Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

occupational exposure

1st line – prophylactic pyrimethamine + sulfadiazine + leucovorin

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INITIAL
|
occupational exposure
1st line – 

prophylactic pyrimethamine + sulfadiazine + leucovorin

This group is composed of patients exposed to Toxoplasma gondii by contact with infected blood or cell cultures.

Anti-Toxoplasma immunoglobulin G should be checked immediately to identify those at risk for acute infection.

All seronegative exposed patients or those with unknown serology should be treated. Most experts would treat all individuals with a definite exposure.

For those with no detectable antibodies, treatment is given for 4 weeks and serology repeated. If seroconversion is documented, patients should be followed clinically.

If seropositive at onset of treatment or known positive prior to exposure, the patient is probably partially protected. Most experts would treat high inoculum deep exposures of a virulent type I strain for 2 weeks.

Primary options

pyrimethamine: adults: 50-75 mg orally once daily

and

sulfadiazine: adults: 1000 mg orally four times daily

and

leucovorin: adults: 10-25 mg orally once daily

HIV-positive with CD4+ T lymphocyte counts <100

1st line – prophylactic trimethoprim/sulfamethoxazole

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INITIAL
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HIV-positive with CD4+ T lymphocyte counts <100
1st line – 

prophylactic trimethoprim/sulfamethoxazole

Given to prevent symptomatic disease.

For all patients with HIV and CD4+ T lymphocyte counts <100 cells per microliter and children <6 years old with CD4 cell percentage <15% who have positive serologies.[25][52]​​ Primary prophylaxis can be discontinued for adolescent and adult patients taking antiretroviral therapy with CD4+ T lymphocyte counts between 100 and 200 cells/microliter if the HIV RNA plasma viral load remains below the limit of detection for at least 3 to 6 months.[25]

Primary options

sulfamethoxazole/trimethoprim: children: 150 mg/square meter of body surface area orally once daily; adults: 160 mg orally once daily

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2nd line – nonsulfonamide prophylactic regimen

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INITIAL
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HIV-positive with CD4+ T lymphocyte counts <100
2nd line – 

nonsulfonamide prophylactic regimen

Second-line options for prophylaxis for patients with HIV who are allergic to, or severely intolerant of, sulfa-based medicines.[25]

Primary options

dapsone: children >1 month of age: 2 mg/kg (or 15 mg/square meter of body surface area) orally once daily, maximum 25 mg/day; adults: 50 mg orally once daily

and

pyrimethamine: children >1 month of age: 1 mg/kg (or 15 mg/square meter of body surface area) orally once daily, maximum 25 mg/day; adults: 50 mg orally once weekly

and

leucovorin: children >1 month of age: 5 mg orally every three days; adults: 25 mg orally once weekly

Secondary options

dapsone: adults: 200 mg orally once weekly

and

pyrimethamine: adults: 75 mg orally once weekly

and

leucovorin: adults: 25 mg orally once weekly

Tertiary options

atovaquone: children 1-3 months of age and >24 months of age: 30 mg/kg orally once daily; children 4-24 months of age: 45 mg/kg orally once daily; adults: 1500 mg orally once daily

OR

atovaquone: children 4-24 months of age: 45 mg/kg orally once daily; adults: 1500 mg orally once daily

and

pyrimethamine: children 4-24 months of age: 1 mg/kg (or 15 mg/square meter of body surface area) orally once daily, maximum 25 mg/day; adults: 25 mg orally once daily

and

leucovorin: children 4-24 months of age: 5 mg orally every three days; adults: 10 mg orally once daily

seronegative recipients of solid organs from seropositive donors; seropositive recipients of allogeneic hematopoietic stem cell transplant

1st line – prophylactic trimethoprim/sulfamethoxazole

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INITIAL
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seronegative recipients of solid organs from seropositive donors; seropositive recipients of allogeneic hematopoietic stem cell transplant
1st line – 

prophylactic trimethoprim/sulfamethoxazole

Given to prevent symptomatic disease.

