African trypanosomiasis overview

# Overview
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.

# Historical Perspective
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.

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

# Pathophysiology
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 13 weeks of the infective bite for Trypanosoma brucei rhodesiense and months to years for Trypanosoma brucei gambiense.

# Causes
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.

# Differentiating  African trypanosomiasis from other diseases
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.

# Epidemiology and Demographics
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.

# Risk Factors
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.

# Natural History, Complications and Prognosis
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%.

# Diagnosis

## History and Symptoms
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.

## Physical examination
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.

## Laboratory Findings
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.

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

## CT scan Findings
There are no CT scan findings associated with African trypanosomiasis.

## MRI Findings
There are no MRI findings associated with African trypanosomiasis.

## Ultrasound Findings
There are no ultrasound findings associated with African trypanosomiasis.

## Other imaging findings
There are no other imaging findings associated with African trypanosomiasis.

## Other Diagnostic Studies
There are no other diagnostic findings for African trypanosomiasis.

# Treatment

## Medical Therapy
Medical treatment of African trypanosomiasis should begin as soon as possible and is based on the infected persons 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.

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

## Primary Prevention
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.

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