Congenital Toxoplasmosis

Congenital toxoplasmosis is infection of the fetus with Toxoplasma gondii, acquired transplacentally after maternal primary infection during pregnancy. Rarely it follows reactivation in an immunosuppressed mother or infection shortly before conception.

Maternal infection arises from ingestion of oocysts (cat faeces, contaminated soil, unwashed vegetables, water) or tissue cysts (undercooked meat, especially pork, lamb and venison).

Transmission risk increases with gestational age:

• about 6 to 15% at 13 weeks
• 30% at 26 weeks
• 60 to 70% at 36 weeks and above

Severity is higher in early infection, and fetal damage is more likely when infection occurs before 24 to 28 weeks.

The birth prevalence is about 1 to 10 per 10,000 live births (higher in France, Brazil and some other regions).

• Most infants (about 70 to 90%) are asymptomatic at birth, but can develop later retinochoroiditis (the commonest late manifestation, in 20 to 80% without treatment, with potential vision loss and recurrent episodes into adulthood), hearing loss, and neurodevelopmental problems
• Classic triad in severe disease: chorioretinitis, hydrocephalus (obstructive from aqueduct stenosis), and intracranial calcifications (diffusely scattered, as opposed to periventricular in CMV)
• Other signs: microcephaly, seizures, jaundice, hepatosplenomegaly, anaemia, thrombocytopenia, lymphadenopathy, rash, fever, strabismus, nystagmus, and microphthalmia
• Stillbirth, miscarriage, hydrops fetalis, and neonatal death in severe fetal infection
• Long term sequelae: visual loss, neurological and cognitive deficits, epilepsy, and learning problems

1. Maternal screening: Toxoplasma IgG and IgM (IgM may persist for years), IgG avidity (high avidity before 16 weeks excludes infection within the preceding 3 to 4 months), and seroconversion monitoring.
2. Fetal diagnosis: PCR of Toxoplasma B1 gene or 529 bp repeat in amniotic fluid. Take it at least 4 weeks after maternal infection and after 18 weeks; sensitivity is about 65 to 90%, specificity near 100%. Fetal ultrasound looks for ventricular dilatation, intracranial calcifications, hepatic calcification and ascites.
3. Neonatal diagnosis: Toxoplasma specific IgM and IgA (more sensitive; at birth and 10 days), serial IgG (persisting beyond 12 months confirms infection; decline in uninfected infants), PCR on blood, CSF or placenta, and comparison of mother infant immunoblots.
4. Evaluation: dilated eye examination, cranial ultrasound and CT or MRI (calcifications), CSF analysis (elevated protein, pleocytosis, xanthochromia in severe disease), hearing assessment, full blood count, and liver tests.

In pregnancy:

• Spiramycin 1 g (3 million IU) orally three times daily, started immediately after maternal infection is diagnosed and continued until delivery if the fetus is not infected (reduces transmission by about 50% when started within 3 weeks of seroconversion)
• If fetal infection is confirmed by PCR (or maternal infection after 18 weeks), switch to:
  • pyrimethamine 50 mg orally twice daily for 2 days then 50 mg daily (avoid pyrimethamine in the first trimester)
  • plus sulfadiazine 75 mg/kg loading then 50 mg/kg twice daily (maximum 4 g/day)
  • with folinic acid (leucovorin) 10 to 25 mg daily
  • continued until delivery; monitor blood counts weekly
• Fetal ultrasound every 2 to 4 weeks; termination is discussed for severe fetal central nervous system abnormalities

Infant treatment:

• Pyrimethamine 1 mg/kg orally twice daily for 2 days, then 1 mg/kg daily for 6 months, then three times weekly for 6 months (some regimens use 1 mg/kg daily for 2 to 6 months).
• Plus sulfadiazine 50 mg/kg orally twice daily.
• Plus folinic acid 10 mg three times weekly (to prevent myelosuppression), for a total of 12 months.
• Weekly then monthly blood counts, with adjustment for neutropenia and thrombocytopenia.
• Add corticosteroids (prednisolone 0.5 to 1 mg/kg/day) for active chorioretinitis threatening the macula or when CSF protein is above 1 g/L, until the inflammation subsides.
• Treat even asymptomatic infants.

Follow up: regular ophthalmological examination (every 3 months in the first year, then every 6 to 12 months for life, as relapses occur), audiology, neurodevelopmental assessment, and imaging for hydrocephalus (ventriculoperitoneal shunt if needed). Toxoplasmic retinochoroiditis recurrences can be treated with trimethoprim-sulfamethoxazole or pyrimethamine sulfadiazine. Trimethoprim-sulfamethoxazole prophylaxis may reduce recurrences.

Prevention: cook meat to above 67 degrees C, wash fruits and vegetables, avoid cat litter in pregnancy (or use gloves), wash hands, avoid unpasteurised goat milk, and use serological screening where recommended.