There are very few data supporting prophylactic regimens other than trimethoprim/sulfamethoxazole for toxoplasmosis in the transplant population.[26] Any treatment decisions should be made in consultation with physicians specializing in transplantation and infectious diseases.

After completing initial treatment, patients should continue to receive secondary prophylaxis to prevent reactivation of disease, for as long as they remain immunocompromised. The optimal duration for prophylaxis after transplant is not known, and it is sometimes continued for life. Lifelong prophylaxis is recommended for high-risk heart transplant recipients (where the donor is Toxoplasma immunoglobulin [Ig] G positive and the recipient is Toxoplasma IgG negative).

Primary options

sulfamethoxazole/trimethoprim: children: consult specialist for guidance on dose; adults: 160 mg orally three times weekly or 80 mg once daily for 3 months, followed by 160 mg once daily thereafter

More

2nd line – nonsulfonamide prophylactic regimen

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INITIAL
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seronegative recipients of solid organs from seropositive donors; seropositive recipients of allogeneic hematopoietic stem cell transplant
2nd line – 

nonsulfonamide prophylactic regimen

In sulfa-allergic patients who are not deficient in glucose-6-phosphate dehydrogenase, an alternative prophylaxis regimen is dapsone plus pyrimethamine and leucovorin. If there is a contraindication to trimethoprim/sulfamethoxazole, consult an infectious diseases specialist for advice on alternative regimens.[26]

After completing initial treatment, patients should continue to receive secondary prophylaxis to prevent reactivation of disease for as long as they remain immunocompromised. The optimal duration for prophylaxis after transplant is unknown, and it is sometimes continued for life. Lifelong prophylaxis is recommended for high-risk heart transplant recipients (where the donor is Toxoplasma immunoglobulin [Ig] G positive and the recipient is Toxoplasma IgG negative).

Primary options

dapsone: children and adults: consult specialist for guidance on dose

and

pyrimethamine: children and adults: consult specialist for guidance on dose

and

leucovorin: children and adults: consult specialist for guidance on dose

ACUTE

newborns: confirmed or highly suspected congenital disease

1st line – pyrimethamine + sulfadiazine + leucovorin

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ACUTE
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newborns: confirmed or highly suspected congenital disease
1st line – 

pyrimethamine + sulfadiazine + leucovorin

Given to newborns with confirmed or highly suspected congenital disease to prevent or limit damage to the central nervous system and eyes and to prevent death.

Initiate before 2.5 months of life and continue for 1 year.[11][52][58]

Benefits include reduced risk of blindness, intellectual disability, seizures, and death.

Risks are side effects from medications (e.g., bone marrow suppression or hypersensitivity reaction).

Primary options

pyrimethamine: 2 mg/kg orally once daily for 2 days, followed by 1 mg/kg once daily for 2-6 months, then 1 mg/kg three times weekly

and

sulfadiazine: 50 mg/kg orally twice daily

and

leucovorin: 10 mg orally/intramuscularly with each dose of pyrimethamine

Consider – prednisone

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ACUTE
|
newborns: confirmed or highly suspected congenital disease
Consider – 

prednisone

Treatment recommended for SOME patients in selected patient group

Given only in the setting of elevated cerebrospinal fluid (CSF) protein (>1 g) or in severe, vision-threatening chorioretinitis, when it is given to prevent loss of vision and blindness, and to reduce the duration of symptomatic disease.[11]

Rapidly taper after resolution of elevated CSF protein or after resolution of ocular inflammation.

Primary options

prednisone: 1 mg/kg/day orally

2nd line – nonsulfonamide regimen

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ACUTE
|
newborns: confirmed or highly suspected congenital disease
2nd line – 

nonsulfonamide regimen

For patients allergic to or severely intolerant of sulfa-based medications.

