African Trypanosomiasis

African trypanosomiasis is a systemic protozoal disease and a type of trypanosomiasis. There are two subtypes that are named depending on the region of Africa in which they are found (East or West). The disease is caused by a parasite named Trypanosoma brucei complex, carried by the tsetse fly.

Female tsetse fly specimen (Glossina spp.). Source: USDA, ARS/Peggy Greb.

Other Names

• Sleeping sickness
• Gambian trypanosomiasis
• Trypanosoma brucei gambiense infection
• Human African trypanosomiasis (HAT)

Types

• East African trypanosomiasis (Trypanosoma brucei rhodesiense)
• West African trypanosomiasis (Trypanosoma brucei gambiense)

Signs and Symptoms

A bite by the tsetse fly will be noticeable as it is often painful. Occasionally, within 1 to 2 weeks, the infective bite develops into a red sore, also called a chancre. Several weeks to months later, other symptoms of sleeping sickness occur. These include:

• Fever
• Rash
• Swelling around the eye and hands
• Severe headaches
• Extreme fatigue
• Aching muscles and joints.
• Weight loss

Sometimes swollen lymph nodes develop on the back of the neck called Winterbottom sign. Progressive confusion, personality changes, slurred speech, irritability, loss of concentration, seizures, and difficulty in walking and talking occurs when infection has invaded the central nervous system. These symptoms become worse as the illness progresses. Sleeping for long periods of the day and having insomnia at night is a common symptom. If left untreated, infection becomes worse and death will occur within several months to years after infection.

Disease due to the T. b. gambiense may run a course of several years; the T. b. rhodesiense disease is lethal within weeks or months without treatment. Both are always fatal without treatment.

Causes

An individual gets 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. The disease is caused by a parasite of the Trypanosoma brucei complex, carried by the tsetse fly;T. b. gambiense is found in west and central Africa (west African trypanosomiasis) and T. b. rhodesiense in the east part of the African continent (east African trypanosomiasis).

VIDEO OF TRYPANOSOMA

Diagnosis

Trypanosoma forms in blood smear from patient with African trypanosomiasis.Source: Phil-CDC

The diagnosis rests upon demonstrating trypanosomes by microscopic examination of chancre fluid, lymph node aspirates, blood, bone marrow, or, in the late stages of infection, cerebrospinal fluid. A wet preparation should be examined for the motile trypanosomes, and in addition a smear should be fixed, stained with Giemsa (or Field), and examined. Concentration techniques can be used prior to microscopic examination. For blood samples, these include centrifugation followed by examination of the buffy coat; mini anion-exchange/centrifugation; and the Quantitative Buffy Coat (QBC) technique. For other samples such as spinal fluid, concentration techniques include centrifugation followed by examination of the sediment.

Treatment

Medication for the treatment of human African trypanosomiasis (HAT)is available. The drugs used for treatment of HAT are:

• Suramin
• Pentamidine
• Eflornithine
• Arsenical melarsoprol

In the United States these drugs can be obtained from the CDC and, in other countries, through the public health institutions and government agencies. Therapy for HAT must be individualized on the basis of the infecting subspecies, the presence or absence of CNS disease, adverse reactions, and occasionally drug resistance.

A new oral drug called DB289 is in the final clinical trial phase. Given its oral administration, it should be considered an important step forward. Unfortunately, the drug requires ten days of treatment, twice a day, and is only effective in the first stage. Consequently, DB289 cannot be considered a new drug that would be a major advance in control of HAT. ^[1]

Hospitalized treatment of HAT should begin as soon as possible and is based on the infected person's symptoms and laboratory results. Hospitalization for treatment is necessary. Periodic follow-up exams that include a spinal tap are required for 2 years.

Prevention

There is neither a vaccine nor recommended drug available to prevent African trypanosomiasis.

