Encephalitis toxoplasma

Sulfamethoxazole/trimethoprim has been shown to be the best form of PCP prophylaxis and also provides protection against Toxoplasma encephalitis therefore, every effort should be made to ensure that where possible patients receive it. 

Atovaquone suspension (1500 mg orally bd) plus either pyrimethamine (75 mg/day after a 200 mg loading dose) or sulfadiazine (1500 mg qds), as treatment for acute Toxoplasma encephalitis (for 6 weeks) and as maintenance therapy (for 42 weeks), has been studied in a randomized phase II trial in HIV-positive patients (17). There were good responses in 21 of 28 patients who received pyrimethamine and nine of 11 who received sulfadiazine. Of 20 patients in the maintenance phase, only one relapsed. Of 40 eligible patients, 11 discontinued treatment as a result of adverse events, nine because of nausea and vomiting or intolerance of the taste of the atovaquone suspension. 

A 44-year-old HIV-1 infected woman from the Ivory Coast, who was taking stavudine, lamivudine, efavirenz, and pyrimethamine plus sulfadiazine for Toxoplasma encephalitis, developed a maculopapular rash on both arms. The sulfadiazine was withdrawn and clindamycin was added. Ten days later her condition had worsened. Her temperature was 40 C, pulse rate 137/minute, and respiratory rate 26/minute. She had a generalized maculopapular rash without mucosal involvement, moderate abdominal tenderness, hepatomegaly, jaundice, and bilateral crackles. Her white cell count was 16 x 10 /1 with 9% eosinophils and 51% lymphocytes. A chest X-ray showed moderate bilateral interstitial pneumonitis. All drugs were withdrawn and she was given intravenous methylprednisolone. The skin rash and aU systemic manifestations resolved within 1 week and HIV treatment was restarted uneventfully with lamivudine, stavudine, and nehinavir. 

Azithromycin is efficacious in animal models of toxoplasmic encephalitis. In a Phase I/II dose-escalation stndy of pyrimethamine (50 mg/day) plus azithromycin (900,1200, or 1500 mg/day) for induction and maintenance treatment in 30 patients with AIDS and definite or snspected Toxoplasma encephalitis, the overall response rate was 67% after 6 weeks of induction therapy (1). However, maintenance therapy for 24 weeks with this combination was associated with a high relapse rate (47%) only six patients snccessfully completed induction and maintenance therapy. Adverse events were common (particn-larly in those taking azithromycin 1500 mg) and inclnded hepatotoxicity, bone marrow suppression, ototoxicity, and gastrointestinal disturbances, which led 20% of patients to withdraw. All adverse events resolved on withdrawal. 

Clarithromycin, a macrolide, and other macrolide and lincosamine antibiotics (azithromycin, clindamycin, spiramycin, and roxithromycin) have been nsed in combination with pjrimethamine in the treatment of Toxoplasma gondii infections, especially cases of Toxoplasma encephalitis. 

Pyrimethamine 50 mg/day has been nsed in combination with clindamycin for the treatment of Toxoplasma encephalitis in AIDS. Adverse effects were common (rash, diarrhea, nansea), bnt the incidence of hematological reactions was lower than with the combination of snlfadiazine and pyrimethamine (SEDA-16, 309). 

In a single-arm, open, prospective study between 1990 and 1995 (before HAART) the prophylactic efficacy of Fansidar was evaluated in 95 HIV-infected patients with successfully treated Pneumocystis proved pneumonia and no history of Toxoplasma encephalitis (3). Patients took Fansidar with folinic acid (15 mg) twice weekly and were followed for a median of 19 (range 1-72) months. Five patients had a Pneumocystis relapse, but three had not taken their therapy. Of the 69 patients positive for. r. t. -Toxoplasma IgG antibodies, only one developed toxoplasma encephalitis after 50 months. A rash developed in 16 patients after a median of 3 weeks, and required withdrawal in six. Two developed Stevens-Johnson syndrome after three or four doses. There was no significantly increased risk of adverse reactions to Fansidar in patients with previous hypersensitivity reactions to co-tri-moxazole. The results of this study are of particular relevance to areas in which HAART is unavailable and where the antimalarial activity of Fansidar may confer additional benefit. 

The safety and efficacy of a fixed combination of pyrimethamine 25 mg + sulfadoxine 500 mg, supplemented with folinic acid 15 mg, both twice a week, as primary prophylaxis of Pneumocystis pneumonia and Toxoplasma encephalitis has been evaluated in 106 patients infected with HIV in a single-arm, open, prospective study (17). There were allergic reactions in 18 patients and permanent withdrawal was required in seven. One patient who took continued prophylaxis despite progressive hypersensitivity reactions developed a serious adverse reaction (Stevens-Johnson syndrome). 

Simon DI, Brosius FC 3rd., Rothstein DM. Sulfadiazine crystalluria revisited. The treatment of Toxoplasma encephalitis in patients with acquired immunodeficiency syndrome. Arch Intern Med 1990 150(ll) 2379-84. 