None of these alternative regimens have been adequately studied to warrant formal recommendations, although they are recommended in the guidelines.​[52]

Primary options

pyrimethamine: 2 mg/kg orally once daily for 2 days, followed by 1 mg/kg once daily for 2-6 months, then 1 mg/kg three times weekly

and

leucovorin: 10 mg orally/intramuscularly with each dose of pyrimethamine

and

clindamycin: consult specialist for guidance on dose

Consider – prednisone

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ACUTE
|
newborns: confirmed or highly suspected congenital disease
Consider – 

prednisone

Treatment recommended for SOME patients in selected patient group

Given only in the setting of elevated cerebrospinal fluid (CSF) protein (>1 g) or in severe, vision-threatening chorioretinitis, when it is given to prevent loss of vision and blindness, and to reduce the duration of symptomatic disease.[11]

Rapidly taper after resolution of elevated CSF protein or after resolution of ocular inflammation.

Primary options

prednisone: 1 mg/kg/day orally

nonpregnant adults and children: confirmed or suspected disease

1st line – pyrimethamine + sulfadiazine + leucovorin

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ACUTE
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nonpregnant adults and children: confirmed or suspected disease
|
immunocompromised
1st line – 

pyrimethamine + sulfadiazine + leucovorin

For all patients with suspected or confirmed disease. Given to prevent death and organ-specific damage.

Duration of treatment for acute disease is at least 6 weeks, but patients may require a longer course if central nervous system lesions have not resolved.[25][26]

Primary options

pyrimethamine: children: 2 mg/kg (maximum 50 mg/dose) orally once daily for 3 days, followed by 1 mg/kg (maximum 25 mg/dose) once daily; adults (body weight <60 kg): 200 mg orally as a loading dose, followed by 50 mg once daily; adults (body weight ≥60 kg): 200 mg orally as a loading dose, followed by 75 mg once daily

and

sulfadiazine: children: 25-50 mg/kg (maximum 1500 mg/dose) orally four times daily; adults (body weight <60 kg): 1000 mg orally four times daily; adults (body weight ≥60 kg): 1500 mg orally four times daily

and

leucovorin: children and adults: 10-25 mg orally once daily

More

Consider – dexamethasone

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ACUTE
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nonpregnant adults and children: confirmed or suspected disease
|
immunocompromised
Consider – 

dexamethasone

Treatment recommended for SOME patients in selected patient group

Given only to treat mass effect or associated edema. Discontinue as soon as clinically feasible.

Primary options

dexamethasone sodium phosphate: children: 1-2 mg/kg intravenously initially, followed by 1 to 1.5 mg/kg/day given in divided doses every 4-6 hours until symptoms resolve, then gradually taper; adults: 10 mg intravenously initially, followed by 4 mg every 6 hours until symptoms resolve, then gradually taper

2nd line – alternative sulfonamide or nonsulfonamide regimen

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ACUTE
|
nonpregnant adults and children: confirmed or suspected disease
|
immunocompromised
2nd line – 

alternative sulfonamide or nonsulfonamide regimen

Treatment is given for at least 6 weeks.

Primary options

pyrimethamine: children: 2 mg/kg (maximum 50 mg/dose) orally once daily for 3 days, followed by 1 mg/kg (maximum 25 mg/dose) once daily; adults (body weight <60 kg): 200 mg orally as a loading dose, followed by 50 mg once daily; adults (body weight ≥60 kg): 200 mg orally as a loading dose, followed by 75 mg once daily

and

clindamycin: children: 5 to 7.5 mg/kg (maximum 600 mg/dose) orally/intravenously every 6 hours; adults: 600 mg orally/intravenously every 6 hours

and

leucovorin: children and adults: 10-25 mg orally once daily

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OR

sulfamethoxazole/trimethoprim: adults: 5 mg/kg intravenously/orally twice daily

More

OR

pyrimethamine: adults (body weight <60 kg): 200 mg orally as a loading dose, followed by 50 mg once daily; adults (body weight ≥60 kg): 200 mg orally as a loading dose, followed by 75 mg once daily

and

atovaquone: adults: 1500 mg orally twice daily

and

leucovorin: adults: 10-25 mg orally once daily

More

OR

atovaquone: adults: 1500 mg orally twice daily

and

sulfadiazine: adults (body weight <60 kg): 1000 mg orally four times daily; adults (body weight ≥60 kg): 1500 mg orally four times daily

