Pediatric Yellow Fever Workup

Updated: May 04, 2017
  • Author: David J Cennimo, MD, FAAP, FACP, AAHIVS; Chief Editor: Russell W Steele, MD  more...
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Approach Considerations

The diagnosis of yellow fever (YF) is made on the basis of any 1 of the following:

  • Isolation of YF virus
  • Isolation of YF virus–specific immunoglobulin M (IgM)
  • Fourfold or greater rise in serum immunoglobulin G (IgG)
  • Positive findings on postmortem liver histopathology
  • Detection of YF antigen in tissues with immunohistochemistry
  • Detection of YF viral genomic sequences with polymerase chain reaction (PCR) evaluation

For guidance on specimen collection and detection of yellow fever virus, contact the Centers for Disease Control and Prevention (CDC).


Laboratory Studies

A complete blood count (CBC) is indicated. 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, blood urea nitrogen (BUN), creatinine, and glucose levels should be measured. 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 typically reveal elevated transaminase and bilirubin levels during the toxic stage of illness. Transaminase levels may remain elevated for as long as 2 months after recovery.

On coagulation studies, an abnormal pattern resembling disseminated intravascular coagulation (DIC) may occur during the toxic stage of illness.

Urinalysis often reveals clinically significant proteinuria. Blood, urine, and cerebrospinal fluid (CSF) cultures should be performed 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 may be helpful. Findings may exclude concurrent malaria. Thick smears are needed to diagnose malaria. Thin smears are used to speciate the parasite.

Samples of acute and convalescent sera should be obtained for viral isolation and diagnosis. Send the samples to the CDC National Center for Infectious Diseases, Division of Vector-Borne Infectious Diseases.


Imaging and Electrocardiography

In general, no specific imaging studies are indicated for the diagnosis and management of YF. Use imaging to diagnose other primary or secondary conditions.

Chest radiography is important early in the course of YF to diagnose primary infection. It is indicated to exclude pneumonia in a patient whose condition deteriorates.

Electrocardiography (ECG) may show nonspecific ST-segment and T-wave changes. It may also show arrhythmias.



Peripheral intravenous (IV) may be done for hydration and administration of medications, including antibiotics as needed.

Central venous catheterization may be done to achieve hydration and to monitor central venous pressure in critically ill patients.

Arterial catheterization may be done to monitor blood pressure in patients who are critically ill and to provide serial measurements of blood gas values.

Bladder catheterization may be done to monitor urine output and to monitor renal function (particularly for proteinuria).


Histologic Findings

YF virus is viscerotropic. Histologic assessment 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.