Sleeping sickness B56.-

Author: Prof. Dr. med. Peter Altmeyer

All authors of this article

Last updated on: 30.09.2022

Dieser Artikel auf Deutsch

Synonym(s)

African trypanosomiasis; Trypanosomiasis African

History
This section has been translated automatically.

Atkins, 1734; Winterbottom, 1803; Bruce, 1894; Dutton, 1902; Stephens and Fantham, 1910

Definition
This section has been translated automatically.

Sleeping sickness (African trypanomiasis) is an infectious disease caused by protozoa of the genus Trypanosoma, which are transmitted to humans by tse tse flies.

Pathogen
This section has been translated automatically.

V.a. Trypanosoma brucei rhodesiense (East and South Africa) and Trypanosoma brucei gambiense (Central and West Africa). The main reservoir is humans. Secondary hosts are versch. Mammals (dog, pig, also wild animals).

Occurrence/Epidemiology
This section has been translated automatically.

300,000-500,000 new cases/year worldwide (according to WHO estimates). Prevalence in endemic areas (esp. Angola, Congo, Sudan): 20-50%.

Endemic areas: sub-Saharan Africa, West and Central Africa (T. b. gambiense), East Africa (T. b. rhodesiense).

Sleeping sickness is rarely imported by tourists. Most cases are T.rhodesiense cases from East African national parks (e.g., Queen Elisabeth National Park in Uganda).

Clinical features
This section has been translated automatically.

The incubation period for infection with T. rhodesiense is 3-21 days and varies with infection with T. gambiense (weeks-years). The clinic proceeds in 2 phases:

  • Stage I (febril-glandular): Moderately painful or painless, 0.5-5.0 cm large furunculoid, inflammatory primary effect for about 1 week (tryponasome chancre). Possible development of central necrosis. The primary effect recedes within 2-3 weeks with post-inflammatory hyper- or depigmentation. Furthermore, irregular fever spikes develop over months, regional or generalized lymphadenopathies, edema, muscle weakness, apathy, pleural effusions, ascites, myocarditis. In the dangerous T. rhodesiense infection, in the stage of generalisation, there is also the development of trunk-accentuated maculo-papular exanthema.
  • Stage II (meningeal): 6-12 months after infection. Apathy, character changes, convulsions, insomnia, meningoencephalitis, finally coma and death.

Diagnosis
This section has been translated automatically.

Microscopic pathogen detection Stage I: from blood (thick drop, concentration method) or in lymph node punctate in the case of T. gambiense infection.

Stage II: cerebrospinal fluid. If the diagnosis of African trypanosomiasis has been made, a cerebrospinal fluid (CSF) puncture should always be performed to exclude CNS involvement (in the absence of pathogen detection but with inflammatory changes in the CSF, therapy should be given according to stage II).

Detection of antibodies in the blood (ELISA, IFT, PHA). For T. gambiense: card agglutination test (CATT).

Complication(s)
This section has been translated automatically.

Toxic encephalopathy with melarsoprol therapy in 2-10% of those treated (often fatal).

Therapy
This section has been translated automatically.

Due to the high toxicity of the drugs, therapy should always be inpatient, moreover symptomatic according to clinic in collaboration with neurologists.

Stage I: Suramin (e.g. Germanin): Initial injection of a test dose of 2 mg/kg bw (max. 100 mg) Suramin slowly applied i.v. (to exclude rare idiosyncrasy). Then infuse 1 g TD (children 20 mg/kg bw) slowly on days 1, 3, 7, 14 and 21.

Alternative: Pentamidine diisethionate (e.g. pentacarinate): 4 mg/kg bw/day i.m. or 2-3 mg/kg bw/day i.v. for min. 5, max. 10 days. Recommended especially in case of infection with T. gambiense.

Stage II: Melarsoprol (arsenic preparation; often Herxheimer reaction and toxic encephalopathies!) 3 times 0.6-1.2 mg/kg bw/day for 3 days, repeated after 10-21 days. Pretreatment with suramin is recommended.

