What is the treatment for Toxoplasmosis gondii?

Treatment of Toxoplasmosis Gondii

The gold standard treatment for toxoplasmosis is pyrimethamine plus sulfadiazine plus leucovorin (folinic acid), with specific regimens varying based on whether the infection is congenital, acquired, or occurring in pregnancy. 1, 2

Treatment by Clinical Scenario

Congenital Toxoplasmosis in Infants

For infants with confirmed or suspected congenital toxoplasmosis, treat for 12 months with the following regimen: 1

• Pyrimethamine:

  • Loading: 2 mg/kg/day orally divided twice daily for 2 days 1
  • Days 3-60 (or to 6 months if symptomatic): 1 mg/kg/day orally once daily 1
  • After 2-6 months: 1 mg/kg orally three times per week 1

• Sulfadiazine: 100 mg/kg/day orally divided twice daily for the entire 12 months 1

• Leucovorin (folinic acid): 10 mg three times per week throughout treatment 1

Add corticosteroids only if severe chorioretinitis is present or CSF protein ≥1 g/dL, and only after 72 hours of anti-Toxoplasma therapy. 1

Acquired Toxoplasmosis in HIV-Infected or Immunocompromised Children

For CNS, ocular, or systemic toxoplasmosis in HIV-infected children, use acute therapy for 6 weeks: 1

• Pyrimethamine: 2 mg/kg/day for 3 days, then 1 mg/kg/day 1
• Sulfadiazine: 25-50 mg/kg/dose four times daily 1
• Leucovorin: 10-25 mg/day 1

Continue acute therapy for at least 6 weeks assuming clinical and radiological improvement; longer courses may be required for extensive disease or poor response. 1

Toxoplasmosis in Pregnancy

For pregnant women with suspected or confirmed acute toxoplasmosis before 18 weeks gestation, initiate spiramycin immediately: 3

• Spiramycin: 1 gram (or 3 million IU) orally three times daily 3
• Spiramycin is not commercially available in the United States but can be obtained at no cost through the FDA (301-796-1600) after consultation with PAMF-TSL (650-853-4828) or NCCCT (773-834-4152) 1

At or after 18 weeks gestation, or if fetal infection is confirmed by positive amniotic fluid PCR, switch to combination therapy: 3

• Pyrimethamine plus sulfadiazine plus folinic acid 1, 3
• The German approach, which has achieved a transmission rate of only 4.8% (versus 30% in other European cohorts), uses spiramycin until 16 weeks, then switches all women to pyrimethamine/sulfadiazine/folinic acid for at least 4 weeks regardless of fetal infection status 1

For HIV-infected pregnant women with toxoplasmosis, use trimethoprim-sulfamethoxazole for prophylaxis, though pyrimethamine-containing regimens should be deferred until after the first trimester due to teratogenicity concerns. 3

Critical Monitoring Requirements

Perform complete blood counts at least weekly during daily pyrimethamine therapy and at least monthly during less-than-daily dosing to detect bone marrow suppression (neutropenia, anemia, thrombocytopenia). 1, 4, 2

Always administer leucovorin concurrently with pyrimethamine and continue for 1 week after pyrimethamine discontinuation due to its long half-life (approximately 96 hours). 1, 4, 2

For infants with congenital toxoplasmosis, perform monthly fetal ultrasounds during pregnancy and comprehensive neonatal evaluation including ophthalmologic examination by a retinal specialist, neurologic assessment, hearing evaluation, head CT or ultrasound, and abdominal ultrasound. 1, 3

Alternative Regimens

When pyrimethamine-sulfadiazine cannot be used due to allergy or intolerance:

• Clindamycin can replace sulfadiazine in combination with pyrimethamine for acute toxoplasmic chorioretinitis or as second-line therapy for toxoplasmic encephalitis 5, 6, 7
• Trimethoprim-sulfamethoxazole as monotherapy has been used but is not superior to pyrimethamine-sulfadiazine 6, 8
• Atovaquone monotherapy or in combination with pyrimethamine has shown promise but lacks superiority data 6, 8, 7

For mild congenital toxoplasmosis only, some experts alternate pyrimethamine/sulfadiazine/folinic acid monthly with spiramycin (50 mg/kg orally twice daily) from months 7-12, but this should NOT be used for moderate-to-severe disease or HIV-infected children. 1

Common Pitfalls to Avoid

Never rely on commercial laboratory IgM results alone for toxoplasmosis diagnosis—false positives are extremely common and lead to unnecessary interventions; always confirm at a reference laboratory. 3

Do not delay spiramycin initiation while awaiting confirmatory testing if acute toxoplasmosis is clinically suspected during pregnancy—early treatment significantly reduces transmission risk. 1, 3

Never use pyrimethamine without leucovorin—this is the primary cause of severe bone marrow suppression. 1, 4

Do not stop leucovorin when pyrimethamine is discontinued; continue for 1 week afterward due to pyrimethamine's long half-life. 1, 4

Avoid prescribing errors with pyrimethamine dosing in children—seizures have been reported with overdoses. 1

Be aware that pyrimethamine is no longer available in retail pharmacies in the United States as of June 2015; it must be obtained through Walgreens Specialty Pharmacy (1-800-222-4991) with special enrollment forms, and medication should be marked "STAT/URGENT" for same-day delivery. 1

Do not assume treatment eradicates tissue cysts—current regimens only target actively replicating tachyzoites, not the dormant bradyzoite cysts in brain and muscle tissue. 8, 9

Monitor for drug interactions: concomitant use of other antifolate drugs (trimethoprim-sulfamethoxazole, methotrexate, zidovudine) significantly increases bone marrow suppression risk. 2

Watch for early warning signs of serious adverse effects: sore throat, pallor, purpura, glossitis, or any skin rash warrant immediate discontinuation and medical evaluation. 2