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How is yellow fever diagnosed by healthcare professionals?

Spotting the symptoms

Yellow fever can manifest in mild or severe forms. In the mildest form, patients experience a sudden onset of fever and headache without additional symptoms. In more severe cases, patients may have a high fever (up to 104°F), along with chills, severe headache, muscle pain, lower back pain, loss of appetite, nausea, vomiting, and dizziness. During this phase, the patient appears acutely ill, and there may be a noticeable slowing of heart rate in relation to the elevated body temperature. This period typically lasts for about three days, during which the virus is detectable in the patient's blood.

Around 15% of infected individuals, following the initial period mentioned above, experience a recurrence of the illness in a more severe form within 48 hours. Symptoms during this phase include fever, nausea, vomiting, upper abdominal pain, jaundice, kidney dysfunction, and cardiovascular instability. Viremia is generally absent at this stage, meaning the virus is no longer present in the blood. Bleeding tendencies may arise, leading to symptoms such as blood in vomit (hematemesis), black, tarry stools (melena), abnormal uterine bleeding (metrorrhagia), blood in urine (hematuria), small red or purple spots on the skin (petechiae), larger patches of bleeding under the skin (ecchymoses), nosebleeds (epistaxis), and bleeding from the gums or injection sites. Physical examination may reveal yellowing of the eyes and skin (scleral and dermal icterus), bleeding manifestations (hemorrhages), and tenderness in the upper abdomen without enlargement of the liver.

Laboratory tests

Laboratory tests can help diagnose yellow fever and provide information on the severity and stage of the disease. During the first week of illness, there may be a decrease in white blood cell count (leukopenia), but during the second week, there can be an increase (leukocytosis). Bleeding abnormalities can occur, along with prolonged clotting times (prothrombin and partial thromboplastin times), reduced platelet count, and presence of products indicating fibrin breakdown. Hyperbilirubinemia (elevated bilirubin levels) may be observed as early as the third day, peaking towards the end of the first week. Elevated levels of liver enzymes can occur in severe cases and may remain high for up to two months after onset.


Diagnosis of yellow fever involves considering the patient's clinical features, vaccination history, and travel history, including destination, time of year, and activities. Laboratory diagnosis is typically achieved by testing the patient's serum for the presence of specific antibodies using serologic assays. It is important to verify the patient's yellow fever vaccination history, as IgM antibodies to the vaccine virus can persist for several years. Cross-reactions with other flaviviruses (such as West Nile or dengue viruses) can occur, so positive results should be confirmed with more specific tests (such as the plaque-reduction neutralization test). In the early stages of the illness (within the first 3-4 days), yellow fever virus or its RNA can often be detected in the serum through virus isolation or nucleic acid amplification testing (e.g., reverse transcription-polymerase chain reaction [RT-PCR]). However, by the time symptoms become apparent, the virus or viral RNA is usually undetectable. Thus, negative results from virus isolation and RT-PCR cannot rule out the diagnosis of yellow fever. Immunohistochemical staining of tissue samples can detect yellow fever virus antigen in formalin-fixed specimens.


Clinical and Laboratory Evaluation | Yellow Fever | CDC. (n.d.).


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