It is apparent that most recent cases of sulfadiazine-induced nephrotoxicity are not prospectively reported, thus the current incidence of sulfadiazine nephrotoxicity is unknown. In 1987, a study of 57 patients with AIDS treated for toxoplasma encephalitis indicated a renal toxicity of 6% [26]. A more recent international bibliographic search (1987 to... 

The risk factors for sulfadiazine nephrotoxicity in patients with AIDS include (a) more prolonged courses of therapy as compared to those for community-acquired infections in normal hosts (b) difficulty in maintaining high oral fluid intake in patients with toxoplasma encephalitis because of chronic illness, anorexia, and altered mental status (c) concurrent fluid loses due to diarrhea (d) levels of plasma creatinine within the range of "normal" despite impaired renal function due to AIDS-associated... 

Molina JM, Belenfant X, Doco-LecompteT, Idatte JM, Modai J. Sulfadiazine-induced crystalluria in AIDS patients with toxoplasma encephalitis. AIDS (London, England). 1991 May 5(5) 587-9. 

Haverkos HW. Assessment of therapy for toxoplasma encephalitis.TheTE Study Group.The American journal of medicine. 1987... 

Diaz F, Collazos J, Mayo J, Martinez E. Sulfadiazine-induced multiple urolithiasis and acute renal failure in a patient with AIDS and Toxoplasma encephalitis.The Annals of pharmacotherapy. 1996 Jan 30(1) 41-2. 

Weiss L, Harris C, Berger M, et al. Pyrimethamine concentrations in semm and cerebrospinal fluid during treatment of acute Toxoplasma encephalitis in patients with AIDS. J Infect Dis 1988 157 580-583. 

Warnke C, Tuazon CU, Kovacs A, et al. Toxoplasma encephalitis in patients with acquired immunodeficiency syndrome Diagnosis and response to therapy. Am J Prop Med Hyg. 1987 36 509. 

Flaverkos FIW - TE Study Group. Assessment of therapy for Toxoplasma encephalitis. Am J Med 1987 82 907-914. 

Toxoplasmosis is common in the United Kingdom and in most cases causes a mild influenza-like illness, although infection during pregnancy can be a cause of abortion or neurological damage in the foetus. In patients with HIV, toxoplasma can be the cause of serious illness. Toxoplasma encephalitis is a common complication of HIV infection. 

Toxoplasma infection is common in the United Kingdom and normally causes a mild illness that can go unnoticed. In pregnancy, it can however damage the developing foetus and may cause abortion. In patients with HIV infection, toxoplasma can cause encephalitis. Pneumocystis can cause serious pneumonia, almost exclusively in AIDS patients. Both toxoplasma and pneumocystis are treated with drugs containing sulphonamides. 

In vitro studies have shown that azithromycin is active against Toxoplasma gondii, and that this activity is additive with pyrimethamine [291]. In vivo studies have shown that azithromycin has some prophylactic and therapeutic activity [292-294]. Only a handful of human cases of cerebral toxoplasmosis treated with azithromycin have been described in the hterature [295-297]. Early results with escalating doses of oral azithromyein of 900, 1200, or 1500 mg daily plus pyrimethamine in 32 evaluable patients with known or suspected toxoplasma encephalitis have been reported [298]. It was concluded that azithromycin plus pyrimethamine is not as effective as the standard therapy for cerebral toxoplasmosis and should be regarded as second-line or salvage therapy. 

Femandez-Martin, J., Leport, C., Morlat, R, Meyohas, M. C., Chauvin, J. R, and Vilde, J. L. (1991). Pyrimethamine-clarithromycin combination for therapy of acute Toxoplasma encephalitis in patients with AIDS. Antimicrob. Agents Chemother. 35, 2049-2052. 

Wiselka, M. J., Read, R., and Rinch, R. G. (1996). Response to oral and intravenous azithromycin in a patient with toxoplasma encephalitis and AIDS. J. Infect. 33,227-229. 

The incidence of crystalluria is low with more soluble agents (e.g., sulfisoxazole). Crystalluria has occurred in volume-depleted patients with the acquired immune deficiency syndrome (AIDS) who were given sulfadiazine for Toxoplasma encephalitis. Fluid intake should be sufficient to ensure a daily urine volume of at least 1.2 L (in adults). Urinary alkalinization may be helpful if urine volume or pH is unusually low. 

Opravil, M. et al., Once-weekly administration of dapsone/pyrimethamine vs. aerosolized pentamidine as a combined prophylaxis for Pneumocystis carinii pneumonia and toxoplasma encephalitis in human immunodeficiency virus-infected patients, Clin. Infect. Dis., 20, 531, 1995. 

Eljaschewitsch J, Schurmann D, Pohle HD, Ruf B. Zidovudine does not antagonize Fansidar in preventing toxoplasma encephalitis in HIV infected patients. 7 International Conference on AIDS Science G lenging AIDS, Florence, Italy, 1991. Abstract W.B.2334. 

Strack, A., Schluter, D., Asensio, V. C., Campbell, I. L., and Deckert, M. (2002). Regulation of the kinetics of intracerebral chemokine gene expression in murine Toxoplasma encephalitis Impact of host genetic factors. Glia 40, 372-377. 

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