Introduction to Congenital Toxoplasmosis

Congenital toxoplasmosis is a severe parasitic infection that occurs when a pregnant woman becomes infected with Toxoplasma gondii and transmits the parasite to her fetus. This condition can lead to significant fetal and neonatal morbidity and mortality if left untreated. Understanding the etiology, epidemiology, clinical presentation, and management of congenital toxoplasmosis is crucial for healthcare providers to ensure optimal outcomes for affected infants.

Etiology of Congenital Toxoplasmosis

Congenital toxoplasmosis is caused by the protozoan parasite Toxoplasma gondii. The primary hosts for this parasite are members of the Felidae family, particularly domestic cats. Humans can become infected through various routes:

• Ingestion of undercooked meat containing tissue cysts
• Consumption of contaminated water or food
• Exposure to cat feces containing oocysts
• Organ transplantation from an infected donor
• Vertical transmission from mother to fetus during pregnancy

In the context of congenital toxoplasmosis, the infection occurs when a pregnant woman becomes infected for the first time during pregnancy and transmits the parasite to the developing fetus through the placenta.

Epidemiology of Congenital Toxoplasmosis

The global prevalence of congenital toxoplasmosis varies widely depending on geographic location, cultural practices, and environmental factors:

• Incidence: Estimated at 1-10 per 10,000 live births globally
• Geographic distribution: Higher rates in South America, some African countries, and parts of Europe; lower rates in North America and Northern Europe
• Risk factors:
  • Consumption of raw or undercooked meat
  • Poor hygiene practices
  • Exposure to contaminated soil or water
  • Owning cats, especially if they hunt outdoors

The risk of fetal infection increases with gestational age at maternal infection, while the severity of fetal disease is inversely related to the gestational age at infection.

Pathophysiology of Congenital Toxoplasmosis

The pathophysiology of congenital toxoplasmosis involves several stages:

1. Maternal infection: T. gondii infects the mother, typically through ingestion of oocysts or tissue cysts.
2. Parasitemia: The parasite multiplies and spreads through the bloodstream.
3. Placental infection: T. gondii invades the placenta, establishing a focus of infection.
4. Fetal transmission: The parasite crosses the placenta and infects the fetus.
5. Fetal damage: T. gondii causes tissue damage and inflammation in various fetal organs, particularly the brain, eyes, and liver.

The severity of fetal infection depends on several factors:

• Gestational age at maternal infection
• Parasite virulence
• Maternal and fetal immune responses
• Timing and effectiveness of treatment

Early fetal infection (first trimester) typically results in more severe outcomes, including spontaneous abortion or severe neurological and ocular damage. Later infections may lead to less severe manifestations or subclinical disease.

Clinical Presentation of Congenital Toxoplasmosis

The clinical presentation of congenital toxoplasmosis can range from asymptomatic infection to severe multisystem disease. The classic triad of symptoms includes:

• Chorioretinitis
• Hydrocephalus
• Intracranial calcifications

Other clinical manifestations may include:

• Neurological:
  • Seizures
  • Microcephaly or macrocephaly
  • Developmental delays
  • Spasticity
• Ocular:
  • Strabismus
  • Nystagmus
  • Optic atrophy
  • Microphthalmia
• Systemic:
  • Hepatosplenomegaly
  • Jaundice
  • Pneumonitis
  • Myocarditis
  • Fever
  • Rash

It's important to note that many infants with congenital toxoplasmosis may appear normal at birth and develop symptoms later in life, particularly ocular disease.

Diagnosis of Congenital Toxoplasmosis

Diagnosis of congenital toxoplasmosis involves a combination of maternal screening, fetal assessment, and neonatal testing:

Maternal Screening:

• Serological testing: IgG and IgM antibodies against T. gondii
• IgG avidity test: To determine the timing of infection
• PCR on amniotic fluid: For definitive diagnosis of fetal infection

Fetal Assessment:

• Ultrasound: To detect fetal abnormalities (e.g., hydrocephalus, intracranial calcifications)
• MRI: For detailed evaluation of fetal brain abnormalities

Neonatal Testing:

• Serological testing: IgG and IgM antibodies
• PCR on blood, urine, and CSF
• Fundoscopic examination
• Neuroimaging: CT or MRI of the brain
• Hearing assessment

A definitive diagnosis of congenital toxoplasmosis requires the demonstration of persistent IgG antibodies beyond 12 months of age or positive PCR results in body fluids.

Treatment of Congenital Toxoplasmosis

Treatment of congenital toxoplasmosis aims to reduce the risk of severe complications and long-term sequelae. The standard treatment regimen includes:

Prenatal Treatment (if maternal infection is diagnosed during pregnancy):

• Spiramycin: To reduce the risk of vertical transmission
• Pyrimethamine, sulfadiazine, and folinic acid: If fetal infection is confirmed

Postnatal Treatment:

• Pyrimethamine: 2 mg/kg/day for 2 days, then 1 mg/kg/day for 6 months, followed by 1 mg/kg three times per week
• Sulfadiazine: 100 mg/kg/day in two divided doses
• Folinic acid: 10 mg three times per week

Treatment duration is typically 12 months but may be extended in severe cases. Regular monitoring of blood counts, liver function, and drug levels is essential during treatment.

Additional Management:

• Ophthalmological follow-up
• Neurodevelopmental assessments
• Hearing evaluations
• Management of complications (e.g., hydrocephalus, seizures)

Prevention of Congenital Toxoplasmosis

Prevention of congenital toxoplasmosis primarily focuses on preventing maternal infection during pregnancy:

Primary Prevention:

• Avoid consumption of raw or undercooked meat
• Wash fruits and vegetables thoroughly
• Practice good hand hygiene, especially after gardening or handling raw meat
• Avoid changing cat litter or use gloves if necessary
• Keep cats indoors and feed them commercial cat food

Secondary Prevention:

• Serological screening of pregnant women
• Early diagnosis and treatment of maternal infection
• Fetal monitoring and intervention when indicated

Some countries, such as France and Austria, have implemented nationwide prenatal screening programs for toxoplasmosis, which have shown success in reducing the incidence of congenital toxoplasmosis.

Prognosis of Congenital Toxoplasmosis

The prognosis for infants with congenital toxoplasmosis varies widely depending on several factors:

• Gestational age at maternal infection
• Severity of fetal involvement
• Timing and adequacy of treatment

Outcomes can range from normal development to severe neurological and ocular impairment. With early diagnosis and appropriate treatment, many infants can have favorable outcomes. However, long-term follow-up is essential as some complications, particularly ocular disease, may manifest later in life.

Potential Long-term Sequelae:

• Visual impairment or blindness
• Hearing loss
• Cognitive and motor delays
• Seizure disorders
• Learning disabilities

Regular follow-up and multidisciplinary care are crucial for optimizing outcomes and addressing any emerging complications.