eMedicine Specialties > Infectious Diseases > Gastrointestinal Tract and Intra-abdominal Infections

Yellow Fever: Differential Diagnoses & Workup

Author: Mary T Busowski, MD, Fellow, Infectious Diseases, Orlando Health
Coauthor(s): Mark Raymond Wallace, MD, Infectious Disease Fellowship Director, Orlando Regional Healthcare; Clinical Professor of Medicine, Florida State University; Janelle L Robertson, MD, Staff Physician, Department of Infectious Diseases, Wilford Hall Medical Center
Contributor Information and Disclosures

Updated: Apr 17, 2009

Differential Diagnoses

Acanthamoeba
Dengue Fever
Hemorrhagic fevers (dengue hemorrhagic, Rift Valley, Venezuelan, Bolivian, Argentine, Lassa, Crimean-Congo, Marburg, and Ebola fevers)
Hepatitis E
Venezuelan Encephalitis

Other Problems to Be Considered

Louse-borne relapsing fever
Liver failure (other causes)
Toxic hepatitis
Malaria
Relapsing fever
Toxin-mediated hepatitis
Typhoid
Typhus
Acute fatty liver of pregnancy

Workup

Laboratory Studies

  • Complete blood cell count
    • Leukopenia with relative neutropenia
    • Thrombocytopenia as part of a consumptive coagulopathy
    • Initial hemoconcentration, increased hemoglobin and hematocrit levels
    • Subsequent hemorrhage and hemodilution resulting in decreasing complete blood cell counts
  • Coagulation studies
    • Reduced fibrinogen and clotting factors II, V, VII, VIII, IX, and X and the presence of fibrin split products indicate disseminated intravascular coagulation.
    • Decreased synthesis of clotting factors may result in an elevated prothrombin time.
    • Prolonged clotting times may be found.
  • Chemistries
  • Urinalysis
    • Elevated urinary protein levels
    • Elevated urobilinogen levels
  • Liver function tests
    • Transaminitis precedes the appearance of jaundice, and the degree of liver dysfunction in the acute phase may be predictive of the clinical course.
    • Serum aspartate transferase (AST) levels exceed alanine transferase (ALT) levels.
    • Direct bilirubin levels are elevated.
  • Hypoalbuminemia - Albuminuria, decreased synthesis, and extravasation of albumin through damaged capillary endothelium
  • Specific tests for yellow fever virus
    • Rapid detection methods include the following:
      • Detection of yellow fever antigen by monoclonal enzyme immunoassay in serum specimens
      • Detection of viral genome sequences in tissue, blood or other body fluid using polymerase chain reaction (PCR)
    • Serologic testing methods include the following:
      • Immunoglobulin M (IgM) antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA) is used to detect the specific IgM for yellow fever; a single positive serum titer is diagnostic.
      • IgM appears 7-10 days following infection.
      • A 4-fold rise in yellow fever antibody titer in a patient with no history of recent yellow fever vaccination
      • Antibodies cross-react with other flaviviruses, so this must be ruled out. This is often aided by detailed travel history.
    • Other diagnostic methods include histopathologic lesions compatible with those of yellow fever or detection of virus in tissue using immunohistochemical staining.

Imaging Studies

  • Chest radiography is used to evaluate the extent of pulmonary edema, to reveal secondary bacterial pulmonary infections, and to aid in ventilator management if intubation is required.
  • When mental status changes occur late in the illness, a brain CT scan is helpful in determining whether intracranial hemorrhage is the cause.

Other Tests

  • ECG and cardiac monitoring
    • Arrhythmias are commonly due to myocarditis.
    • Cardiac involvement by yellow fever is evidenced by ST-T wave abnormalities.
    • Electrolyte abnormalities, hypoxia, and hypoperfusion states also are common causes of arrhythmias in patients who are severely ill.

Procedures

  • Liver biopsy can aid in diagnosis but is generally avoided because of the high risk of hemorrhage.

Histologic Findings

In the acute phase of yellow fever, gross examination of liver biopsy reveals mottled yellow (boxwood) color and friable texture.

Histopathologic changes consistent with yellow fever include midzonal necrosis with sparing of cells around the central vein and portal tracts, steatosis, and Councilman bodies. Councilman bodies are acidophilic inclusion bodies resulting from apoptotic death of hepatocytes characteristic of viral hemorrhagic fevers and other acute viral hepatitis.

Late in the illness, biopsy may reveal only severe, nonspecific necrotic changes.

