What is the recommended treatment and management for toxoplasmosis, particularly in immunocompromised or pregnant individuals?

Treatment and Management of Toxoplasmosis in Immunocompromised and Pregnant Individuals

The recommended first-line treatment for toxoplasmosis is the combination of pyrimethamine plus sulfadiazine with leucovorin supplementation, which has been proven highly effective for both acute treatment and prevention of recurrence. 1, 2

Treatment Regimens for Different Patient Populations

Immunocompromised Patients (HIV/AIDS)

Primary Treatment

• Pyrimethamine: Loading dose of 200 mg orally, followed by 50-75 mg/day
• Sulfadiazine: 1000-1500 mg orally every 6 hours (4-6 g/day)
• Leucovorin (folinic acid): 10-25 mg/day (to prevent hematologic toxicity)
• Continue acute therapy for at least 6 weeks beyond resolution of signs and symptoms 1

Maintenance Therapy

• Patients who have had toxoplasmic encephalitis (TE) should receive lifelong suppressive therapy to prevent relapse 2, 1
• Pyrimethamine: 25-50 mg/day orally
• Sulfadiazine: 2000-4000 mg/day (in 2-4 divided doses)
• Leucovorin: 10-25 mg/day

Alternative Regimens (for sulfa-allergic patients)

• Pyrimethamine + Clindamycin + Leucovorin
  • Clindamycin: 600 mg IV or orally every 6 hours 1
  • Note: This combination does not provide protection against PCP 2
• Atovaquone-based regimens:
  • Atovaquone 1500 mg orally twice daily with meals, plus pyrimethamine and leucovorin 1

Pregnant Women

For Maternal Infection <18 Weeks Gestation

• Spiramycin: 1 g (3 million IU) orally three times daily (total 9 million IU/day) 2
• Continue until delivery if amniotic fluid PCR is negative and follow-up ultrasound is normal
• Spiramycin is not teratogenic but available in the US only through FDA's Investigational New Drug process 2

For Maternal Infection ≥18 Weeks or Confirmed Fetal Infection

• Pyrimethamine + Sulfadiazine + Leucovorin 2
• Pyrimethamine is teratogenic; avoid in first trimester if possible 2
• TMP-SMZ can be used for prophylaxis during pregnancy 1

Congenital Toxoplasmosis

• Pyrimethamine: 2 mg/kg/day orally divided twice daily for first 2 days, then 1 mg/kg/day for 2-6 months, followed by 1 mg/kg/day three times weekly
• Sulfadiazine: 100 mg/kg/day orally divided twice daily
• Leucovorin: 10 mg three times weekly
• Total treatment duration: 12 months 1

Prophylaxis Recommendations

Primary Prophylaxis for HIV Patients

• Indicated for CD4+ count <100 cells/μL and positive Toxoplasma serology 2
• First choice: TMP-SMZ (also provides PCP prophylaxis) 2
• Alternatives:
  • Dapsone + pyrimethamine + leucovorin
  • Atovaquone with or without pyrimethamine 1

Discontinuing Primary Prophylaxis

• May be considered if CD4+ count increases to >200 cells/μL for >3 months in response to ART 2
• Resume if CD4+ count decreases to <200 cells/μL 2

Secondary Prophylaxis

• Lifelong therapy is recommended after treatment of active disease in immunocompromised patients 1
• May consider discontinuation if:
  • Completed initial therapy
  • Remains asymptomatic
  • CD4+ count >200 cells/μL for >6 months on ART 2
• Restart if CD4+ count decreases to <200 cells/μL 2

Monitoring During Treatment

• Weekly complete blood count while on daily pyrimethamine (due to potential bone marrow suppression) 1
• Monthly monitoring when on less frequent dosing
• Ophthalmologic examinations to monitor for chorioretinitis
• Clinical and radiological response evaluation after 6 weeks of treatment 1

Prevention Strategies

• Cook meat thoroughly to an internal temperature of 165°F (73.8°C) 1, 3
• Wash hands after handling raw meat, gardening, or contact with soil
• Wash fruits and vegetables thoroughly before eating raw
• Pregnant women and immunocompromised individuals should:
  • Avoid changing cat litter or wear gloves and wash hands thoroughly
  • Keep cats indoors and feed only commercial or well-cooked food
  • Avoid drinking untreated water 3, 4

Special Considerations

Children

• TMP-SMZ for PCP prophylaxis also provides protection against toxoplasmosis 2
• Children >12 months receiving alternative PCP prophylaxis should have Toxoplasma antibody testing 2
• If seropositive, provide prophylaxis for both PCP and toxoplasmosis (dapsone plus pyrimethamine) 2

Adverse Effects and Monitoring

• Pyrimethamine: Bone marrow suppression (monitor CBC), teratogenic in first trimester 5
• Sulfadiazine: Rash, fever, leukopenia, hepatitis, crystalluria 1
• Clindamycin: Gastrointestinal symptoms including pseudomembranous colitis 1

Toxoplasmosis management requires careful consideration of patient factors, particularly immune status and pregnancy. Early diagnosis and appropriate treatment significantly reduce morbidity and mortality, especially in congenital cases and immunocompromised individuals.