Human African trypanosomiasis or HAT, also known as African sleeping sickness, is a deadly parasitic disease. It is caused by infection with protozoan parasites through a bite by tsetse flies. These flies are only found in Africa.
Human African trypanosomiasis takes two forms, depending on the parasite involved: Trypanosoma brucei gambiense causes the most common type of West African sleeping sickness (98% of reported cases) and T. b. rhodesiense the East African sleeping sickness
Other parasite species and subspecies of the Trypanosoma genus are pathogenic to animals and cause animal trypanosomiasis in wild and domestic animals. In cattle the disease is called Nagana.
Please find more information on this disease in the text below or watch expert interview:
Human African trypanosomiasis
What is the disease?
How dangerous is human African trypanosomiasis?
Human African trypanosomiasis is potentially fatal if it is not treated as soon as possible. When not treated early, particularly in the second stage, there is a high risk of remaining handicapped.
Who is at risk?
People living in rural areas and depending on farming, fishing, live-stock breeding or hunting are most exposed to the tsetse fly and therefore the disease.
Even in areas where the disease is present, most flies do not carry the parasite, so the risk of infection increases with the number of times a person is bitten by a tsetse fly.
Tourists are not at great risk for contracting human African trypano-somiasis unless they are traveling and spending long periods of time in rural areas of the tropical of Africa (e.g. game reserves) where the disease is present.
Travelers to urban areas are not at risk.
How many people are affected by human African trypanosomiasis?
Due to massive interventions of WHO, in 2009 the number reported dropped below 10 000 for the first time in 50 years and further decreased to less than 2000 reported cases in 2017.
However, there are still cases that are not diagnosed and or reported due to e.g. inaccessibility of some endemic areas because of armed conflicts.
Where is African trypanosomiasis found?
Sleeping sickness occurs in 36 sub-Saharan Africa countries where there are tsetse flies that transmit the disease.
The more common type of the disease, infection with trypanosoma brucei gambiense, is found in 24 countries in West and central Africa. This form currently accounts for 98 percent of reported cases of sleeping sickness and causes a chronic infection.
Over 95 percent of the reported cases are found in the Democratic Republic of Congo, Angola, Sudan, the Central African Republic, the Republic of Congo, Chad, and northern Uganda.
Trypanosoma brucei rhodesiense is found in 13 countries in Eastern and Southern Africa. Nowadays, this form represents under 2 percent of reported cases and causes an acute infection. Only Uganda presents both forms of the disease, but in separate zones.
More in-depth information on the current disease distribution:
In the last 10 years, over 70 percent of reported cases occurred in the Democratic Republic of the Congo (DRC) which in 2017 was carry-ing the highest disease burden with 1100 reported cases.
The DRC is the only country that currently reports more than 1000 new cases annually and accounts for 84 percent of the cases reported in 2015.
Central African Republic is the only country that declared between 100 and 200 new cases in 2015.
Countries such as Angola, Burkina Faso, Cameroon, Chad, Congo, Côte d'Ivoire, Equatorial Guinea, Gabon, Gjana, Guinea, Malawi, Nigeria, South Sudan, Uganda, United Republic of Tanzania, Zambia and Zimbabwe are reporting fewer than 100 new cases per year.
Countries like Benin, Botswana, Burundi, Ethiopia, Gambia, Guinea Bissau, Kenya, Liberia, Mali, Mozambique, Namibia, Niger, Rwanda, Senegal, Sierra Leone, Swaziland and Togo have not reported any new cases for over a decade.
How do people get African trypanosomiasis?
A person gets human African trypanosomiasis through the bite of an infected tsetse fly.
Occasionally a pregnant woman may pass the infection to her baby.
In theory, the infection can be transmitted through a blood transfusion, but such cases rarely have been documented.
What are the signs and symptoms of African trypanosomiasis?
In the initial stage, now and then, within one to three weeks, the infective bite develops into a red sore, also called a chancre.
Several weeks to months after a person has been bitten, rather unspecific symptoms like fever, rash, swelling of the face and hands, headaches, fatigue, aching muscles and joints, itching skin, and swollen lymph nodes occur, which are often misdiagnosed as e.g. malaria. Weight loss follows as the illness progresses.
How is the disease developing?
In the secondary stage, after invading the central nervous system the disease causes progressive confusion, personality changes, which most recognized gave the disease its name, and other neurologic problems. These symptoms become worse as the illness progresses.
