1. Congenital Toxoplasmosis: Clinical Manifestations and Diagnosis
Andrew J Seier, MS4

2. Epidemiology
Estimated age-adjusted seroprevalence in the United States: 11% among women 15 to 44 years old
Up to 50% of acutely infected people do not recall identifiable risk factors or symptoms
Feline exposure
Undercooked meat (esp. pork, lamb, and venison)
Flu-like symptoms, with lymphadenopathy and myalgias for a month or more

3. Prevention
Consensus: low-risk, no good treatment options, do not screen
Society guidelines: screen once per trimester
High-risk: screen once every 3 weeks (SYROCOT, 2007)
Treatment after <3 weeks of seroconversion reduced mother-to-child transmission compared with treatment started after ≥8 weeks
Treatment initiated within 3-8 weeks after seroconversion showed a trend toward reduced maternal-to-child transmission

4. Prognosis Untreated infants with overt disease at birth
Poor prognosis. High risk of neonatal death, chorioretinitis, seizures, and severe psychomotor retardation.
Treated infants
Ocular prognosis usually is satisfactory, although as many as 30% develop late-onset chorioretinitis
Treatment may result in diminution or resolution of intracranial calcifications, consonant with improved neurological function

5. Severity vs. transmission risk
Severity of disease
Risk of transmission
Gestational age

6. The Classic Triad chorioretinitis calcifications hydrocephalus
All 3 findings together: rare, but highly suggestive

7. Other neonatal findings
Chorioretinitis
Eventually develops in >70% of untreated cases
And up to 30% of treated cases
microcephaly, seizures, hearing loss, strabismus, maculopapular rash, generalized lymphadenopathy, hepatomegaly, splenomegaly, jaundice, pneumonitis, diarrhea, hypothermia, anemia, petechiae, and thrombocytopenia

8. Maternal diagnostic testing
Gold-standard testing
Serologic: IgG (dye test), IgM (EIA)
Confirm with Toxoplasma PCR and/or biopsy immunoperoxidase staining (TSL-PAMFRI)
Timing: AC/HS test, avidity
EIA can detect IgM 2 weeks after infection
Kaleida chemistry lab
IgG and IgM via coated-well ELISA
Positive IgM confirmed with IFA

9. Neonatal Testing Gold-standard testing Kaleida chemistry lab
Serologic: IgG/IgM by ISAGA method, IgA (EIA)
Confirm with CSF, blood, and urine PCR
Sensitivity of above tests, combined, is 93%
CSF: elevated protein (sometimes >1 g/dL) or mononuclear CSF pleocytosis
Kaleida chemistry lab
IgG and IgM via coated-well ELISA
Positive IgM confirmed with IFA
Red Book: “The indirect fluorescent assay or EIA for IgM should not be relied on to diagnose congenital infection.”

10. Special Tests
All aforementioned tests available as panels from TSL-PAMFRI
Platinum-standard testing: Mouse inoculation?

11. Who to treat Prenatally diagnosed with congenital toxoplasmosis
Suspected congenital toxoplasmosis who have confirmation serology or PCR performed by a reference laboratory
Evidence of recent maternal infection with clinical findings compatible with congenital toxoplasmosis in the infant
Asymptomatic infants with equivocal serology, pending definitive diagnosis

12. Treatment Maternal Infant <18 weeks: spiramycin (IND)
>18 weeks: pyrimethamine-sulfadiazine-leucovorin
Infant
Pyrimethamine-sulfadiazine-leucovorin for 1 year
Pyrimethamine should be temporarily withheld if the ANC <500. The dose of folinic acid may be increased as needed if the ANC<1000.
Clindamycin mg/kg/day in 4 divided doses may be substituted for sulfadiazine in cases of renal insufficiency or allergy

13. References
Remington J.S., Wilson C.B., Baker C.J. and Klein, J.O. (eds.) Infectious Diseases of the Fetus and Newborn Infant, Sixth Edition. Philadelphia: Elsevier Saunders Company, 2006, pp
Toxoplasma gondii Infections. Redbook Online. kid=1484# Accessed February 15, 2018.
Pomares C, Montoya JG. Laboratory Diagnosis of Congenital Toxoplasmosis. Journal of Clinical Microbiology. 2016;54(10): doi: /jcm
Guerina NG, Marquez L. Congenital toxoplasmosis: Treatment, outcome, and prevention. UpToDate. treatment-outcome-and-prevention. Accessed February 15, 2018.
Toxoplasma Serology Laboratory: A Guide for Clinicians. Palo Alto Medical Foundation. Accessed February 15, 2018.