Diagnosis
Yellow fever is a clinical diagnosis, which often relies on the whereabouts of the diseased person during the incubation time. Mild courses of the disease can only be confirmed virologically. Since mild courses of yellow fever can also contribute significantly to regional outbreaks, every suspected case of yellow fever (involving symptoms of fever, pain, nausea and vomiting six to ten days after leaving the affected area) has to be treated seriously.
If yellow fever is suspected, the virus cannot be confirmed until six to ten days after the illness. A direct confirmation can be obtained by reverse transcription polymerase chain reaction where the genome of the virus is amplified. Another direct approach is the isolation of the virus and its growth in cell culture using blood plasma; this can take one to four weeks.
Serologically, an enzyme linked immunosorbent assay during the acute phase of the disease using specific IgM against yellow fever or an increase in specific IgG-titer (compared to an earlier sample) can confirm yellow fever. Together with clinical symptoms, the detection of IgM or a fourfold increase in IgG-titer is considered sufficient indication for yellow fever. Since these tests can cross-react with other flaviviruses, like Dengue virus, these indirect methods can never prove yellow fever infection.
Liver biopsy can verify inflammation and necrosis of hepatocytes and detect viral antigens. Because of the bleeding tendency of yellow fever patients, a biopsy is only advisable post mortem to confirm the cause of death.
In a differential diagnosis, infections with yellow fever have to be distinguished from other feverish illnesses like malaria. Other viral hemorrhagic fevers, such as Ebola virus, Lassa virus, Marburg virus and Junin virus, have to be excluded as cause.
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