Yellow Fever Workup
- Author: Mary T Busowski, MD; Chief Editor: Mark R Wallace, MD, FACP, FIDSA more...
Laboratory abnormalities during the initial viremic phase of yellow fever include leukopenia, often present at the onset of illness, and elevation of direct bilirubin and hepatic transaminases on days 2-3 of the illness.[3, 17] Transaminase levels increase relative to the degree of hepatic injury.
In the toxic phase, end-organ dysfunction is reflected by laboratory values, as follows:
Prothrombin time, activated partial thromboplastin time, international rationalized ratio (INR), and clotting times are invariably prolonged
Diminished levels of factor VIII, fibrinogen, and platelets, along with the presence of fibrin split products, indicate presence of DIC
Albuminuria usually is noted via urinalysis studies; proportional rises in blood urea nitrogen (BUN) and creatinine will be present in serum
Complete blood count
Findings in a complete blood count (CBC) for patients with yellow fever include the following:
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 reveal the following in patients with yellow fever:
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
Chemistry studies in patients with yellow fever show the following:
Elevated serum creatinine level
Hypoglycemia secondary to hepatic dysfunction
Urinalysis in patients with yellow fever reveals the following:
Elevated urinary protein levels
Elevated urobilinogen levels
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 computed tomography (CT) scan is helpful in determining whether intracranial hemorrhage is the cause.
ECG and cardiac monitoring
Electrocardiography (ECG) may identify prolongation of PR and QT intervals. 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.
Specific Tests for Yellow Fever Virus
Rapid detection methods
Rapid detection methods include the following:
Detection of yellow fever antigen using monoclonal enzyme immunoassay in serum specimens
Detection of viral genome sequences in tissue or in blood or other body fluid using polymerase chain reaction (PCR) assay
Serologic testing methods
Serologic tests, such as enzyme-linked immunosorbent assay (ELISA), aid in making an exact diagnosis. Confirmation is difficult because of cross-reactivity with other viruses, particularly in Africa, where multiple flaviviruses exist. Ruling out other flaviviruses is often aided by a detailed travel history.
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. This assay is 95% sensitive when serum specimens are collected 7-10 days after the onset of illness.
A confirmed case of yellow fever infection is defined as a clinically compatible case and 4-fold rise in antibody titer in a patient who has no history of a recent yellow fever vaccination and cross-reactivity to other flaviviruses has been excluded. During the acute phase of the illness, 3-10 days from onset of symptoms, a positive IgM ELISA provides a probable diagnosis.A rise in yellow fever–specific antibody titer in paired acute and convalescent samples confirms a laboratory diagnosis.
Immunohistochemical staining of tissues
Immunohistochemical staining of tissues (liver, heart, or kidneys) for the yellow fever antigen can also provide a definitive diagnosis. One should not attempt a liver biopsy during infection because of the risk of complications from hemorrhage.
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.
Liver function tests also reveal the following:
Serum AST levels - Exceed ALT levels
Direct bilirubin levels - Elevated
Hypoalbuminemia - Albuminuria, decreased synthesis, and extravasation of albumin through damaged capillary endothelium
In the acute phase of yellow fever, gross examination of liver biopsy reveals a mottled yellow (boxwood) color and friable texture. With the availability of serology to provide diagnosis, a liver biopsy is likely not necessary to provide diagnostic confirmation of infection, and the risks versus benefits of a liver biopsy need to be carefully considered. During acute illness, a liver biopsy should be avoided.
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; they are characteristic of viral hemorrhagic fevers and other acute viral hepatitis. Late in the illness, biopsy may reveal only severe, nonspecific necrotic changes.
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