What is the recommended prophylaxis treatment for Toxoplasma gondii?

Prophylaxis Treatment for Toxoplasma gondii

For HIV-infected patients who are Toxoplasma-seropositive with CD4+ counts <100 cells/µL, trimethoprim-sulfamethoxazole (TMP-SMX) one double-strength tablet daily is the recommended prophylaxis, which also provides cross-protection against PCP and common bacterial infections. 1, 2

Who Needs Prophylaxis

HIV-Infected Patients

• All HIV-infected persons should be tested for IgG antibody to Toxoplasma at the time of HIV diagnosis to identify those with latent infection who are at risk for reactivation 1, 2
• Initiate prophylaxis when CD4+ count falls below 100 cells/µL in Toxoplasma-seropositive patients 1, 2
• Toxoplasma-seronegative patients not on active prophylaxis should be retested when CD4+ drops below 100 cells/µL to detect seroconversion 1

Hematopoietic Stem Cell Transplant Recipients

• All allogeneic HSCT recipients and donors should undergo pretransplantation Toxoplasma IgG and IgM screening 3
• Toxoplasma-seropositive HSCT recipients require prophylaxis for at least 6 months post-transplant or until immunosuppression ends, whichever is longer 3, 4
• Universal prophylaxis with TMP-SMX should be implemented by all transplant programs for seropositive allogeneic HSCT patients 4

Solid Organ Transplant Recipients

• Toxoplasma-seronegative renal transplant recipients are at risk for primary infection and should continue TMP-SMX prophylaxis 5
• Discontinuation of TMP-SMX prophylaxis has been associated with development of primary toxoplasmosis with 50% mortality 5

First-Line Prophylaxis Regimen

TMP-SMX Dosing Options

• Preferred: One double-strength tablet (160mg TMP/800mg SMX) daily 1
• Alternative: One single-strength tablet daily (may be better tolerated while maintaining efficacy) 1
• Alternative: One double-strength tablet three times weekly 1

Additional Benefits of TMP-SMX

• The double-strength daily dose provides cross-protection against toxoplasmic encephalitis, PCP, and common respiratory bacterial infections 1
• Lower doses of TMP-SMX may also confer protection against toxoplasmosis, though the double-strength daily dose has the strongest evidence 1

Managing TMP-SMX Intolerance

• For non-life-threatening adverse reactions, continue TMP-SMX if clinically feasible 1
• Consider desensitization with gradual dose escalation - up to 70% of patients can tolerate reinstitution 1
• Reintroduce at reduced dose or frequency after adverse event resolution 1

Alternative Prophylaxis Regimens (When TMP-SMX Cannot Be Tolerated)

For Toxoplasma-Seropositive Patients

The following regimens provide dual protection against both toxoplasmosis and PCP:

• Dapsone 50mg daily PLUS pyrimethamine 50mg weekly PLUS leucovorin 25mg weekly 1

  • This is the preferred alternative for Toxoplasma-seropositive patients 1
  • Check G6PD levels before initiating dapsone 6
  • Monitor CBC monthly for hematologic toxicity 6

• Atovaquone 1500mg daily with or without pyrimethamine 1

  • Must be administered with fatty foods to ensure adequate absorption 7
  • Substantially more expensive than other regimens 1

Regimens That Do NOT Protect Against Toxoplasmosis

The following should be avoided in Toxoplasma-seropositive patients:

• Dapsone monotherapy - does not provide adequate protection against toxoplasmosis 1
• Aerosolized pentamidine - provides no protection against toxoplasmic encephalitis 1, 2
• Pyrimethamine, azithromycin, or clarithromycin monotherapy 1

Discontinuing Primary Prophylaxis

In HIV Patients on HAART

• Prophylaxis can be safely discontinued when CD4+ count increases to >200 cells/µL for at least 3-6 months 1
• Most supporting data comes from patients on protease inhibitor-containing regimens with median CD4+ counts >300 cells/µL at discontinuation 1
• Many patients also had sustained viral suppression below detection limits 1

Restarting Prophylaxis

• Reinitiate prophylaxis if CD4+ count decreases to <200 cells/µL (for PCP) or <100 cells/µL (specifically for toxoplasmosis) 1

Secondary Prophylaxis (After Active Toxoplasmic Encephalitis)

Lifelong Suppressive Therapy

• Patients with prior toxoplasmic encephalitis require lifelong secondary prophylaxis with pyrimethamine plus sulfadiazine plus leucovorin 1, 2
• Alternative for sulfa-allergic patients: pyrimethamine plus clindamycin (does not protect against PCP) 1, 2

Discontinuing Secondary Prophylaxis

• Can be discontinued if CD4+ count increases to >200 cells/µL for ≥6 months on HAART 2

Prevention of Exposure (Counseling for Seronegative Patients)

All HIV-infected persons, particularly those who are Toxoplasma-seronegative, should receive the following counseling:

• Do not eat raw or undercooked meat (cook to internal temperature of 150°F/65.5°C; meat no longer pink inside reaches 165°F/73.8°C) 1
• Wash hands after contact with raw meat, gardening, or soil contact 1
• Wash fruits and vegetables thoroughly before eating raw 1
• If owning a cat: change litter box daily (preferably by HIV-negative person), or wash hands thoroughly after changing 1
• Keep cats indoors; do not adopt or handle stray cats 1
• Feed cats only canned/dried commercial food or well-cooked table food - not raw or undercooked meats 1
• Patients need not part with their cats or have cats tested for toxoplasmosis 1

Common Pitfalls to Avoid

• Do not use aerosolized pentamidine for Toxoplasma-seropositive patients - it provides zero protection against toxoplasmic encephalitis despite protecting against PCP 1, 2
• Do not discontinue TMP-SMX prophylaxis prematurely in transplant recipients - primary toxoplasmosis occurring in the first 90 days post-transplant has 100% mortality in some series 5
• Do not administer atovaquone without food - bioavailability increases 1.4-fold with fatty foods; failure to do so may result in treatment failure 7
• Do not assume lower TMP-SMX doses provide equivalent toxoplasmosis protection - while one double-strength tablet daily has the strongest evidence for dual protection, lower doses may still be effective 1