How should congenital and acquired toxoplasmosis be treated in newborns, older children, and immunocompromised children, including drug choices, dosing, duration, monitoring, and prophylaxis?

Treatment of Toxoplasmosis in Children

All infants with confirmed or suspected congenital toxoplasmosis must receive 12 months of treatment with pyrimethamine plus sulfadiazine plus leucovorin, regardless of symptom severity at birth, as this regimen significantly reduces long-term neurologic and ocular sequelae. 1, 2

Congenital Toxoplasmosis in Newborns

Treatment Regimen (12-Month Duration)

Pyrimethamine dosing: 1, 2, 3

• Loading dose: 2 mg/kg/day orally for 2 days
• Maintenance: 1 mg/kg/day for months 2-6
• Then: 1 mg/kg three times weekly for months 7-12

Sulfadiazine dosing: 1, 2, 4

• 50 mg/kg orally twice daily (100 mg/kg/day total) throughout the entire 12 months

Leucovorin (folinic acid) - MANDATORY: 1, 2, 3

• 10-25 mg orally daily during pyrimethamine therapy
• Continue for 1 week after stopping pyrimethamine due to its long half-life
• Critical pitfall: Folic acid CANNOT substitute for folinic acid and will not prevent bone marrow suppression 2, 5

Special Considerations for Mild Disease

For infants with mild congenital toxoplasmosis (without HIV), some experts alternate monthly between pyrimethamine/sulfadiazine/leucovorin and spiramycin (50 mg/kg orally twice daily) from months 7-12, but this is NOT recommended for moderate-to-severe disease or HIV-infected infants who require the full 12-month pyrimethamine/sulfadiazine regimen. 1

HIV-Infected Pregnant Women and Their Newborns

If an HIV-infected woman has symptomatic toxoplasmosis during pregnancy, empiric treatment of the newborn should be strongly considered regardless of whether maternal treatment occurred. 1 The same 12-month regimen applies to HIV-infected infants with congenital toxoplasmosis. 1

Acquired Toxoplasmosis in Older Children

CNS, Ocular, or Systemic Disease in HIV-Infected Children

Acute therapy (6 weeks minimum): 1, 2, 5

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

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

Ocular Toxoplasmosis Specifics

For vision-threatening lesions near the macula or optic disk, add corticosteroids: 5

• Prednisone 1 mg/kg/day divided twice daily (maximum 40 mg/day)
• Critical timing: Start corticosteroids ONLY after 72 hours of antimicrobial therapy to avoid worsening infection 5
• Continue until resolution of severe inflammation, then rapid taper

Treatment duration: Continue for at least 1-2 weeks after complete resolution of all clinical signs, with total duration of 4-6 weeks. 5

Alternative Regimens for Sulfa Allergy

Primary alternative: 1, 2, 5

• Clindamycin 5.0-7.5 mg/kg orally four times daily (maximum 600 mg/dose) plus pyrimethamine plus leucovorin

Other alternatives (less studied in children): 1, 5

• Pyrimethamine plus azithromycin (adult dose 900-1,200 mg/day; pediatric dosing not established)
• Trimethoprim-sulfamethoxazole for 6 weeks in acquired ocular toxoplasmosis 5
• Atovaquone with or without pyrimethamine (substantially more expensive) 5

Immunocompromised Children (Non-HIV)

Use the same acute treatment regimen as for HIV-infected children with CNS/systemic disease. Lifelong maintenance therapy may be required for severely immunocompromised patients with CD4+ <100 cells/µL after acute therapy to prevent relapse. 5

Critical Monitoring Requirements

Hematologic Monitoring (MANDATORY)

Complete blood count frequency: 1, 2, 5

• At least weekly during daily pyrimethamine therapy
• At least monthly during less-than-daily dosing
• Monitor for neutropenia, anemia, and thrombocytopenia

Management of bone marrow suppression: 1, 3

• Increase leucovorin dose if marrow suppression develops
• If signs of folate deficiency develop, discontinue pyrimethamine and administer leucovorin until normal hematopoiesis returns

Additional Monitoring for Congenital Toxoplasmosis

During treatment year: 1

• Clinical and ophthalmologic examination every 1-3 months
• Head imaging as clinically indicated
• Serologic testing every 3 months

Long-term follow-up (ESSENTIAL): 1

• Ophthalmologic examinations every 3-6 months for years 2-3, then yearly indefinitely
• Chorioretinitis can occur at any age (>20% prevalence by age 10 years) despite treatment 1, 6
• Neurologic and developmental assessments at regular intervals

Common Pitfalls to Avoid

1. Never use pyrimethamine without leucovorin - this is the primary cause of severe bone marrow suppression 1, 2, 3

2. Never substitute folic acid for folinic acid (leucovorin) - folic acid will not prevent pyrimethamine-induced bone marrow toxicity 2, 5

3. Never start corticosteroids before 72 hours of antimicrobial therapy in ocular disease - this can worsen the infection 5

4. Never rely on commercial laboratory IgM results alone for diagnosis - false positives are extremely common and lead to unnecessary interventions; always confirm at a reference laboratory 2, 7

5. Never discontinue treatment early in congenital toxoplasmosis - inadequate duration leads to increased risk of late-onset chorioretinitis and neurologic sequelae 1, 5, 6

6. Never assume asymptomatic newborns don't need treatment - 70-90% of congenitally infected infants are asymptomatic at birth but the majority develop late sequelae without treatment 1, 6

Prophylaxis in HIV-Infected Children

For HIV-infected children with CD4+ counts <100 cells/µL who are Toxoplasma seropositive, trimethoprim-sulfamethoxazole is the preferred prophylaxis regimen. 7 Alternative prophylaxis options include dapsone plus pyrimethamine plus leucovorin, or atovaquone. 5