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 and 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, lamb, or beef) 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 infection who are seropositive for T. gondii. There have been case reports of CNS toxoplasmosis in the setting of immune reconstitution on antiretroviral therapy (ART); see chapter Immune Reconstitution Inflammatory Syndrome.
CNS toxoplasmosis is an AIDS-defining condition that can be progressive and fatal. However, antimicrobial therapy, especially if given in conjunction with 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).
The patient may complain of subacute onset of dull, constant headache, fever, visual changes or other focal neurologic symptoms, confusion, or disorientation. Seizures may occur. Caregivers may report subtle alterations in mental status or mood.
Take a careful history from the patient and caregivers about the symptoms listed above and their duration, progression, and severity. Inquire about other related symptoms. Ask whether the patient is taking Toxoplasma prophylaxis or ART.
Rule out other infectious or neoplastic causes of headache, fever, and neurologic changes. A partial differential diagnosis includes the following:
Definitive diagnosis requires identification of T. gondii in tissue biopsy or body fluid samples from a patient with a compatible clinical presentation. Brain biopsy usually is not performed if toxoplasmosis is strongly suspected; instead, presumptive diagnosis is made on the basis of clinical presentation, laboratory and imaging tests, and response to therapy. Brain biopsy should be considered for patients who do not respond to therapy and for those whose diagnosis is unclear.
Treatment consists of two phases: acute therapy and chronic maintenance therapy. If possible, consult with an expert on the management of toxoplasmosis.
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 should be given for at least 6 weeks, and until the patient has shown improvement by clinical and radiographic measures.
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 taking other agents that cause bone marrow suppression, such as zidovudine, valganciclovir, and ganciclovir.
Note: Patients at risk of G6PD deficiency should be checked for G6PD deficiency before starting pyrimethamine.
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 (e.g., dexamethasone 4 mg PO or IV Q6H) may be indicated for patients with CNS mass effect or edema. Use is based on clinical judgment and should be discontinued as soon as it is feasible to do so.
Anticonvulsant therapy should be given to patients with seizures.
Ventilatory support may be necessary if severe CNS symptomatology is present.
After at least 6 weeks of initial therapy and significant clinical and radiologic improvement, chronic maintenance therapy can be considered.
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.
All pregnant women should be tested for T. gondii. If the result is positive, evaluate the pregnant woman for signs or symptoms of 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 maternal-fetal and infectious disease specialists. 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.