melarsoprol

Melarsoprol is an organoarsenical antiparasitic medication used to treat late-stage African trypanosomiasis (human African trypanosomiasis, HAT), caused by Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. It is effective against parasites that have invaded the central nervous system and is able to cross the blood-brain barrier, enabling treatment of stage 2 disease.

Administration is parenteral, typically given by intravenous infusion or intramuscular injection over a multi-day course; regimens historically involve daily injections for around 10 days, but exact protocols vary by country and form of infection. Melarsoprol is usually reserved for situations where other therapies are unsuitable or unavailable because of its toxicity.

Mechanism: Melarsoprol is a trivalent organoarsenical that disrupts trypanosomal redox metabolism, inhibiting key enzymes such as trypanothione reductase, leading to accumulation of oxidative stress and parasite death.

Safety: Melarsoprol is highly toxic. The most significant adverse effect is post-treatment reactive encephalopathy (PTE/PBE) which can be fatal; other adverse effects include fever, headache, rash, abdominal pain, nausea, vomiting, lymphopenia, hepatotoxicity, nephrotoxicity, peripheral neuropathy, and bone marrow suppression. Because of these risks, treatment requires careful monitoring, and use is generally restricted to settings with experienced staff.

History and status: Melarsoprol was introduced in the mid-20th century and remained a mainstay for second-stage HAT when other drugs were not available. With the development of safer regimens such as eflornithine, nifurtimox-eflornithine combination therapy (NECT), and newer agents, melarsoprol use has declined, but it remains an essential option in some regions due to limited drug availability and specific resistance patterns; WHO recommends prioritizing safer alternatives where feasible.