Toxoplasmosis in the immunocompromisedpatient

Acute infection

Immuno-compromised patients should always be treated when the infection is acute. The therapy should be given for at least three weeks, but up to six weeks or more may be required for severely ill patients who have not achieved a complete response. Pyrimethamine combined with sulphadiazine and folinic acid is a therapy of choice for AIDS patients with toxoplasmosis. This regimen has been associated with clinical response in 68-95% of cases with

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encephalitis, but unfortunately up to 40% of the patients develop side effects, requiring discontinuation of therapy (Leport and Raguin 1990; Luft et al. 1993). Substitution of clindamyacin for sulphadiazine while continuing with pyrimethamine is an acceptable solution. However, there is little evidence to support regular first use of clindamycin in preference to sulphadiazine-pyrimethamine. Cotrimoxazole has also, on occasions been successfully used as an alternative to sulphadiazine (Solbreux et al. 1990). However, its regular use is questionable as encephalitis has developed in patients receiving cotrimoxazole for P. carinii infections (Haverkos 1987). Of the newer agents azithromycin and atoquavone are now on trial (Torres et al. 1995).

Maintenance and prophylaxis

When suppressive therapy is discontinued, surviving tissue cysts may induce Toxoplasma encephalitis and other clinical manifestations in up to 80% of AIDS patients. Since the standard regimen does not eliminate the tissue cysts, it is generally agreed that AIDS patients will require life-long maintenance therapy. Many clinicians favour continuing therapy with the same drug combinations in the same daily doses as used for acute infection. Others believe that both doses and frequency can be reduced. One regimen of pyrimethamine (25mg) and sulphadiazine (75 mg/kg) twice a week plus folinic acid (10 mg daily) was fully effective (Pedrol 1990). In contrast, pyrimethamine plus clindamycine twice weekly was less effective. A recent trial recommends cotrimoxazole as prophylactic therapy, while in high-risk patients with <100 CD4 cells/mm3 pyrimethamine (50 mg) should be given three times weekly (Leport et al. 1996). Other agents under study include Fanzidar and Dapsone, which have a long half-life. In the future, there is a possibility that drugs which eliminate the tissue cysts may become available. These drugs would be of enormous benefit for AIDS patients and congenitally infected infants.

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