East African Trypanosomiasis
There are two types of African trypanosomiasis (also called sleeping sickness); each is named for the region of Africa in which they were found historically. East African trypanosomiasis is caused by the parasite Trypanosoma brucei rhodesiense, which is carried by the tsetse fly. Each year, a few hundred cases of East African trypanosomiasis are reported to the World Health Organization. However, many cases are not recognized or reported and the true number of new cases is higher. Since 1967, 40 cases of East African trypanosomiasis have been diagnosed or treated in the United States, all among individuals who had traveled to eastern Africa.
West African Trypanosomiasis
There are two types of African trypanosomiasis (also called sleeping sickness); each named for the region of Africa in which it was found historically. Individuals can become infected with West African trypanosomiasis if they receive a bite from an infected tsetse fly, which is only found in Africa. West African trypanosomiasis, also called Gambian sleeping sickness, is caused by a parasite called Trypanosoma brucei gambiense carried by the tsetse fly. In recent years, 7,000-10,000 new cases of West African trypanosomiasis have been reported to the World Health Organization annually. However, many cases are not recognized or reported and the true number of annual cases is likely to be higher. Cases of West African trypanosomiasis imported into the United States are extremely rare.

Epidemiology & Risk Factors
There are two subspecies of the parasite Trypanosoma brucei that cause disease in humans. The clinical features of the infection depend on the subspecies involved. The two subspecies are found in different regions of Africa. At present, there is no overlap in their geographic distribution.
T. b. rhodesiense (East African sleeping sickness) is found in focal areas of eastern and southeastern Africa. Each year a few hundred cases are reported to the World Health Organization. Over 95% of the cases of human infection occur in Tanzania, Uganda, Malawi, and Zambia. Animals are the primary reservoir of infection. Cattle have been implicated in the spread of the disease to new areas and in local outbreaks. A wild animal reservoir is thought to be responsible for sporadic transmission to hunters and visitors to game parks. Infection of international travelers is rare, but it occasionally occurs. In the U.S., one case per year, on average, is diagnosed. Most cases of sleeping sickness imported into the U.S. have been in travelers who were on safari in East Africa.
T. b. gambiense (West African sleeping sickness) is found predominantly in central Africa and in limited areas of West Africa. Most of the sleeping sickness in Africa is caused by this form of the parasite. Epidemics of sleeping sickness have been a significant public health problem in the past, but the disease is reasonably well-controlled at present, with 7,000-10,000 cases reported annually in recent years. Over 95% of the cases of human infection are found in Democratic Republic of Congo, Angola, Sudan, Central African Republic, Chad, and northern Uganda. Humans are the important reservoir of infection, although the parasite can sometimes be found in domestic animals (e.g., pigs, dogs, goats). Imported infection in the U.S. is extremely rare, and most cases have occurred in African nationals who have immigrated rather than in returning U.S. travelers.
Both forms of sleeping sickness are transmitted by the bite of the tsetse fly (Glossina species). 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 streams. 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.

Disease
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. 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 1-2 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.

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 1-2 years, there is evidence of central nervous system involvement, with 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 6-7 years and more often kills in about 3 years.

Diagnosis
The diagnosis of African Trypanosomiasis is made through laboratory methods, because the clinical features of infection are not sufficiently specific. The diagnosis rests on finding the parasite in body fluid or tissue by microscopy. The parasite load in T. b. rhodesiense infection is substantially higher than the level in T. b. gambiense infection.

T. b. rhodesiense parasites can easily be found in blood. They can also be found in lymph node fluid or in fluid or biopsy of a chancre. Serologic testing is not widely available and is not used in the diagnosis, since microscopic detection of the parasite is straightforward.

The classic method for diagnosing T. b. gambiense infection is by microscopic examination of lymph node aspirate, usually from a posterior cervical node. It is often difficult to detect T. b. gambiense in blood. Concentration techniques and serial examinations are frequently needed. Serologic testing is available outside the U.S. for T. b. gambiense; however, it normally is used for screening purposes only and the definitive diagnosis rests on microscopic observation of the parasite.

All patients diagnosed with African trypanosomiasis must have their cerebrospinal fluid examined to determine whether there is involvement of the central nervous system, since the choice of treatment drug(s) will depend on the disease stage. The World Health Organization criteria for central nervous system involvement include increased protein in cerebrospinal fluid and a white cell count of more than 5. Trypanosomes can often be observed in cerebrospinal fluid in persons with second stage infection.

Treatment
All persons diagnosed with African Trypanosomiasis should receive treatment. The specific drug and treatment course will depend on the type of infection (T. b. gambiense or T. b. rhodesiense) and the disease stage (i.e. whether the central nervous system has been invaded by the parasite). Pentamidine, which is the recommended drug for first stage T. b. gambiense infection, is widely available in the U.S. The other drugs (suramin, melarsoprol, eflornithine, and nifurtimox)  used to treat African Trypanosomiasis are available in the U.S. only from the CDC. Physicians can consult with CDC staff for advice on diagnosis and management and to obtain otherwise unavailable treatment drug.
There is no test of cure for African Trypanosomiasis. After treatment patients need to have serial examinations of their cerebrospinal fluid for 2 years, so that relapse can be detected if it occurs.

Prevention & Control
There is no vaccine or drug for prophylaxis against African Trypanosomiasis. Preventive measures are aimed at minimizing contact with tsetse flies. Local residents are usually aware of the areas that are heavily infested and they can provide advice about places to avoid. Other helpful measures include:

• Wear long-sleeved shirts and pants of medium-weight material in neutral colors that blend with the background environment. Tsetse flies are attracted to bright or dark colors, and they can bite through lightweight clothing.
• Inspect vehicles before entering. The flies are attracted to the motion and dust from moving vehicles.
• Avoid bushes. The tsetse fly is less active during the hottest part of the day but will bite if disturbed.
• Use insect repellent. Permethrin-impregnated clothing and insect repellent have not been proved to be particularly effective against tsetse flies, but they will prevent other insect bites that can cause illness.

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, the main control strategy for this subspecies is active case-finding through population screening, followed by treatment of the infected persons that are identified. Tsetse fly traps are sometimes used as an adjunct.  Reducing the reservoir of infection is more difficult for T. b. rhodesiense, since there are a variety of animal hosts. Vector control is the primary strategy in use. This is usually done with traps or screens, in combination with insecticides and odors that attract the flies.