RISK-FACTORS FOR ENCEPHALOPATHY AND MORTALITY DURING MELARSOPROL TREATMENT OF TRYPANOSOMA-BRUCEI-GAMBIENSE SLEEPING SICKNESS

This paper reviews the incidence of, and risk factors for, drug-induce d encephalopathy and mortality (from all causes) during treatment with melarsoprol of 1083 patients with Trypanosoma brucei gambiense sleepi ng sickness in Nioki hospital (Zaire) between 1983 and 1990. Sixty-fou r patients (5.9%) developed encephalopathy and 62 (5.7%) died: 43 from reactive encephalopathy and 19 from other causes. Univariate and mult ivariate analyses showed that the administration of prednisolone reduc ed significantly the incidence of encephalopathy and mortality during treatment, especially in patients with trypanosomes observed in the ce rebrospinal fluid (CSF) and/or with a CSF white blood cell (WBC) count of 100 or more per mm(3). The risk of encephalopathy was associated m ore strongly with the CSF WBC count than with the presence of CSF tryp anosomes. In the subgroup of patients with a CSF WBC count of 100 or m ore mm(3), changing the melarsoprol regimen to 3 series of 3 injection s instead of 3 series of 4 injections halved the mortality rate during treatment. Treatment of patients who do develop reactive encephalopat hy with the heavy metal chelator dimercaprol, in addition to intraveno us steroids and anticonvulsants, may be harmful. The data suggest that a further reduction of the total dose of melarsoprol may decrease tox icity without jeopardizing efficacy.