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African trypanosomiasis

Last updated: May 3, 2021

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African trypanosomiasis (sleeping sickness) is an infectious disease caused by the protozoan parasite Trypanosoma brucei and is transmitted by the bite of the tsetse fly. The disease is endemic to sub-Saharan Africa; all cases that occur in the US are the result of travel to endemic regions. There are two forms of the disease with distinct geographical distributions and rates of clinical progression. West African sleeping sickness is caused by T. b. gambiense and progresses slowly, while East African sleeping sickness is caused by T. b. rhodesiense and progresses rapidly. Patients with either subtype of the disease initially present with a painful nodule or chancre at the site of the bite, followed by a hemolymphatic phase with fever and lymphadenopathy (stage I). Eventually, patients develop CNS symptoms (stage II), which are characterized by behavioral changes and a reversal of the sleep-wake cycle. If the disease is left untreated, patients will succumb to coma and die. The disease is diagnosed if the trypomastigote is found in chancre fluid, lymph node aspirates, or blood smears. The drugs of choice for stage I T. b. gambiense infection are pentamidine and fexinidazole, while suramin is the drug of choice for stage I T. b. rhodesiense. An eflornithine-nifurtimox combination and fexinidazole monotherapy are the therapy of choice for stage II T. b. gambiense infection, while melarsoprol is the drug of choice for stage II T. b. rhodesiense. No vaccine or chemoprophylaxis for African trypanosomiasis is available.

  • Distribution: sub-Saharan Africa
  • Incidence: 980 new cases were reported in 2019 [1]

Epidemiological data refers to the US, unless otherwise specified.

Stage I (hemolymphatic phase)

Stage II (neurologic phase)

West African sleeping sickness (Gambian trypanosomiasis) East African sleeping sickness (Rhodesian trypanosomiasis)
Pathogen
  • Trypanosoma brucei gambiense
  • Trypanosoma brucei rhodesiense
Vector
  • Glossina palpalis
  • Glossina morsitans
Regional distribution
  • Central and West Africa
  • Eastern and southeastern Africa
Incidence in the US
  • Extremely rare [1]
  • 1–2 cases per year

Primary reservoir

  • Humans
  • Cattle, antelope

Clinical course

General findings

Confirmatory tests

A history of travel to an endemic region is an important diagnostic clue for trypanosomiasis.

CSF examination must be performed for all patients with suspected or confirmed African trypanosomiasis to rule out stage II disease because the drug of choice depends on the stage of the disease.

General

  • Early in-patient treatment is very important.
  • The drug of choice for trypanosomiasis is dependent on the stage of the disease and the subspecies of T. brucei (see the table below).
  • Follow-up: CSF examination should be repeated every 6 months for 2 years.

Trypanosomal therapy [3]

West African sleeping sickness East African sleeping sickness
Stage I (bloodborne disease)
  • Suramin
Stage II (CNS invasion)
  • Melarsoprol

African trypanosomiasis is generally lethal without therapy.

To remember that in East African sleeping sickness bloodborne disease is treated with suramin and melarsoprol is used to treat invasion of the brain (CNS), think: “BLOODy SURe, this MELody is stuck in my BRAIN.”

Mechanism of action [4][5] CNS penetration Side effects
Pentamidine
  • No
Suramin
  • No
Eflornithine
  • Yes
Nifurtimox
  • Not clearly understood
  • Most likely induces reactions that create oxidative stress
  • Yes
Melarsoprol
  • A prodrug that contains arsenic
  • Taken up by amino-purine transporters (e.g., P2) of T. brucei → metabolized into an active melarsen oxide → lysis of T. brucei through an unknown mechanism
  • Yes
  • Instructions for people traveling to or working in endemic regions [6]
    • Use preventive measures in the daytime (tsetse flies bite during the day)
    • Wear long-sleeved protective clothing with neutral colors
    • Use insect repellants
    • Avoid tsetse fly habitats (e.g., thickets, bushes)
    • Inspect vehicles before entering
  • Public health measures in endemic regions
    • Vector control methods such as insecticide spraying and fly traps
    • Population screening programs and early treatment of infections to decrease the number of human hosts

No chemoprophylaxis and no vaccine is available for T. brucei.

  1. WHO interim guidelines for the treatment of gambiense human African trypanosomiasis. https://apps.who.int/iris/bitstream/handle/10665/326178/9789241550567-eng.pdf. Updated: August 1, 2019. Accessed: July 9, 2020.
  2. Human African trypanosomiasis. https://www.who.int/gho/neglected_diseases/human_african_trypanosomiasis/en/. Updated: January 1, 2020. Accessed: July 27, 2020.
  3. H Denise, M P Barrett. Uptake and mode of action of drugs used against sleeping sickness. Biochemical Pharmacology. 2001 .
  4. Parasites - African Trypanosomiasis (also known as Sleeping Sickness) - Diagnosis. https://www.cdc.gov/parasites/sleepingsickness/health_professionals/index.html. Updated: May 20, 2020. Accessed: July 28, 2020.
  5. Parasites - African Trypanosomiasis (also known as Sleeping Sickness). https://www.cdc.gov/parasites/sleepingsickness/prevent.html. Updated: March 9, 2020. Accessed: July 28, 2020.
  6. Jamonneau V, Ilboudo H, Kaboré J, et al. Untreated Human Infections by Trypanosoma brucei gambiense Are Not 100% Fatal. PLoS Negl Trop Dis. 2012; 6 (6): p.e1691. doi: 10.1371/journal.pntd.0001691 . | Open in Read by QxMD