Eflornithine

Eflornithine in trypanosomiasis

Melarsoprol (an arsenical compound) is still the most effective compound against stage II (nervous system) disease in both East and West African trypanosomiasis. However, it is toxic and causes death in about 2–8% of subjects treated. Eflornithine is an alternative to melarsoprol for West African trypanosomiasis (both early and late). However, it is very expensive, and its usefulness in endemic areas may therefore be limited. The standard regimen is 100 mg/kg intravenously 6-hourly for 14 days. There have been some anecdotal reports that a shorter 7-day course may be equally effective, with obvious cost-saving advantages.

Observational studies

There has been a multicenter, randomized, open comparison of treatment with eflornithine for 7 or 14 days (n = 321) [ ]. The subjects were divided into new cases and relapses. The 14-day course of eflornithine was superior to the 7-day course for the new cases, but there was no difference in the relapsing cases. However, the numbers of patients who relapsed were small (n = 47) and this may not have allowed the detection of a small difference between the groups. The most common adverse events associated with eflornithine were convulsions, altered consciousness, diarrhea, vomiting, nausea, abdominal pain, and secondary infections. Diarrhea and secondary infection were more common in subjects who took the 14-day course.

In 42 patients with late-stage Trypanosoma brucei gambiense trypanosomiasis, who relapsed after initial treatment with melarsoprol, a sequential combination of intravenous eflornithine (100 mg/kg every 6 hours for 4 days) followed by three daily injections of melarsoprol (3.6 mg/kg, up to 180 mg) was used [ ]. They were followed for 24 months. In one case, the administration of eflornithine had to be interrupted for 48 hours because of convulsions, but treatment was then resumed without recurrence. Other adverse effects during treatment were abdominal pain or vomiting (n = 4 each), diarrhea (n = 1), and loss of hearing (n = 1). Two patients died during treatment:

• A 37-year-old man died of an acute cholera-like syndrome, with severe diarrhea, vomiting, and dehydration, after the last dose of eflornithine but before receiving his first dose of melarsoprol.

• A 34-year-old man died of an unknown cause after having received all 16 doses of eflornithine as well as the first injection of melarsoprol.

There has been a comparison of melarsoprol 2.2 mg/kg/day plus prednisolone 20 mg/day (n = 708) and eflornithine (400 mg/kg given as a slow intravenous infusion in four 3-hour doses daily for 14 days; n = 251) in patients with trypanosomiasis who presented with meningoencephalitis [ ]. Acute reactive encephalopathy occurred in 80 (11%) of those who took melarsoprol and in one (0.4%) who took eflornithine. Of those who took melarsoprol 25 (3.5%) died (23 because of acute reactive encephalopathy) while only two (0.8%) of those who took eflornithine died. Fever, hypertension, macular rash, severe headache, peripheral neuropathy, and tremors were more common in those who took melarsoprol, while diarrhea was more frequent in those who took eflornithine. After 12 months of follow-up there was no significant difference between the rates of relapse.

Eflornithine is the only alternative to melarsoprol in the treatment of second stage African trypanosomiasis. The latter is associated with severe topical adverse effects and treatment failure, but eflornithine requires intravenous infusion every 6 hours for 14 days. In 1055 patients in Sudan with newly diagnosed second-stage human trypanosomiasis, who were given eflornithine 400 mg/kg/day for 14 days (adults) or 600 mg/kg/day (children) [ ]. There were 2824 drug reactions (2.7 per patient) during the stay in hospital, 1219 (43%) of which occurred after the first week. Severe reactions affected 138 patients (13%), mainly seizures, fever, diarrhea, and bacterial infections; there were 15 deaths. Of 924 patients (88%) who were followed up, 16 (1.7%) died during treatment, 70 (7.6%) relapsed, 15 (1.6%) died from the disease, and 403 (44%) were cured.