If left untreated, death will eventually occur after several years of infection.
More in-depth information:
The clinical course of human African trypanosomiasis has two stages. In the first stage, the parasite is found in the peripheral circulation, but it has not yet invaded the central nervous system.
Once the parasite crosses the blood-brain barrier and infects the central nervous system, the disease enters the second stage.
The subspecies that cause African trypanosomiasis have different rates of disease progression, and the clinical features depend on which form of the parasite (T. b. rhodesiense or T. b. gambiense ) is causing the infection.
However, infection with either form will eventually lead to coma and death if not treated.
T. b. gambiense infection (West African sleeping sickness) progresses more slowly.
At first, there may be only mild symptoms. Infected persons may have intermittent fevers, headaches, muscle and joint aches, and malaise. Itching of the skin, swollen lymph nodes, and weight loss can occur.
Usually, after one to two years, there is evidence of the second stage of the disease with central nervous system involvement, personality changes, daytime sleepiness with nighttime sleep disturbance, and progressive confusion. Other neurologic signs, such as partial paralysis or problems with balance or walking may occur, as well as hormonal imbalances.
The course of untreated infection rarely lasts longer than six to seven years and more often kills in about three years.
T. b. rhodesiense infection (East African sleeping sickness) progresses rapidly.
In some patients, a large sore (a chancre) will develop at the site of the tsetse bite.
Most patients develop fever, headache, muscle and joint aches, and enlarged lymph nodes within one to two weeks of the infective bite. Some people develop a rash.
After a few weeks of infection, the parasite invades the central nervous system and eventually causes mental deterioration and other neurologic problems.
Death ensues usually within months.
How is African trypanosomiasis diagnosed?
Diagnosis and treatment of the disease is complex and requires specifically skilled staff.
Common tests include examination of blood samples and a spinal tap. A sample of fluid from swollen lymph nodes may also be taken.
More in-depth information:
Disease management is made in three steps:
- Screening for potential infection. This involves using serological tests which are only available for T.b.gambiense and checking for clinical signs - especially swollen cervical lymph nodes.
- Diagnosing by establishing whether the parasite is present in body fluids.
- Staging to determine the state of disease progression. This entails examining the cerebrospinal fluid obtained by lumbar puncture.
Diagnosis must be made as early as possible to avoid progressing to the neurological stage in order to elude complicated and risky treatment procedures.
The long, relatively asymptomatic first stage of T. b. gambiense sleeping sickness is one of the reasons why an exhaustive, active screening of the population at risk is recommended, in order to identify patients at an early stage and reduce transmission by removing their status of reservoir.
Exhaustive screening requires a major investment in human and material resources. In Africa such resources are often scarce, particularly in remote areas where the disease is mostly found. As a result, some infected individuals may die before they can ever be diagnosed and treated.
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
How is African trypanosomiasis treated?
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.
The earlier the disease is identified, the better the prospect of a cure. The type of treatment depends on the disease stage. 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.
Drugs used in first stage treatment:
- Pentamidine: discovered in 1940, used for the treatment of the first stage of T.b. gambiense sleeping sickness.
- Suramin: discovered in 1920 is still used for the treatment of the first stage of T.b. rhodesiense.
Drugs used in second stage treatment:
Melarsoprol: discovered in 1949, has been used for the treatment of both gambiense and rhodesiense infections. Since it is derived from arsenic and has many undesirable side effects, the most dramatic of which is reactive encephalopathy which in three to ten percent of all cases can be fatal, it is not used anymore.
Currently it is still 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.
- Eflornithine: registered in 1990, can be used as mono therapy but only in the second stage of T.b. gambiense infection. The infusion regimen is complex and difficult to apply.
Nifurtimox: developed in the 1960s at Bayer AG under the name "Bayer 2502“, the substance has been used to treat Chagas disease since 1967. A combination treatment of nifurtimox and Eflornithine was introduced in 2009. It simplifies the use of Eflornithine by reducing the duration of treatment and the number of IV infusions.
After safety and efficacy data provided by clinical trials, its use in combination with Eflornithine has been included in the "WHO List of Essential Medicines" and is currently recommended as first-line treatment for the T.b. gambiense form.
Both drugs are provided free of charge by WHO to endemic countries in a patient treatment kit containing all the material needed for its administration even in resource poor settings.
