Sleeping sickness (human African trypanosomiasis): symptoms, diagnosis and treatment

Sleeping sickness is the common name for human African trypanosomiasis (HAT), a vector-borne parasitic disease. The WHO says it is caused by protozoans of the genus Trypanosoma, transmitted to humans by the bites of tsetse flies that have acquired the parasites from infected humans or animals. Tsetse flies live in sub-Saharan Africa and only certain species transmit the disease.

It is not the same as Chagas disease, which occurs mainly in Latin America. WHO notes that Chagas disease, or American trypanosomiasis, is caused by a different parasite, transmitted by a different vector, and has very different characteristics.

The disease has a patchy distribution, from single villages to whole regions. WHO says that rural populations who depend on agriculture, fishing, animal husbandry or hunting are the most exposed, and that in many areas where tsetse flies are found, HAT is not.

WHO says HAT takes two forms depending on the parasite subspecies. Trypanosoma brucei gambiense is found in 24 countries of west and central Africa, accounts for 92% of reported cases and causes a chronic illness. A person can be infected for months or years without major signs or symptoms, and by the time evident symptoms emerge the disease is often advanced and the central nervous system already affected.

Trypanosoma brucei rhodesiense is found in 13 countries of eastern and southern Africa and accounts for 8% of reported cases. It causes an acute disease, with first signs and symptoms appearing a few weeks or months after infection and rapid development with multi-organ invasion, including the brain. WHO says domestic and wild animals are the main reservoir of T. b. rhodesiense.

MSF, which runs sleeping sickness programmes, quotes a higher proportion (over 98%) for the gambiense form, citing WHO data. This guide uses the figure in WHO's own fact sheet.

WHO says that initially the trypanosomes multiply in subcutaneous tissue, blood and lymph. This first, haemo-lymphatic stage entails bouts of fever, headache, enlarged lymph nodes, joint pains and itching. MSF adds weakness to the list and describes this stage as easy to treat but difficult to diagnose because the symptoms are non-specific.

Later the parasites cross the blood-brain barrier into the central nervous system, causing the meningo-encephalitic or second stage. WHO says this is generally when more obvious signs appear: behaviour changes, confusion, sensory disturbances and poor coordination. Disturbance of the sleep cycle, which gives the disease its name, is a prominent feature. MSF describes an inability to sleep during the night but being overcome by sleep during the day, with other neurological and psychiatric symptoms such as poor coordination, confusion and convulsions.

Anyone who has been in a sub-Saharan tsetse fly area and develops fever, headache or neurological symptoms, even weeks or months later, should tell a doctor about their travel. In the UK, fever after travel should be assessed promptly through a GP or NHS 111, or emergency services if someone is seriously unwell.

WHO says diagnosis involves three steps: screening for potential infection using serological tests (only available for T. b. gambiense) and clinical examination; confirmation by seeing the parasite under a microscope in body fluids; and staging the disease by clinical examination and analysis of cerebrospinal fluid obtained by lumbar puncture if needed.

Staging matters because it determines treatment. MSF notes that diagnosis before the second stage is difficult because of the non-specific symptoms, and that once the parasite is detected a lumbar puncture is made to examine the cerebrospinal fluid, which determines the stage and the appropriate treatment. WHO stresses that early diagnosis is important to avoid progression to the neurological stage, with its more complex and risky treatment.

WHO says the choice of treatment depends on the disease form and stage, and the earlier the disease is treated the better the prospect of cure. Treatment in the second stage requires drugs that cross the blood-brain barrier. Follow-up for up to 24 months with clinical assessment and laboratory examinations is needed because parasites may remain viable and reproduce the disease many months after treatment.

WHO lists six drugs. For gambiense disease, pentamidine is used in the first stage, eflornithine is given by infusion usually together with oral nifurtimox (NECT) in the second stage, and fexinidazole is an oral treatment for the first stage and non-severe second stage that must be taken after a solid meal under supervision. For rhodesiense disease, suramin is used in the first stage and melarsoprol, an arsenic derivative with many adverse effects including a reactive encephalopathy that is 3 to 10% fatal, in the second stage.

MSF describes fexinidazole as the first all-oral treatment that works for both stages, developed with the Drugs for Neglected Diseases initiative and approved in late 2018, and NECT as safe and highly effective but cumbersome. Rare imported tropical infections are generally managed by specialist hospital services rather than in general practice.

WHO describes control through screening and treatment of exposed populations, with the aim of removing infected people as a reservoir. MSF says prevention efforts such as vector control are crucial. The WHO fact sheet does not describe a vaccine. If you plan to travel to sub-Saharan Africa, ask a GP or travel clinic for current advice for your destination.

The outlook is good with early treatment and poor without it. WHO says that without treatment HAT is usually fatal, although rare cases of self-cure have been reported. The number of cases has fallen dramatically: WHO reports reaching a historic low of under 1,000 cases in 2018 and remaining below that threshold as of 2022.