Cerebral Toxoplasmosis
It is caused by the protozoon Toxoplasma gondii. Although T. gondii usually causes encephalitis, it also causes disease in various organs including the eyes and lungs. Infection is acquired by contact with cats or birds, and eating undercooked meat, especially pork, lamb or venison. Encephalitis occurs from reactivation of latent cysts, and is most common among HIV-positive people with CD4 counts <50 cells/mm3 . Anti-Toxoplasma antibodies are not protective and only indicate prior infection.
Clinical features
Symptoms include headache, fever, confusion, progressive focal neurological deficits, seizures, abnormal behaviour, motor weakness and coma.
Diagnosis
Serum IgG and IgM anti-Toxoplasma antibodies can be estimated, but do not indicate active disease. Polymerase chain reaction (PCR) tests have high specificity but low sensitivity. CT or MRI scans showing focal lesions may be helpful in making a diagnosis, although differentiation from other CNS diseases such as lymphoma may be difficult. Newer imaging devices such as positron emission tomography (PET) or single photon emission computed tomography (SPECT) scans may be more helpful, although more expensive. Stereotactic CT-guided brain biopsy is reserved for patients who fail to respond to therapy.
Treatment
If CNS toxoplasmosis is suspected, treatment should precede confirmation of diagnosis. Brain biopsy is required only if the patient does not respond to treatment. Biopsy may be required to diagnose toxoplasmosis of other tissues such as the lungs.
A combination of pyrimethamine, sulfadiazine and leucovorin is the recommended initial regimen. Pyrimethamine is started orally at a dose of 100–200 mg daily, followed by a lower dose. It penetrates the brain parenchyma even if there is no inflammation. Leucovorin contains folate, and decreases the haematological side-effects of pyrimethamine. Sulfadiazine is given orally four times a day at a dose of 4–8 g/day. Clindamycin or TMP–SMX can be used in case sulfadiazine is not available. Other combnations used include: atovaquone + sulfadiazine; atovaquone + pyrimethamine + leucovorin; azithromycin + pyrimethamine + leucovorin. Dapsone, 5-fluorouracil, clarithromycin, and minocycline have all been used with in various permutations and combinations. Initially, high doses of these medications are given for 4–6 weeks followed by lower doses as maintenance therapy to prevent recurrence. Maintenance therapy can be discontinued in an asymptomatic patient on HAART with a CD4 count >200 cells/mm3 for at least 6 months. It has to be restarted if the CD4 count falls or the MRI/CT shows persistent cerebral mass lesions. Corticosteroids such as dexamethasone may help control inflammation of the brain in patients with focal neurological symptoms. However, they need to be used carefully, given that corticosteroids may precipitate other OIs. Anticonvulsants should be administered only if there is a history of seizures and should not be used prophylactically.
Adverse events
Pyrimethamine can cause rash, nausea and bone marrow suppression. Sulfadiazine and TMP–SMX can cause rash, fever, leucopenia, hepatitis, nausea, vomiting, diarrhoea, crystalluria, hepatotoxicity and Clostridium difficile colitis. Drug interactions between anticonvulsants and ART may necessitate adjustment of dosages.
Prevention
The best way to prevent toxoplasmosis is to avoid contact with T. gondii. Meats such as pork, lamb or venison should be well cooked. Precautions should be followed while handling cats and birds. Daily TMP–SMX is the most effective regimen to prevent toxoplasmosis. For patients who are allergic, dapsone + pyrimethamine + folic acid once a week is a good alternative
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| Toxoplasmosis Treatment using Sulfadiazine 500mg Tablets |
