African Trypanosomiasis (Sleeping Sickness) Clinical Presentation

  • Author: Randy O Odero; Chief Editor: Burke A Cunha, MD   more...
 
Updated: Jan 11, 2012
 

History

  • Stage 1 (early, or hemolymphatic, stage)
    • Painless skin chancre that appears about 5-15 days after the bite, resolving spontaneously after several weeks (seen less commonly in T brucei gambiense infection)
    • Intermittent fever (refractory to antimalarials), general malaise, myalgia, arthralgias, and headache, usually 3 weeks after bite
    • Generalized or regional lymphadenopathy (Posterior cervical lymphadenopathy [Winterbottom sign] is characteristic of T brucei gambiense African trypanosomiasis [sleeping sickness].)
    • Facial edema (minority of patients)
    • Transient urticarial, erythematous, or macular rashes 6-8 weeks after onset
    • Trypanids (ill-defined, centrally pale, evanescent, annular or blotchy edematous erythematous macules on trunk)
  • Stage 2 (late, or CNS, stage)
    • Persistent headaches (refractory to analgesics)
    • Daytime somnolence followed by nighttime insomnia
    • Behavioral changes, mood swings, and, in some patients, depression
    • Loss of appetite, wasting syndrome, and weight loss
    • Seizures in children (rarely in adults)
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Physical

  • Stage 1 (early, or hemolymphatic, stage)
    • Indurated chancre at bite site
    • Skin lesions (trypanids) in light-skinned patients
    • Lymphadenopathy: Axillary and inguinal lymphadenopathy are more common in patients with East African trypanosomiasis. Cervical lymphadenopathy is more common in patients with West African trypanosomiasis. The classic Winterbottom sign is clearly visible (ie, enlarged, nontender, mobile posterior cervical lymph node).
    • Fevers, tachycardia, irregular rash, edema, and weight loss
    • Organomegaly, particularly splenomegaly (T brucei gambiense African trypanosomiasis)
  • Stage 2 (late, or CNS, stage)
    • CNS symptoms: The CNS symptoms of West African trypanosomiasis have a slower onset of, ie, months to a year. Symptoms include irritability, tremors, increased muscle rigidity and tonicity, occasional ataxia, and hemiparesis, but rarely overt meningeal signs. East African trypanosomiasis usually has a faster onset, ie, weeks to a month, and does not exhibit a clear distinction between the two stages.
    • Kerandel sign, including delayed pain on compression of patient's soft tissue
    • Behavioral changes consistent with mania or psychosis, speech disorders, and seizures
    • Stupor and coma (giving rise to the name sleeping sickness)
    • Psychosis
    • Sensory disorders, tremor, and ataxia
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Causes

  • A bite from an infected tsetse fly causes African trypanosomiasis (see Pathophysiology).
  • Blood transfusions are a rare cause of parasitic transmission.
  • In rare cases, accidental transmission in the laboratory has been implicated.
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Contributor Information and Disclosures
Author

Randy O Odero  MB, ChB, Attending Physician, Infectious Diseases

Randy O Odero is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America, and Society for Healthcare Epidemiology of America

Disclosure: Nothing to disclose.

Coauthor(s)

Kerry O Cleveland, MD  Associate Professor of Medicine, University of Tennessee College of Medicine; Consulting Staff, Department of Internal Medicine, Division of Infectious Diseases, Methodist Healthcare of Memphis

Kerry O Cleveland, MD is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America, and Society for Healthcare Epidemiology of America

Disclosure: Nothing to disclose.

Kitonga P Kiminyo, MD  Consulting Staff, ID Consultants Inc

Kitonga P Kiminyo, MD is a member of the following medical societies: Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Daniel R Lucey, MD, MPH  Chief, Fellowship Program Director, Department of Internal Medicine, Division of Infectious Diseases, Washington Hospital Center; Professor, Department of Internal Medicine, Uniformed Services University of the Health Sciences

Daniel R Lucey, MD, MPH is a member of the following medical societies: Alpha Omega Alpha and American College of Physicians

Disclosure: Nothing to disclose.

Specialty Editor Board

Gary L Gorby, MD  Associate Professor, Departments of Internal Medicine and Medical Microbiology and Immunology, Division of Infectious Diseases, Creighton University School of Medicine; Associate Professor of Medicine, University of Nebraska Medical Center; Associate Chair, Omaha Veterans Affairs Medical Center

Gary L Gorby, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, and New York Academy of Sciences

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Joseph F John Jr, MD, FACP, FIDSA, FSHEA  Clinical Professor of Medicine, Molecular Genetics and Microbiology, Medical University of South Carolina College of Medicine; Associate Chief of Staff for Education, Ralph H Johnson Veterans Affairs Medical Center

Disclosure: Nothing to disclose.

Eleftherios Mylonakis, MD  Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital

Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD  Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

References

  1. Truc P, Lando A, Penchenier L, Vatunga G, Josenando T. Human African trypanosomiasis in Angola: clinical observations, treatment, and use of PCR for stage determination of early stage of the disease. Trans R Soc Trop Med Hyg. Jan 2012;106(1):10-4. [Medline].

  2. Simarro PP, Cecchi G, Franco JR, Paone M, Fèvre EM, Diarra A, et al. Risk for human african trypanosomiasis, central Africa, 2000-2009. Emerg Infect Dis. Dec 2011;17(12):2322-4. [Medline].

