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, but the risk of severe disease is highest if infected in first trimester and lowest in third trimester1
• See also toxoplasmosis in pregnancy

Trimester	Transmission to Fetus	Severity of Disease				Overall Probability of Any Symptomatic Disease
		Asymptomatic	Mild	Severe	Fetal Death
first	15%	18%	6%	41%	35%	11%
second	30%	67%	18%	8%	7%	10%
third	60%	89%	11%	0%	0%	6%
overall	33%	72%	13%	8%	7%	8%

Clinical Manifestations

• At birth, 85% of infected babies are asymptomatic and only 15% are symptomatic
  • Risk of infection is related to trimester of infection: 6-15% in first, 30-40% in second, and 60-72% 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
• Somewhere between 24 and 85% of children who are asymptomatic at birth will later develop chorioretinitis, strabismus, blindness, hydrocephalus, microcephaly, cerebral calcifications, developmental delay, epilepsy, deafness in the months to years following birth

Diagnosis

• 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
• If clinical suspicion is high, also get ophthalmologic evaluation, hearing assessment, ultrasound or CT of the brain, and lumbar puncture

Management

• 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
• For prevention, refer to the management of toxoplasmosis in pregnancy