Alternative: (only effective in case of infection with T. gambiense): Eflornithine 4 times 50-75 mg/kg bw/day i.v. for 6 weeks.

Prophylaxis
This section has been translated automatically.

Avoidance of tsetse-infested endemic areas (e.g., river courses or savannas). Vector control (destruction of insects), avoidance of tsetse fly bites by wearing appropriate clothing (tsetse flies prefer dark colors) and the use of insect repellents (e.g. Icaridin, Zanzarin) or insecticides. Special care should be taken to avoid tsetse flies in the car (tsetse flies usually bite during the day).

No chemoprophylaxis (to be rejected because of the potential toxicity of the drugs, development of resistance, and possible suppression of clinical symptoms in less sensitive trypanosome strains)!

Note(s)
This section has been translated automatically.

The APOL1 gene encodes the protein apolipoprotein L1 (APOL1), which circulates mainly bound to HDL particles. This circulating fraction of APOL1 confers resistance to trypanosomiasis by rapidly lysing infecting trypanosomes of the species Trypanosoma brucei, trypanosome parasites endemic to Africa. APOL1 is thus an innate immune effector that protects humans from infection by some trypanosome parasites.

The seminal discovery that genetic variations in the APOL1 gene are associated with non-diabetic kidney disease in people of African descent has led to investigation of the biological mechanisms underlying this association (O'Toole JF et al 2017). The high allele frequency of these variants is thought to be due to the resistance they confer to the disease-causing trypanosome species involved in human African sleeping sickness. People of African descent have an increased risk of developing kidney disease, largely due to two variants in the apolipoprotein L1 (APOL1) gene that are unique to people of West African descent. These variants are thought to be genetically dominant because they provide protection against African sleeping sickness (Tzur S et al. 2010

Literature
This section has been translated automatically.

  1. Atkins J (1734) The navy surgeon or a practical system of surgery. Caesar Ward and Richard Chandler, London.
  2. Bruce D (1915) Croonian lectures. Br Med J 1: 1073-1078
  3. Docampo R et al (2003) Current chemotherapy of human African trypanosomiasis. Parasitol Res 90(Suppl1): S10-13
  4. Bastidas G et al. (2016) Human African trypanosomiasis diagnosis by peripheral blood smear review in a Spanish traveler. Blood 127:167.
  5. Dutton JE (1902) Preliminary note upon a trypanosome occurring in the blood of man. Thompson Yates Lab Rep 4: 455-468.
  6. Jones J (2000) African sleeping sickness returns to UK after four years. BMJ 321: 1177
  7. Milford F et al (1992) Efficacy and toxicity of eflornithine for treatment of trypanosoma brucei gambiense sleeping sickness. Lancet 340: 652-655
  8. O'Toole JF et al (2017) The Cell Biology of APOL1. Seminars in nephrology 37: 538-545.

  9. Pays E et al (2014) The molecular arms race between African trypanosomes and humans. Nat Rev Microbiol 12:575-584.

  10. Ripamonti D et al. (2002) African sleeping sickness in tourists returning from Tanzania: the first 2 Italian cases from a small outbreak among European travelers. Clin Infect Dis 34: E18-22

  11. Stephens JWW, Fantham HB (1910) On the peculiar morphology of a trypanosome from a case of sleeping sickness and the possibility of its being a new species (T. rhodesiense). Proc R Soc London Ser B 83: 28-33.
  12. Tzur S et al (2010) Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene. Hum Genet 128:345-350.

  13. Wamwiri FN et al. (2016) Tsetse Flies (Glossina) as Vectors of Human African

  14. Trypanosomiasis: A Review. Biomed Res Int doi
    :10.1155/2016/6201350.
  15. Winterbottom TM (1803) An account of the native Africans in the neighbourhood of Sierra Leone to which is added an account of the present state of medicine among them. C. Whittingham, London, vol. 2, pp. 29-31.

Disclaimer

Please ask your physician for a reliable diagnosis. This website is only meant as a reference.

Authors

Last updated on: 30.09.2022