Yellow fever laboratory tests

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]

Overview

Multiple laboratory abnormalities can be observed in patients with yellow fever, including leukopenia or leukocytosis, bleeding dyscrasias, thrombocytopenia, increased bilirubin and transaminases. Laboratory diagnosis of yellow fever is generally accomplished by testing of serum to detect virus-specific IgM and neutralizing antibodies. Sometimes the virus can be found in blood samples taken early in the disease.

Laboratory Findings

Routine Tests

• Laboratory findings can vary depending on the severity and stage of illness.
• In the first week of the illness, leukopenia (with relative neutropenia) might occur; however, leukocytosis also can occur during the second week of the disease.
• Bleeding dyscrasias also can occur, together with elevated prothrombin and partial thromboplastin times, decreased platelet count, and presence of fibrin-split products.
• Hyperbilirubinemia might be present as early as the third day but usually peaks toward the end of the first week of illness.
• Elevations of serum transaminase levels occur in severe hepatorenal disease and might remain elevated for up to 2 months after onset.

Serology

• Laboratory diagnosis generally is accomplished by testing serum to detect virus-specific immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies by serologic assays.
• Initial serological testing will be performed using IgM-capture ELISA, MIA (Microsphere-based Immunoassay) and IgG ELISA.
• It is important to obtain a yellow fever vaccination history, as IgM antibodies to yellow fever vaccine virus can persist for several years following vaccination.
• Serologic cross-reactions occur with other flaviviruses (e.g., West Nile or dengue viruses), so positive results should be confirmed with a more specific test (e.g., plaque-reduction neutralization test).

Molecular Tests

• During the first 3-4 days of infection, yellow fever virus or yellow fever virus RNA often can be detected in the serum by virus isolation or nucleic acid amplification testing.
• However, by the time overt symptoms are recognized, the virus or viral RNA usually is undetectable. Therefore, negative virus isolation and RT-PCR results cannot rule-out the diagnosis of yellow fever.
• Immunohistochemical staining of formalin-fixed material can detect yellow fever virus antigen in histopathologic specimens.

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