Human African trypanosomiasis

Symptoms, diagnosis and treatment


Following the bite of the infected fly (both male and female can transmit infection), the parasite multiplies in the lymph and the blood of the person bitten, causing unspecific symptoms and signs such as headaches, fever, weakness, pain in the joints, lymphadenopathy, and stiffness. People who become infected may or may not show signs of illness immediately, but over time the parasite crosses the blood-brain barrier and migrates to the central nervous system. Here it causes various neurological changes which include the sleep disorder (hence the name “sleeping sickness”), deep sensory disturbances, abnormal tone and mobility, ataxia, psychiatric disorders, seizures, coma and ultimately death.

In the case of T.b. rhodesiense infections, the disease is acute, lasting from a few weeks to several months while in T.b. gambiense infections the disease is chronic, generally progressing slowly over several years.


Diagnosis of the stage of disease is a necessary step to complete a diagnosis of HAT and is vital for appropriate treatment. HAT progresses in two stages. Diagnosis requires confirming the presence of the parasite in any body fluid, usually in the blood and lymph system. Early diagnosis is difficult because of the lack of specific signs or symptoms in the first stage of the disease and also because of the lack of sensitivity of the parasitological methods available.

Initially, trypanosomes disseminate and proliferate in lymph, blood and other tissues. This haemo-lymphatic period, which is the first or early stage, evolves into a second or meningo-encephalitic stage, in which trypanosomes invade the central nervous system (CNS). Progression into the second-stage occurs after a mean of 300–500 days in gambiense HAT, while in rhodesiense HAT brain invasion is estimated to take place after 3 weeks to 2 months of infection. For both forms of the disease, stage is determined by examination of the cerebrospinal fluid (CSF). Lumbar puncture for staging is usually performed immediately after parasitological diagnosis of trypanosome infection or when indications of infection are present that justify this relatively invasive intervention (e.g. indicative clinical signs or strong serological suspicion). In the case of T. b. rhodesiense infection, staging is, in practice, often performed only after a dose of suramin has been administered, as it is considered that blood parasitaemia should be cleared before a lumbar puncture in order to avoid the risk for introducing the parasite into CSF in cases of traumatic lumbar puncture.

The disease stage is defined from the number of white blood cells (WBCs) in the CSF and the presence of trypanosomes. Although determination of the total protein concentration was recommended for staging in the past, it is now determined only rarely for staging HAT and has little impact on the staging decision. Furthermore, as the total CSF protein concentration is influenced by the high immunoglobulin levels in blood, it is already moderately increased in the first disease stage. Only in the case of dysfunction of the blood–CSF barrier, which is relatively rare in HAT, do protein levels become markedly abnormal.

The most significant progress in diagnostics occurred in the late 1970s when the Card Agglutination Trypanosomiasis Test (CATT) was developed for serological screening. Unfortunately CATT is only applicable to T.b. gambiense infections. Since the 1980s the test has been progressively used for screening the population at risk in western and central Africa where the Gambiense form of the disease is prevalent. Since the 2010s, the tools for screening of gambiense HAT have been complemented by the development of rapid individual serological tests that are better adapted to passive screening at health facilities.

Confirmation of infection requires parasitological tests to demonstrate the presence of trypanosomes in the patient. The parasites can be present in any body fluid. However, the number of parasites can be so low (mainly in the gambiense form of the disease) that available parasitological methods may not be sensitive enough to find them. Thus a negative parasitological result in the presence of a positive serological test does not necessarily indicate absence of infection, and tests may have to be repeated over time to achieve diagnosis.

For effective control and surveillance of sleeping sickness, new tests are still needed. New diagnostic tests should be affordable, implementable with simple protocols at any health structure level requiring minimum training and equipment, thus easy to execute by any health worker. They should provide rapid and reliable results with optimal sensitivity and specificity, for an uncontroversial diagnosis of both forms of the disease. This should enable immediate treatment, avoiding cumbersome parasitological examinations. In addition, the tests should be stable at room temperature, requiring no refrigeration and having a reasonable volume for easy storage and transport. Improved methods for staging are also needed. Stage markers in other body fluids such as serum, urine, or saliva would be ideal to avoid the invasive procedure of a lumbar puncture.


Sleeping sickness is notoriously difficult to treat considering the toxicity and complex administration of the drugs currently available for treatment. Furthermore, parasite resistance to existing drugs is always a risk.

Only four drugs are registered for the treatment of human African trypanosomiasis: pentamidine, suramin, melarsoprol and eflornithine. A fifth drug, nifurtimox, is used in combination under special authorizations. However, none of them are anodyne as all have a certain level of toxicity. Pentamidine and suramin are used in the first or early stage of T.b.gambiense and T.b. rhodesiense infections respectively.

Eflornithine can be used in monotherapy but only in the second stage of T.b.gambiense infection since it has been found not to be effective against the disease due to T.b rhodesiense. Since 2009, the combination of eflornithine and nifurtimox (NECT) has been adopted as first line treatment for second stage gambiense human African trypanosomiasis in all disease endemic countries. The combination of both drugs reduces the duration of eflornithine monotherapy treatment and is easier to administer, while improving the level of efficacy and safety.

Eflornithine is cumbersome to administer requiring enough skilled staff and bulky supplementary material and therefore elaborate logistics. To ensure its extensive use by National Sleeping Sickness Control Programmes (SSNCP) the medicine is distributed free of charge in a kit containing all the materials, expendables and equipment needed for its administration. WHO also trained national staff on how to manage the drug.

Melarsoprol is the only treatment available for late stage of T.b. rhodesiense, being also used as second line drug for the second or advanced stage of T. b. gambiense infections.

Access to medicines

All drugs currently used for the treatment of human African trypanosomiasis are donated to WHO for free distribution by the manufacturers: Sanofi and Bayer. Drugs are stored and shipped by MSF-Logistics.

Drugs can be requested by contacting:

Dr Jose Ramon Franco
Department of Control of Neglected Tropical Diseases
World Health Organization
Telephone: +41 22 791 3313

Dr Gerardo Priotto
Department of Control of Neglected Tropical Diseases
World Health Organization
Telephone: +41 22 791 1375