Congenital toxoplasmosis

Background

• Can be acquired during maternal parasitemia associated with primary infection
  • However, it is possible to acquire from reactivation of latent toxoplasmosis in an HIV-infected mother
• Risk of transplacental infection of fetus is lowest in first trimester and highest in third

Clinical Manifestations

• Often no history of illness during pregnancy
  • Symptoms, if present, tend to be mild with low-grade fever, malaise, and lymphadenopathy
• At birth, 85% of infected babies are asymptomatic and only 15% are symptomatic
  • Risk of infection is related to trimester of infection: 6% in first, 40% in second, and 72% in third
  • Risk of signs of congenital infection is inversely related to trimester of infection: 61% in first, 25% in second, and 9% in third
• Classic triad of chorioretinitis (most common), intraparenchymal cerebral calcifications, and hydrocephalus
• Others: thrombocytopenia, hepatitis, hepatosplenomegaly, cataracts, strabismus, microphthalmia

Diagnosis

In pregnancy

• Molecular
  • Definitive diagnosis is based on PCR of amniotic fluid around 18 months, usually done after maternal serology to confirm intrauterine infection
    • Sensitivity is 64 to 92% and specificity 100% (NPR around 88 to 98%)
    • Earlier than 18 weeks has unknown sensitivity and specificity, and has a higher risk of spontaneous abortion
  • Can also be done on fetal blood
• Serology
  • Can check maternal IgM and IgG
  • IgM is not specific to recent infection, however, as it can be present for more than a year
  • IgG avidity testing is used to determine recency of infection
    • Low avidity is 35-50% and high is >60%
    • Low avidity is unhelpful, as avidity can remain low for more than a year
    • High avidity, on the other hand, suggests infected at least 3-4 months prior
  • Therefore, if infection is suspected in the first 16 weeks of gestation, avidity testing may be able to rule out infection during pregnancy
• Needs serial head ultrasound to monitor for hydrocephalus and intraparenchymal brain calcifications
  • May also see hepatic calcifications, splenomegaly, and ascites

In children

• Standard workup starts with serology, then adds PCR and other investigations if clinical suspicion is high
• Serology
  • In neonates, IgG serology reflects maternal status, so use IgM and IgA instead
• Molecular testing
  • If clinical suspicion is high, add PCR of the peripheral blood, urine, and CSF to the serology
• Other
  • If clinical suspicion is high, also get ophthalmologic evaluation, hearing assessment, ultrasound or CT of the brain, and lumbar puncture

Management

In pregnancy

• If infected < 14 weeks gestation, spiramycin 3 g/day until delivery
  • However, it doesn't cross the placenta and it's unclear whether it affects outcomes in the baby
  • Likely most effective if given within 8 weeks of maternal infection
  • Second-line would be monotherapy with sulfadiazine or clindamycin
• If age ≥ 14 weeks gestation and documented fetal infection, or if suspected infection was ≥14 weeks gestation, use standard therapy
  • Standard therapy is: pyrimethamine 50 mg q12h for 2 days followed by 50 mg daily (plus folinic acid 10-20 mg daily until 1 week after stopping pyrimethamine), and sulfadiazine 75 mg/kg load followed by 50 mg/kg q12h (maximum 4 g/day)
  • This treatment crosses the placenta, which is why it is used in cases of documented or suspected fetal infection, as well as in later-term infections when the risk of fetal infection is higher
  • Therefore, if initially started on spiramycin, then switch to standard therapy if amniotic fluid PCR is positive or ultrasound is abnormal
  • However, it is teratogenic until 14 weeks gestation so spiramycin is used until then

In children

• Postnatal treatment of neonates is with standard therapy for at least 12 months
  • Sulfadiazine 50 mg/kg q12h
  • Pyrimethamine 1 mg/kg q12h for 2 days (load), followed by 1 mg/kg for 2 to 6 months, followed by 1 mg/kg qMWF
  • Folinic acid 10 mg PO thrice weekly until 1 week after pyrimethamine is stopped
• Treatment of congenital infection in older children is standard therapy until 1 to 2 weeks after resolution of signs or symptoms
  • Pyrimethamine 1 mg/kg q12h (max 50 mg) for 2 days, followed by 1 mg/kg/day (max 25 mg)
  • Sulfadiazine 75 mg/kg load, followed by 50 mg/kg q12h (max 4 g/day)
  • Folinic acid 10-20 mg po thrice weekly
  • Can add prednisone for severe chorioretinits at 1 mg/kg/day divided bid (max 40 mg/day), followed by a rapid taper
• Serial evaluations with a clinical assessment, neuroradiology, ophthalmology, and CSF analysis