Melarsoprol (brand name Arsobal) is an arsenic-based drug used to treat the late, brain-invading stage of African sleeping sickness. For most of the twentieth century it was the main treatment for advanced disease, because it was one of the few medicines that could reach the parasites once they had entered the central nervous system. It was also dangerous. According to the Drugs for Neglected Diseases initiative (DNDi), until 2008 the most widely available treatment for advanced sleeping sickness was melarsoprol, an arsenic-derivative drug “so toxic it killed 1 in 20 patients.”
That history is why today’s guidance has moved away from it. In June 2024 the World Health Organization updated its treatment guidelines so that an oral drug, fexinidazole, is now the first-line choice for most patients with the East African (rhodesiense) form, and combination therapy or fexinidazole is used for the West and Central African (gambiense) form. Melarsoprol has not vanished, though: it remains a first choice in one narrow situation, described below. This guide explains what melarsoprol is, why it is so risky, how it fits into treatment now, what the alternatives are, and what travelers and families should know. It replaces our separate page on Arsobal.
This is general information based on public health guidance and published sources, not medical advice. Sleeping sickness is a medical emergency that needs specialist treatment. In the United States, doctors who suspect it should consult the CDC.
Melarsoprol at a glance
| Drug class | Organic arsenical (arsenic-containing) antiparasitic |
|---|---|
| Brand name | Arsobal |
| Used for | Second-stage (brain-invading) African sleeping sickness, mainly T. b. rhodesiense |
| Given | Intravenously, typically over about 10 days |
| Main danger | Reactive encephalopathy (brain inflammation), which can be fatal |
| Other problems | Painful injections, vein damage, skin, heart, kidney, and stomach effects |
| Today’s role | Reserved mainly for young children with second-stage rhodesiense disease; largely replaced by safer drugs |
What sleeping sickness is
Human African trypanosomiasis, or sleeping sickness, is caused by Trypanosoma brucei parasites spread by the bite of tsetse flies. DNDi describes it as a disease that can cause severe neuropsychiatric symptoms and is almost always fatal if left untreated. There are two forms:
- T. b. gambiense occurs in West and Central Africa and tends to progress slowly over months or years.
- T. b. rhodesiense occurs in East and Southern Africa and is more acute, sometimes progressing in weeks.
The illness has two stages:
- First (hemolymphatic) stage. Parasites are in the blood and lymph. Symptoms include fever, headache, joint pain, and swollen lymph nodes.
- Second (meningoencephalitic) stage. Parasites cross into the brain and spinal fluid. Symptoms include confusion, personality changes, disrupted sleep (the source of the name), difficulty walking and speaking, seizures, and eventually coma and death.
Doctors stage the disease by examining the cerebrospinal fluid obtained by lumbar puncture, looking at the white blood cell count and for parasites. Treatment choice depends on the species, the stage, and the patient’s age and weight. Our guides to eflornithine, nifurtimox, and pentamidine cover other medicines in this field.
What melarsoprol is
Melarsoprol is an organic arsenical, a compound in which arsenic is bound to organic molecules. It kills the trypanosome parasite, including forms that have entered the brain, and it crosses the blood-brain barrier, which many other drugs cannot. It was developed in the mid-twentieth century and became the standard for late-stage disease because for many years it was the only affordable option that worked there.
The details of exactly how it kills the parasite are not fully settled, but arsenicals interfere with the parasite’s energy metabolism. The same property that makes it toxic to trypanosomes makes it toxic to human tissue.
Melarsoprol is given by intravenous injection, and drug references describe a 10-day course. The injections are painful and are given by experienced staff in a treatment setting, since leakage outside the vein can cause tissue damage.
Why it is so dangerous
Reactive encephalopathy
The most serious risk is a post-treatment reactive encephalopathy, a sudden inflammation of the brain that can cause seizures, confusion, coma, and death. The World Health Organization’s Essential Medicines Committee documents describe melarsoprol as frequently associated with severe complications, noting that post-treatment reactive encephalopathy occurs in up to 10% of treated patients. The DNDi figure that it killed about 1 in 20 patients reflects the fatal outcomes across programs before safer drugs arrived.
Think about what that means in practice: a treatment meant to save people from a fatal disease itself killed a meaningful fraction of them.
Other adverse reactions
The MSD Manual lists the main toxicities of melarsoprol as:
- Encephalopathic reactions
- Exfoliative dermatitis (widespread skin peeling)
- Cardiovascular toxicity, including high blood pressure, heart rhythm problems, and heart failure
- Itching
- Gastrointestinal and kidney toxicity
The CDC notes that adverse reactions to melarsoprol can be severe and life-threatening, and that other reactions include stomach and skin problems, fever, and peripheral neuropathy. Intravenous injections are painful and can cause phlebitis. WHO documents add that they often cause thrombophlebitis and vein fibrosis (scarring of the veins), which can make repeat injections difficult.
