toxoplasma DNA (by NAAT [e.g., PCR]) performed on any tissue or body fluid, OR
• Visualization of Toxoplasma in any tissue or body fluid, OR
• Detection of Toxoplasma antigen in any tissue by immunohistochemistry, OR
• Isolation of Toxoplasma whole live parasite from any tissue or body fluid, OR
• A fourfold or greater increase in Toxoplasma-specific IgG antibody titer in paired sera samples collected at least three weeks apart, OR
• Evidence of Toxoplasma-specific IgG antibody seroconversion over two sequential samples collected up to 12 weeks apart, or during current pregnancy for pregnant persons.

Presumptive Laboratory Evidence:

• Detection of Toxoplasma-specific IgG antibodies in blood.

Supportive Laboratory Evidence:

• Detection of Toxoplasma-specific IgM antibodies in blood, not confirmed at a reference laboratory.²

Note: The categorical labels used here to stratify laboratory evidence are intended to support the standardization of case classifications for public health surveillance. The categorical labels should not be used to interpret the utility or validity of any laboratory test methodology.
²In the United States, the toxoplasmosis reference laboratory is the Palo Alto Medical Foundation: Dr. Jack S. Remington Laboratory for Specialty Diagnostics
³This determination is made by the reference laboratory based on the results of additional Toxoplasma testing such as AC/HS differential agglutination, avidity, IgA and IgE.

Epidemiologic Linkage

Evidence of a shared exposure that is associated with at least one probable or confirmed case of active toxoplasmosis-primary infection.

Suspect

• Meets toxoplasmosis epidemiologic linkage criteria AND toxoplasmosis clinical criteria, OR
• Meets toxoplasmosis supportive laboratory evidence.

Probable

• Meets toxoplasmosis epidemiologic linkage criteria AND toxoplasmosis supportive laboratory evidence AND toxoplasmosis clinical criteria.

Confirmed

• Meets toxoplasmosis confirmatory laboratory evidence AND has no previous evidence of toxoplasmosis (such as a previous positive Toxoplasma-specific IgG or previous clinical diagnosis of toxoplasmosis).

Laboratory Criteria

Confirmatory Laboratory Evidence:

• Detection of Toxoplasma-specific IgM antibodies in blood, confirmed at a reference laboratory,² with laboratory evidence of acute pattern of infection,³ OR
• Detection of Toxoplasma DNA (by NAAT [e.g., PCR]) performed on any tissue or body fluid, OR
• Visualization of Toxoplasma in any tissue or body fluid, OR
• Detection of Toxoplasma antigen in any tissue by immunohistochemistry, OR
• Isolation of Toxoplasma whole live parasite from any tissue or body fluid, OR
• A fourfold or greater increase in Toxoplasma-specific IgG antibody titer in paired sera samples collected at least three weeks apart, OR
• Evidence of Toxoplasma-specific IgG antibody seroconversion over two sequential samples collected up to 12 weeks apart, or during current pregnancy for pregnant persons.

Presumptive Laboratory Evidence:

• Detection of Toxoplasma-specific IgG antibodies in blood.

Note: The categorical labels used here to stratify laboratory evidence are intended to support the standardization of case classifications for public health surveillance. The categorical labels should not be used to interpret the utility or validity of any laboratory test methodology.
²In the United States, the toxoplasmosis reference laboratory is the Palo Alto Medical Foundation: Dr. Jack S. Remington Laboratory for Specialty Diagnostics
³This determination is made by the reference laboratory based on the results of additional Toxoplasma testing such as AC/HS differential agglutination, avidity, IgA and IgE.

Probable

In the absence of another more likely etiology:

• Reactivation toxoplasmic encephalitis: Meets toxoplasmosis presumptive laboratory evidence AND toxoplasmosis clinical criteria of brain imaging that demonstrates typical toxoplasmic encephalitis radiographic appearance (e.g. ring-enhancing lesion[s]), AND has compatible clinical syndrome (e.g. headache, mental status changes or other neurologic symptoms) AND is immunocompromised AND criteria for probable active toxoplasmosis- primary infection are not already met, OR
• Reactivation ocular toxoplasmosis: A person with retinochoroiditis with evidence of a scar⁸, OR clinician diagnosis of new onset of recurrent toxoplasmosis ocular lesion.

Confirmed

• Meets toxoplasmosis confirmatory laboratory evidence AND has previous evidence of toxoplasmosis (such as a previous positive Toxoplasma-specific IgG, previous clinical diagnosis of toxoplasmosis, or clinician diagnosis of new onset of recurrent toxoplasmosis ocular lesion).

⁸This may appear as a single discrete, yellow-white focus of dense inflammatory material within and overlying the retina arising from the border of a scar. Findings of intraocular inflammation, such as transient elevation of intraocular pressure at onset of activity, cellular reactions in ocular fluids (aqueous humor, vitreous humor), or retinal vascular sheathing (anywhere in the fundus) would be further evidence of active disease.

Laboratory Criteria

Presumptive Laboratory Evidence:

• Detection of Toxoplasma-specific IgG antibodies in blood.

Note: The categorical labels used here to stratify laboratory evidence are intended to support the standardization of case classifications for public health surveillance. The categorical labels should not be used to interpret the utility or validity of any laboratory test methodology.

Confirmed

• Meets toxoplasmosis presumptive laboratory evidence AND
• Criteria for probable or confirmed active toxoplasmosis (primary infection or reactivation disease) or congenital toxoplasmosis are not already met.