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35-01: African Trypanosomiasis (Sleeping Sickness)

Philip J. Rosenthal

Key Clinical Updates in African Trypanosomiasis (Sleeping Sickness)

Fexinidazole is recommended by the World Health Organization as first-line therapy and is FDA-approved for treatment of early and advanced (CNS) West African disease.

Hidalgo J et al. Cureus. [PMID: 34513456]

ESSENTIALS OF DIAGNOSIS

  • Exposure to tsetse flies; chancre at bite site uncommon.

  • Hemolymphatic disease: Irregular fever, headache, joint pain, rash, edema, lymphadenopathy.

  • Meningoencephalitic disease: Somnolence, severe headache, progressing to coma.

  • Trypanosomes in blood or lymph node aspirates; positive serologic tests.

  • Trypanosomes and increased white cells and protein in cerebrospinal fluid (CSF).

GENERAL CONSIDERATIONS

African trypanosomiasis is caused by the hemoflagellates Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. The organisms are transmitted by bites of tsetse flies (genus Glossina), which inhabit shaded areas along streams and rivers. Trypanosomes ingested in a blood meal develop over 18–35 days in the fly; when the fly feeds again on a mammalian host, the infective stage is injected. Human disease occurs in rural areas of sub-Saharan Africa from south of the Sahara to about 30 degrees south latitude. T b gambiense causes West African trypanosomiasis and is transmitted in the moist sub-Saharan savannas and forests of west and central Africa. T b rhodesiense causes East African trypanosomiasis and is transmitted in the savannas of east and southeast Africa.

T b rhodesiense infection is primarily a zoonosis of game animals and cattle; humans are infected sporadically. Humans are the principal mammalian host for T b gambiense, but domestic animals can be infected (eFigure 35–1). The number of reported cases has decreased greatly since the 1990s, although cases are reported from over 20 countries. Total incidence has been estimated at less than 5000 cases per year, mostly due to T b gambiense, with the largest number in the Democratic Republic of the Congo. Infections are rare among travelers, including visitors to game parks.

eFigure 35–1.

Life cycle of Trypanosoma brucei gambiense. [T b gambiense] [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

image. Inside the host, they transform into bloodstream trypomastigotes
image, are carried to other sites throughout the body, reach other body fluids (eg, lymph, spinal fluid), and continue the replication by binary fission
image. The entire life cycle of African trypanosomes is represented by extracellular stages. The tsetse fly becomes infected with bloodstream trypomastigotes when taking a blood meal on an infected mammalian host
image,
image). In the fly's midgut, the parasites transform into procyclic trypomastigotes, multiply by binary fission
image, leave the midgut, and transform into epimastigotes
image. The epimastigotes reach the fly's salivary glands and continue multiplication by binary fission
image. The cycle in the fly takes approximately 3 weeks. Humans are the main reservoir for T b gambiense...

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