Where melarsoprol fits today
Treatment has changed dramatically thanks to safer drugs developed with international partners.
The modern alternatives
- Fexinidazole. The first all-oral treatment for sleeping sickness. It was approved by the FDA in July 2021 for both stages of T. b. gambiense disease in patients 6 years and older weighing at least 20 kg, with a limitation because of reduced effectiveness in severe second-stage disease. According to DNDi, its indication was expanded in 2023 to cover the rhodesiense form as well, and the course is a 10-day, once-daily oral treatment. The FDA label itself covers the gambiense form.
- NECT (nifurtimox-eflornithine combination therapy). Introduced for second-stage T. b. gambiense disease. The CDC notes NECT appears more effective and less toxic than eflornithine alone.
- Suramin. Used for the first stage of rhodesiense disease. According to the MSD Manual, it is the only drug effective for the hemolymphatic stage of T. b. rhodesiense.
- Pentamidine. Used for early-stage gambiense disease and as interim therapy while waiting for definitive drugs.
WHO guidance, June 2024
The CDC summarizes the WHO’s June 2024 updated guidelines for rhodesiense sleeping sickness:
| Patient | First-stage or second-stage rhodesiense HAT |
|---|---|
| Adults and children 6 years and older weighing 20 kg or more | Fexinidazole is first-line for both stages |
| Children under 6 or under 20 kg, first stage (CSF has 5 or fewer white cells per microliter and no parasites) | Suramin is the first choice |
| Children under 6 or under 20 kg, second stage (more than 5 white cells per microliter in CSF, or parasites present) | Melarsoprol is the first choice |
| Interim therapy while awaiting recommended drugs | Pentamidine may be used |
A 2025 review of the guideline change states that fexinidazole replaces suramin and melarsoprol as the first-line therapy in individuals aged 6 years and older with a body weight of 20 kg or more. It also notes that because fexinidazole is not approved for children under 6 or under 20 kg, a lumbar puncture to stage the disease is still needed in those young children, while for older patients, since fexinidazole works in both stages, staging by lumbar puncture is no longer required.
The bottom line: melarsoprol has gone from the standard of care for advanced disease to a treatment reserved for the smallest children with late-stage rhodesiense disease when no safer approved alternative exists for them.
Why it is still used
The MSD Manual notes that intravenous melarsoprol is often used in African countries because of the limited availability of newer drugs such as fexinidazole. Availability, cost, distribution, and the need for diagnostic capability all affect what patients actually receive. This is one reason global health groups have pushed to expand access to safer options and to keep improving treatments for young children.
The two forms of sleeping sickness compared
| T. b. gambiense | T. b. rhodesiense | |
|---|---|---|
| Region | West and Central Africa | East and Southern Africa |
| Speed | Slow, months to years | Acute, days to weeks |
| Main reservoir | Mostly humans | Animals (livestock and wildlife), with humans as incidental hosts |
| Current first-line drugs (2024 guidance) | Fexinidazole or NECT, depending on severity and access | Fexinidazole for ages 6 and up and 20 kg or more; suramin or melarsoprol for young children by stage |
| Melarsoprol’s role | Largely replaced | Reserved for second-stage disease in young children |
| Travelers | Rarely infected | Occasionally infected on safaris |
The FDA label for fexinidazole covers the gambiense form. Its use for rhodesiense disease is described in WHO and DNDi guidance, and DNDi notes that its indication was expanded to cover that form in 2023.
Diagnosis and staging
Because treatment depends on stage and species, diagnosis matters as much as the drug:
- Finding the parasite. Doctors look for trypanosomes under the microscope in blood, lymph node fluid, or cerebrospinal fluid. In rhodesiense disease, parasites are often easy to find in blood.
- Blood tests. Screening tests for antibodies are used in gambiense areas.
- Lumbar puncture. Staging uses cerebrospinal fluid, counting white blood cells and looking for parasites. Under the 2024 guidance, patients 6 and older weighing at least 20 kg with rhodesiense disease can receive fexinidazole without staging, but young children still need it to choose between suramin and melarsoprol.
- Other clues. Fever, headache, swollen glands, a bite sore, personality change, or disturbed sleep after time in a tsetse-fly area should prompt testing.
Follow-up after treatment
Sleeping sickness treatment is followed by monitoring to make sure the infection has not returned. The specifics depend on the drug and the program, but generally involve repeat examinations and sometimes spinal fluid checks over a period of months to years. A review of the rhodesiense guidelines reported relapse rates in earlier studies of treatment regimens, which is one reason follow-up matters. Families should keep every follow-up appointment and report any return of fever, headache, confusion, or sleep changes right away.
