- Author: Randy O Odero, MB, ChB; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD more...
African trypanosomiasis (sleeping sickness) (see the image below) is an illness endemic to sub-Saharan Africa. It is caused by 2 subspecies of the flagellate protozoan Trypanosoma brucei, which are transmitted to human hosts by bites of infected tsetse flies.
Signs and symptoms
Symptoms of stage 1 (early or hemolymphatic stage) disease may include the following:
Painless skin chancre
Intermittent fever (refractory to antimalarials), general malaise, myalgia, arthralgias, and headache
Generalized or regional lymphadenopathy
Transient urticarial, erythematous, or macular rashes 6-8 weeks after onset
Skin lesions (trypanids)
Symptoms of stage 2 (late or neurologic stage) disease may include the following:
Persistent headaches (refractory to analgesics)
Daytime somnolence followed by nighttime insomnia
Behavioral changes, mood swings, or depression
Loss of appetite, wasting syndrome, and weight loss
Seizures (more common in children)
Physical findings in stage 1 (early or hemolymphatic stage) disease may include the following:
Indurated chancre at bite site
Trypanids in light-skinned patients
Fevers, tachycardia, irregular rash, edema, and weight loss
Organomegaly, particularly splenomegaly
Physical findings in stage 2 (late or neurologic stage) disease may include the following:
CNS manifestations (irritability, tremors, increased muscle rigidity and tonicity, ataxia, hemiparesis)
Behavioral changes consistent with mania or psychosis, speech disorders, and seizures
Stupor and coma
See Presentation for more detail.
Although general laboratory studies may be helpful, a definitive diagnosis of African trypanosomiasis requires actual detection of trypanosomes.
Significant laboratory abnormalities include the following:
Low complement levels
Elevated erythrocyte sedimentation rate (ESR)
Studies performed to detect trypanosomes include the following:
Blood smear (unstained or Giemsa-stained)
Lymph node aspiration
Bone marrow aspiration
Lumbar puncture and CSF assay
CSF assay is also done to measure white blood cell (WBC) counts, protein, and IgM in patients with parasitemia or positive serologies or symptoms.
The following studies may also be considered:
Computed tomography (CT) of the head
Magnetic resonance imaging (MRI) of the head
See Workup for more detail.
The type of drug treatment used depends on the type and stage of disease, as follows:
East African trypanosomiasis, stage 1 - Suramin
East African trypanosomiasis, stage 2 - Melarsoprol
West African trypanosomiasis, stage 1 - Pentamidine isethionate or suramin
West African trypanosomiasis, stage 2 - Melarsoprol or eflornithine
For the treatment of late-stage West African trypanosomiasis, combination therapy (eg, melarsoprol-nifurtimox or nifurtimox-eflornithine) may be more effective than monotherapy.
No vaccine is available for African trypanosomiasis. Chemoprophylaxis is unavailable.
In both early- and late-stage trypanosomiasis, symptoms usually resolve after treatment, and the parasitemia clears on repeat blood smears.
Patients who have recovered from late-stage East African trypanosomiasis should undergo lumbar punctures every 3 months for the first year. Patients who have recovered from West African trypanosomiasis should undergo lumbar punctures every 6 months for 2 years.
African trypanosomiasis, also referred to as sleeping sickness, is an illness endemic to sub-Saharan Africa. It is caused by the flagellate protozoan Trypanosoma brucei, which exists in the following 2 morphologically identical subspecies:
T brucei rhodesiense (East African or Rhodesian African trypanosomiasis)
T brucei gambiense (West African or Gambian African trypanosomiasis)
Both of these parasites are transmitted to human hosts by bites of infected tsetse flies (Glossina palpalis for T brucei gambiense and Glossina morsitans for T brucei rhodesiense), which are found only in Africa.
In West African trypanosomiasis, the reservoirs of infection for these vectors are exclusively human. East African trypanosomiasis, however, is a zoonotic infection with animal vectors. African trypanosomiasis must be distinguished from American trypanosomiasis, which is caused by Trypanosoma cruzi and has different vectors, clinical manifestations, and therapies.
