What is the recommended treatment for toxoplasmosis?

Treatment of Toxoplasmosis

The treatment of toxoplasmosis depends critically on the clinical context: pyrimethamine plus sulfadiazine plus leucovorin is the gold standard for active disease in immunocompromised patients and congenital infection, while spiramycin is used for pregnant women with suspected maternal infection but no confirmed fetal involvement. 1, 2

Treatment by Clinical Scenario

Congenital Toxoplasmosis (Postnatal Treatment of Infected Infants)

For infants with confirmed congenital toxoplasmosis, the standard regimen is pyrimethamine plus sulfadiazine plus leucovorin for 12 months. 1, 2, 3

• Pyrimethamine dosing: Loading dose of 2 mg/kg/day for 2 days, then 1 mg/kg/day for 2-6 months, followed by 1 mg/kg three times weekly 1, 2
• Sulfadiazine dosing: 50 mg/kg/dose twice daily 1, 2
• Leucovorin (folinic acid): Must be administered concurrently to prevent bone marrow suppression 1, 4
• Duration: Full 12-month course is essential, particularly for children with moderate to severe disease 2, 3

Critical monitoring: Complete blood count should be performed at least weekly during daily pyrimethamine dosing and at least monthly during less-than-daily dosing to detect bone marrow suppression early 2, 3

Maternal Treatment During Pregnancy

The treatment strategy differs based on gestational age and whether fetal infection is confirmed:

Before 18 Weeks or Unconfirmed Fetal Infection

Spiramycin 1 g (3 million IU) orally three times daily should be administered until delivery if amniocentesis is negative and fetal ultrasound shows no abnormalities. 1

• Spiramycin is not teratogenic and reduces vertical transmission risk 1
• In the United States, spiramycin is only available through the FDA Investigational New Drug process (telephone: 301-796-1600) 1
• Total daily dose: 3 g (9 million IU) per day 1

At or After 18 Weeks with Confirmed or Suspected Fetal Infection

Switch to pyrimethamine plus sulfadiazine plus folinic acid if: (1) acute infection is confirmed at or after 18 weeks gestation, (2) amniotic fluid PCR is positive, or (3) fetal ultrasound shows abnormalities suggestive of congenital toxoplasmosis. 1

• Pyrimethamine: 100 mg/day orally divided twice daily for 2 days, then 50 mg/day once daily 1
• Sulfadiazine: 75 mg/kg loading dose, then 100 mg/kg/day divided twice daily (maximum 4 g/day) 1
• Folinic acid: Must be given concurrently 1

Important caveat: Spiramycin should NOT be used if the fetus is documented or suspected to be infected, as it does not adequately cross the placenta to treat established fetal infection. 1

Toxoplasmic Encephalitis in HIV/AIDS Patients

The preferred acute treatment is pyrimethamine plus sulfadiazine plus leucovorin for at least 6 weeks, assuming clinical and radiological improvement. 1, 3

• This combination is highly effective and also provides protection against Pneumocystis pneumonia 1
• Alternative for sulfa-allergic patients: Pyrimethamine plus clindamycin, though this does not protect against PCP 1
• Another alternative: TMP-SMX (trimethoprim-sulfamethoxazole) for 6 weeks 3

After acute therapy, lifelong secondary prophylaxis (chronic maintenance therapy) is required to prevent relapse unless immune reconstitution occurs with HAART. 1

• Secondary prophylaxis can be discontinued if CD4+ count increases to >200 cells/µL for ≥6 months on HAART 1
• Prophylaxis must be restarted if CD4+ count drops below 200 cells/µL 1

Primary Prophylaxis in HIV Patients

All HIV-infected patients should be tested for Toxoplasma IgG antibody at initiation of care. 2

Toxoplasma-seropositive patients with CD4+ count <100 cells/µL should receive prophylaxis against toxoplasmic encephalitis. 1, 2

• Preferred regimen: TMP-SMX double-strength tablet daily, which also protects against PCP 1, 2
• Alternative: Dapsone plus pyrimethamine, which also protects against PCP 1
• Note: Aerosolized pentamidine does NOT protect against toxoplasmic encephalitis 1

Common Pitfalls and Caveats

Drug Toxicity and Monitoring

Pyrimethamine-sulfadiazine therapy carries significant risk of bone marrow suppression, particularly neutropenia, especially when leucovorin is not administered. 1

• Adverse events occur in 20-50% of treated infants in some series, though Danish data suggest only 14% have poor tolerability 1
• Seizures have been reported with pyrimethamine overdose from prescription dosing errors—extreme caution is needed with pediatric dosing 1, 4
• Pyrimethamine should be kept out of reach of children; deaths have been reported after accidental ingestion 4

Pregnancy Considerations

Pyrimethamine is Pregnancy Category C and should be avoided in the first trimester due to teratogenic potential (cleft palate, microphthalmia in animal studies). 4

• The American College of Obstetricians and Gynecologists recommends consultation with specialists for pregnant women with suspected or confirmed primary toxoplasmosis 2
• Despite teratogenicity concerns, pyrimethamine-sulfadiazine may be necessary after 18 weeks if fetal infection is confirmed, as the benefit of treating established fetal infection outweighs risks 1

Spiramycin Neurotoxicity

Spiramycin causes acral paresthesia (neurotoxic complications) significantly more frequently than pyrimethamine-sulfadiazine (19.5% vs 0%). 5

• Despite this, overall toxicity rates between spiramycin and pyrimethamine-sulfadiazine are not significantly different 5
• However, pyrimethamine-sulfadiazine is more effective at treating established fetal infection and should be preferred when fetal infection is confirmed 5

Treatment Efficacy Considerations

No regimen is active against the latent (cyst) stage of toxoplasmosis—all current treatments only target actively replicating tachyzoites. 6

• Alternative regimens (pyrimethamine with clindamycin, atovaquone, clarithromycin, or azithromycin; or monotherapy with TMP-SMX or atovaquone) have not been shown to be superior to pyrimethamine-sulfadiazine 6
• Efficacy against ocular toxoplasmosis remains uncertain for most regimens 6

German vs. French Treatment Approaches

The German approach (spiramycin until 16 weeks, then pyrimethamine-sulfadiazine-folinic acid for ≥4 weeks regardless of fetal infection status) results in lower transmission rates (4.8%) and clinical manifestations (1.6%) compared to the French approach (spiramycin only unless fetal infection proven). 7

• This suggests more aggressive treatment may be beneficial, though the French approach with spiramycin alone has also shown efficacy 8
• Rapid treatment initiation following primary infection is associated with better outcomes 7