What is the recommended prophylaxis regimen for immunocompromised patients, such as those with Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) and pregnant women, to prevent toxoplasmosis?

Toxoplasmosis Prophylaxis in Immunocompromised Patients and Pregnant Women

HIV/AIDS Patients

For HIV-infected patients with CD4+ counts <100 cells/µL who are Toxoplasma-seropositive, trimethoprim-sulfamethoxazole (TMP-SMZ) at doses used for PCP prophylaxis provides effective dual protection against both Pneumocystis pneumonia and toxoplasmic encephalitis. 1

Primary Prophylaxis Regimen

• TMP-SMZ is the preferred agent because it simultaneously prevents both PCP and toxoplasmic encephalitis with a single medication 1
• The standard dosing is one double-strength tablet (160mg/800mg) daily, which is the same regimen used for PCP prophylaxis 1
• This approach is highly effective and represents the most practical option for patients requiring prophylaxis 1

Alternative Regimens for Sulfa-Allergic Patients

• Dapsone plus pyrimethamine is the preferred alternative for patients who cannot tolerate TMP-SMZ, providing protection against both PCP and toxoplasmosis 1
• Atovaquone may also provide protection against toxoplasmosis when used for PCP prophylaxis 1
• Aerosolized pentamidine does NOT protect against toxoplasmosis and should not be relied upon for this purpose 1
• Monotherapy with dapsone alone, pyrimethamine alone, azithromycin, clarithromycin, or atovaquone alone cannot be recommended for toxoplasmosis prophylaxis 1

Serologic Testing Strategy

• All HIV-infected patients should undergo Toxoplasma IgG antibody testing at initial evaluation to determine serostatus 2
• Toxoplasma-seronegative patients not taking TMP-SMZ or another effective regimen should be retested when CD4+ counts fall below 100 cells/µL to identify seroconversion 1
• Patients who seroconvert require immediate initiation of prophylaxis 1

Discontinuation Considerations

• Limited data suggest discontinuing prophylaxis may be safe when CD4+ counts increase to >100-200 cells/µL with HAART, but insufficient evidence exists to routinely recommend this practice 1
• Patients with history of toxoplasmic encephalitis require lifelong suppressive therapy with pyrimethamine plus sulfadiazine plus leucovorin to prevent relapse 1, 2

Pregnant Women

For HIV-infected pregnant women, TMP-SMZ can be safely administered for toxoplasmosis prophylaxis using the same regimen as for PCP, while pyrimethamine-containing regimens should be deferred until after the first trimester due to teratogenicity concerns. 1

Prophylaxis During Pregnancy

• TMP-SMZ is the preferred agent and can be used throughout pregnancy for women requiring prophylaxis 1
• Pyrimethamine-containing regimens should be avoided in the first trimester because pyrimethamine is Pregnancy Category C and has demonstrated teratogenic effects in animal studies 3
• The low incidence of toxoplasmic encephalitis during pregnancy supports deferring pyrimethamine-based prophylaxis until after delivery when feasible 1

Treatment of Acute Infection in Pregnancy

• For suspected or confirmed acute toxoplasmosis before 18 weeks gestation, spiramycin 1g (3 million IU) orally three times daily should be initiated immediately 2, 4
• At or after 18 weeks gestation, or if fetal infection is confirmed by positive amniotic fluid PCR, switch to pyrimethamine plus sulfadiazine plus folinic acid 2, 4
• Amniocentesis for PCR testing should not be performed before 18 weeks gestation and should wait at least 4 weeks after suspected maternal infection to avoid false-negative results 5

Secondary Prophylaxis in Pregnancy

• For women with history of toxoplasmic encephalitis who are now pregnant, most clinicians favor continuing lifelong suppressive therapy given the high risk of relapse if treatment is stopped 1
• The decision requires careful discussion between provider and patient about teratogenicity risks versus benefits of continued therapy 1
• Consultation with appropriate specialists (maternal-fetal medicine, infectious disease) is strongly recommended 1, 4

Monitoring and Follow-up

• Monthly fetal ultrasound should be performed to detect intracranial calcification, microcephaly, hydrocephalus, ascites, hepatosplenomegaly, or severe intrauterine growth restriction 2, 5
• All infants born to HIV-infected women with serologic evidence of Toxoplasma infection should be evaluated for congenital toxoplasmosis 1
• Neonatal testing should be performed at a toxoplasmosis reference laboratory, not commercial laboratories 2

Pediatric Patients

• TMP-SMZ administered for PCP prophylaxis also provides effective toxoplasmosis prophylaxis in children 1
• Children >12 months of age receiving alternative PCP prophylaxis agents (not TMP-SMZ or atovaquone) should undergo Toxoplasma antibody testing 1, 2
• Severely immunosuppressed children who are Toxoplasma-seropositive and not receiving TMP-SMZ or atovaquone should receive dapsone plus pyrimethamine for dual PCP and toxoplasmosis prophylaxis 1, 2

Critical Safety Monitoring

• Weekly complete blood counts are mandatory for all patients receiving pyrimethamine-based regimens to monitor for bone marrow suppression, particularly neutropenia 2, 3
• Concurrent folinic acid (leucovorin) 5-15mg daily is strongly recommended with all pyrimethamine-containing regimens to prevent folate deficiency 2, 3
• If signs of folate deficiency develop, reduce pyrimethamine dosage or discontinue and increase leucovorin until normal hematopoiesis is restored 2, 3

Prevention of Exposure

• Toxoplasma-seronegative individuals should avoid eating raw or undercooked meat, particularly pork, lamb, and venison 2
• Wash hands thoroughly after contact with raw meat, after gardening or soil contact, and after changing cat litter 1, 2
• Wash fruits and vegetables well before eating raw 2
• Keep cats indoors, do not adopt stray cats, and feed cats only canned/dried commercial food or well-cooked table food 1
• Avoid sexual practices that may result in oral exposure to feces 1, 2