The major epidemiologic factor in African trypanosomiasis is contact between humans and tsetse flies. This interaction is influenced by an increasing tsetse fly density, changing feeding habits, expanding human development into tsetse fly–infested areas, and an increasing number of immunologically naïve persons in previously endemic areas. Major outbreaks from 1920 to 1950 led to extensive treatment and, apparently, immunity for 50 years. However, infection is now recurring as the same populations lose their immunity.
Pathophysiology and Etiology
Trypanosomes are parasites with a 2-host life cycle: mammalian and arthropod. The life cycle starts when the trypanosomes are ingested during a blood meal by the tsetse fly from either a human reservoir (West African trypanosomiasis) or an animal reservoir (East African trypanosomiasis). The trypanosomes multiply over a period of 2-3 weeks in the fly midgut; then, the trypanosomes migrate to the salivary gland, where they develop into epimastigotes.
Humans are infected with T brucei after a fly bite, which occasionally causes a skin chancre at the site. The injected parasites further mature and divide in the blood and lymphatic system, causing malaise, intermittent fever, rash, and wasting. Eventually, the parasitic invasion reaches the central nervous system (CNS), causing behavioral and neurologic changes (eg, encephalitis and coma). Death may occur.
The parasites escape the initial host defense mechanisms through extensive antigenic variation of parasite surface glycoproteins (major variant surface glycoprotein [VSG]). This evasion of humoral immune responses contributes to virulence. During the parasitemia, most pathologic changes occur in the hematologic, lymphatic, cardiac, and central nervous systems. This may be the result of immune-mediated reactions against antigens on red blood cells, cardiac tissue, and brain tissue, resulting in hemolysis, anemia, pancarditis, and meningoencephalitis.
A hypersensitivity reaction causes skin problems, including persistent urticaria, pruritus, and facial edema. Increased lymphocyte levels in the spleen and lymph nodes infested with the parasite lead to fibrosis but rarely to splenomegaly. Monocytes, macrophages, and plasma cells infiltrate blood vessels, causing endarteritis and increased vascular permeability.
The gastrointestinal (GI) system is also affected. Kupffer cell hyperplasia occurs in the liver, along with portal infiltration and fatty degeneration. Hepatomegaly is rare. A pancarditis may develop secondary to extensive cellular infiltration and fibrosis (particularly in the East African form). Arrhythmia or cardiac failure can cause death before the development of CNS manifestations (including perivascular infiltration into the interstitium in the brain and spinal cord, leading to meningoencephalitis with edema, bleeding, and granulomatous lesions.
In rare instances, parasitic transmission can result from blood transfusions. Accidental transmission in the laboratory has also been implicated in a small number of cases.
United States statistics
All cases of African trypanosomiasis in the United States are imported from Africa by travelers to endemic areas. Infections among travelers are rare (< 1 case/year among US travelers). Most of these infections are caused by T brucei rhodesiense and are acquired in East African game parks.
African trypanosomiasis is confined to tropical Africa between latitudes 15°N and 20°S, or from north of South Africa to south of Algeria, Libya, and Egypt. The prevalence of African trypanosomiasis outside this area varies by country and region. In 2005, major outbreaks occurred in Angola, the Democratic Republic of Congo, and Sudan. In the Central African Republic, Chad, Congo, Côte d’Ivoire, Guinea, Malawi, Uganda, and Tanzania, African trypanosomiasis remains a major public health problem.[3, 4, 5]
Fewer than 50 new cases per year are reported in Burkina Faso, Cameroon, Equatorial Guinea, Gabon, Kenya, Mozambique, Nigeria, Rwanda, Zambia, and Zimbabwe. In Benin, Botswana, Burundi, Ethiopia, Gambia, Ghana, Guinea Bissau, Liberia, Mali, Namibia, Niger, Senegal, Sierra Leone, Swaziland, and Togo, T brucei transmission seems to have stopped, and no new cases of African trypanosomiasis have been reported for several decades.
