African trypanosomiasis

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.

• Pathogen: Trypanosoma brucei
  • T. brucei is a hemoflagellate protozoan
  • Two subspecies: Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense
  • A rare but new form of T. evansi that causes sleeping sickness has been identified in India.
• Route of infection: vector transmission by the bite of the tsetse fly (the bite is usually painful and remembered by the patient)

• 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 CNS → Immune-mediated damage causes progressive meningoencephalitis and diffuse demyelination.

Stage I (hemolymphatic phase)

• Intermittent fever: caused by antigenic variation
• Painless lymph node enlargement
• Winterbottom sign: painless cervical lymphadenopathy in the posterior triangle of the neck
• Trypanosomal chancre (local primary lesion)
  • A red, painful, indurated, nodular swelling; 2–5 cm in size that develops at the bite site within 2 weeks of the bite
  • Resolves spontaneously within 1–2 weeks
  • The nodule may ulcerate and form a painful chancre.
• Erythematous, annular (targetoid), or maculopapular rash that may or may not be pruritic
• Malaise, headache, arthralgia
• Symptoms of anemia
• Facial edema
• Possible hepatosplenomegaly
• Occasionally, arrhythmias, hypotension, and symptoms of myocarditis

Stage II (neurologic phase)

• Headache
• Weight loss
• Behavioral changes: confusion, apathy, psychosis
• Daytime somnolence, which may be associated with night-time insomnia
• Ataxia
• Kerandel sign: delayed hyperesthesia
• Cachexia
• Coma
• Death ^[2]

General findings

• CBC: anemia, granulocytopenia
• ↑ ESR
• ↑ IgM levels

Confirmatory tests

• Local primary lesion: direct visualization of trypomastigotes using a Giemsa stain in chancre fluid
• Stage I: direct visualization of trypomastigotes in thin and thick peripheral blood smears or lymph node aspirates using a Giemsa stain
• Stage II: lumbar puncture and CSF examination
  • Trypomastigotes may be directly visualized.
  • Lymphocytic pleocytosis
  • ↑ IgM and protein levels
  • Morula cells of Mott

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]

For more information about drugs used in the treatment of African trypanosomiasis, please see “Overview of antiprotozoal agents.”

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.”

• Instructions for people traveling to or working in endemic regions ^[4]
  • 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.