What is the recommended management for toxoplasmosis, particularly in immunocompromised patients or pregnant women?

Management of Toxoplasmosis

Immunocompromised Patients (HIV/AIDS)

For acute toxoplasmic encephalitis in HIV-infected patients with CD4+ counts <100 cells/µL, initiate pyrimethamine plus sulfadiazine plus leucovorin for at least 6 weeks, followed by lifelong secondary prophylaxis unless immune reconstitution occurs. 1, 2

Acute Treatment Regimen

• Administer pyrimethamine plus sulfadiazine plus leucovorin as the gold standard treatment for active toxoplasmosis in immunocompromised patients 1
• Continue acute therapy for at least 6 weeks, assuming clinical and radiological improvement 1, 2
• This combination provides dual protection against both toxoplasmic encephalitis and Pneumocystis pneumonia (PCP) 1, 2
• Perform weekly complete blood counts to monitor for bone marrow suppression, particularly neutropenia 1, 3

Alternative Regimens for Sulfa-Allergic Patients

• Use pyrimethamine plus clindamycin plus leucovorin as the preferred alternative, though this does not protect against PCP 1, 2
• TMP-SMX (5 mg/kg trimethoprim plus 25 mg/kg sulfamethoxazole IV or orally twice daily) can be used for 6 weeks and provides dual coverage for toxoplasmosis and PCP 1, 2

Secondary Prophylaxis (Chronic Maintenance Therapy)

• After completing acute therapy, lifelong secondary prophylaxis is required to prevent relapse unless immune reconstitution occurs with HAART 1, 2
• Continue pyrimethamine plus sulfadiazine plus leucovorin as maintenance therapy 4
• Alternative maintenance regimen: TMP-SMX double-strength (160 mg/800 mg) daily, which provides adequate suppression and PCP prophylaxis 2

Discontinuation of Prophylaxis

• Secondary prophylaxis can be discontinued if CD4+ count increases to >200 cells/µL for ≥6 months on HAART 1
• Restart secondary prophylaxis if CD4+ count decreases to <200 cells/µL 4

Primary Prophylaxis

• Test all HIV-infected patients 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 1, 2
• The preferred prophylaxis regimen is TMP-SMX double-strength tablet daily, which also protects against PCP 1, 2
• Alternative: dapsone plus pyrimethamine provides protection against both toxoplasmic encephalitis and PCP 1

Pregnant Women

For pregnant women with suspected or confirmed toxoplasmosis before 18 weeks gestation, initiate spiramycin 1g (or 3 million IU) orally three times daily immediately; switch to pyrimethamine plus sulfadiazine plus folinic acid at or after 18 weeks gestation or if fetal infection is confirmed. 5, 4

Antepartum Treatment Algorithm

• Start spiramycin immediately for suspected acute primary infection before 18 weeks gestation without waiting for confirmatory testing 5, 6
• Switch to pyrimethamine plus sulfadiazine plus folinic acid at or after 18 weeks gestation or if fetal infection is confirmed by amniocentesis 5, 4
• If already receiving spiramycin when fetal infection is confirmed, stop spiramycin and switch to pyrimethamine-sulfadiazine combination 4

Diagnostic Approach

• Perform maternal Toxoplasma serology and amniocentesis at or after 18 weeks gestation for amniotic fluid Toxoplasma PCR 4, 6
• Do not perform amniocentesis before 18 weeks gestation and wait at least 4 weeks after suspected acute maternal infection to lower false-negative results 6
• Suspected recent infection should be confirmed at a toxoplasmosis reference laboratory before intervention 6
• Repeat testing should be performed within 2 to 3 weeks if acute infection is suspected 6

Fetal Monitoring

• Perform fetal ultrasound every month until delivery to detect intracranial calcification, microcephaly, hydrocephalus, ascites, hepatosplenomegaly, or severe intrauterine growth restriction 4, 5

