eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Yellow Fever: Differential Diagnoses & Workup

Author: William H Shoff, MD, DTM&H, Director, PENN Travel Medicine, Associate Professor, Department of Emergency Medicine, Hospital of the University of Pennsylvania
Coauthor(s): Patrick B Hinfey, MD, Associate Residency Director, Department of Emergency Medicine, Newark Beth Israel Medical Center; Amy J Behrman, MD, Associate Professor, Department of Emergency Medicine, Director, Division of Occupational Medicine, University of Pennsylvania School of Medicine; Suzanne Moore Shepherd, MD, MS, DTM&H, FACEP, FAAEM, Associate Professor, Department of Emergency Medicine, Hospital of the University of Pennsylvania; Director of Education and Research, PENN Travel Medicine
Contributor Information and Disclosures

Updated: Sep 15, 2009

Differential Diagnoses

Bacteremia
Meningitis, Aseptic
Dengue
Meningitis, Bacterial
Hepatitis A
Meningococcal Infections
Hepatitis B
Mononucleosis and Epstein-Barr Virus Infection
Hepatitis C
Rickettsial Infection
Leptospirosis
Viral Hemorrhagic Fevers
Malaria

Other Problems to Be Considered

Arboviral infections - Lassa fever, chikungunya
Carbon tetrachloride poisoning
Influenza
Hepatitis E
Sepsis
Typhoid fever
West Nile virus infection (with hepatitis)

Workup

Laboratory Studies

  • Laboratory diagnosis
    • Diagnosis of yellow fever (YF) involves any one of the following:
      • Isolation of yellow fever virus
      • Isolation of yellow fever virus–specific immunoglobulin (Ig)M
      • Four-fold or more rise in serum IgG
      • Positive findings on postmortem liver histopathology
      • Detection of yellow fever antigen in tissues by immunohistochemistry
      • Detection of yellow fever viral genomic sequences by polymerase chain reaction
    • For guidance on specimen collection and detection of yellow fever virus, contact the CDC (see Background).
  • CBC count
    • Leukopenia with neutropenia may be observed during the initial stage of yellow fever infection.
    • Thrombocytopenia may be observed during the toxic stage of yellow fever infection.
  • Electrolyte, BUN, creatinine, and glucose measurements
    • Results may reveal azotemia.
    • Hypoglycemia may occur because of a lack of oral intake and hepatic dysfunction.
    • Hyperkalemia may be secondary to renal dysfunction.
  • Liver function tests
    • Elevated transaminase and bilirubin levels are observed during the toxic stage of illness.
    • Transaminase levels may remain elevated for as long as 2 months after recovery.
  • Coagulation studies: During the toxic stage of illness, an abnormal pattern resembling disseminated intravascular coagulation (DIC) may occur.
  • Urinalysis: Clinically significant proteinuria often occurs.
  • Blood, urine, and cerebrospinal fluid (CSF) cultures to exclude other infections: CSF findings may be typical of yellow fever, with increased pressure, elevated protein levels, cell counts in the reference range, or pleocytosis.
  • Malaria smears
    • Findings may exclude concurrent malaria.
    • Thick smears are needed to diagnose malaria.
    • Thin smears are used to speciate the parasite.
  • Analysis of acute and convalescent sera: Samples are obtained for viral isolation and diagnosis. Send samples to CDC National Center for Infectious Diseases, Division of Vector-Borne Infectious Diseases (see Background).

Imaging Studies

  • In general, no specific studies are indicated for the diagnosis and management of yellow fever. Use imaging to diagnose other primary or secondary conditions.
  • Chest radiography is important early in the illness to diagnose primary infection. It is indicated to exclude pneumonia in a patient whose condition deteriorates.

Other Tests

  • ECG may show nonspecific ST-segment and T-wave changes.
  • ECG may also show arrhythmias.

