African trypanosomiasis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Pilar Almonacid, Aditya Ganti M.B.B.S. [2]

Sleeping sickness or African trypanosomiasis is a parasitic disease of people and animals caused by protozoa of the genus Trypanosoma and transmitted by the tsetse fly. The disease is endemic to certain regions of Sub-Saharan Africa, covering about 36 countries and 60 million people. 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 (Trypanosoma brucei rhodesiense or Trypanosoma brucei gambiense) is causing the infection. However, infection with either form will eventually lead to coma and death if not treated.

African trypanosomiasis has been present in Africa for thousands of years. In 1903, David Bruce identified the causative agent vector. In 1910, the differentiation between the subspecies of the protozoa was established.^[1]

African trypanosomiasis can be classified based upon the pathogen and geographic location into two types, East African trypanosomiasis and West African trypanosomiasis.^[2]

African trypanosomiasis is a human tropical parasitic disease usually caused by protozoan hemo-flagellates belonging to the complex Trypanosoma brucei. Infection is usually transmitted via the tsetse fly bite to the human host. A trypanosomal chancre develops on the site of inoculation. This is followed by a hemo-lymphatic stage with symptoms including fever, lymphadenopathy, and pruritus. In the meningoencephalitic stage, invasion of the central nervous system can cause headaches, somnolence, abnormal behavior, and lead to loss of consciousness and coma. The course of infection is much more acute with Trypanosoma brucei rhodesiense than Trypanosoma brucei gambiense. Clinical manifestations generally appear within 1–3 weeks of the infective bite for Trypanosoma brucei rhodesiense and months to years for Trypanosoma brucei gambiense.

African trypanosomiasis is a human tropical parasitic disease usually caused by protozoan hemo-flagellates belonging to the complex Trypanosoma brucei. Two subspecies that are morphologically indistinguishable cause distinct disease patterns in humans: Trypanosoma brucei gambiense causes West African sleeping sickness and Trypanosoma brucei rhodesiense causes East African sleeping sickness.

The hemo-lymphatic stage of African trypanosomiasis presents with a rash, fever, and anemia and must be differentiated from other diseases such as brucellosis, typhoid fever, malaria, tuberculosis, lymphoma, dengue, and leptospirosis. The most prominent symptoms in the neurological stage of African trypanosomiasis are mental status changes and sleep disturbances, so differential diagnoses include CNS tuberculosis, meningitis, and HIV-related opportunistic infections, including cryptococcal meningitis.^[3][4][5][6]

Currently, it is estimated that the annual prevalence of African trypanosomiasis is less than 20,000. In 2014, 3,796 cases of sleeping sickness were reported to the World Health Organization and Trypanosoma brucei gambiense accounted for >98% of cases. There is no age predilection for African trypanosomiasis disease.^{[7][8][9][10]}

Risk factors for African trypanosomiasis include residence in Central or South America, living in old houses with mud and stick wall constructions or straw roofs, ingestion of contaminated water, or receiving blood transfusions or organ donation from individuals in regions with high endemicity. The risk of infection increases with the number of times a person is bitten by the tsetse fly. The neonatal risk is highest among those who breastfeed from bleeding or cracked nipples of infected mothers and infants who are delivered from seropositive mothers with active disease.

If African trypanosomiasis is left untreated, the patient will develop symptoms of progressive mental deterioration, which is irreversible and eventually leads to death. Common complications that can develop as a result of African trypanosomiasis include anemia, aspiration pneumonia, meningoencephalitis, seizures, coma, perinatal death, or abortion (congenital infection). The prognosis of African trypanosomiasis is good with treatment. Without treatment, the mortality rate of African sleeping sickness is close to 100%.^[11][12]

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 (Trypanosoma brucei rhodesiense or Trypanosoma brucei gambiense) is causing the infection. However, infection with either form will eventually lead to coma and death if not treated.^{[13][14][15][16]}

Physical examination findings of African trypanosomiasis depend upon the stage of the disease. Skin lesions are more prominent in stage 1 of the disease; neurological findings such as altered level of consciousness and hemiparesis predominate in stage 2.

The diagnosis of African trypanosomiasis rests upon demonstrating trypanosomes by microscopic examination of chancre fluid, lymph node aspirates, blood, bone marrow, and cerebrospinal fluid in the late stages of infection.

There are no x-ray findings associated with African trypanosomiasis.

There are no CT scan findings associated with African trypanosomiasis.

There are no MRI findings associated with African trypanosomiasis.

There are no ultrasound findings associated with African trypanosomiasis.

There are no other imaging findings associated with African trypanosomiasis.

