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

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

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prophylactic pyrimethamine + sulfadiazine + calcium folinate

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

calcium folinate: adults: 10-25 mg orally once daily

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prophylactic trimethoprim/sulfamethoxazole

Given to prevent symptomatic disease.

For all patients with HIV and CD4+ T lymphocyte counts <100 cells/microlitre and children <6 years old with CD4 cell percentage <15% who have positive serologies.[24][49]​​ Primary prophylaxis can be discontinued for adolescent and adult patients taking antiretroviral therapy with CD4+ T lymphocyte counts between 100 and 200 cells/microlitre if the HIV RNA plasma viral load remains below the limit of detection for at least 3 to 6 months.[24]

Primary options

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

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non-sulfonamide prophylactic regimen

Second-line options for prophylaxis for patients with HIV who are allergic to, or severely intolerant of, sulfonamides.[24]

Primary options

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

and

calcium folinate: 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

calcium folinate: 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 metre of body surface area) orally once daily, maximum 25 mg/day; adults: 25 mg orally once daily

and

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

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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.[25] Any treatment decisions should be made in consultation with physicians specialising 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

trimethoprim/sulfamethoxazole: 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

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non-sulfonamide prophylactic regimen

In sulfa-allergic patients who are not deficient in glucose-6-phosphate dehydrogenase, an alternative prophylaxis regimen is dapsone plus pyrimethamine and calcium folinate. If there is a contraindication to trimethoprim/sulfamethoxazole, consult an infectious diseases specialist for advice on alternative regimens.[25]

After completing initial treatment, patients should continue to receive secondary prophylaxis to prevent re-activation 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 isToxoplasma 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

calcium folinate: children and adults: consult specialist for guidance on dose

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pyrimethamine + sulfadiazine + calcium folinate

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][49][55]

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

Risks are side effects from medicines (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

calcium folinate: 10 mg orally/intramuscularly with each dose of pyrimethamine

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prednisolone

Additional 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

prednisolone: 1 mg/kg/day orally

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non-sulfonamide regimen

For patients allergic to or severely intolerant of sulfonamides.

None of these alternative regimens have been adequately studied to warrant formal recommendations, although they are recommended in the guidelines.​[49]

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

calcium folinate: 10 mg orally/intramuscularly with each dose of pyrimethamine

and

clindamycin: consult specialist for guidance on dose

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prednisolone

Additional 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

prednisolone: 1 mg/kg/day orally

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pyrimethamine + sulfadiazine + calcium folinate

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.[24][25]

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

calcium folinate: children and adults: 10-25 mg orally once daily

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dexamethasone

Additional treatment recommended for SOME patients in selected patient group

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

Primary options

dexamethasone: 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

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alternative sulfonamide or non-sulfonamide 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

calcium folinate: children and adults: 10-25 mg orally once daily

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OR

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

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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

calcium folinate: adults: 10-25 mg orally once daily

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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

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dexamethasone

Additional treatment recommended for SOME patients in selected patient group

Given only to treat mass effect or associated oedema.

Primary options

dexamethasone: 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

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observation and assessment

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

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pyrimethamine + sulfadiazine + calcium folinate + prednisolone

Additional 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.[57][58] 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.[57][58][59]

Standard treatment is with pyrimethamine, sulfadiazine, calcium folinate, and prednisolone. 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.[62][63][64]

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

calcium folinate: children and adults: 10-25 mg orally once daily

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and

prednisolone: 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

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spiramycin OR pyrimethamine + sulfadiazine + calcium folinate

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] Although marketed worldwide, it is not currently licensed for toxoplasmosis in the UK where it can be obtained on named-patient use.

If maternal infection occurs after 18 weeks gestation, or fetal transmission has been documented on amniotic fluid PCR at ≥18 weeks gestation, pyrimethamine/sulfadiazine/calcium folinate 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

calcium folinate: 10-20 mg orally once daily

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pyrimethamine + sulfadiazine + calcium folinate

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/microlitre for 6 or more months, or in transplant recipients on no immunosuppressive medications.[24]

Primary options

pyrimethamine: children: 1 mg/kg (or 15 mg/square metre 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

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

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alternative maintenance regimen

Alternative regimens given after initial course of treatment to all patients to prevent relapse of symptomatic disease.[24]

However, it may be stopped in patients with HIV on antiretroviral therapy who have CD4+ T lymphocytes >200 cells/microlitre for 6 or more months, or in transplant recipients on no immunosuppressive medicines.[24]

Primary options

pyrimethamine: children: 1 mg/kg (or 15 mg/square metre 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

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

OR

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

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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 metre of body surface area) orally once daily, maximum 25 mg/day; adults: 25 mg orally once daily

and

calcium folinate: 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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