These steps should help prevent bites from the tsetse fly:

1. Wearing protective clothing, including long-sleeved shirts and pants. The tsetse fly can bite through thin fabrics, so clothing should be made of thick material.
2. Wearing khaki or olive colored clothing. The tsetse fly is attracted to bright colors and very dark colors.
3. Using insect repellant. Though insect repellants have not proven effective in preventing tsetse fly bites, they are effective in preventing other insects from biting and causing illness.
4. Using bed netting when sleeping.
5. Inspecting vehicles for tsetse flies before entering.
6. Not riding in the back of jeeps, pickup trucks or other open vehicles. The tsetse fly is attracted to the dust that moving vehicles and wild animals create.
7. Avoiding bushes. The tsetse fly is less active during the hottest period of the day. It rests in bushes but will bite if disturbed.

Research

There is no vaccine for human African trypanosomiasis yet, and few drugs are available. But the recent publication of the genome sequence for Trypanosoma brucei, has increased hope for new drug targets and a vaccine.^[2]

One promising target is the flagellum – the 'tail' that propels the parasite through the bloodstream. Professor Keith Gull at the University of Oxford and colleagues have shown that the flagellum plays a critical role in cell division and is, therefore, essential for parasite survival. They have identified flagellar proteins that, being unique to the trypanosome, have potential as drug targets.^[3]

Other studies have revealed further chinks in the trypanosome's armour. Trypanosomes use an unusual mechanism to regulate gene activity, in which messenger RNAs are held by RNA-binding proteins until they are needed. By interfering with this system, Dr Ed Hendriks and Dr Keith Matthews were able to alter a specific step in differentiation – the first time this process has been genetically modified in trypanosomes.^[4]

Clinical Trials

There are currently no recruiting clinical trials for African trypanosomiasis: ClinicalTrials.gov

Epidemiology

Map of Africa Showing the Epidemiological Status of Countries Considered Endemic for Trypanosomiasis. Source Simarro et al.^[5]

In 2000 some 50 to 60 million people in Africa were exposed to the bite of the tsetse fly. At that time WHO considered that close to 300,000 children, women, and men on the African continent were affected by the disease. In 2005, the number of new cases reported was 16,378, however, many cases are not reported due to a lack of infrastructure and the true number of new cases is undoubtedly much higher. West African trypanosomiasis accounts for more than 90% of reported cases of sleeping sickness, and causes a chronic, potentially fatal infection. East African Trypanosomiasis represents less than 10% of reported cases, and causes an acute infection.^[6]

Tsetse flies can be found in Western and Central African forests, in areas of thick shrubbery and trees by rivers and waterholes. Risk of infection increases with the number of times a person is bitten by the tsetse fly. Therefore, tourists are not at great risk for contracting West African trypanosomiasis unless they are traveling and spending long periods of time in rural areas of Western and Central Africa.

The rural populations that live in regions where transmission occurs and depend on agriculture, fishing, animal husbandry, or hunting are the most exposed to the bite of the tsetse fly and therefore to the disease. Displacement of populations, war, and poverty are important factors leading to increased transmission. The disease develops in areas whose size can range from a village to an entire region. Within a given area, the intensity of the disease can vary from one village to the next.

References

1. ↑ Simarro PP, Jannin J, Cattand P. Eliminating human African trypanosomiasis: where do we stand and what comes next? PLoS Med. 2008 Feb;5(2):e55. Full Text PDF
2. ↑ Bloom S.Parasite genome similarities offer hope for new drugs and vaccines. J Clin Invest. 2005 Sep;115(9):2300-1. Full Text PDF
3. ↑ Broadhead R et al. Flagellar motility is required for the viability of the bloodstream trypanosome. Nature 2006;440(7081):224–7. Abstract
4. ↑ Hendriks EF, Matthews KR. Disruption of the developmental programme of Trypanosoma brucei by genetic ablation of TbZFP1, a differentiation-enriched CCCH protein. Mol Microbiol 2005;57(3):706–16.Abstract | Full Text
5. ↑ Simarro PP, Jannin J, Cattand P. Eliminating human African trypanosomiasis: where do we stand and what comes next? PLoS Med. 2008 Feb;5(2):e55. Abstract | Full Text
6. ↑ WHO African Trypanosomiasis

External Links

• CDC:African Trypanosomiasis

• The Medical Letter: Trypanosomiasis treatment PDF

• Scivee.tv PubCast: Trypansoma

• University of Dundee: Tropical Disease Initiative