TreatmentUpdate59; Vol 7, No. 5 - May 1995
Sean Hosein

One of the more common life-threatening brain infections seen in patients with AIDS is toxo (toxoplasmosis). The parasite that causes toxo (T. gondii) is found in "some birds and [other animals] including humans." Humans become infected with the parasite while they are in the womb or when they eat "raw or undercooked meat", or accidentally eat feces from infected cats. People can also be infected through blood transfusions. Although T. gondii can infect the brain, other parts of the body - eye, heart, lung - may also become infected.

* SIGNS/SYMPTOMS OF TOXO

As T. gondii "can infect any cell in the brain" patients can have a variety of symptoms. Moreover, initial symptoms may be mild at first but become worse over a period of weeks as the infection spreads. Magnetic and X-ray scans of the brain can detect lesions that suggest toxo. Signs/symptoms can include:

- seizures - fever - coma - confusion - problems understanding speech - weakening 'arm strength' - headache - problems with speech/vision - muscle control - loss of control of muscles on one side of the body - problems walking

As CMI (cell-mediated immunity) weakens, the immune system is less able to keep infections under control. As well, the parasite that causes toxo seems able to further weaken cells of the immune system when they find the parasite. Toxo is more likely to happen in patients with less than 200 CD4+ cells. Some patients may have anti-toxo antibodies in their blood and are at increased risk for developing toxo.

* STANDARD TREATMENT

Patients usually receive a combination of 2 drugs- pyrimethamine and sulphadiazine. On the first day doctors may prescribe 200 mg/day of pyrimethamine which is later reduced to 50 or 75 mg/day. Patients may also receive sulphadiazine in doses of 4 to 6 grams/day. This therapy usually continues for 6 weeks. Doctors may also prescribe between 5 and 10 mg/day of the B-vitamin folic acid to protect the bone marrow from the toxicity of the antibiotics. Sulphadiazine may also affect the kidneys. Some doctors stop prescribing AZT because it may weaken the effect of pyrimethamine.

* CLINDAMYCIN AND OTHER DRUGS

As some patients may not be able to tolerate sulpha drugs, doctors may substitute 2.4 to 4.5 g/day of clindamycin for sulphadiazine. In some cases clindamycin may be sent directly into patients' veins especially if they have nausea and vomiting. Treatment with Bactrim/Septra or Mepron may be useful for some patients who cannot tolerate pyrimethamine.

* MAINTENANCE

Patients will need to keep taking antibiotics to suppress the infection for the rest of their lives. For maintenance doctors may use between 25 and 50 mg/day of pyrimethamine and between 2 and 4 g/day of sulphadiazine. Patients who cannot tolerate sulpha drugs may use a minimum of 1200 mg/day of clindamycin. Some doctors prescribe Bactrim/Septra 1 DS (double strength) tablet taken every day or 3 days weekly. Others may use dapsone (75 to 300 mg/ week) with or without pyrimethamine (50 to 200 mg/ week). Doctors may prescribe between 1 and 15 g/day of clarithromycin with minocycline 100 to 200 mg/ day.

* EXPERIMENTAL DRUGS

A number of research teams are conducting laboratory experiments with toxo-infected mice testing combinations of various antibiotics. Promising combinations may include pyrimethamine with:

- clarithromycin or azithromycin or roxithromycin - Mepron(R)/Wellvone(R) - rifabutin and/or clindamycin and/or Mepron

REFERENCES:

1. Luft BJ, Hafner R, Korzum MS, et al. Toxoplasmic encephalitisin patients with the Acquired Immunodeficiency Syndrome. New England Journal of Medicine 1993;329(14):995-1000.

2. St. Georgiev V. Management of toxoplasmosis. Drugs 1994;48(2):179-188

3. Smith G. Treatment of infections in the patient with Acquired Immunodeficiency Syndrome. Archives of Internal Medicine 1994;154:949-973.

4. New L and Holliman RE. Toxoplasmosis and Human Immunodeficiency Virus (HIV) disease. Journal of Antimicro- bial Chemotherapy 1994;33:1079-1082.

5. Haque S, Khan I, Hague A and Caspar L. Impairment of the cellular immune response in acute murine toxoplasmosis: regulation of interleukin 2 production and macrophage-mediated inhibitory effects. Infection and Immunity 1994;62(7):2908-2916

6. Alder J, Hutch T, Meulbroek J and Clement J. Treatment of experimental Toxoplasmic gondii infection by clarithromycin-based combination therapy with minocycline or pyrimethamine. Journal of Acquired Immunodeficiency Syndrome 1994;7(11):1141-1148.

7. Bran-Pascaud M, Chad F, Simonpoli A-M, et al. Experimental evaluation of combined prophylaxis against murine pneumocystosis and toxoplasmosis. Journal of Infectious Diseases 1994; 170:653- 658.

8. Aerugo F, Silver T and Remington J. Rifabutin is active in murine model of toxoplasmosis. Antimicrobial Agents and Chemotherapy 1994;38(3):570-575.

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Copyright © 1995 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284  http://www.catie.ca