Diagnostic Considerations
Based on its clinical presentation, yellow fever may be mistaken for other infectious diseases present in tropical regions; however, failure to consider this illness in a febrile traveler could have a grave outcome. [26] Leptospirosis and louse-borne relapsing fever most closely mimic yellow fever and can manifest as jaundice, hemorrhage, and DIC in severe cases. Other viral hemorrhagic fevers (with dengue and Crimean-Congo hemorrhagic fever being the most similar in presentation) also remain among the differential diagnoses for severe yellow fever during the intoxication period and are important to consider, as they require unique isolation precautions. Malaria is also important to consider because of the overlapping distribution, a mosquito vector, and the potential for a fatal outcome without targeted therapy.
Important diagnostic considerations include other flaviviruses circulating in the area, as these can have similar presentations and can cross-react on diagnostic testing (ie, on ELISA). Noninfectious causes of DIC and acute liver failure are also important to consider.
Differential Diagnoses
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A broad differential diagnosis, including noninfectious causes such as like acute fatty liver of pregnancy and toxin-mediated hepatitis.
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Flavivirus
Many other flaviviruses share some clinical features and geographic distributions and can complicate diagnosis because of cross-reactivity on ELISA testing.
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Hemorrhagic Fevers
While most viral hemorrhagic fevers (VHF) do not result in jaundice, dengue and Crimean-Congo hemorrhagic fever can occasionally present with similar features.
-- Dengue Hemorrhagic Fever
-- Rift Valley Fever
-- South American VHF: Venezuelan Hemorrhagic fever, Bolivian Hemorrhagic fever, Argentine Hemorrhagic fever
-- Lassa Fever
-- Crimean-Congo Hemorrhagic Fever
-- Marburg Hemorrhagic Fever
-- Ebola Hemorrhagic Fever
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Viral hepatitis should remain among the differential diagnoses, especially hepatitis E virus, which can occur in outbreaks.
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One of two pathogens that can most closely mimic the presentation of yellow fever, which can present with jaundice, hemorrhage, and DIC in severe cases
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Especially important to screen for as presentations are both protean and can be nonspecific, and malaria can be fatal without targeted treatment.
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Louse-borne relapsing fever (Borrelia recurrentis) is one of the two pathogens that can most closely mimic the presentation of severe yellow fever with jaundice, hemorrhage, and DIC in severe cases
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Viral Encephalitides
Especially including other flaviviruses such as West Nile virus and Japanese encephalitis (which does not currently have geographic overlap)
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Yellow fever virus. Image courtesy of the Centers for Disease Control and Prevention.
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This female Aedes aegypti mosquito is shown after landing on a human host. The A aegypti mosquito is a known transmitter of dengue fever and yellow fever. A aegypti is sometimes referred to as the yellow fever mosquito. The viruses are transferred to the host when he or she has been bitten by a female mosquito. Image courtesy of the CDC/World Health Organization (WHO).
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Global distribution of yellow fever. Image courtesy of the Centers for Disease Control and Prevention.
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Transmission cycles of yellow fever in Africa and South America. Adapted from Annu Rev Entomol. 2007. 52:209-29.
