What is the recommended treatment for toxoplasmosis?

Treatment of Toxoplasmosis

The recommended first-line treatment for toxoplasmosis is the combination of pyrimethamine plus sulfadiazine with leucovorin (folinic acid) supplementation. 1, 2

Treatment Regimens Based on Clinical Scenario

Non-pregnant Immunocompetent Adults with Active Toxoplasmosis

• First-line therapy:
  • Pyrimethamine: Loading dose of 2 mg/kg/day orally divided twice daily for first 2 days, then 1 mg/kg/day daily (maximum 75 mg/day) 1
  • Sulfadiazine: 100 mg/kg/day orally divided twice daily (maximum 4-6 g/day) 1
  • Leucovorin (folinic acid): 10-25 mg orally three times weekly (mandatory to prevent bone marrow suppression) 1, 2
  • Duration: 4-6 weeks, continuing for 1-2 weeks after resolution of clinical signs and symptoms 1

HIV/Immunocompromised Patients with Toxoplasmic Encephalitis (TE)

• Acute treatment:
  • Same regimen as above but often higher doses
  • Duration: At least 6 weeks, until clinical and radiological improvement 1
• Secondary prophylaxis (maintenance therapy):
  • Must be continued lifelong unless immune reconstitution occurs 3
  • Same medications at reduced doses, or alternative regimens 3
  • Can consider discontinuing if CD4+ count >200 cells/μL for >6 months on ART 3, 1

Pregnant Women with Acute Toxoplasmosis

• Before 18 weeks of pregnancy:

  • Spiramycin: 1 g (3 million IU) orally three times daily until delivery if no fetal infection 3, 1
  • Available in the US only through FDA's Investigational New Drug process 3

• After 18 weeks of pregnancy or confirmed fetal infection:

  • Switch to pyrimethamine + sulfadiazine + leucovorin 3, 1
  • Pyrimethamine should be avoided in first trimester due to teratogenicity 1, 2

Congenital Toxoplasmosis

• Treatment duration:
  • 6 months for asymptomatic or moderately symptomatic cases
  • 12 months for severely symptomatic cases 1
• Dosing:
  • Pyrimethamine: 2 mg/kg/day for 2 days, then 1 mg/kg/day
  • Sulfadiazine: 100 mg/kg/day divided twice daily
  • Leucovorin: 10 mg three times weekly 1

Alternative Treatment Regimens

For patients who cannot tolerate sulfadiazine:

• Pyrimethamine + clindamycin + leucovorin:

  • Clindamycin: 5-7.5 mg/kg orally 4 times daily (maximum 600 mg/dose) 3, 1
  • Note: This combination does not provide protection against PCP 3

• Trimethoprim-sulfamethoxazole (TMP-SMX):

  • 5 mg/kg trimethoprim plus 25 mg/kg sulfamethoxazole twice daily 1
  • Effective for both treatment and prophylaxis

• Atovaquone-based regimens:

  • Atovaquone 1,500 mg orally twice daily with meals
  • Can be combined with pyrimethamine + leucovorin or used alone in patients intolerant to both pyrimethamine and sulfadiazine 1

Monitoring During Treatment

• Weekly complete blood count while on daily pyrimethamine (risk of bone marrow suppression) 1, 2
• Monthly CBC when on less frequent dosing 1
• Ophthalmologic follow-up every 2-3 weeks during active treatment for ocular toxoplasmosis 1
• Clinical and radiological response evaluation after 6 weeks of treatment 1

Important Precautions

• Pyrimethamine warnings:

  • Can cause folate deficiency leading to bone marrow suppression 2
  • Concurrent leucovorin administration is mandatory 2
  • Use with caution in patients with seizure disorders, renal or hepatic impairment 2
  • Teratogenic - avoid in first trimester of pregnancy 2

• Drug interactions:

  • Avoid concurrent use of other antifolic drugs or myelosuppressive agents 2
  • Mild hepatotoxicity reported when used with lorazepam 2

Prophylaxis Recommendations

• Primary prophylaxis for HIV patients:

  • Recommended for CD4+ count <100 cells/μL and positive Toxoplasma serology 3, 1
  • First choice: TMP-SMX (also provides PCP prophylaxis) 3, 1
  • Can discontinue if CD4+ count >200 cells/μL for >6 months on ART 3, 1

• Secondary prophylaxis after treated toxoplasmosis:

  • Lifelong unless immune reconstitution occurs 3
  • Pyrimethamine + sulfadiazine + leucovorin is highly effective 3

Prevention Measures

• Cook meat thoroughly to internal temperature of 165°F (73.8°C) 1
• Wash hands after handling raw meat, gardening, or contact with soil 1
• Wash fruits and vegetables thoroughly before eating raw 1
• For cat owners: change litter box daily (preferably by HIV-negative, non-pregnant person) 1

The most recent evidence shows that early treatment initiation significantly reduces transmission rates and clinical manifestations, particularly when started within 3 weeks of infection 4, 5, emphasizing the importance of prompt diagnosis and treatment.