Procedures

  • Peripheral intravenous cannulation for hydration and the administration of medications, including antibiotics as needed
  • Central venous catheterization to achieve hydration and to monitor central venous pressure in critically ill patients
  • Arterial catheterization to monitor blood pressure in patients who are critically ill and to serially measure blood gases
  • Bladder catheterization to monitor urine output and to monitor renal function, particularly proteinuria

Histologic Findings

  • Yellow fever virus is viscerotropic. Histology of infected liver tissue may reveal initial infection of the Kupffer cells, followed by coagulation necrosis of the midzone (zone 2) hepatocytes, which spares zones adjacent to the central vein and portal triad. Intracellular hyaline deposits (Councilman bodies) are present with eosinophilic degeneration of hepatocytes, Torres bodies, intranuclear inclusions, microvesicular fat accumulation, deposition of eosinophilic pigment, and minimal mononuclear inflammatory infiltrate.
  • Recovery leads to complete healing without cirrhosis. When renal involvement occurs, the kidney is generally edematous, and the cells of the tubular epithelium and glomerular endothelium are swollen. Mesangial proliferation occurs. Viral antigen is found in the glomeruli and tubules. Acute tubular necrosis occurs secondary to circulatory collapse. Heart tissue may demonstrate myocardial cell degeneration and fatty infiltration.

More on Yellow Fever

Overview: Yellow Fever
Differential Diagnoses & Workup: Yellow Fever
Treatment & Medication: Yellow Fever
Follow-up: Yellow Fever
Multimedia: Yellow Fever
References
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References

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Further Reading

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Keywords

yellow fever, YF, Flaviviridae, tropical infections, viral infections, yellow fever virus, yellow jack, proteinuria, mosquito, disseminated intravascular coagulation, DIC, high temperatures, chills, anxiety, confusion, lethargy, prostration, jaundice, epistaxis, anorexia, epigastric pain, nausea, vomiting, hematemesis, melena, lumbosacral pain, pneumonia, sepsis, infection, treatment, diagnosis

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Contributor Information and Disclosures

Author

William H Shoff, MD, DTM&H, Director, PENN Travel Medicine, Associate Professor, Department of Emergency Medicine, Hospital of the University of Pennsylvania
William H Shoff, MD, DTM&H is a member of the following medical societies: American College of Physicians, American Society of Tropical Medicine and Hygiene, International Society of Travel Medicine, Society for Academic Emergency Medicine, and Wilderness Medical Society
Disclosure: Glaxo Smith Kline Consulting fee Consulting; Glaxo Smith Kline Honoraria Speaking and teaching

Coauthor(s)

Patrick B Hinfey, MD, Associate Residency Director, Department of Emergency Medicine, Newark Beth Israel Medical Center
Patrick B Hinfey, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, Emergency Medicine Residents Association, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Amy J Behrman, MD, Associate Professor, Department of Emergency Medicine, Director, Division of Occupational Medicine, University of Pennsylvania School of Medicine
Amy J Behrman, MD is a member of the following medical societies: American College of Occupational and Environmental Medicine
Disclosure: Nothing to disclose.

Suzanne Moore Shepherd, MD, MS, DTM&H, FACEP, FAAEM, Associate Professor, Department of Emergency Medicine, Hospital of the University of Pennsylvania; Director of Education and Research, PENN Travel Medicine
Suzanne Moore Shepherd, MD, MS, DTM&H, FACEP, FAAEM is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American Society of Tropical Medicine and Hygiene, International Society of Travel Medicine, Society for Academic Emergency Medicine, and Wilderness Medical Society
Disclosure: Nothing to disclose.

Medical Editor

Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility
Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; sanofi pasteur Honoraria Speaking and teaching; Baxter Healthcare Honoraria Speaking and teaching

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Leslie L Barton, MD, Professor, Program Director, Department of Pediatrics, University of Arizona School of Medicine
Leslie L Barton, MD is a member of the following medical societies: American Academy of Pediatrics, Association of Pediatric Program Directors, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.

CME Editor

Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine
Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine
Disclosure: Baxter Honoraria Consulting

Chief Editor

Russell W Steele, MD, Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine
Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association
Disclosure: None None None

 
 
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