African trypanosomiasis threatens millions of people in 36 countries of sub-Saharan Africa. The current situation is difficult to assess in numerous endemic countries, because of a lack of surveillance and diagnostic expertise.
In 1986, a panel of experts convened by the World Health Organization (WHO) estimated that 70 million people lived in areas where transmission of African trypanosomiasis is possible. In 1998, almost 40,000 cases of the disease were reported, but in view of the remoteness of the affected regions and the focal nature of the disease, it was clear that this number did not reflect the true situation. It was estimated that 300,000-500,000 more cases were undiagnosed and thus went untreated.
During some epidemic periods, prevalence reached 50% in several villages in the Democratic Republic of Congo, Angola, and Southern Sudan. African trypanosomiasis was considered the first or second greatest cause of mortality in those communities, even ahead of HIV infection and AIDS. By 2005, surveillance had been reinforced, and the number of new cases reported throughout the continent had been substantially reduced; between 1998 and 2004, the figures for both forms of African trypanosomiasis together fell from 37,991 to 17,616.
At present, there are an estimated 50,000-70,000 cases of African trypanosomiasis. The current epidemic, which began in 1970, is thought to have been facilitated by factors such as the halting of screening programs, population migration, civil war, economic decline, and reduced healthcare financing.
Age-, sex-, and race-related demographics
Exposure can occur at any age. Congenital African trypanosomiasis occurs in children, causing psychomotor retardation and seizure disorders. African trypanosomiasis has no sexual or racial predilection.
In early (stage 1) trypanosomiasis, most patients recover fully after treatment. In late (stage 2) trypanosomiasis, the CNS manifestations are ultimately fatal if untreated. The cure rate approaches 95% with drugs that work inside the CNS (eg, melarsoprol).
The symptoms of East African trypanosomiasis develop more quickly (starting 1 month after a bite) than the symptoms of West African trypanosomiasis, which can begin months to a year after the first bite.
Both types of African trypanosomiasis cause the same generalized symptoms, including intermittent fevers, rash, and lymphadenopathy. Notably, individuals with the East African form are more likely to experience cardiac complications and develop CNS disease more quickly, within weeks to a month. The CNS manifestations of behavioral changes, daytime somnolence, nighttime insomnia, stupor, and coma result in death if untreated.
In West African trypanosomiasis, the asymptomatic phase may precede onset of fevers, rash, and cervical lymphadenopathy. If unrecognized, the symptoms then progress to weight loss, asthenia, pruritus, and CNS disease with a more insidious onset. Meningismus is rare. Death at this point is usually due to aspiration or seizures caused by CNS damage.
Franco JR, Simarro PP, Diarra A, Jannin JG. Epidemiology of human African trypanosomiasis. Clin Epidemiol. 2014. 6:257-75. [Medline].
Truc P, Lando A, Penchenier L, Vatunga G, Josenando T. Human African trypanosomiasis in Angola: clinical observations, treatment, and use of PCR for stage determination of early stage of the disease. Trans R Soc Trop Med Hyg. 2012 Jan. 106(1):10-4. [Medline].
Simarro PP, Cecchi G, Franco JR, Paone M, Fèvre EM, Diarra A, et al. Risk for human african trypanosomiasis, central Africa, 2000-2009. Emerg Infect Dis. 2011 Dec. 17(12):2322-4. [Medline].
Rock KS, Torr SJ, Lumbala C, Keeling MJ. Quantitative evaluation of the strategy to eliminate human African trypanosomiasis in the Democratic Republic of Congo. Parasit Vectors. 2015 Oct 22. 8 (1):532. [Medline].
Pandey A, Atkins KE, Bucheton B, Camara M, Aksoy S, Galvani AP, et al. Evaluating long-term effectiveness of sleeping sickness control measures in Guinea. Parasit Vectors. 2015 Oct 22. 8 (1):550. [Medline].