- Fexinidazole: Results of clinical trials in phase II/III indicated that it can be used in future as an oral drug in early and late stages of both forms of HAT.
Treatment of West African trypanosomiasis should begin as soon as possible and is based on the infected person’s laboratory results.
Hospitalization for treatment is usually necessary.
Periodic follow-up exams that include a spinal tap are required for two years.
How can I prevent infection?
The basic situation:
There is neither a vaccine nor recommended drug available to prevent West African trypanosomiasis.
The only preventive measures are aimed at minimizing contact with tsetse flies because insect repellants have not proven effective in preventing tsetse fly bites.
To avoid the bite of the tsetse fly
- wear protective clothing, including long-sleeved shirts and pants of medium-weight material because tsetse flies can bite through thin fabrics
- wear neutral-colored clothing because tsetse flies are attracted to bright colors and dark colors, especially blue
- move slowly because the tsetse fly is attracted to moving objects.
- avoid bushes because the tsetse fly ill bite if disturbed while resting in bushes during the hottest period of the day
How is African trypanosomiasis transmitted?
Both forms of sleeping sickness are transmitted by the bite of the Glossina species of the tsetse fly.
Tsetse flies inhabit rural areas, living in the woodlands and thickets that dot the East African savannah. In central and West Africa, they live in the forests and vegetation along rivers.
Tsetse flies bite during daylight hours. Both male and female flies can transmit the infection, but even in areas where the disease is endemic, only a very small percentage of flies are infected.
Although the vast majority of infections are transmitted by the tsetse fly, other modes of transmission are possible. Occasionally, a pregnant woman can pass the infection to her unborn baby.
In theory, the infection can also be transmitted by blood transfusion or sexual contact, but such cases have rarely been documented.
What exactly does the vector do?
The tsetse fly is a large, brown, biting fly that serves as both a host and vector for the trypanosome parasites. The flies bite during daylight hours.
While taking blood from a mammalian host, an infected tsetse fly injects parasitic larvae (metacyclic trypomastigotes) into skin tissue. From the bite, parasites first enter the lymphatic system and then pass into the bloodstream.
Inside the mammalian host, they transform into bloodstream trypomastigotes, and are carried to other sites throughout the body, reach other body fluids e.g., lymph, spinal fluid, and continue to replicate by binary fission.
The entire life cycle of African trypanosomes is represented by extracellular stages. A tsetse fly becomes infected with bloodstream trypomastigotes when taking a blood meal on an infected mammalian host. In the fly's midgut, the parasites transform into procyclic trypomastigotes, multiply by binary fission, leave the midgut, and transform into epimastigotes. The epimastigotes reach the fly's salivary glands and continue multiplication by binary fission.
The entire life cycle of the fly takes about three weeks.
How can the vector be controlled?
Control of African trypanosomiasis rests on two strategies: reducing the disease reservoir and controlling the tsetse fly vector.
Because humans are the significant disease reservoir for T. b. gambiense, active case-finding through population screening by mobile intervention teams, followed by treatment of the infected persons are the main control strategy.
Tsetse fly traps are sometimes used as an adjunct.
Animals can also be infected with T.b. gambiense and act as a reservoir to a lesser extent.
Reducing the reservoir of infection is more difficult for T. b. rhodesiense, because of the many animal hosts especially wild animals in e.g. game reserves.
Vector control is usually done with traps or screens, in combination with insecticides and odors that attract the flies.
What are the difficulties and challenges in fighting African trypanosomiasis?
- maintaining and consolidating advances made in disease control
- increasing access to diagnosis and treatment for infected people
- developing better diagnostics, medication with less side effects and/or a vaccine to prevent infection
- increasing awareness of the disease among both the vulnerable population and all decision-makers who have an impact on the elimination of the disease
- underfunding of vector control and decentralization of facilities and manpower
- overcoming the stigmatization of African trypanosomiasis as a punishment of the gods and the patients being bewitched
What programs exist against African trypanosomiasis?
In 2000 and 2001, WHO established long-term public-private partnerships with Sanofi, donating pentamidine, melarsoprol and eflornithine, and Bayer, donating suramin which enabled the creation of a WHO-led control and surveillance program, providing support to endemic countries in their control activities and the supply of medicines free of charge. Since 2009, the introduction of the Nifurtimox-Eflornithine Combination Treatment (NECT), Bayer donates also Nifurtimox. On behalf of WHO MSF-Logistics is packing the patient treatment kits and arranges the shipments to the endemic countries.