Why melarsoprol’s story matters
Melarsoprol is a case study in how medicine improves. For decades, doctors in affected countries used it because nothing else was available, knowing that a substantial fraction of patients would suffer severe reactions and some would die from the treatment. The development of safer drugs came through collaboration between research groups, drug companies, and health programs, and it changed what patients and doctors face. Today, most patients can receive safer oral or combination treatments, and the remaining challenge is making sure those treatments, and better options for young children, reach everyone who needs them.
Treating melarsoprol’s risks
Because of its toxicity, melarsoprol is given only:
- In a hospital or treatment center with trained staff
- With careful monitoring of the brain, heart, blood pressure, skin, and kidney function
- With a plan to recognize and respond rapidly to encephalopathy
- After the diagnosis has been confirmed by tests
Families should expect an inpatient stay, and should tell the team right away about headache, confusion, seizures, fever, rash, or breathing difficulty.
What travelers should know
Sleeping sickness is rare outside Africa, but travelers to certain rural parts of East and Southern Africa, particularly national parks and game reserves where tsetse flies live, can be infected. In East Africa the acute rhodesiense form causes illness within days to weeks, and a painful sore can appear at the bite site. If you develop fever, headache, a bite sore, rash, or swelling after travel to these regions, tell your doctor about your travel history, since it is rare and easily missed.
Ways to reduce risk include:
- Wearing long-sleeved shirts and long pants in neutral colors (tsetse flies are attracted to bright and dark blue or black clothing)
- Using insect repellent
- Checking vehicles for flies before driving away, and keeping windows up
- Avoiding bushy areas during the day when flies are most active
In the United States, doctors who suspect African trypanosomiasis should contact the CDC for diagnostic and treatment guidance, since some medicines are not widely available.
How melarsoprol relates to other arsenic-based medicines
Arsenic compounds have been used in medicine for over a century, including for syphilis and, more recently, in a form of leukemia (arsenic trioxide). Melarsoprol is an unusual example where the benefit came with severe risk. Its story shows how public-private partnerships, such as those between DNDi, drug companies, the WHO, and national programs, can replace highly toxic drugs with safer ones for neglected diseases.
Questions to ask the care team
- Which species and stage of sleeping sickness does this patient have, and how was it confirmed?
- Is fexinidazole an option, based on age and weight?
- If melarsoprol is recommended, why is it the best option, and what are the alternatives?
- How will encephalopathy be monitored, and what will you do if it starts?
- What symptoms should the family report immediately?
- How long will the hospital stay be, and what follow-up is needed?
- How will we know the treatment worked, and how long will follow-up last?
Frequently asked questions
What is melarsoprol used for?
To treat second-stage African sleeping sickness, especially the East African (rhodesiense) form, when parasites have invaded the brain.
What is the difference between melarsoprol and Arsobal?
Arsobal is a brand name of melarsoprol.
Why is melarsoprol dangerous?
It is an arsenic-based drug that can cause a life-threatening brain inflammation (reactive encephalopathy) in up to about 10% of patients, along with painful veins, skin, heart, and kidney problems. DNDi reports it killed about 1 in 20 patients before safer drugs.
Is melarsoprol still used?
Yes, in a narrow role. WHO’s 2024 guidelines list it as the first choice for second-stage rhodesiense disease in children under 6 or under 20 kg, and it is still used in some African settings where newer drugs are less available.
What replaced melarsoprol?
Fexinidazole, an oral drug taken for 10 days, is now first-line for rhodesiense in patients 6 and older weighing at least 20 kg. NECT (nifurtimox-eflornithine) and fexinidazole are used for gambiense disease.
How is melarsoprol given?
By intravenous injection over about 10 days in a treatment center. The injections are painful and can damage veins.
Can you get sleeping sickness in the United States?
Not locally. Cases are rare and are seen in travelers returning from parts of Africa where tsetse flies live. Doctors should consult the CDC for suspected cases.
How is sleeping sickness diagnosed?
By finding parasites in blood, lymph fluid, or cerebrospinal fluid, and by staging with a lumbar puncture in many cases.
Is sleeping sickness curable?
Yes, with the right treatment, especially when diagnosed early. It is almost always fatal if untreated.
References
- DNDi. Sleeping sickness disease factsheet (2024).
- CDC. Clinical care of human African trypanosomiasis (sleeping sickness).
- WHO. Guidelines for the treatment of human African trypanosomiasis (June 2024).
- Lindner AK, et al. New WHO guidelines for treating rhodesiense human African trypanosomiasis. The Lancet Infectious Diseases, 2025.
- MSD Manual Professional Edition. Treatment of human African trypanosomiasis (HAT).
- WHO Essential Medicines Committee, MSF comments. Fexinidazole: Trypanosoma brucei rhodesiense (r-HAT) (2025).
- DNDi. Fexinidazole for T.b. rhodesiense.
- FDA. Fexinidazole tablets prescribing information (2021).
- Medscape. African trypanosomiasis (sleeping sickness): treatment and management.