Toxoplasmosis

Toxoplasma gondii is a common intracellular protozoan that preferentially infects the central nervous system (CNS) of immunodeficient patients, causing severe neurologic disease. T gondii also can cause local disease such as chorioretinitis or pneumonia. Toxoplasma has an infectious reservoir in almost all animals; humans acquire infection either through ingestion of tissue cysts contained in undercooked meat (usually pork or lamb) or oocysts on contaminated vegetables or through exposure to cat feces containing oocysts. There is no transmission by person-to-person contact.

Clinical disease usually occurs through reactivation of latent infection in patients who have CD4 counts of <100 cells/µL. Seroprevalence varies widely, from 15% in the United States to 75% in some European countries, and even higher in certain resource-limited countries. In the absence of prophylaxis, toxoplasmic encephalitis occurs in more than 30% of patients with advanced HIV disease who are seropositive for T gondii.

CNS toxoplasmosis is an AIDS-defining condition that can be progressive and fatal. However, antimicrobial therapy, especially if given in conjunction with antiretroviral therapy (ART) that results in immune reconstitution, can be successful in treating toxoplasmosis. Specific prophylaxis and effective ART also may be used to prevent toxoplasmosis in patients with advanced AIDS who have latent T gondii infection (as demonstrated by the presence of anti-Toxoplasma immunoglobulin G [IgG] antibodies; see chapter Preventing Exposure to Opportunistic and Other Infections).

Treatment consists of 2 phases: acute therapy and chronic maintenance therapy.

Presumptive treatment often is begun on the basis of clinical presentation, positive Toxoplasma IgG, and results of brain imaging studies. If patients do not respond quickly to treatment, other diagnoses should be considered. The following recommendations are based on treatment guidelines published by the Centers for Disease Control and Prevention, National Institutes of Health, and HIV Medicine Association/Infectious Diseases Society of America (see References below).

Acute Therapy

Preferred Pyrimethamine 200 mg orally as a single loading dose, then 50 mg (<60 kg body weight) to 75 mg (>60 kg body weight) daily + sulfadiazine 1,000 mg (<60 kg body weight) to 1,500 mg orally every 6 hours (>60 kg body weight) + folinic acid (leucovorin) 10-20 mg daily. Dosage adjustments to the lower end of therapeutic range of pyrimethamine and sulfadiazine may be considered for patients who have significant bone marrow suppression despite folinic acid supplementation. Monitor patients carefully for cytopenias, especially if they are on other agents that cause bone marrow suppression, such as zidovudine, valganciclovir, and ganciclovir. Note: Patients at risk for G6PD deficiency should be checked for G6PD deficiency before starting pyrimethamine. Alternatives Pyrimethamine + folinic acid (administered as described above) + 1 of the following: Clindamycin 600 mg orally or intravenously every 6 hours; recommended for patients with significant allergic reactions to sulfa medications Atovaquone 1500 mg orally every 12 hours Azithromycin 900-1,200 mg orally once daily Trimethoprim-sulfamethoxazole (TMP-SMX) 5 mg/kg TMP and 25 mg/kg SMX orally or intravenously every 12 hours. This can be considered when the availability of other regimens is limited or when patients need intravenous therapy. Atovaquone 1,500 mg orally twice daily + sulfadiazine 1,000-1,500 mg orally every 6 hours. Note: The regimens that contain sulfadiazine, TMP-SMX, or atovaquone also are effective in preventing Pneumocystis jiroveci pneumonia (PCP), so patients on these regimens do not need additional PCP prophylaxis. Adjunctive corticosteroids (eg, dexamethasone 4 mg orally or intravenously every 6 hours) may be indicated for patients with significant CNS edema or mass effect. Use is based on clinical judgment and should be discontinued as soon as clinically feasible. Anticonvulsant therapy should be given to patients with seizures. Ventilatory support may be necessary if severe CNS symptomatology is present.

Chronic Maintenance Therapy

After at least 6 weeks of initial therapy, and significant clinical and radiologic improvement, chronic maintenance therapy can be considered. Preferred Pyrimethamine 25-50 mg orally once daily + sulfadiazine 500-1,000 mg orally every 6 hours + folinic acid 10 mg orally once daily (also effective as PCP prophylaxis). Alternatives Pyrimethamine 25-50 mg orally once daily + clindamycin 300-450 mg orally every 6-8 hours + folinic acid 10 mg orally once daily. Pyrimethamine 25-50 mg orally once daily + atovaquone 1,500 mg orally once daily + folinic acid 10 mg orally once daily (also effective as PCP prophylaxis). Chronic maintenance therapy generally should be continued for life. For patients who complete acute therapy successfully, have resolution of signs and symptoms of toxoplasmosis, and have immune reconstitution (with CD4 counts >200 cells/µL) for more than 6 months on ART, it is reasonable to consider discontinuing maintenance therapy. Some specialists would require resolution of CNS lesions on radiologic studies before discontinuation of therapy. Patients must be observed for recurrence of symptoms, and treatment should be restarted if the CD4 count decreases to <200 cells/µL.

Considerations in Pregnancy

All pregnant women should be tested for T gondii. If the result is positive, evaluate the mother for toxoplasmosis and the neonate for evidence of congenital infection. Perinatal transmission usually occurs only with acute maternal infection, but in advanced HIV, it may occur with reactivation of chronic infection. If T gondii infection occurs during pregnancy, consult with a maternal-fetal specialist. Treatment for pregnant women is the same as for nonpregnant adults (see above). Note that sulfadiazine taken at the time of delivery may increase the risk of neonatal hyperbilirubinemia and kernicterus.