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Yellow fever

Thomas P Monath, MD, FACP, FASTMH
Section Editor
Martin S Hirsch, MD
Deputy Editor
Elinor L Baron, MD, DTMH


Yellow fever is a mosquito-borne viral hemorrhagic fever with a high case-fatality rate. Clinical manifestations include hepatic dysfunction, renal failure, coagulopathy, and shock. Travelers to tropical regions of South America and sub-Saharan Africa where the disease is endemic are at risk for acquisition of infection and require immunization.

Issues related to virology, pathogenesis, epidemiology, clinical manifestations, diagnosis, treatment, and prevention of yellow fever will be reviewed here.


Yellow fever is the prototype member of the family Flaviviridae, a group of small (40 to 60 nm), enveloped, positive-sense, single-stranded RNA viruses that replicate in the cytoplasm of infected cells. Yellow fever virus is a single serotype and is antigenically conserved, so the vaccine protects against all strains of the virus. At the nucleotide sequence level, it is possible to distinguish seven major genotypes representing West Africa (two genotypes), Central-East Africa and Angola (three genotypes), and South America (two genotypes) [1,2]. Humans are highly susceptible to infection and disease. Most nonhuman primate species are susceptible to infection, and some species of nonhuman primates develop clinical manifestations.

An infected female mosquito inoculates approximately 1000 to 100,000 virus particles intradermally during blood feeding. Virus replication begins at the site of inoculation, probably in dendritic cells in the epidermis, and spreads through lymphatic channels to regional lymph nodes. Lymphoid cells, particularly monocyte-macrophages and large histiocytes, appear to be the preferred cell types for primary replication. The virus reaches other organs via the lymph and then the bloodstream, seeding other tissues. Large amounts of virus are produced in the liver, lymph nodes, and spleen and are released into the blood. During the viremic phase (days three to six), infection may be transmitted to blood-feeding mosquitoes.

Yellow fever is characterized by hepatic dysfunction, renal failure, coagulopathy, and shock [3-6]. The midzone of the liver lobule is principally affected, with sparing of cells bordering the central vein and portal tracts [7]. Viral antigen localizes to the midzone, indicating that it is the site of direct viral injury. Very high virus loads have been found in the liver and spleen of fatal cases [8].


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