eMedicine Specialties > Infectious Diseases > Parasitic Infections

African Trypanosomiasis (Sleeping Sickness): Differential Diagnoses & Workup

Author: Randy O Odero, MB, ChB, Infectious Disease Fellow, University of Tennessee at Memphis
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; Kitonga P Kiminyo, MD, Consulting Staff, ID Consultants Inc; 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
Contributor Information and Disclosures

Updated: Feb 16, 2009

Differential Diagnoses

Other Problems to Be Considered

Stage 1 (early) African trypanosomiasis (sleeping sickness) symptoms

Differential diagnoses of recurrent fever include malaria, HIV infection, borreliosis, brucellosis, typhoid fever, and other enteric fevers.

Differential diagnoses of lymphadenopathy include tuberculosis (TB) lymphadenitis, HIV infection, and cancer.

Stage 2 (late) African trypanosomiasis symptoms

Differential diagnoses of mental status changes include TB, meningitis, and HIV-related opportunistic infections, including cryptococcal meningitis.

Workup

Laboratory Studies

  • General
    • In African trypanosomiasis (sleeping sickness), the most significant laboratory abnormalities include anemia, hypergammaglobulinemia, low complement levels, elevated erythrocyte sedimentation rate (ESR), thrombocytopenia, and hypoalbuminemia, but not eosinophilia or abnormal liver function.
    • In West African trypanosomiasis, the total immunoglobulin M (IgM) level is notably higher in blood and CSF (along with high CSF protein).
    • A definitive diagnosis of infection requires actual detection of trypanosomes in blood, lymph nodes, CSF, skin chancre aspirates, or bone marrow. However, symptomatic improvement after empiric treatment is the usual confirmatory test in areas where diagnostic studies are not readily available.
  • Lymph node aspiration at a high dry magnification (X400) is commonly used as a rapid test for trypanosomes. It requires immediate search for parasites because they are mobile for only 15-20 minutes. This test has more utility in T brucei gambiense trypanosomiasis.
  • Blood smear
    • A wet smear of unstained blood or Giemsa-stained thick smear (more sensitive) is used to evaluate for mobile trypanosomes, again for 15-20 minutes. Wright and Leishman stains are inadequate. This technique is most sensitive in early stages of disease, when the number of circulating parasites is highest (≥5000/mL), particularly in T brucei rhodesiense trypanosomiasis.
    • Better assays are now available, including the hematocrit centrifugation technique for buffy coat examination and the miniature anion-exchange centrifugation technique (mAECT), which filters out the red cells but not the trypanosomes. This test can be used to detect parasitemia levels as low as 5 parasites/mL; the test can be repeated on subsequent days to increase the yield when results are negative.
  • Chancre aspirate can be used as a wet preparation, especially in East African trypanosomiasis, but a blood smear is more sensitive.
  • Bone marrow aspiration results may be positive in some patients.
  • CSF assay
    • Lumbar puncture should be performed whenever trypanosomiasis is suspected. CSF examination helps to diagnose and stage the disease. However, a negative result does not necessarily rule out the diagnosis.
    • The double centrifugation technique is the most sensitive method to detect the trypanosomes.
    • Other CSF findings include elevated WBC count, elevated IgM levels, elevated total protein levels, and raised intracranial pressure. An uncommon characteristic finding is Mott cells, which are thought to be large eosinophilic plasma cells containing IgM that have failed to secrete their antibodies.
    • Increased intrathecal synthesis of IgM has been found to be the most sensitive indicator of CNS involvement in African trypanosomiasis.

Imaging Studies

  • CT scanning and MRI of the head: Both head CT scanning and MRI reveal cerebral edema and white matter enhancement, respectively, in patients with late-stage African trypanosomiasis.
  • EEG in neurologic involvement usually shows slow wave oscillations (delta waves), a nonspecific finding.

Other Tests

  • General: Field serology-based diagnosis of African trypanosomiasis has been slow to progress over the past decades. Although many research tools are available for diagnosis, few are used clinically in endemic areas.
  • Serologic antibody detection
    • The standard serologic assay to diagnose West African trypanosomiasis is the card agglutination test for trypanosomiasis (CATT).
    • The CATT can be conducted in the field without electricity, and results are available in only 10 minutes. It is highly sensitive (96%) but less specific because of cross-reactivity with animal trypanosomes.
    • Commercial antibody tests for Eastern African trypanosomiasis are not available.
  • Antigen detection tests based on enzyme-linked immunosorbent assay (ELISA) technology have been developed. They have shown inconsistent results and are not yet commercially available.
  • Culture of CSF, blood, bone marrow aspirate, or tissue specimens can be performed in liquid media.
  • Other tests developed but not frequently used clinically include antibody detection in the CSF and intrathecal space (low sensitivity), polymerase chain reaction (PCR), and serum proteomic tests.
  • Research tools such as isoenzyme analysis and restriction fragment length polymorphism (RFLP) are used for definitive subspecies identification.

Procedures

  • Lumbar puncture: CSF fluid is used to detect trypanosomes and to measure WBC counts, protein, and IgM in patients with parasitemia or positive serologies or symptoms. Importantly, CNS disease can manifest early in East African trypanosomiasis.

More on African Trypanosomiasis (Sleeping Sickness)

Overview: African Trypanosomiasis (Sleeping Sickness)
Differential Diagnoses & Workup: African Trypanosomiasis (Sleeping Sickness)
Treatment & Medication: African Trypanosomiasis (Sleeping Sickness)
Follow-up: African Trypanosomiasis (Sleeping Sickness)
Multimedia: African Trypanosomiasis (Sleeping Sickness)
References
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References

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Further Reading

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Keywords

sleeping sickness, African trypanosomiasis, human African trypanosomiasis, HAT, Trypanosoma brucei, T brucei, Trypanosoma brucei rhodesiense, Trypanosoma brucei gambiense, tsetse flies, Glossina species, East African trypanosomiasis, Rhodesian African trypanosomiasis, West African trypanosomiasis, Gambian African trypanosomiasis, trypanosomes

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Contributor Information and Disclosures

Author

Randy O Odero, MB, ChB, Infectious Disease Fellow, University of Tennessee at Memphis
Randy O Odero, MB, ChB 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, American Medical Association, 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.

Medical Editor

Gary L Gorby, MD, Program Director of Adult Infectious Diseases Fellowship, Associate Professor, Department of Internal Medicine, Division of Infectious Disease, St Joseph Medical Center, Creighton University School of Medicine
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.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Joseph F John Jr, MD, FACP, FIDSA, FSHEA, Clinical Professor of Medicine, Molecular Genetics and Microbiology, Medical University of South Carolina; Associate Chief of Staff for Education, Ralph H Johnson Veterans Affairs Medical Center
Disclosure: BioMerieux Honoraria Review panel membership; Cubist Honoraria Review panel membership; Pfizer Honoraria Speaking and teaching; Merck Stock dividends stock holdings

CME Editor

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.

 
 
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