Toxoplasma gondii Encephalitis

Primary Prophylaxis

Start: if CD4 count < 200 cells/μL, or CD4 percentage < 14%, oral thrush, or relevant concomitant immunosuppression, see Primary prophylaxis of OIs

Stop: if CD4 count > 100 cells/μL and HIV-VL undetectable over 3 months

	Drug / Dose	Comments
Preferred prophylaxis	TMP-SMX 80/400 mg qd po or 160/800 mg qd po or 160/800 mg x 3/week po	All regimens are also effective against PcP
Alternative prophylaxis	atovaquone suspension 1500 mg qd po (with food)
	dapsone 200 mg/week po + pyrimethamine 75 mg/week po + folinic acid 25-30 mg/week po	Check for G6PD-deficiency
	atovaquone suspension 1500 mg qd po (with food) + pyrimethamine 75 mg/week po + folinic acid 25-30 mg/week po

Diagnosis and treatment

Diagnosis:
Definitive diagnosis: clinical symptoms, typical focal lesions neuroradiology AND cytological / histological detection of organism in brain tissue. Toxoplasma PCR in CSF has high specificity (95-100%) but low sensitivity (50%)

Presumptive diagnosis: clinical symptoms, serum Ig G toxoplasma Ab, typical focal lesions neuroradiology AND response to empirical treatment. This is the standard in most clinical settings

Notes on treatment:
- Treat 6 weeks, then secondary prophylaxis until CD4 count > 200 cells/μL and HIV-VL undetectable over 6 months
- In patients with cerebral lesions (or surrounding edema) causing mass effect, corticosteroids (dexamethasone) could be used as adjunctive therapy. Corticosteroids should be discontinued as soon as clinically feasible to prevent immunosuppression
- See also anti-infective/ART interaction table for treatment optimization

	Drug / Dose	Comments
Preferred therapies	pyrimethamine Day 1: 200 mg qd po, then If ≥ 60 kg: 75 mg qd po; If < 60 kg: 50 mg qd po + sulfadiazine If ≥ 60 kg: 3000 mg bid po/iv; If < 60 kg: 2000 mg bid po/iv + folinic acid 10-15 mg/day po	Monitor for myelotoxicity of pyrimethamine, mostly neutropenia Sulfadiazine is associated with crystalluria and may lead to renal failure and urolithiasis. Good hydration is essential. Check renal function and urine sediment for microhematuria and crystalluria
TMP-SMX 5 mg TMP/kg bid iv/po + 25 mg SMX/kg bid iv/po	Preferred intravenous regimen if oral route not possible A recent meta-analysis showed that this regimen is as effective and possibly safer than pyrimethamine-based regimens. Furthermore, in countries where there are supply shortages for pyrimethamine or it cannot be administered due to its high price, TMP-SMX should be the preferred therapeutic option. Monitor myelotoxicity (mainly neutropenia), kidney function and electrolytes (mainly high potassium)
Alternative therapies	pyrimethamine Day 1: 200 mg qd po, then • If ≥ 60 kg: 75 mg qd po • If < 60 kg: 50 mg qd po + clindamycin 600-900 mg qid po/iv + folinic acid 10-15 mg qd po	Monitor for myelotoxicity of pyrimethamine, mostly neutropenia Additional PcP prophylaxis is necessary
OR pyrimethamine Day 1: 200 mg qd po, then If ≥ 60 kg: 75 mg qd po; If < 60 kg: 50 mg qd po + atovaquone 1500 mg bid po (with food) + folinic acid 10-15 mg qd po	Monitor for myelotoxicity of pyrimethamine, mostly neutropenia
OR sulfadiazine If ≥ 60 kg: 3000 mg bid po/iv; If < 60 kg: 2000 mg bid po/iv + atovaquone 1500 mg bid po (with food)	Sulfadiazine is associated with crystalluria and may lead to renal failure and urolithiasis. Good hydration is essential. Check renal function and urine sediment for microhematuria and crystalluria
OR pyrimethamine Day 1: 200 mg qd po, then If ≥ 60 kg: 75 mg qd po; If < 60 kg: 50 mg qd po + azitromycin 900-1200 mg qd po + folinic acid 10-15 mg qd po	Monitor for myelotoxicity of pyrimethamine, mostly neutropenia