The success in curbing the number of sleeping sickness cases has encouraged other private partners to sustain the WHO’s initiative towards eliminating the disease as a public health problem.
In 2009, WHO set up a biological specimen bank that is available to researchers to facilitate the development of new and affordable diagnostic tools. The bank contains samples of blood, serum, cerebrospinal fluid, saliva and urine from patients infected with both forms of the disease as well as samples from uninfected people from areas where the disease is endemic.
In 2014 a coordination network for human African trypanosomiasis was established under WHO leadership. The stakeholders include national sleeping sickness control programs, groups developing new tools to fight the disease, international and non-governmental organizations, and donors.
The objectives of the WHO program are to:
- strengthen and coordinate control measures and ensure field activities are sustained
- strengthen surveillance systems
- ensure accessibility to the diagnosis and the best treatment available; support the monitoring of treatment and drug resistance
- develop an information database for epidemiological analysis, including the atlas of the human African trypanosomiasis, completed in collaboration with the Food and Agriculture Organization (FAO)
- ensure skilled staff by offering training activities
- support operational research to improve diagnostic and treatment tools
- promote collaboration with the FAO in charge of animal trypanosomiasis and the International Atomic Energy Agency (IAEA) dealing with vector control through male flies made sterile by radiation
- synergize vector and disease control activities in collaboration with the Pan African Tsetste and Trypanosomosis Eradication Campaign (PATTEC) of the African Union.
Drugs for Neglected Diseases initiative (DNDi) is a collaborative, patients’ needs-driven, non-profit drug research and development (R&D) organization that is developing new treatments for neglected diseases.
DNDi aims to deliver:
A safe, effective, and orally administered drug to replace current first-line HAT treatments, and to improve and simplify current case management.
The ideal goal is to develop two drugs that are effective against both stage 1 and 2 HAT and both subspecies of the parasite.
If successful, this would represent a fundamental shift in disease management, as it would remove the need both for a risky and painful lumbar puncture test to confirm the disease stage, and for hospitalization, as treatment would no longer rely on administering a drug intravenously.
- Fexinidazole, the result of DNDi’s compound mining activities, will – once it is approved – remove the need for hospitalization, potentially even enabling some patients to take their treatment at home. Therapy will consist of one daily dose of pills for ten days, and will be the same for both stages of the disease, meaning no more lumbar punctures.
- Acoziborole is the first DNDi new chemical entity resulting from its own lead optimization program to enter clinical development. Thanks to an unusually long half-life when tested in healthy volunteers, acoziborole could be administered as a single dose. If proved safe and effective, acoziborole will become a key tool to sustain the elimination after 2020.
What does Bayer contribute to the fight against African trypanosomiasis?
Bayer provides two of the medicines that are used in the fight against African trypanosomiasis. One of them contains the active ingredient Nifurtimox, which is on the WHO's list of essential drugs and had already once been granted a license for treating African trypanosomiasis under the trade name Lampit™ in 1967. Production was halted in 1997 due to insufficient demand but resumed again in 2000 in consultation with the WHO.
Since that time Bayer has been supporting the WHO with donated medicines, which since 2012 have amounted to one million Lampit™ tablets a year containing 120 mg of Nifurtimox.
What is the societal burden of African trypanosomiasis?
There are no current studies that provide an overall view of the socio-economic burden, but the following examples show the local effects of the disease in different endemic areas.
The socio-economic burden of human African trypanosomiasis and the coping strategies of households in the South Western Kenya foci (excerpt)
Socio-economic impacts included, disruption of daily activities, food insecurity, neglect of homestead, poor academic performance/school drop-outs and death. Delayed diagnosis of HAT caused 93% of the affected households to experience an increase in financial expenditure (ranging from US$ 60–170) in seeking treatment. Out of these, 81.5% experienced difficulties in raising money for treatment resorting to various ways of raising it. The coping strategies employed to deal with the increased financial expenditure included: sale of agricultural produce (64%); seeking assistance from family and friends (54%); sale/lease of family assets (22%); seeking credit (22%) and use of personal savings (17%).
