Toxoplasmosis Diagnosis and Management
The first-line treatment for toxoplasmosis in immunocompromised patients is pyrimethamine plus sulfadiazine with leucovorin (folinic acid) supplementation, with pyrimethamine dosed at 2 mg/kg/day loading dose for 2-3 days, followed by 1 mg/kg/day maintenance, and sulfadiazine at 100 mg/kg/day divided twice daily. 1
Diagnosis
Serologic Testing
- Test for Toxoplasma IgG antibody in HIV-infected patients soon after diagnosis to detect latent infection 2
- Retest Toxoplasma-seronegative persons when CD4+ count drops below 100/μL to identify seroconversion 2
- Complete brain MRI should be performed in immunocompromised patients even without focal neurological symptoms 1
Treatment Regimens
First-Line Treatment
- Pyrimethamine plus sulfadiazine with leucovorin supplementation:
Alternative Regimens
- For sulfa-allergic patients: Pyrimethamine plus clindamycin with leucovorin 2
- Note: This combination does not provide concurrent PCP prophylaxis 2
- Trimethoprim-sulfamethoxazole (TMP-SMX) can be used as an alternative, particularly in resource-limited settings 1, 4, 5
- Atovaquone with or without pyrimethamine may be considered in patients who cannot tolerate other regimens 2, 1
Duration of Treatment
- Initial acute therapy: 6 weeks, with clinical and radiological evaluation after this period 1
- For congenital toxoplasmosis: 12 months 1
- For immunocompromised patients with toxoplasmic encephalitis (TE): Lifelong suppressive therapy after initial treatment 2, 1
Prophylaxis
Primary Prophylaxis
- Indicated for Toxoplasma-seropositive HIV patients with CD4+ count <100/μL 2
- Preferred regimen: TMP-SMX (one double-strength tablet daily) 2
- Alternatives if TMP-SMX not tolerated:
Secondary Prophylaxis (Maintenance Therapy)
- Required for all patients who have had TE to prevent relapse 2
- Preferred regimen: Pyrimethamine plus sulfadiazine with leucovorin 2
- Alternative: Pyrimethamine plus clindamycin with leucovorin 2
Monitoring
- Weekly complete blood count while on daily pyrimethamine, then monthly when dosing frequency is reduced 1, 3
- Regular monitoring of renal and liver function tests 1
- Ophthalmologic examinations to monitor for chorioretinitis 1
- If signs of folate deficiency develop, reduce dosage or discontinue pyrimethamine 3
Special Considerations
Pregnancy
- TMP-SMX can be used for prophylaxis during pregnancy 2
- Pyrimethamine-containing regimens should be avoided during pregnancy if possible due to teratogenicity concerns 2, 3
- Pregnant HIV-infected women with evidence of primary toxoplasmic infection should be managed in consultation with specialists 2
Children
- TMP-SMX for PCP prophylaxis also provides protection against toxoplasmosis 2
- Children >12 months receiving agents other than TMP-SMX for PCP prophylaxis should be tested for Toxoplasma antibody 2
Prevention Measures
- Avoid raw or undercooked meat, particularly pork, lamb, or venison 2
- Cook meat to internal temperature of 165°F (73.8°C) 2, 1
- Wash hands after handling raw meat, gardening, or contact with soil 2
- Wash fruits and vegetables thoroughly before eating raw 2
- If owning a cat:
Common Pitfalls and Caveats
- Pyrimethamine has a narrow therapeutic window and can cause significant bone marrow suppression 3
- Concurrent administration of leucovorin is essential to prevent hematologic toxicity 3
- Treatment discontinuation often leads to relapse, particularly in immunocompromised patients 6
- Drug interactions: Pyrimethamine should be used cautiously with other antifolic drugs or myelosuppressive agents 3
- Side effects requiring monitoring include hematologic toxicity and cutaneous rash 6
- Relapses commonly occur within 6 weeks of treatment discontinuation in AIDS patients, necessitating lifelong therapy 6