Drug / Dose

Comments

Preferred therapies

pyrimethamine
Day 1: 200 mg qd po,
then
If ≥ 60 kg: 75 mg qd po;
If < 60 kg: 50 mg qd po

+ sulfadiazine
If ≥ 60 kg: 3000 mg bid po/iv;
If < 60 kg: 2000 mg bid po/iv

+ folinic acid
10-15 mg/day po

Monitor for myelotoxicity of pyrimethamine, mostly neutropenia

Sulfadiazine is associated with crystalluria and may lead to renal failure and urolithiasis. Good hydration is essential. Check renal function and urine sediment for microhematuria and crystalluria

TMP-SMX
5 mg TMP/kg bid iv/po +
25 mg SMX/kg bid iv/po

Preferred intravenous regimen if oral route not possible
A recent meta-analysis showed that this regimen is as effective and possibly safer than pyrimethamine-based regimens. Furthermore, in countries where there are supply shortages for pyrimethamine or it cannot be administered due to its high price, TMP-SMX should be the preferred therapeutic option.
Monitor myelotoxicity (mainly neutropenia), kidney function and electrolytes (mainly high potassium)

Alternative therapies

pyrimethamine
Day 1: 200 mg qd po, then
• If ≥ 60 kg: 75 mg qd po
• If < 60 kg: 50 mg qd po

+ clindamycin
600-900 mg qid po/iv

+ folinic acid
10-15 mg qd po

Monitor for myelotoxicity of pyrimethamine, mostly neutropenia

Additional PcP prophylaxis is necessary

OR pyrimethamine
Day 1: 200 mg qd po, then
If ≥ 60 kg: 75 mg qd po;
If < 60 kg: 50 mg qd po

+ atovaquone
1500 mg bid po (with food)

+ folinic acid
10-15 mg qd po

Monitor for myelotoxicity of pyrimethamine, mostly neutropenia

OR sulfadiazine
If ≥ 60 kg: 3000 mg bid po/iv;
If < 60 kg: 2000 mg bid po/iv

+ atovaquone
1500 mg bid po (with food)

OR pyrimethamine
Day 1: 200 mg qd po, then
If ≥ 60 kg: 75 mg qd po;
If < 60 kg: 50 mg qd po

+ azitromycin
900-1200 mg qd po

+ folinic acid
10-15 mg qd po

Monitor for myelotoxicity of pyrimethamine, mostly neutropenia

Secondary Prophylaxis, Maintenance Therapy

Stop: if CD4 count > 200 cells/μL and HIV-VL undetectable over 6 months

Regimens listed are alternatives

Drug / Dose	Comments
sulfadiazine 2000-4000 mg daily po in 2-4 doses + pyrimethamine 25-50 mg qd po + folinic acid 10-15 mg qd po
OR TMP-SMX 160/800 mg bid po
OR clindamycin 600 mg tid po + pyrimethamine 25-50 mg qd po + folinic acid 10-15 mg qd po	Additional PcP prophylaxis is necessary
OR atovaquone suspension 750-1500 mg bid po (with food) + pyrimethamine 25-50 mg qd po + folinic acid 10-15 mg qd po
OR atovaquone suspension 750-1500 mg bid po (with food)

Drug / Dose

Comments

sulfadiazine
2000-4000 mg daily po
in 2-4 doses

+ pyrimethamine
25-50 mg qd po

+ folinic acid
10-15 mg qd po

OR TMP-SMX
160/800 mg bid po

OR clindamycin
600 mg tid po

+ pyrimethamine
25-50 mg qd po

+ folinic acid
10-15 mg qd po

Additional PcP prophylaxis is necessary

OR atovaquone suspension
750-1500 mg bid po (with food)

+ pyrimethamine
25-50 mg qd po

+ folinic acid
10-15 mg qd po

OR atovaquone suspension
750-1500 mg bid po (with food)