Bonnet J, Boudot C, Courtioux B. Overview of the Diagnostic Methods Used in the Field for Human African Trypanosomiasis: What Could Change in the Next Years?. Biomed Res Int. 2015. 2015:583262. [Medline].
Nzou SM, Fujii Y, Miura M, Mwau M, Mwangi AW, Itoh M, et al. Development of multiplex serological assay for the detection of human African trypanosomiasis. Parasitol Int. 2015 Nov 10. 65 (2):121-127. [Medline].
Büscher P, Mertens P, Leclipteux T. Sensitivity and specificity of HAT Sero-K-SeT, a rapid diagnostic test for serodiagnosis of sleeping sickness caused by Trypanosoma brucei gambiense: a case-control study. Lancet Glob Health. June 2014. 2 (6):e359–e363. [Medline]. [Full Text].
Abramowicz M. Drugs For Parasitic Infections. Abramowicz M, ed. The Medical Letter on Drugs and Therapeutics. New Rochelle, NY: The Medical Letter, Inc; 2000. 1-12.
Bisser S, N'Siesi FX, Lejon V, Preux PM, Van Nieuwenhove S, Miaka Mia Bilenge C, et al. Equivalence trial of melarsoprol and nifurtimox monotherapy and combination therapy for the treatment of second-stage Trypanosoma brucei gambiense sleeping sickness. J Infect Dis. 2007 Feb 1. 195(3):322-9. [Medline].
Priotto G, Kasparian S, Ngouama D, Ghorashian S, Arnold U, Ghabri S, et al. Nifurtimox-eflornithine combination therapy for second-stage Trypanosoma brucei gambiense sleeping sickness: a randomized clinical trial in Congo. Clin Infect Dis. 2007 Dec 1. 45(11):1435-42. [Medline].
Gilles Eperon, Manica Balasegaram, Julien Potet, Charles Mowbray, Olaf Valverde and François Chappuis. Treatment options for second-stage gambiense human African trypanosomiasis. Expert Rev Anti Infect Ther. 2014 Nov 1. 12(11):1407–1417. [Medline]. [Full Text].
Franco JR, Simarro P, Diarra A. Monitoring the use of nifurtimox-eflornithine combination therapy (NECT) in the treatment of second stage gambiense human African trypanosomiasis. Res Rep Trop Med. 2012. 3:1 - 9.
Schmid C, Kuemmerle A, Blum J. In-hospital safety in field conditions of nifurtimox eflornithine combination therapy (NECT) for T. b. gambiense sleeping sickness. PLoS Negl Trop Dis. 2012. 6(11):e1920. [Medline]. [Full Text].
Alirol E, Schrumpf D, Amici Heradi J. Nifurtimox-eflornithine combination therapy for second-stage gambiense human African trypanosomiasis: medecins Sans Frontieres experience in the Democratic Republic of the Congo. Clin Infect Dis. 2013. 56(2):195–203. [Medline]. [Full Text].
|Type of Trypanosomiasis||Medications|
|Stage 1 (Early or Hemolymphatic Stage)||Stage 2 (Late or Neurologic Stage)|
|East African trypanosomiasis (caused by Trypanosoma brucei rhodesiense)||Suramin 100-200 mg IV test dose, then 1 g IV on days 1, 3, 7, 14, 21||Melarsoprol 2-3.6 mg/kg/day IV for 3 days; after 1 week, 3.6 mg/kg/day for 3 days; after 10-21 days, repeat cycle|
|West African trypanosomiasis (caused by Trypanosoma brucei gambiense)||Pentamidine isethionate 4 mg/kg/day IM for 10 days
Suramin 100-200 mg IV test dose, then 1 g IV on days 1, 3, 7, 14, 21
|Nifurtimox-eflornithine combination therapy (NECT): Nifurtimox 5 mg/kg PO q8h for 10 days and eflornithine 200 mg/kg IV q12h for 7 days
Eflornithine 400 mg/kg/day IV in 2 divided doses for 14 days
Melarsoprol IV for 10 days