HIV-Infected Pregnant Women

• TMP-SMX can be administered for toxoplasmosis prophylaxis in HIV-infected pregnant women 4, 5
• Pyrimethamine-containing regimens may be deferred until after the first trimester due to teratogenicity concerns, given the low incidence of toxoplasmic encephalitis during pregnancy 4, 5
• In rare cases, HIV-infected pregnant women with serologic evidence of remote toxoplasmic infection have transmitted Toxoplasma to the fetus in utero 4
• Pregnant HIV-infected women with evidence of primary toxoplasmic infection or active toxoplasmosis should be evaluated and managed in consultation with appropriate specialists 4

Chronic Infection in Pregnancy

• Anti-toxoplasma treatment is not indicated for maternal serologic results consistent with infection acquired before pregnancy and more than 3 months before conception, unless the woman is severely immunocompromised 4, 6

Congenital Toxoplasmosis

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

Treatment 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
• Sulfadiazine: 50 mg/kg/dose twice daily 1
• Leucovorin: supplementary dosing throughout treatment 1

Neonatal Diagnostic Testing

• Perform neonatal testing at a toxoplasmosis reference laboratory, not commercial laboratories 4, 5
• Test peripheral blood for Toxoplasma IgG, IgM ISAGA (not IgM ELISA), and IgA as soon as possible after birth 4
• Negative Toxoplasma IgM ELISA at commercial laboratories cannot exclude the diagnosis of congenital toxoplasmosis 4, 5
• Test neonatal Toxoplasma IgG antibodies in parallel with maternal Toxoplasma IgG antibodies 4
• If Toxoplasma IgM ISAGA is positive, repeat at least 5 days after birth to exclude false-positive results from maternal blood contamination during labor (half-life of IgM is 5 days) 4
• Perform additional testing with Toxoplasma PCR in blood/urine/CSF 4

Neonatal Evaluation

• Conduct ophthalmologic examination, neurologic assessment, and hearing evaluation for all infants born to TORCH-positive mothers 5

Monitoring During Treatment

• Perform complete blood count at least weekly while on daily pyrimethamine and at least monthly while on less than daily dosing to monitor for bone marrow suppression 1, 3
• Pyrimethamine-sulfadiazine therapy carries significant risk of bone marrow suppression, particularly neutropenia, with adverse events occurring in 20-50% of treated infants when leucovorin is not administered 1

Pediatric Patients

• TMP-SMZ, when administered for PCP prophylaxis, also provides prophylaxis against toxoplasmosis 4
• Children aged >12 months who qualify for PCP prophylaxis and are receiving an agent other than TMP-SMZ or atovaquone should have serologic testing for Toxoplasma antibody 4
• Severely immunosuppressed children not receiving TMP-SMZ or atovaquone who are seropositive for Toxoplasma should be administered prophylaxis for both PCP and toxoplasmosis (dapsone plus pyrimethamine) 4
• Children with a history of toxoplasmosis should be administered lifelong prophylaxis to prevent recurrence 4

Prevention of Exposure

• Toxoplasma-seronegative HIV-infected persons should avoid eating raw or undercooked meat, wash hands after contact with raw meat and after gardening or soil contact, and wash fruits and vegetables well before eating raw 1
• HIV-infected persons should avoid contact with human and animal feces and sexual practices that might result in oral exposure to feces 4
• Pregnant women should receive education about prevention of toxoplasmosis as part of prenatal care 6

Critical Monitoring and Safety Considerations

• If signs of folate deficiency develop (anorexia, vomiting, pallor, purpura, glossitis, sore throat), reduce the dosage or discontinue pyrimethamine and administer folinic acid (leucovorin) 5-15 mg daily until normal hematopoiesis is restored 3
• At the first appearance of a skin rash, stop pyrimethamine immediately and seek medical attention 3
• Pyrimethamine has a narrow therapeutic window and should be kept out of reach of children, as they are extremely susceptible to adverse effects from overdose; deaths in pediatric patients have been reported after accidental ingestion 3
• Inadequate duration of therapy may lead to relapse, particularly in immunocompromised patients 1