There are no other diagnostic findings for African trypanosomiasis.

Medical treatment of African trypanosomiasis should begin as soon as possible and is based on the infected person’s symptoms and laboratory results. Medications are the mainstay of treatment for African trypanosomiasis. Pentamidine isethionate and suramin are the drugs of choice to treat the hemo-lymphatic stages of West and East African Trypanosomiasis, respectively. Melarsoprol is the drug of choice for late disease with central nervous system involvement (infections by Trypanosoma brucei gambiense or Trypanosoma brucei rhodesiense). Hospitalization is necessary in the second stage of the disease. Periodic follow-up exams that include a spinal tap are required for 2 years. If a person fails to receive medical treatment for African trypanosomiasis, death will occur within several weeks to months.^{[17][18][19][20]}

Surgical intervention is not recommended for the management of African trypanosomiasis.

Primary prevention and control focus on the eradication of the parasitic host, the tsetse fly. Methods of primary prevention of African trypanosomiasis include use of insecticides to control the vector, use of new construction compounds in building walls and roofs, and organ and blood testing prior to donation. Regular active surveillance, involving case detection and treatment, in addition to tsetse fly control, is the backbone of the strategy for control of sleeping sickness.

The primary and secondary prevention strategies for African trypanosomiasis are the same.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Pilar Almonacid, Aditya Ganti M.B.B.S. [2]

African trypanosomiasis has been present in Africa for thousands of years. In 1903, David Bruce identified the vector of causative agent. In 1910, the differentiation between the subspecies of the protozoa was established.

• In 1841, Valentin, a professor of physiology, discovered a trypanosome-like flagellate for the first time in the blood of a trout.^[1]
• In 1843, Gruby gave a detailed description of trypanosomes based on the work done independently by Gluge and Mayer in the blood of frogs.
• In 1891, Nepveu identified trypanosomes for the first time in human blood.
• In 1898, Brault suggested trypanosomes as the cause of sleeping sickness.
• In 1901, Forde and Dutton described Trypanosoma brucei gambiense in human blood for the first time.
• In 1902, the First and Second Sleeping Sickness Commissions led by Low and Bruce were conducted in Uganda.
• In 1902, Castellani identified trypanosomes in the cerebrospinal fluid of patients suffering from sleeping sickness for the first time.
• In 1903, David Bruce recognized the tsetse fly as the arthropod vector.
• In 1905, Bruce suggested that tsetse flies transmit trypanosomes mechanically.
• In 1909, Kleine demonstrated the cyclical transmission of trypanosomes in tsetse flies.
• In 1910, Stevens and Fantham identified Trypanosoma brucei rhodesiense as the cause of acute sleeping sickness.
• In 1914, Ritz described the antigenic variation of trypanosomes.
• In 1969, Vickerman described the coat of trypanosomes as the source of antigenic variation.

• In 1902, Laveran and Mesnil discovered that sodium arsenite can be used to kill trypanosomes.
• In 1945, DDT was used for the first time in controlling tsetse flies.
• In 1949, melarsoprol was used for the first time as an anti-trypanosome drug.
• In 1992, eflornithine was used for the treatment of human sleeping sickness.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

African trypanosomiasis can be classified based upon the pathogen and geographic location into two types, East African trypanosomiasis and West African trypanosomiasis.

African trypanosomiasis can be classified based upon the pathogen and geographic location into the following types:^[1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Pilar Almonacid, Aditya Ganti M.B.B.S. [2]

African trypanosomiasis is a human tropical parasitic disease usually caused by protozoan hemoflagellates belonging to the complex Trypanosoma brucei. A trypanosomal chancre develops on the site of inoculation. This is followed by a hemolymphatic stage with symptoms that include fever, lymphadenopathy, and pruritus. In the meningoencephalitic stage, invasion of the central nervous system can cause headaches, somnolence, abnormal behavior, loss of consciousness and coma. The course of infection is much more acute with Trypanosoma brucei rhodesiense than with Trypanosoma brucei gambiense. Clinical manifestations generally appear within 1–3 weeks of the infective bite for Trypanosoma brucei rhodesiense and months to years for Trypanosoma brucei gambiense.

African trypanosomiasis is a human tropical parasitic disease usually caused by protozoan hemoflagellates belonging to the complex Trypanosoma brucei. A trypanosomal chancre develops on the site of inoculation. This is followed by a hemolymphatic stage with symptoms that include fever, lymphadenopathy and pruritus. In the meningoencephalitic stage, invasion of the central nervous system can cause headaches, somnolence, abnormal behavior, and lead to loss of consciousness and coma. The course of infection is much more acute with Trypanosoma brucei rhodesiense than Trypanosoma brucei gambiense. Clinical manifestations generally appear within 1–3 weeks of the infective bite for Trypanosoma brucei rhodesiense and months to years for Trypanosoma brucei gambiense.^{[1][2][3][4][5][6]}

• Infection is usually transmitted via the tsetse fly bite to the human host.

