What is the recommended treatment guideline for toxoplasmosis?

Treatment Guidelines for Toxoplasmosis

The gold standard treatment for active toxoplasmosis in immunocompromised patients and congenital infection is pyrimethamine plus sulfadiazine plus leucovorin, as recommended by the American Academy of Pediatrics and CDC. 1, 2

Treatment by Clinical Scenario

Toxoplasmic Encephalitis in HIV/AIDS Patients

For acute toxoplasmic encephalitis in HIV/AIDS patients, administer pyrimethamine plus sulfadiazine plus leucovorin for at least 6 weeks, assuming clinical and radiological improvement. 1, 3

• After completing acute therapy, lifelong secondary prophylaxis (chronic maintenance therapy) is required to prevent relapse unless immune reconstitution occurs with HAART 1
• Secondary prophylaxis can be discontinued if CD4+ count increases to >200 cells/µL for ≥6 months on HAART 1
• The combination of pyrimethamine plus sulfadiazine also provides protection against PCP 4

Alternative regimens for sulfa-allergic patients:

• Pyrimethamine plus clindamycin is the preferred alternative, though it does not protect against PCP 4
• TMP-SMX (co-trimoxazole) can be used for 6 weeks in acquired CNS toxoplasmosis 3

Congenital Toxoplasmosis

For confirmed congenital toxoplasmosis, treat for 12 months with pyrimethamine plus sulfadiazine plus leucovorin. 1, 2

Specific dosing regimen:

• Pyrimethamine: 2 mg/kg/day for 2 days (loading dose), then 1 mg/kg/day for 2-6 months, followed by 1 mg/kg three times weekly for the remainder of the 12-month course 1, 2
• Sulfadiazine: 50 mg/kg/dose twice daily 2
• Leucovorin: supplementary dosing throughout treatment 2

Toxoplasmosis in Pregnancy

For pregnant women with suspected maternal infection but no confirmed fetal involvement, administer spiramycin 1 g (3 million IU) orally three times daily until delivery if amniocentesis is negative and fetal ultrasound shows no abnormalities. 1

• In Germany, a more aggressive approach uses spiramycin until week 16, followed by at least 4 weeks of pyrimethamine, sulfadiazine, and folinic acid regardless of fetal infection status, which has shown lower transmission rates (4.8%) and clinical manifestations (1.6%) 5
• If fetal infection is confirmed or severe ultrasound findings are present (hydrocephalus, ventricular dilation), continue pyrimethamine-sulfadiazine-folinic acid until delivery with regular drug level monitoring 5
• Because of teratogenicity concerns with pyrimethamine, some clinicians defer pyrimethamine-containing regimens until after the first trimester 4
• Pregnant women with suspected or confirmed primary toxoplasmosis should be managed in consultation with appropriate specialists 1, 2

Primary Prophylaxis in HIV Patients

All HIV-infected patients should be tested for Toxoplasma IgG antibody at initiation of care. 1, 2

Toxoplasma-seropositive patients with CD4+ count <100 cells/µL should receive prophylaxis against toxoplasmic encephalitis. 4, 1

The preferred prophylaxis regimen is TMP-SMX double-strength tablet daily, which also protects against PCP. 4, 1

Alternative prophylaxis regimens for TMP-SMX intolerant patients:

• Dapsone plus pyrimethamine provides protection against both toxoplasmic encephalitis and PCP 4
• Atovaquone may provide protection, though data are limited 4, 2
• Aerosolized pentamidine does NOT protect against toxoplasmic encephalitis 4

For toxoplasma-seronegative patients:

• Retest for IgG antibody when CD4+ count falls below 100 cells/µL to determine if seroconversion has occurred 4
• If seroconverted, initiate prophylaxis as above 4

Prevention of Exposure

Toxoplasma-seronegative HIV-infected persons should be counseled on avoiding new infection: 4, 2

• Do not eat raw or undercooked meat, particularly pork, lamb, or venison; cook meat to internal temperature of 150°F (meat cooked until no longer pink inside reaches 165°F) 4
• Wash hands after contact with raw meat and after gardening or soil contact 4
• Wash fruits and vegetables well before eating raw 4
• If owning a cat, change litter box daily (preferably by HIV-negative person), or wash hands thoroughly after changing 4
• Keep cats inside, do not adopt or handle stray cats 4
• Feed cats only canned/dried commercial food or well-cooked table food, not raw or undercooked meats 4
• Patients need not part with their cats or have cats tested for toxoplasmosis 4

Monitoring During Treatment

Complete blood count should be performed at least weekly while on daily pyrimethamine and at least monthly while on less than daily dosing to monitor for bone marrow suppression. 2, 3

• In patients receiving high-dose therapy, semiweekly blood counts including platelet counts should be performed 6
• Monitor for signs of folate deficiency: anorexia, vomiting, sore throat, pallor, purpura, glossitis 6
• If signs of folate deficiency develop, reduce dosage or discontinue pyrimethamine and administer folinic acid 5-15 mg daily until normal hematopoiesis is restored 6

Common Pitfalls and Caveats

Pyrimethamine-sulfadiazine therapy carries significant risk of bone marrow suppression, particularly neutropenia, especially when leucovorin is not administered, with adverse events occurring in 20-50% of treated infants in some series. 1

• Concurrent administration of folinic acid (leucovorin) is strongly recommended when pyrimethamine is used for treatment of toxoplasmosis in all patients 6
• The dosage of pyrimethamine required for treatment has a narrow therapeutic window 6
• Concomitant use of other antifolate drugs or myelosuppressive agents (sulfonamides, TMP-SMX, proguanil, zidovudine, methotrexate) may increase risk of bone marrow suppression 6
• Pyrimethamine should be kept out of reach of children as they are extremely susceptible to adverse effects; deaths in pediatric patients have been reported after accidental ingestion 6
• At first appearance of skin rash, stop pyrimethamine immediately and seek medical attention 6
• Anorexia and vomiting may be minimized by taking medication with meals 6
• Inadequate duration of therapy may lead to relapse, particularly in immunocompromised patients 3
• Repeated neuroimaging 2 weeks after initiating therapy is needed to assess treatment efficacy in CNS toxoplasmosis 7
• Tissue diagnosis should be established in patients who do not respond to treatment, who have solitary lesions, or in non-AIDS patients 7