African Trypanosomiasis (Sleeping Sickness) 

Human African trypanosomiasis (HAT), also called sleeping sickness, is an illness endemic to sub-Saharan Africa. It is caused by the flagellate protozoan Trypanosoma brucei, which exists in 2 morphologically identical subspecies: Trypanosoma brucei rhodesiense (East African or Rhodesian African trypanosomiasis) and Trypanosoma 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 transmits T brucei gambiense and Glossina morsitans transmits T brucei rhodesiense), which are found only in Africa.

The reservoirs of infection for these vectors are exclusively human in West African trypanosomiasis. However, East African trypanosomiasis is a zoonotic infection with animal vectors. African trypanosomiasis is distinct from American trypanosomiasis, which is caused by Trypanosoma cruzi and has different vectors, clinical manifestations, and therapies.

The major epidemiology 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 1920-1950 led to extensive treatment and, apparently, immunity for 50 years. Now, infection is occurring again as the same populations lose their immunity.

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 a human reservoir in West African trypanosomiasis or an animal reservoir in the East African form. 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. The metacyclic trypomastigotes infect humans.

Humans are infected with T brucei following a fly bite, which occasionally causes a skin chancre at the site. These injected trypomastigotes 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 such as encephalitis and coma. Death may occur.

The parasites escape the initial host defense mechanisms by extensive antigenic variation of parasite surface glycoproteins known as major variant surface glycoprotein (VSG). This evasion of the humoral immune responses contributes to parasite 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 leads to fibrosis but rarely hepatosplenomegaly. Monocytes, macrophages, and plasma cells infiltrate blood vessels, causing endarteritis and increased vascular permeability.

The gastrointestinal system is also affected. Kupffer cell hyperplasia occurs in the liver, along with portal infiltration and fatty degeneration. Hepatomegaly is rare. More commonly in East African trypanosomiasis, a pancarditis affecting all heart tissue layers develops secondary to extensive cellular infiltration and fibrosis. Arrhythmia or cardiac failure can cause death prior to the development of CNS manifestations. CNS problems include perivascular infiltration into the interstitium in the brain and spinal cord, leading to meningoencephalitis with edema, bleeding, and granulomatous lesions.

Frequency

United States

All cases of African trypanosomiasis are imported from Africa by travelers to endemic areas. Infections among travelers are rare, with less than 1 case per year reported among US travelers. Most of these infections are caused by T brucei rhodesiense and are acquired in East African game parks.

International

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 varies by country and region. In 2005, major outbreaks were observed in Angola, the Democratic Republic of Congo, and Sudan.^[1]

In Central African Republic, Chad, Congo, Côte d'Ivoire, Guinea, Malawi, Uganda, and United Republic of Tanzania, sleeping sickness remains an important public health problem.^[2]

Fewer than 50 new cases per year are reported in countries such as Burkina Faso, Cameroon, Equatorial Guinea, Gabon, Kenya, Mozambique, Nigeria, Rwanda, Zambia, and Zimbabwe.^[3]

T brucei transmission seems to have stopped and no new cases of African trypanosomiasis have been reported for several decades in countries such as Benin, Botswana, Burundi, Ethiopia, Gambia, Ghana, Guinea Bissau, Liberia, Mali, Namibia, Niger, Senegal, Sierra Leone, Swaziland, and Togo.

Sleeping sickness 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 this number did not reflect the true situation given the remoteness of affected regions and the focal nature of the disease. Between 300,000 and 500,000 more cases were estimated as remaining undiagnosed and therefore untreated.

During recent epidemic periods, the prevalence of sleeping sickness has reached 50% in several villages in the Democratic Republic of Congo, Angola, and Southern Sudan. Sleeping sickness 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 substantially reduced; between 1998 and 2004, the figures for both forms of African trypanosomiasis together fell from 37,991 to 17,616.

The estimated number of cases is currently between 50,000 and 70,000. 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 health care financing.

Mortality/Morbidity

• The symptoms of East African trypanosomiasis develop more quickly (starting 1 mo after 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.

Race

African trypanosomiasis has no racial predilection.

Sex

African trypanosomiasis has no sexual predilection.

Age

Exposure can occur at any time. Congenital African trypanosomiasis occurs in children, causing psychomotor retardation and seizure disorders.