Estimating the economic and social consequences for patients diagnosed with human African trypanosomiasis in Muchinga, Lusaka and Eastern Provinces of Zambia (2004–2014) (excerpt)
Sixty four cases were identified in the study. The majority were identified in second stage, and the mortality rate was high (12.5%). The total number of DALYs was 285 without discounting or age-weighting. When long-term disabilities were included this estimate increased by 50% to 462. The proportion of years lived with disability (YLD) increased from 6.4% to 37% of the undiscounted and un-age-weighted DALY total. When a more active surveillance method was applied in 2013–2014 the cases identified increased dramatically, suggesting a high level of under-reporting. Similarly, the proportion of females increased substantially, indicating that passive surveillance may be especially failing this group.
An average of 4.9 months of productive time was lost per patient as a consequence of infection. The health consequences included pain, amnesia and physical disability. The social consequences included stigma, dropping out of education, loss of friends and self-esteem. Results obtained from focus group discussions revealed misconceptions among community members which could be attributed to lack of knowledge about rHAT.
We found 47 households (21% of all households) with >1 new HAT case diagnosed since 2000. We located 57 of the 77 HAT patients reported by PNLTHA in Buma-centre and Kimpolo (74%) during 2000–2002. Four persons died of HAT during this time in this community of 1,300 persons. Table 1 describes the household characteristics. All but 1 patient eventually sought treatment after varying time periods since diagnosis. Patient median age was 26 years (range 4–72 years), and 57% of patients were female. Fifty (87%) of the 57 cases were detected by the mobile team during active case finding. At the time of diagnosis, 36 (63%) were in the first stage of the disease. The median time of patient hospitalization was 10 days (range 7–45 days), and time after hospitalization (including enforced rest) was 90 days (range 30–270 days); time spent by caregiver during and after patient’s hospitalization was 10 days (range 0–94 days). The percentages of out-of-pocket expenditures incurred by the 47 households in Buma for 57 HAT cases were as follows: indirect costs 94.55%, hospitalization 04.16%, treatment 01.11%, consultation 00.10%, and laboratory 00.09%. The median value of a day’s work per household was US $1.2. The median cost of HAT case per household was US $163.98 (range $32.30–$3,731.70). This cost represents 43% of the annual revenue of a household (an estimated US $384 [range $0–$1980]) and is based on agricultural production and small trade.
Human African Trypanosomiasis in a Rural Community, Democratic Republic of Congo (excerpt)
We found 47 households (21% of all households) with >1 new HAT case diagnosed since 2000. We located 57 of the 77 HAT patients reported by PNLTHA in Buma-centre and Kimpolo (74%) during 2000–2002. Four persons died of HAT during this time in this community of 1,300 persons. All but 1 patient eventually sought treatment after varying time periods since diagnosis. Patient median age was 26 years (range 4–72 years), and 57% of patients were female. Fifty (87%) of the 57 cases were detected by the mobile team during active case finding. At the time of diagnosis, 36 (63%) were in the first stage of the disease. The median time of patient hospitalization was 10 days (range 7–45 days), and time after hospitalization (including enforced rest) was 90 days (range 30–270 days); time spent by caregiver during and after patient’s hospitalization was 10 days (range 0–94 days). The percentages of out-of-pocket expenditures incurred by the 47 households in Buma for 57 HAT cases were as follows: indirect costs 94.55%, hospitalization 04.16%, treatment 01.11%, consultation 00.10%, and laboratory 00.09%. The median value of a day’s work per household was US $1.2. The median cost of HAT case per household was US $163.98 (range $32.30–$3,731.70). This cost represents 43% of the annual revenue of a household (an estimated US $384 [range $0–$1980]) and is based on agricultural production and small trade.
An attempt to identify HAT cases from before 2000 by using verbal autopsy and other methods was not successful, most likely because this outbreak was recent. A total of 2,145 DALYs (27 per case) would have occurred in this community had no intervention taken place. Under the current control strategy of repeated active population screening and treatment, the disease still caused 737 DALYs. We conclude that the intervention enabled 1,408 DALYs to be averted at a savings of US $17 per DALY. At a cost of US $301 for HAT control per case detected and patient cured, the total intervention for 79.8 cases (57 cases detected; 1.4 assuming 40% of cases remain undetected) was $24,019.80.
How did the history of the disease proceed?
