Indication	First Choice	Alternative	Comments/Special Issues
Primary Prophylaxis	TMP-SMX 150/750 mg/m2 body surface area once daily by mouth	For Children Aged ≥1 Month: Dapsone 2 mg/kg body weight or 15 mg/m2 body surface area (maximum 25 mg) by mouth once daily, plus Pyrimethamine 1 mg/kg body weight (maximum 25 mg) by mouth once daily, plus Leucovorin 5 mg by mouth every 3 days For Children Aged 1–3 Months and >24 Months: Atovaquone 30 mg/kg body weight by mouth once daily Children Aged 4–24 Months: Atovaquone 45 mg/kg body weight by mouth once daily, with or without pyrimethamine 1 mg/kg body weight or 15 mg/m2 body surface area (maximum 25 mg) by mouth once daily, plus Leucovorin 5 mg by mouth every 3 days Acceptable Alternative Dosage Schedules for TMP-SMX: TMP-SMX 150/750 mg/m2 body surface area per dose once daily by mouth 3 times weekly on 3 consecutive days per week TMP-SMX 75/375 mg/m2 body surface area per dose twice daily by mouth every day TMP-SMX 75/375 mg/m2 body surface area per dose twice daily by mouth 3 times weekly on alternate days	Primary Prophylaxis Indicated For: IgG Antibody to Toxoplasma and Severe Immunosuppression: HIV-infected children aged <6 years with CD4 percentage <15%; HIV-infected children aged ≥6 years with CD4 count <100 cells/mm3 Criteria for Discontinuing Primary Prophylaxis: Note: Do not discontinue in children aged <1 year After ≥6 months of cART, and Aged 1 to <6 years; CD4 percentage is ≥15% for >3 consecutive months Aged ≥6 years; CD4 count >200 cells/mm3 for >3 consecutive months Criteria for Restarting Primary Prophylaxis: Aged 1 to <6 years with CD4 percentage <15% Aged ≥6 years with CD4 count <100 to 200 cells/mm3
Secondary Prophylaxis (Suppressive Therapy)	Sulfadiazine 42.5–60 mg/kg body weight per dose twice daily* (maximum 2–4 g per day) by mouth, plus Pyrimethamine 1 mg/kg body weight or 15 mg/m2 body surface area (maximum 25 mg) by mouth once daily, plus Leucovorin 5 mg by mouth once every 3 days	Clindamycin 7–10 mg/kg body weight per dose by mouth 3 times daily, plus Pyrimethamine 1 mg/kg body weight or 15 mg/m2 body surface area (maximum 25 mg) by mouth once daily, plus Leucovorin 5 mg by mouth once every 3 days Children Aged 1–3 Months and >24 Months: Atovaquone 30 mg/kg body weight by mouth once daily Leucovorin, 5 mg by mouth every 3 days TMP-SMX, 150/750 mg/m2 body surface area once daily by mouth Children Aged 4–24 Months: Atovaquone 45 mg/kg body weight by mouth once daily, with or without pyrimethamine 1 mg/kg body weight or 15 mg/m2 body surface area (maximum 25 mg) by mouth once daily, plus Leucovorin, 5 mg by mouth every 3 days TMP-SMX, 150/750 mg/m2 body surface area once daily by mouth	Secondary Prophylaxis Indicated: Prior toxoplasmic encephalitis Note: Alternate regimens with very limited data in children. TMP-SMX only to be used if patient intolerant to other regimens Criteria for Discontinuing Secondary Prophylaxis If All of the Following Criteria are Fulfilled: Completed ≥6 months of cART, completed initial therapy for TE, asymptomatic for TE, and Aged 1 to < 6 years; CD4 percentage ≥15% for >6 consecutive months Aged ≥6 years; CD4 cell count >200 cells/mm3 for >6 consecutive months Criteria For Restarting Secondary Prophylaxis: Aged 1 to <6 years with CD4 percentage <15% Aged ≥6 years with CD4 cell count <200 cells/mm3
Treatment	Congenital Toxoplasmosis: Pyrimethamine loading dose—2 mg/kg body weight by mouth once daily for 2 days, then 1 mg/kg body weight by mouth once daily for 2–6 months, then 1 mg/kg body weight by mouth 3 times weekly, plus Leucovorin (folinic acid) 10 mg by mouth or IM with each dose of pyrimethamine, plus Sulfadiazine 50 mg/kg body weight by mouth twice daily Treatment Duration: 12 months Acquired Toxoplasmosis Acute Induction Therapy (Followed by Chronic Suppressive Therapy): Pyrimethamine: loading dose—2 mg/kg body weight (maximum 50 mg) by mouth once daily for 3 days, then 1 mg/kg body weight (maximum 25 mg) by mouth once daily, plus Sulfadiazine 25–50 mg/kg body weight (maximum 1– 1.5 g/dose) by mouth per dose 4 times daily, plus Leucovorin 10–25 mg by mouth once daily, followed by chronic suppressive therapy Treatment Duration (Followed by Chronic Suppressive Therapy): ≥6 weeks (longer duration if clinical or radiologic disease is extensive or response in incomplete at 6 weeks)	For Sulfonamide-Intolerant Patients: Clindamycin 5–7.5 mg/kg body weight (maximum 600 mg/dose) by mouth or IV per dose given 4 times a day can be substituted for sulfadiazine combined with pyrimethamine and leucovorin	Congenital Toxoplasmosis: For infants born to mothers with symptomatic Toxoplasma infection during pregnancy, empiric therapy of the newborn should be strongly considered irrespective of the mother’s treatment during pregnancy. Acquired Toxoplasmosis: Pyrimethamine use requires CBC monitoring at least weekly while on daily dosing and at least monthly while on less than daily dosing. TMP-SMX—TMP 5 mg/kg body weight plus SMX 25 mg/kg body weight per dose IV or by mouth given twice daily has been used as an alternative to pyrimethamine-sulfadiazine in adults, but has not been studied in children. Atovaquone (for adults, 1.5 g by mouth twice daily—double the prophylaxis dose) in regimens combined with pyrimethamine/leucovorin, with sulfadiazine alone, or as a single agent in patients intolerant to both pyrimethamine and sulfadiazine, has been used in adults, but these regimens have not been studied in children. Azithromycin (for adults, 900–1,200 mg/day, corresponding to 20 mg/ kg/day in children) has also been used in adults combined with pyrimethamine-sulfadiazine, but has not been studied in children. Corticosteroids (e.g., prednisone, dexamethasone) have been used in children with CNS disease when CSF protein is very elevated (>1,000 mg/dL) or there are focal lesions with significant mass effects, with discontinuation as soon as clinically feasible. Anticonvulsants should be administered to patients with a history of seizures and continued through the acute treatment; but should not be used prophylactically.

^*Note: Sulfadiazine may be given as 2–4 equal doses per day as long as the total daily dose is 85–120 mg/kg body weight.

Key to Acronyms: cART = combination antiretroviral therapy; CBC = complete blood count; CD4 = CD4 T lymphocyte; CNS = central nervous system; CSF = cerebrospinal fluid; IgG = Immunoglobulin G; IM = intramuscular; IV = intravenous; TE = toxoplasmic encephalitis; TMP-SMX = trimethoprim-sulfamethoxazole