What is the treatment for congenital toxoplasmosis in a pregnant woman diagnosed with Toxoplasma gondii infection?

Treatment of Congenital Toxoplasmosis in Pregnant Women

Pregnant women diagnosed with acute Toxoplasma gondii infection should be treated immediately with spiramycin before 18 weeks gestation, then switched to combination therapy with pyrimethamine, sulfadiazine, and folinic acid at or after 18 weeks gestation or if fetal infection is confirmed at any gestational age. 1

Treatment Algorithm Based on Gestational Age and Fetal Status

Before 18 Weeks Gestation

• Initiate spiramycin immediately upon suspected or confirmed maternal acute infection, without waiting for confirmatory testing 1, 2
• Spiramycin prevents placental transmission but does not treat established fetal infection 3
• Continue spiramycin until 18 weeks if fetal infection has not been confirmed 4

At or After 18 Weeks Gestation

• Switch to triple therapy (pyrimethamine + sulfadiazine + folinic acid) regardless of fetal infection status 1, 4
• This combination treats both maternal infection and established fetal disease 5

If Fetal Infection Confirmed at Any Gestational Age

• Immediately switch to triple therapy (pyrimethamine + sulfadiazine + folinic acid) even before 18 weeks 1, 6
• Fetal infection is confirmed by positive amniotic fluid PCR performed at ≥18 weeks gestation and ≥4 weeks after suspected maternal infection 2

Critical Timing Considerations

Early treatment initiation is paramount for reducing both transmission risk and disease severity. When treatment is started within 3 weeks of maternal seroconversion, the odds of mother-to-child transmission decrease by 52% compared to delayed treatment (≥8 weeks) 4

• Treatment initiated 3-5 weeks after seroconversion: 36% reduction in transmission risk 4
• Treatment initiated 6-8 weeks after seroconversion: 40% reduction in transmission risk 4
• Early treatment reduces symptomatic disease in infected infants from 11% to 4% 4

The most recent meta-analysis (2025) demonstrates that triple therapy shows more consistent results (RR: 0.22) compared to spiramycin alone (RR: 0.54) in preventing neonatal infection and clinical manifestations 7

Specific Treatment Regimens

Spiramycin Monotherapy

• Used for maternal prophylaxis before 18 weeks or when fetal infection is not confirmed 1, 2
• Prevents placental transmission but does not cross the placenta to treat fetal infection 3
• Continue throughout pregnancy if fetal infection is ruled out 4

Triple Therapy (Pyrimethamine + Sulfadiazine + Folinic Acid)

• Pyrimethamine: Loading dose followed by maintenance dosing 6
• Sulfadiazine: 50 mg/kg/dose twice daily 6
• Folinic acid (leucovorin): Must be given concurrently and continued for 1 week after pyrimethamine discontinuation due to its long half-life 1, 8
• This combination treats established fetal infection and reduces severe neurologic sequelae (OR: 0.24) 4

Essential Monitoring Requirements

Complete blood counts must be performed at least weekly during daily pyrimethamine therapy to detect bone marrow suppression, which occurs in 20-50% of treated patients when leucovorin is inadequate 1, 5, 8

• Monitor for neutropenia, thrombocytopenia, and anemia 8
• Never administer pyrimethamine without concurrent folinic acid—this is the primary cause of severe bone marrow toxicity 1, 5
• Watch for early warning signs: sore throat, pallor, purpura, or glossitis 8

Critical Pitfalls to Avoid

Never delay spiramycin initiation while awaiting confirmatory testing if acute toxoplasmosis is clinically suspected—early treatment significantly reduces transmission risk and disease severity 1, 2

Never rely on commercial laboratory IgM results alone—false positives are extremely common and lead to unnecessary interventions; always confirm at a reference laboratory 1

Do not perform amniocentesis before 18 weeks gestation or less than 4 weeks after suspected maternal infection—this increases false-negative results 2

Never use pyrimethamine without folinic acid—this combination error causes the majority of severe hematologic complications 1, 5, 8

Consultation and Specialized Care

Every case of suspected acute maternal Toxoplasma infection should be discussed with an expert in toxoplasmosis management before finalizing treatment decisions 2

• Pregnant women with confirmed or suspected primary toxoplasmosis should be managed in consultation with appropriate specialists 6
• The American College of Obstetricians and Gynecologists and CDC emphasize specialist involvement for optimal outcomes 6

Evidence Quality and Real-World Effectiveness

While no randomized controlled trials exist (making RCTs ethically difficult given widespread treatment adoption), observational data from multiple countries consistently demonstrates treatment effectiveness 4

• Austrian data shows sixfold lower transmission in treated versus untreated women (9% vs 51%) 4
• German protocols using spiramycin followed by triple therapy achieved only 4.8% transmission rates 4
• French mandatory screening reduced transmission from 29% to 24% and symptomatic disease from 11% to 4% 4

The 2025 systematic review and meta-analysis confirms treatment reduces both infection risk (RR: 0.34) and clinical manifestations (RR: 0.30), with triple therapy showing superior consistency 7