• Clinical manifestations generally appear within 1–3 weeks of the infective bite for Trypanosoma brucei rhodesiense and months to years for Trypanosoma brucei gambiense.

• Humans are the main reservoir for Trypanosoma brucei gambiense.
• Wild animals are the main reservoir for Trypanosoma brucei rhodesiense.

• During a blood meal on the mammalian host, an infected tsetse fly (genus Glossina) injects metacyclic trypomastigotes into skin tissue.
• The parasites enter the lymphatic system and pass into the bloodstream.
• Inside the host, the microbe transforms into bloodstream trypomastigotes.
• They are carried to other sites throughout the body, reach other blood fluids (e.g., lymph, spinal fluid), and continue replication by binary fission.
• The entire life cycle of African trypanosomes consists of extracellular stages.

• The 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 and multiply by binary fission.
• Procyclic trypomastigotes leave the midgut and transform into epimastigotes.
• The epimastigotes reach the fly’s salivary glands and continue multiplication by binary fission.
• The cycle in the fly takes approximately 3 weeks.

• Metacyclic trypomastigotes

• Bloodstream trypomastigotes

• Trypomastigotes have proteins on their surface known as major variant surface glycoprotein (VSG). Approximately 10 million copies of a single VSG are present on each trypomastigote.
• Once inside the host, they undergo antigenic variation.
• This VSG antigenic variation leads to non-specific polyclonal B cell activation.
• Immunoglobulin M is produced in large quantities in response to B cell activation.
• Immune complexes form and secondary hyperplasia of the reticuloendothelial system occurs.
• This process may lead to downregulation of the immune system.

• Tumor necrosis factor α (TNF-α) is produced upon activation of cell mediated immunity, stimulating T lymphocytes and macrophages. Virulent trypanomastigotes tend to suppress the activity of tumor necrosis factor α (TNF-α) and IFN-gamma.
• Cytokines such as interleukin (IL) 12, promote Interferon γ (IFN-γ) responses.
• IFN-γ drives TH1-type responses and stimulates macrophage activation.
• Cytokines including IL-6, IL-4, and IL-10 downregulate the protective response.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Pilar Almonacid

African trypanosomiasis is a human tropical parasitic disease usually caused by protozoan hemo-flagellates belonging to the complex Trypanosoma brucei. Two subspecies that are morphologically indistinguishable cause distinct disease patterns in humans. Trypanosoma brucei gambiense causes West African sleeping sickness and Trypanosoma brucei rhodesiense causes East African sleeping sickness.

Protozoan hemo-flagellates belonging to the complex Trypanosoma brucei cause African trypanosomiasis. Two subspecies that are morphologically indistinguishable cause distinct disease patterns in humans. Trypanosoma brucei gambiense causes West African sleeping sickness and Trypanosoma brucei rhodesiense causes East African sleeping sickness.

• The disease is caused by a parasite named Trypanosoma brucei rhodesiense, carried by the tsetse fly.
• An individual will contract East African trypanosomiasis if they are bitten by a tsetse fly infected with the Trypanosoma brucei rhodesiense parasite.
• The tsetse fly is common only in Africa.

• West African trypanosomiasis, also called Gambian sleeping sickness, is caused by a parasite called Trypanosoma brucei gambiense carried by the tsetse fly.
• An individual gets West African trypanosomiasis through the bite of an infected tsetse fly, found only in Africa.
• On rare occasions, a pregnant woman may pass the infection to her baby, or an individual may become infected through a blood transfusion or organ transplant.^[1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

The hemo-lymphatic stage of African trypanosomiasis presents with a rash, fever, and anemia and must be differentiated from other diseases such as brucellosis, typhoid fever, malaria, tuberculosis, lymphoma, dengue, and leptospirosis. The most prominent symptoms in the neurological stage of African trypanosomiasis are mental status changes and sleep disturbances; accordingly, differential diagnoses include CNS tuberculosis, meningitis, and HIV-related opportunistic infections, including cryptococcal meningitis.

