What is the recommended treatment for Toxoplasma (Toxoplasmosis) infection in immunosuppressed individuals?

Treatment of Toxoplasma Infection in Immunosuppressed Individuals

The recommended first-line treatment for toxoplasmosis in immunosuppressed individuals is the combination of pyrimethamine plus sulfadiazine with leucovorin supplementation. 1

First-Line Treatment Regimen

Pyrimethamine + Sulfadiazine + Leucovorin

• Pyrimethamine dosing:
  • Loading dose: 2 mg/kg/day orally divided twice daily for first 2 days
  • Maintenance dose: 1 mg/kg/day for 2-6 months
  • Followed by: 1 mg/kg/day three times weekly 1
• Sulfadiazine dosing:
  • 100 mg/kg/day orally divided twice daily 1
• Leucovorin (folinic acid):
  • 10 mg three times weekly 1
  • Must be administered with pyrimethamine to prevent bone marrow suppression 2
  • Should be continued for 1 week after pyrimethamine is discontinued due to the drug's long half-life 3

Alternative Regimens for Sulfa-Allergic Patients

For patients who develop sulfonamide hypersensitivity, the primary alternative is:

Pyrimethamine + Clindamycin + Leucovorin

• Clindamycin dosing: 5.0-7.5 mg/kg orally 4 times daily (maximum 600 mg/dose) 3
• Continue pyrimethamine and leucovorin as above

Other Alternatives

• Pyrimethamine + Azithromycin + Leucovorin
  • Azithromycin: 900-1,200 mg/day 3
• Atovaquone-based regimens:
  • Atovaquone (1,500 mg orally twice daily with meals) plus pyrimethamine and leucovorin, or
  • Atovaquone with sulfadiazine alone, or
  • Atovaquone as a single agent for patients intolerant to both pyrimethamine and sulfadiazine 3
• Trimethoprim-sulfamethoxazole (TMP-SMX):
  • 5 mg/kg trimethoprim plus 25 mg/kg sulfamethoxazole intravenously or orally twice daily 3

Treatment Duration and Monitoring

• Acute treatment: Continue for at least 6 weeks, then evaluate clinical and radiological response 1
• Maintenance therapy: Lifelong suppressive therapy is indicated after treatment to prevent recurrence in immunosuppressed patients 3, 1
• Monitoring:
  • Complete blood count weekly while on daily pyrimethamine and at least monthly while on less frequent dosing 3, 1, 2
  • Regular ophthalmologic examinations to monitor for chorioretinitis 1

Special Considerations

Central Nervous System Disease

• For patients with CNS disease with elevated CSF protein (>1,000 mg/dL) or focal lesions with substantial mass effects, corticosteroids (e.g., dexamethasone or prednisone) may be added 3
• Corticosteroids should be discontinued as soon as possible due to their immunosuppressive effects 3

Prophylaxis for High-Risk Immunosuppressed Patients

• Primary prophylaxis: TMP-SMX for patients with HIV who have CD4+ counts <100 cells/μL 3, 1
• Alternative prophylaxis regimens:
  • Dapsone-pyrimethamine plus leucovorin
  • Atovaquone with or without pyrimethamine 1

Pregnancy

• Pyrimethamine-containing regimens should be avoided during pregnancy due to teratogenicity concerns 3, 1, 2
• TMP-SMX can be used for prophylaxis during pregnancy 1

Potential Adverse Effects

• Pyrimethamine: Bone marrow suppression (neutropenia, anemia, thrombocytopenia), rash, nausea 2
• Sulfadiazine: Rash, fever, leukopenia, hepatitis, gastrointestinal symptoms, crystalluria 3
• Clindamycin: Fever, rash, gastrointestinal symptoms (including pseudomembranous colitis), hepatotoxicity 3

Prevention Strategies for Immunosuppressed Patients

• Avoid raw or undercooked meat
• Cook meat to internal temperature of 165°F (73.8°C)
• Wash hands after handling raw meat, gardening, or contact with soil
• Wash fruits and vegetables thoroughly before eating raw
• For cat owners:
  • Change litter box daily (preferably by an HIV-negative, non-pregnant person)
  • Keep cats indoors
  • Feed cats only commercial or well-cooked food 1

The combination of pyrimethamine plus sulfadiazine with leucovorin remains the gold standard for treatment of toxoplasmosis in immunosuppressed patients, with several alternative regimens available for those who cannot tolerate this combination 4.