Initial clinical evaluation of the newborn/infant with suspected congenital toxoplasmosis

Test	Comment
Clinical evaluations
Complete physical examination	Fever, jaundice, hepatosplenomegaly, and lymphadenopathy are common findings in symptomatic infants (but the examination is normal in most cases)
Detailed neurologic examination	Evaluate for abnormal motor tone and/or delayed milestones
Eye examination by ophthalmologist experienced in retinal examinations in newborn and young infants	Chorioretinitis may be the only manifestation
Auditory brainstem response	Routine newborn hearing screening is performed in many regions (including the United States); however, diagnostic ABR testing may be preferred, especially for infants with symptomatic disease, since this test is more sensitive than the automated tests used in screening protocols
Lumbar puncture
CSF glucose, protein, cell count	CSF abnormalities may be the only manifestation; CSF protein may be >1 g/dL in severely affected infants but is typically lower in mild or subclinical disease
Toxoplasma-specific PCR*^¶	Performed when there is a strong suspicion for congenital toxoplasma infection; can establish the diagnosis
Neuroimaging^Δ	Intracranial calcifications or hydrocephalus may be the only formation
Serology^¶ (performed in conjunction with maternal serology)
Toxoplasma-specific IgG	Does not differentiate maternal from infant infection in the newborn period
Toxoplasma-specific IgM (ELISA or ISAGA)^¶	Indicative of congenital infection if not contaminated with maternal blood; if there is concern for false-positive due to contamination of infant's blood with maternal blood during labor, the test should be repeated at least 5 days after birth False-positive test results can be caused by blood product transfusion; test should be repeated at least 7 days after last transfusion Negative IgM does not exclude congenital toxoplasmosis^◊
Toxoplasma-specific IgA (ELISA or ISAGA)^¶	Especially useful if IgG and IgM assays are indeterminate Indicative of congenital infection if not contaminated with maternal blood; if there is concern for false-positive due to contamination of infant's blood with maternal blood during labor, the test should be repeated at least 10 days after birth False-positive test results can be caused by blood product transfusion; test should be repeated at least 7 days after last transfusion
Blood tests (primarily performed before initiating treatment in confirmed or suspected cases)
CBC with differential and platelet count	Anemia and thrombocytopenia are common in symptomatic infants; also necessary to establish baseline before treatment, which may cause bone marrow suppression
Evaluation for G6PD deficiency (before initiation of treatment)	Treatment with sulfadiazine may cause hemolysis in G6PD-deficient children
Liver function tests (aspartate aminotransferase, alanine aminotransferase, total and direct bilirubin)	Primarily for baseline studies before initiating treatment; both direct and cholestatic jaundice may occur in infected infants
Serum creatinine and urinalysis (before initiation of treatment)	Sulfadiazine (or sulfamerazine or sulfamethazine) dosing requires adjustment in patients with renal insufficiency
Testing for other infections
Urine for CMV and other congenital infections as appropriate based on maternal exposure (eg, Zika)^§	To exclude other congenital infections which may have similar clinical manifestations; coinfection with cytomegalovirus and toxoplasmosis may occur

ABR: auditory brainstem response; CT: computed tomography; CMV: cytomegalovirus; CSF: cerebrospinal fluid; PCR: polymerase chain reaction; IgG: immunoglobulin G; ELISA: enzyme-linked immunosorbent assay; IgM: immunoglobulin M; IgA: immunoglobulin A; ISAGA: immunosorbent agglutination assay; CBC: complete blood count; G6PD: glucose-6-phosphate-dehydrogenase; MRI: magnetic resonance imaging.
* Blood and urine Toxoplasma PCR may also be useful.
¶ Testing should be performed or confirmed in a reference laboratory (eg, the Toxoplasmosis Serology Laboratory at the Palo Alto Medical Foundation Research Institute -- www.pamf.org/serology; the WHO/FAO International Centre for Research and Reference on Toxoplasmosis, Staten Serum Institute, Copenhagen, Denmark; the Toxoplasma Reference Laboratory, Public Health Laboratory, Singleton Hospital, Swansea, United Kingdom).
Δ CT is generally the preferred modality for neuroimaging because it has a high sensitivity for detection of calcifications and it readily detects other structural abnormalities (eg, ventriculomegaly and hydrocephalus). Head ultrasonography can detect ventriculomegaly and hydrocephalus but does not detect calcification well. Ultrasonography has been used in regions where the rate of symptomatic congenital toxoplasmosis is very low compared with the United States (ie, mainly in Europe). MRI is a reasonable option for initial evaluation because it obviates the risk of radiation associated with CT.
◊ If maternal serologic titers were suggestive of an acute primary infection acquired late in gestation, initially negative Toxoplasma IgM and IgA results at birth may be attributable to delayed antibody production; repeat testing 2 to 4 weeks after birth and every 4 weeks thereafter until 3 months of age may be warranted in such cases.
§ For the approach testing for congenital CMV, Zika virus, and other congenital infections, refer to separate UpToDate content.

Adapted from:

Maldonado YA, Read JS, COMMITTEE ON INFECTIOUS DISEASES. Diagnosis, Treatment, and Prevention of Congenital Toxoplasmosis in the United States. Pediatrics 2017; 139.
Remington JS, McLeod R, Wilson CB, Desmonts G. Toxoplasmosis. In: Infectious Diseases of the Fetus and Newborn Infant, 7th ed, Remington JS, Klein JO, Wilson CB, et al (Eds), Elsevier Saunders, Philadelphia 2011. p.918.

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Initial clinical evaluation of the newborn/infant with suspected congenital toxoplasmosis