• The hemo-lymphatic stage of African trypanosomiasis presents with a rash, fever, and anemia and must be differentiated from other diseases such as brucellosis, typhoid fever, malaria, tuberculosis, lymphoma, dengue, and leptospirosis.
• The most prominent symptoms in neurological stage of African trypanosomiasis are mental status changes and sleep disturbances. Differential diagnoses includes CNS tuberculsosis, meningitis, and HIV-related opportunistic infections, including cryptococcal meningitis.^[1][2][3][4]

The table below summarizes the findings that differentiate African trypanosomiasis from other conditions that cause fever, rash and altered mental status

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Pilar Almonacid, Aditya Ganti M.B.B.S. [2]

Currently, it is estimated that the annual prevalence of African trypanosomiasis is less than 20,000. In 2014, 3,796 sleeping sickness cases were reported to the World Health Organization and Trypanosoma brucei gambiense accounted for > 98% of cases. There is no predilection for a specific age group for African trypanosomiasis.

• The global incidence of African trypanosomiasis is estimated to be 7,000-10,000.
• In 2014, 3,796 sleeping sickness cases were reported to the World Health Organization; Trypanosoma brucei gambiense accounted for > 98% of cases.
• Currently, it is estimated that the annual prevalence of African trypanosomiasis is less than 20,000.

• There is no predilection for a specific age group for African trypanosomiasis.^[1][2][3][4]
• The rate of African trypanosomiasis is high among neonates due to risk of vertical transmission during pregnancy.

• Men and women are affected equally by African trypanosomiasis.
• Male gender is thought to be associated with worse prognosis than female gender.

• Given the endemicity of the disease in South America, the majority of individuals with African trypanosomiasis are of Hispanic origin.
• However, there is no evidence to demonstrate that there is any racial predilection to the acquisition of the infection.

• African trypanosomiasis is endemic to rural sub-Saharan Africa.
• Trypanosoma brucei rhodesiense is found in eastern and southeastern Africa, mainly Tanzania, Uganda, Malawi, Zambia, and Zimbabwe.
• Trypanosoma brucei gambiense is found in central Africa and in limited areas of West Africa, primarily in the Democratic Republic of the Congo, Central African Republic, Angola, South Sudan, Guinea, Cameroon, Gabon, Côte d’Ivoire, Congo, Chad, and northern Uganda.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Risk factors for African trypanosomiasis include residence in Central or South America, living in old houses with mud and stick wall constructions or straw roofs, ingestion of contaminated water, or receiving blood transfusions or organ donation from individuals in regions with high endemicity. The risk of infection increases with the number of times a person is bitten by the tsetse fly. The neonatal risk is highest among those who breastfeed from bleeding or cracked nipples of infected mothers and infants who are delivered from seropositive mothers with active disease.

Common risk factors in the development of African trypanosomiasis include:^[1]

• Living in Central or South America
• Residing in a house constructed before the year 2000
• Exposure to either wall constructions composed of mud and sticks or straw roofs
• Ingestion of contaminated water
• Living in a hut where reduvid bugs live in the walls
• Poverty
• Receiving either a blood transfusion or an organ transplant from a person in regions with high endemicity
• Maternal seropositivity and exacerbation of infection during pregnancy
• Bleeding/cracked nipples of infected mother during breastfeeding
• Immunosuppression

In addition to the bite of the tsetse fly, the disease is contractible in the following ways:

• Vertical transmission:
  • The trypanosome can cross the placenta and infect the fetus, causing perinatal death
• Laboratories:
  • Accidental infections (for example, through the handling of blood of an infected person or organ transplantation, although this is uncommon)
• Blood transfusion

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Pilar Almonacid, Aditya Ganti M.B.B.S. [2]

If left untreated, the patient will develop symptoms of progressive mental deterioration, which are irreversible and will eventually lead to death. Common complications that can develop as a result of African trypanosomiasis include anemia, aspiration pneumonia, meningoencephalitis, seizures, coma, perinatal death, or abortion (congenital infection). The prognosis of African trypanosomiasis is good with treatment. Without treatment, the mortality rate of African sleeping sickness is close to 100%.^[1][2]

If African trypanosomiasis is left untreated, the patient will develop symptoms of progressive mental deterioration, which is irreversible and will eventually lead to death.

Common complications that can develop as a result of African trypanosomiasis include:^[1][2]

• Anemia
• Aspiration pneumonia
• Meningoencephalitis
• Seizures
• Coma
• Perinatal death or abortion (congenital infection)

The prognosis of African trypanosomiasis is good with treatment. Symptoms in both early and late stage trypanosomiasis often resolve along with negative parasitemia on repeat blood smears after treatment. The presence of mental status changes and focal neurological deficits is associated with a particularly poor prognosis among patients with African trypanosomiasis. Without treatment, the mortality rate of African sleeping sickness is close to 100%.^[1][2]