OR

atovaquone: adults: 1500 mg orally twice daily

Consider – dexamethasone

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ACUTE
|
nonpregnant adults and children: confirmed or suspected disease
|
immunocompromised
Consider – 

dexamethasone

Treatment recommended for SOME patients in selected patient group

Given only to treat mass effect or associated edema.

Primary options

dexamethasone sodium phosphate: children: 1-2 mg/kg intravenously initially, followed by 1 to 1.5 mg/kg/day given in divided doses every 4-6 hours until symptoms resolve then gradually taper; adults: 10 mg intravenously initially, followed by 4 mg every 6 hours until symptoms resolve then gradually taper

1st line – observation and assessment

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ACUTE
|
nonpregnant adults and children: confirmed or suspected disease
|
immunocompetent
1st line – 

observation and assessment

Most infections in healthy people are mild and self-limiting and do not need treatment; such patients should be observed.

Consider – pyrimethamine + sulfadiazine + leucovorin + prednisone

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ACUTE
|
nonpregnant adults and children: confirmed or suspected disease
|
immunocompetent
Consider – 

pyrimethamine + sulfadiazine + leucovorin + prednisone

Treatment recommended for SOME patients in selected patient group

Patients with chorioretinitis who are immunocompetent may require treatment to prevent loss of vision and to reduce the duration of symptomatic disease. Treatment for both congenital and acquired ocular disease is controversial and depends on expert evaluation of the clinical findings. It should be undertaken only in conjunction with an ophthalmologist.

One systematic review concluded that antibiotic treatment probably reduces the risk of recurrent toxoplasmic chorioretinitis, but there was a lack of evidence that antibiotics resulted in better visual outcomes, and there were no data evaluating the effects of adjunctive corticosteroids.[60][61] Despite a lack of evidence to support routine antibiotic treatment, treatment is warranted for severe or persistent lesions involving the macula or optic nerve, for large retinal lesions with severe inflammation, and for any lesion in a person who is immunocompromised.[60][61][62]

Standard treatment is with pyrimethamine, sulfadiazine, leucovorin, and prednisone. Treatment should be continued for 1 to 2 weeks after signs and symptoms resolve.

Other treatment regimens, such as those containing clindamycin, trimethoprim/sulfamethoxazole or azithromycin, have been used to variable effect, but there is insufficient evidence to recommend these treatments.[65][66][67]

Primary options

pyrimethamine: children: 2 mg/kg (maximum 50 mg/dose) orally once daily for 3 days, followed by 1 mg/kg (maximum 25 mg/dose) once daily; adults (body weight <60 kg): 200 mg orally as a loading dose, followed by 50 mg once daily; adults (body weight ≥60 kg): 200 mg orally as a loading dose, followed by 75 mg once daily

and

sulfadiazine: children: 25-50 mg/kg (maximum 1500 mg/dose) orally four times daily; adults (body weight <60 kg): 1000 mg orally four times daily; adults (body weight ≥60 kg): 1500 mg orally four times daily

and

leucovorin: children and adults: 10-25 mg orally once daily

More

and

prednisone: children and adults: 1 mg/kg/day orally, maximum 40 mg/day, continue until signs of active, vision-threatening chorioretinitis subside, then taper and discontinue

pregnant: with seroconversion

1st line – spiramycin OR pyrimethamine + sulfadiazine + leucovorin

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ACUTE
|
pregnant: with seroconversion
1st line – 

spiramycin OR pyrimethamine + sulfadiazine + leucovorin

Spiramycin can be given if maternal infection occurs before 18 weeks' gestation and is continued throughout pregnancy if there is no evidence of transmission of infection to the fetus.[11] It has orphan drug status in the US and must be obtained from the Food and Drug Administration after consultation and confirmatory testing with a reference laboratory.