Sleeping sickness threatens millions of people in 36 countries in sub- Saharan Africa. Many of the affected populations live in remote rural areas with limited access to adequate health services, which complicates the surveillance and therefore the diagnosis and treatment of cases. In addition, displacement of populations, war and poverty are important factors that facilitate transmission.
There have been several epidemics in Africa over the last century:
- one between 1896 and 1906, mostly in Uganda and the Congo Basin
- one in 1920 in a number of African countries
- the most recent epidemic started in 1970 and lasted until the late 1990s
The 1920 epidemic was controlled thanks to mobile teams which carried out the screening of millions of people at risk. By the mid-1960s, the disease was under control with less than 5000 cases reported in the whole continent.
After this success, surveillance was relaxed, and the disease reappeared, reaching epidemic proportions in several regions by 1970.
In 1998, almost 40 000 cases were reported, but estimates were that 300 000 cases were undiagnosed and therefore untreated.
During the most recent epidemic the prevalence reached 50 percent in several villages in Angola, the Democratic Republic of the Congo, and South Sudan. Sleeping sickness was the first or second greatest cause of mortality in those communities, even ahead of HIV/AIDS.
The efforts of WHO, national control programs, bilateral cooperation and nongovernmental organizations (NGOs) during the 1990s and early 21st century reversed the curve.
Since the number of new human African trypanosomiasis cases reported between 2000 and 2012 dropped by 73 percent.
In 2009, after continued control efforts, the number of cases reported was below 10 000 for the first time in 50 years.
This decline in number of cases has continued with less than 2000 new cases reported in 2017, the lowest level since the start of systematic global data-collection 76 years ago. The WHO Roadmap to fight Neglected Tropical Diseases roadmap published in 2012 targeted the elimination of human African trypanosomiasis as a public health problem by 2020.
The causative agent and vector of African sleeping sickness were identified in 1903 by David Bruce, and the subspecies of the protozoa were differentiated in 1910. Bruce had earlier shown that T. brucei was the cause of a similar disease in horses and cattle that was transmitted by the tse-tse fly (Glossina morsitans).
- Atoxyl was the first effective treatment, an arsenic-based drug developed by Paul Ehrlich and Kiyoshi Shiga. It was introduced in 1910, but blindness was a serious side effect.
- Suramin was first synthesized by Oskar Dressel and Richard Kothe in 1916 for Bayer. It was introduced in 1920 to treat the first stage of the disease. By 1922, Suramin was generally combined with tryparsamide (another pentavalent organoarsenic drug), the first drug to enter the nervous system and be useful in the treatment of the second stage of the gambiense form. The product is on the Essential Drug List of WHO and been donated by Bayer to WHO since the year 2000.
- Tryparsamide was announced in the Journal of Experimental Medicine in 1919 and tested in the Belgian Congo by Louise Pearce of the Rockefeller Institute in 1920. It was used during the grand epidemic in West and Central Africa on millions of people and was the mainstay of therapy until the 1960s. American medical missionary Arthur Lewis Piper was active in using tryparsamide to treat sleeping sickness in the Belgian Congo in 1925.
- Pentamidine, a highly effective drug for the first stage of the disease, has been used since 1937. During the 1950s, it was widely used as a prophylactic agent in western Africa, leading to a sharp decline in infection rates.
- The organoarsenical melarsoprol (Arsobal) developed in the 1940s is effective for patients with second-stage sleeping sickness. However, 3–10% of those injected have reactive encephalopathy causing convulsions, progressive coma, or psychotic reactions, and 10–70% of such cases result in death. Melarsoprol can cause brain damage in those who survive the encephalopathy. However, due to its effectiveness, it is still used today.
- Eflornithine (difluoromethylornithine or DFMO), the most modern treatment, was developed in the 1970s by Albert Sjoerdsma and underwent clinical trials in the 1980s. The drug was approved by the United States Food and Drug Administration in 1990. Aventis, the company responsible for its manufacture, halted production in 1999. In 2001, Aventis, in association with Médecins Sans Frontières and the World Health Organization, signed a long-term agreement to manufacture and donate the drug.
- The launch of the Nifurtimox-Eflornithine Combination Treatment (NECT) in 2009 was a major breakthrough in the treatment of the second stage of the disease (central nervous system involvement). Since then Bayer donates Nifurtimox and Sanofi Eflornithine to WHO. Both products are listed as WHO Essential Drugs.