• Clinical science

African trypanosomiasis (African sleeping sickness)

Abstract

African trypanosomiasis (sleeping sickness) is an infectious disease caused by the protozoan parasite Trypanosoma brucei, which 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 drug of choice for stage I T. b. gambiense infection is pentamidine, while suramin is the drug of choice for stage I T. b. rhodesiense. An eflornithine-nifurtimox combination is the drug 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.

Epidemiology

  • Distribution: Sub-Saharan Africa
  • Incidence: < 15,000 estimated cases in 2014

Epidemiological data refers to the US, unless otherwise specified.

Etiology

Classification

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

Primary reservoir

Humans

Cattle, antelope

Clinical course

Chronic, slowly progressive disease

Acute disease with poor demarcation between stages

Pathophysiology

  • Life cycle in the tsetse fly
    1. Ingestion of the trypomastigote form of T. brucei by the tsetse fly during a blood meal
    2. Transformation of the trypanosomal form of T. brucei into procyclic trypomastigotes within the gut of the tsetse fly
    3. Procyclic trypomastigotes leave the gut and transform into epimastigotes.
    4. Migration of epimastigotes to the salivary glands, where they transform into metacyclic trypomastigotes
    5. Injection of metacyclic trypomastigotes from the salivary gland to the bite site during the next blood meal
  • Life cycle in the human body
    1. Multiplication of the metacyclic trypomastigotes at the inoculation site causes a primary indurated lesion
    2. Entry into the bloodstream and transformation of metacyclic trypomastigotes into trypomastigotes
    3. Stage I (hemolymphatic phase): multiplication of trypomastigotes in blood (parasitemia) and lymphoid tissue
    4. Stage II (neurologic phase): Trypomastigotes cross the blood-brain barrier and enter the CNSImmune-mediated damage causes progressive meningoencephalitis and diffuse demyelination.

Clinical features

Stage I (hemolymphatic phase)

Stage II (neurologic phase)

  • Headache
  • Behavioral changes: confusion, apathy, psychosis
  • Daytime somnolence, which may be associated with night-time insomnia
  • Ataxia
  • Kerandel sign: delayed hyperesthesia
  • Cachexia
  • Coma
  • Death

Diagnostics

A history of travel to an endemic region is an important diagnostic clue!

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.

Treatment

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 six months for two years.

Trypanosomal therapy

West African sleeping sickness East African sleeping sickness
Stage I

Suramin

Stage II

Melarsoprol

African trypanosomiasis is considered lethal without therapy!

Drugs used in the treatment of African trypanosomiasis

Pentamidine Suramin Eflornithine Nifurtimox Melarsoprol
Mechanism of action Pentamidine is a cationic, aromatic diamidine with a mechanism of action that is not clearly understood but is thought to involve the inhibition of mitochondrial activity or topoisomerases in trypanosomes. Suramin is a polysulfonated naphthylamine derivative of urea with a mechanism of action that is not clearly understood but is thought to involve the inhibition of enzymes involved in DNA replication and protein synthesis. Eflornithine acts as a trypanostatic agent by inhibiting ornithine carboxylase, which is required for cell differentiation and proliferation. Nifurtimox is a nitrofuran compound with a mechanism of action that is not clearly understood but is thought to involve reactions that create oxidative stress. Melarsoprol is a trivalent, organic prodrug that contains arsenic → The prodrug is taken up by amino-purine transporters (e.g., P2) of T. brucei and then metabolized into an active melarsen oxide → Melarsen oxide causes the lysis of T. brucei through an unknown mechanism.
CNS penetration × ×
Side effects
  • Hypersensitivity
  • Nephrotoxicity
  • Peripheral neuropathy
  • Hypogonadism among male patients

Prevention

  • Instructions for people traveling to or working in endemic regions
    • Use preventive measures in the daytime
    • 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 for T. brucei is available.

last updated 11/11/2018
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