If maternal infection occurs after 18 weeks gestation, or fetal transmission has been documented on amniotic fluid PCR at ≥18 weeks gestation, pyrimethamine/sulfadiazine/leucovorin should be given.[11]

Ultrasound follow-up should include examination of the fetus every 4 weeks, with a focus on brain, eye, and growth assessment.[11][53]

Primary options

<18 weeks’ gestation

spiramycin: 1 g orally every 8 hours

OR

≥18 weeks’ gestation

pyrimethamine: 50 mg orally twice daily for 2 days, followed by 50 mg once daily

and

sulfadiazine: 75 mg/kg orally as a single dose, followed by 50 mg/kg twice daily, maximum 4000 mg/day

and

leucovorin: 10-20 mg orally once daily

ONGOING

immunocompromised: following symptomatic disease

1st line – pyrimethamine + sulfadiazine + leucovorin

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ONGOING
|
immunocompromised: following symptomatic disease
1st line – 

pyrimethamine + sulfadiazine + leucovorin

Given after the initial course of treatment to all patients to prevent relapse of symptomatic disease.

However, it may be stopped in patients with HIV on antiretroviral therapy who have CD4+ T lymphocytes >200 cells/microliter for 6 or more months, or in transplant recipients on no immunosuppressive medications.[25]

Primary options

pyrimethamine: children: 1 mg/kg (or 15 mg/square meter of body surface area) orally once daily, maximum 25 mg/day; adults: 25-50 mg orally once daily

and

sulfadiazine: children: 42.5 to 60 mg/kg orally twice daily, maximum 4000 mg/day; adults: 2000-4000 mg/day orally given in 2-4 divided doses

and

leucovorin: children: 5 mg orally every three days; adults: 10-25 mg orally once daily

2nd line – alternative maintenance regimen

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ONGOING
|
immunocompromised: following symptomatic disease
2nd line – 

alternative maintenance regimen

Alternative regimens given after initial course of treatment to all patients to prevent relapse of symptomatic disease.[25]

However, it may be stopped in patients with HIV on antiretroviral therapy who have CD4+ T lymphocytes >200 cells/microliter for 6 or more months, or in transplant recipients on no immunosuppressive medications.[25]

Primary options

pyrimethamine: children: 1 mg/kg (or 15 mg/square meter of body surface area) orally once daily, maximum 25 mg/day; adults: 25-50 mg orally once daily

and

clindamycin: children: 7-10 mg/kg orally three times daily; adults: 600 mg orally three times daily

and

leucovorin: children: 5 mg orally every three days; adults: 10-25 mg orally once daily

OR

sulfamethoxazole/trimethoprim: children: 150 mg/square meter of body surface area orally once daily; adults: 160 mg orally once or twice daily

More

OR

atovaquone: children 4-24 months of age: 45 mg/kg orally once daily; adults: 750-1500 mg orally twice daily

and

pyrimethamine: children 4-24 months of age: 1 mg/kg (or 15 mg/square meter of body surface area) orally once daily, maximum 25 mg/day; adults: 25 mg orally once daily

and

leucovorin: children 4-24 months of age: 5 mg orally every three days; adults: 10 mg orally once daily

OR

atovaquone: children 1-3 months of age and >24 months of age: 30 mg/kg orally once daily; children 4-24 months of age: 45 mg/kg orally once daily; adults: 750-1500 mg orally twice daily

OR

atovaquone: adults: 750-1500 mg orally twice daily

and

sulfadiazine: adults: 2000-4000 mg/day orally given in 2-4 divided doses

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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