More on Yellow Fever

Overview: Yellow Fever
Differential Diagnoses & Workup: Yellow Fever
Treatment & Medication: Yellow Fever
Follow-up: Yellow Fever
Multimedia: Yellow Fever
References
[ CLOSE WINDOW ]

References

  1. Bob Arnebeck. A Short History of Yellow Fever in the US. Available at http://www.geocities.com/bobarnebeck/history.html. Accessed November 11, 2008.

  2. Kean BH, Dahlby T. Coming of age in Panama. In: One Doctor's Adventures Among the Famous and Infamous from the Jungles of Panama to a Park Avenue Practice. New York, NY: Ballantine Books; 1990:Ch 2.

  3. Tsai TF, Vaughn DW, Solomon T. Flaviviruses. In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. Vol 2. 6th ed. Philadelphia, Pennsylvania: Elsevier, Inc.; 2005:Ch 149; 1926-9.

  4. Centers for Disease ControlMMR WeeklyApril 14, 2000/49(14);303-5. Fatal Yellow Fever in a Traveler Returning from Venezula, 1999. CDC. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm491a3.htm. Accessed November 11, 2008.

  5. World Health Organization 2008. Yellow Fever. Pub Med. Available at http://www.who.int/mediacentre/factsheets/fs100/en/print.html. Accessed November 2008.

  6. Barnett ED. Yellow fever: epidemiology and prevention. Clin Infect Dis. Mar 15 2007;44(6):850-6. [Medline].

  7. CDC Health Information for International Travel 2008. Center for Disesae Control; 2008.

  8. Roukens, AH, Visser LG. Yellow fever vaccine: past, present and future. Expert Opinion Biol Ther. November 2008;8(11):1787-95. [Medline].

  9. McFarland JM, Baddour LM, Nelson JE, et al. Imported yellow fever in a United States citizen. Clin Infect Dis. Nov 1997;25(5):1143-7. [Medline].

  10. Peters CJ. Infections caused by arthropod- and rodent-borne viruses. In: Kasper DL, Fauci AS, Longo DL, Braunwald E, Hauser SL, Jameson JL, eds. Harrison's Principles of Internal Medicine. 16th ed. United States: McGraw Hill; 2005:Ch 180; 1172-3.

  11. Robertson SE, Hull BP, Tomori O, et al. Yellow fever: a decade of reemergence. JAMA. Oct 9 1996;276(14):1157-62. [Medline].

  12. Thompson C, O'Leary JP. Yellow fever in New Orleans. Am Surg. May 1996;62(5):424-6. [Medline].

  13. Tsai TF. Yellow fever virus. In: Gorbach SL, Bartlett JG, Blacklow NR, eds. Infectious Diseases. 2nd ed. Philadelphia, Pa: WB Saunders and Co; 1998:2234-37.

  14. Van der Stuyft P, Gianella A, Pirard M, et al. Urbanisation of yellow fever in Santa Cruz, Bolivia. Lancet. May 8 1999;353(9164):1558-62. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

yellow fever, sylvatic fever, jungle yellow fever, viral hemorrhagic fever, VHF, epidemic yellow fever, urban yellow fever, Flavivirus, Aedes aegypti, A aegypti, Haemagogus mosquito, yellow fever virus

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Mary T Busowski, MD, Fellow, Infectious Diseases, Orlando Health
Mary T Busowski, MD is a member of the following medical societies: American Academy of Hospice and Palliative Medicine, American College of Physicians, American Medical Association, Florida Medical Association, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Coauthor(s)

Mark Raymond Wallace, MD, Infectious Disease Fellowship Director, Orlando Regional Healthcare; Clinical Professor of Medicine, Florida State University
Mark Raymond Wallace, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Tropical Medicine and Hygiene, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Janelle L Robertson, MD, Staff Physician, Department of Infectious Diseases, Wilford Hall Medical Center
Janelle L Robertson, MD is a member of the following medical societies: American College of Physicians
Disclosure: Nothing to disclose.

Medical Editor

Thomas Herchline, MD, Professor of Medicine, Wright State University Boonshoft School of Medicine; Medical Director, Public Health, Dayton and Montgomery County, Ohio
Thomas Herchline, MD is a member of the following medical societies: American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Pharmacy Editor

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

Managing Editor

Richard B Brown, MD, FACP, Chief, Division of Infectious Diseases, Baystate Medical Center; Professor, Department of Internal Medicine, Tufts University School of Medicine
Richard B Brown, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, and Massachusetts Medical Society
Disclosure: Nothing to disclose.

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.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.