  3. Kohagne TL, M'eyi MP, Kamkuimo RG, Kaba D, Louis JF, Mimpfoundi R. Transmission of human African trypanosomiasis in the Komo-Mondah focus, Gabon. Pan Afr Med J. 2011;8:36. [Medline]. [Full Text].

  4. Abramowicz M. Drugs For Parasitic Infections. In: Abramowicz M, ed. The Medical Letter on Drugs and Therapeutics. New Rochelle, NY: The Medical Letter, Inc; 2000:1-12.

  5. [Best Evidence] Bisser S, N'Siesi FX, Lejon V, Preux PM, Van Nieuwenhove S, Miaka Mia Bilenge C, et al. Equivalence trial of melarsoprol and nifurtimox monotherapy and combination therapy for the treatment of second-stage Trypanosoma brucei gambiense sleeping sickness. J Infect Dis. Feb 1 2007;195(3):322-9. [Medline].

  6. Priotto G, Kasparian S, Ngouama D, Ghorashian S, Arnold U, Ghabri S, et al. Nifurtimox-eflornithine combination therapy for second-stage Trypanosoma brucei gambiense sleeping sickness: a randomized clinical trial in Congo. Clin Infect Dis. Dec 1 2007;45(11):1435-42. [Medline].

  7. Barrett MP. The fall and rise of sleeping sickness. Lancet. Apr 3 1999;353(9159):1113-4. [Medline].

  8. Brun R, Balmer O. New developments in human African trypanosomiasis. Curr Opin Infect Dis. Oct 2006;19(5):415-20. [Medline].

  9. Centers for Disease Control and Prevention. Trypanosomiasis Fact Sheet. CDC. May, 2000;[Full Text].

  10. Chappuis F, Loutan L, Simarro P, Lejon V, Büscher P. Options for field diagnosis of human african trypanosomiasis. Clin Microbiol Rev. Jan 2005;18(1):133-46. [Medline].

  11. Drugs for Parasitic Infections. Medical Lett Drugs Ther. August/2004.

  12. Hide G. History of sleeping sickness in East Africa. Clin Microbiol Rev. Jan 1999;12(1):112-25. [Medline].

  13. Kozarsky PE, Arguin PM, Navin AW. African Trypanosomiasis (African Sleeping Sickness). Travelers' Health: Yellow Book. Health Information for International Travel, 20. 2005-2006;[Full Text].

  14. Legros D, Evans S, Maiso F, Enyaru JC, Mbulamberi D. Risk factors for treatment failure after melarsoprol for Trypanosoma brucei gambiense trypanosomiasis in Uganda. Trans R Soc Trop Med Hyg. Jul-Aug 1999;93(4):439-42. [Medline].

  15. Lejon V, Büscher P. Review Article: cerebrospinal fluid in human African trypanosomiasis: a key to diagnosis, therapeutic decision and post-treatment follow-up. Trop Med Int Health. May 2005;10(5):395-403. [Medline].

  16. Micromedex. Antiparasitic drug information. Micromedex electronic database. May, 2000.

  17. Pepin J. African Trypanosomiasis. In: Strickland GT, ed. Hunter's Tropical Medicine. 7th ed. Philadelphia, Pa: WB Saunders; 1998:643-53.

  18. Pepin J, Milord F, Guern C. Trial of prednisolone for prevention of melarsoprol-induced encephalopathy in gambiense sleeping sickness. Lancet. Jun 3 1989;1(8649):1246-50. [Medline].

  19. Schmid C, Richer M, Bilenge CM, Josenando T, Chappuis F, Manthelot CR, et al. Effectiveness of a 10-day melarsoprol schedule for the treatment of late-stage human African trypanosomiasis: confirmation from a multinational study (IMPAMEL II). J Infect Dis. Jun 1 2005;191(11):1922-31. [Medline].

  20. Sinha A, Grace C, Alston WK. African trypanosomiasis in two travelers from the United States. Clin Infect Dis. Oct 1999;29(4):840-4. [Medline].

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  23. World Health Organization. Control and surveillance of African trypanosomiasis. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser. 1998;881:I-VI, 1-114. [Medline].

  24. World Health Organization. WHO fact sheet on African Trypanosomiasis. WHO fact sheets. Revised August 2006;Fact sheet 259:[Full Text].

 
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African trypanosomiasis (sleeping sickness). Human trypanosomes blood smear.
Table 1. Medications Recommended for Treatment of African Trypanosomiasis
Type of TrypanosomiasisMedications



Stage 1



(Hemolymphatic Stage)



Medications



Stage 2



(Neurologic [CNS] Stage)



East African trypanosomiasis (caused by T brucei rhodesiense)Suramin 100-200 mg IV test dose, then 1 g IV on days 1, 3, 7, 14, 21Melarsoprol 2-3.6 mg/kg/d IV for 3 d; after 1 wk, 3.6 mg/kg/d for 3 d; after 10-21 d, repeat the cycle
West African trypanosomiasis (caused by T brucei gambiense)Pentamidine isethionate 4 mg/kg/d IM for 10 d



or



Suramin 100-200 mg IV test dose, then 1 g IV on days 1, 3, 7, 14, 21



Melarsoprol 2-3.6 mg/kg/d IV for 3 d; after 1 wk, 3.6 mg/kg/d for 3 days; after 10-21 d, repeat the cycle



or



Eflornithine 400 mg/kg/d IV in 4 divided doses for 14 d



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