Human
African trypanosomiasis (HAT), or sleeping sickness, is currently on the rise. HAT develops in two stages, the first involving the hemolymphatic system, and the second, the neurological system. Left untreated, HAT is invariably fatal. There have been no therapeutic advances in more than 40 years. Stage 1 can be treated with
pentamidine and
suramin, but stage 2 can only be treated with
melarsoprol, a toxic
arsenic derivative that has a 2-12% incidence of fatal side-effects (
encephalopathy).
Eflornithine has never achieved widespread use because it is difficult to administer under field conditions.
Nifurtimox has been used successfully in the treatment of
American trypanosomiasis, or
Chagas disease, but only in small studies or as a compassionate use treatment. There is little research and development for new drugs in this area: only one
prodrug is in the clinical development phase, a
pentamidine analog that offers hope for the replacement of
injectable pentamidine with an orally administered
drug. Current efforts appear to be focused on reevaluating older drugs. A course of treatment with
melarsoprol for 10 days at 2.2 mg/kg/day is now in the multicenter evaluation phase. Orally administered
eflornithine is also slated for reevaluation. In addition, studies of
drug combinations are recommended to determine possible combined or synergistic effects and find ways to reduce toxicity.