What are the current treatments for sleeping sickness and their limitations?

Disease is caused by two subspecies of Trypanosoma brucei (T. b.) gambiense (g-HAT; 98% of reported sleeping sickness cases) and T. b. rhodesiense (r-HAT), and occurs in two stages: the early stage has non-specific symptoms and is often un- or misdiagnosed, and the late stage, where the parasite crosses the blood-brain barrier, causing serious neurological disorders including sleep cycle disruptions, paralysis, and progressive mental deterioration.

Without effective treatment, the disease usually leads to death.

 

Treatment of stage 1 & stage 2 sleeping sickness

  • Fexinidazole (2018): the first all-oral treatment for stage 1 and stage 2 g-HAT, requires one daily dose of pills for ten days.

Treatment of stage 1 sleeping sickness

  • Pentamidine (1940) for g-HAT and suramin (1920s) for r-HAT, require injections and are ineffective for stage 2.

Treatment of stage 2 sleeping sickness

  • NECT – nifurtimox-eflornithine combination therapy (2009): for stage 2 g-HAT, requires 14 slow intravenous infusions of eflornithine of 2 hours each over 7 days, together with three times a day oral nifurtimox for 10 days. Requires specialized hospital administration and trained staff. Since its addition to the EML, NECT is first-line treatment for stage 2 g-HAT.
  • Eflornithine (1981): today seldom used alone, requires an extended stay in hospital during administration (56 intravenous infusions – four times per day, over 14 days).
  • Melarsoprol (1949): No longer used for g-HAT. Remains the only drug available for stage 2 r-HAT – a toxic arsenic derivative that causes pain and fatal encephalopathy in up to 5% of patients who receive it.