Treatment perspectives for human African trypanosomiasis.
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.
Bouteille
Bernard
B
Institut d'Epidémiologie Neurologique et de Neurologie Tropicale (UPRES EA 3174), Faculté de Médecine, 2 rue du Docteur Marcland, F-87025 Limoges Cedex, France. bouteille@unilim.fr
Oukem
Odile
O
Bisser
Sylvie
S
Dumas
Michel
M
D000818:Animals; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006801:Humans; D014344:Trypanocidal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014347:Trypanosoma brucei gambiense / Q000187:drug effects; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects; D014353:Trypanosomiasis, African / Q000188:drug therapy* / Q000469:parasitology
D014344:Trypanocidal Agents