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

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

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

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

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

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

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

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

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.”

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

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

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 20-30 mg/kg/day in 4 divided doses may be substituted for sulfadiazine in cases of renal insufficiency or allergy

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 1009-1010. Toxoplasma gondii Infections. Redbook Online. https://redbook.solutions.aap.org/chapter.aspx?sectionid=88187256&boo kid=1484#91041315. Accessed February 15, 2018. Pomares C, Montoya JG. Laboratory Diagnosis of Congenital Toxoplasmosis. Journal of Clinical Microbiology. 2016;54(10):2448-2454. doi:10.1128/jcm.00487-16. Guerina NG, Marquez L. Congenital toxoplasmosis: Treatment, outcome, and prevention. UpToDate. https://www.uptodate.com/contents/congenital-toxoplasmosis- treatment-outcome-and-prevention. Accessed February 15, 2018. Toxoplasma Serology Laboratory: A Guide for Clinicians. Palo Alto Medical Foundation. http://www.pamf.org/Serology/clinicianguide.html. Accessed February 15, 2018.