Difluoromethylornithine, an effective new treatment of gambian trypanosomiasis: Results in five patients

Recent studies have shown DL-alpha-difluoromethylornithine (eflornithine), an inhibitor of polyamine biosynthesis, to be curative in various Trypanosoma species infections of laboratory animals. Five patients are described with Gambian trypanosomiasis treated in Belgium with difluoromethylornithine, using various intravenous and oral dosage schedules. Three patients had late-stage and two had early-stage disease. Difluoromethylornithine treatment was associated with clearing of parasites from blood within one to four days, a trend towards normalization of all altered biologic values associated with the disease, and marked amelioration of clinical symptoms. Side effects of difluoromethylornithine, including loose stools in three patients and both anemia, and a decrease in auditory acuity in one patient, were mild, transient, and never required interruption of drug treatment. The presence of difluoromethylornithine in cerebrospinal fluid, determined in three patients, demonstrated that difluoromethylornithine penetrates into the central nervous system. In three patients, follow-up of at least 24 months after treatment demonstrated a continued healthy state without evidence of relapse. These promising, albeit preliminary, results of difluoromethylonithine therapy, even in patients with central nervous system involvement, indicate that extended clinical trials are warranted to determine the optimal dosage regimen in patients with early- and late-stage disease.