Brief Summary

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Yellow fever, the first described viral hemorrhagic fever (VHF), was one of the most feared lethal diseases before the discovery that mosquito vectors are responsible for transmission (a hypothesis that was confirmed at the dawn of the 20th century, making it possible to control the disease by controlling mosquitoes) and the development of highly effective vaccines in the 1930s. Despite these major advances, today yellow fever still affects thousands of people in tropical Africa and South America and is a continued threat to people who travel to these regions without vaccination. Fortunately, the yellow fever virus has never emerged in Asia (for reasons that are not clear), but Asia is considered vulnerable to the establishment of yellow fever due to the presence of a large susceptible human population and the presence of the main urban mosquito vector, Aedes aegypti.

Yellow fever is a zoonotic infection, maintained in nature by wild non-human primates and diurnally active mosquitoes that breed in tree-holes in the forest canopy (mainly Haemagogus spp. in the Americas and Aedes spp. in Africa). Humans are exposed to infected mosquitoes when they enter these natural areas during occupational or recreational activities (yellow fever contracted this way is often referred to as “jungle yellow fever”). In the moist savanna regions of Africa, tree-hole-breeding Aedes mosquitoes reach very high densities and are implicated in endemic and epidemic transmission, transferring the virus from monkey to people and between people. Aedes aegypti, a domestic mosquito that breeds in man-made containers, may transmit yellow fever virus between human beings (“urban yellow fever”). The virus is maintained over the dry season by vertical transmission in mosquitoes. Mosquito eggs containing virus survive in dry tree-holes and hatch infectious progeny mosquitoes when the rains resume. Recent increases in the density and distribution of A. aegypti, as well as the great increase in air travel, increase the risk of introduction and spread of yellow fever to North and Central America, the Caribbean, and Asia.

Yellow fever virus is the prototype of the genus Flavivirus (family Flaviviridae), which comprises approximately 70 known viruses, most of which are arthropod-borne. Flaviviruses are positive-sense, single-stranded RNA viruses—obligate intracellular pathogens that replicate in the cytoplasm of infected cells.The earliest description of yellow fever is found in a Mayan manuscript from 1648, but genome analyses suggest that yellow fever virus evolved from other mosquito-borne viruses around 3000 years ago, probably in Africa, from where it was imported to the New World during the slave trade. Yellow fever was a major scourge in the 18th and 19th centuries in colonial settlements in the Americas and West Africa.

(Monath 2001)

Official reports of yellow fever incidence (during the first decade of the 21st century, 50 to 120 cases annually from South America and 200 to 1200 annually from Africa) probably substantially underestimate the true number of cases. Although most humans infected with yellow fever virus are asymptomatic or have clinically inapparent infections, symptoms can range from mild fevers to hemorrhagic fever with multi-organ involvement; in severe cases with hepatic and renal involvement, the mortality rate is around 20% to 50%. Because no antiviral treatment exists for the disease, prevention through use of personal protection measures and vaccination is critical to lowering disease risk and mortality. Although immunity from vaccination likely lasts for a lifetime, the vaccine is officially treated as effective from 10 days to 10 years after receiving it. Vaccination of travelers to regions where yellow fever is endemic not only protects travelers themselves, but also prevents the spread of the disease.

(Jentes et al. 2011;Lown et al. 2012)

Monath (2001) provides a thorough overview of the epidemiology and pathology of yellow fever. Jentes et al. (2011) discuss a range of issues relating to developing and maintaining an effective vaccination program to control yellow fever. Lown et al. (2012) discuss the challenges clinicians face in recommending to individual patients whether or not they should be vaccinated given the risks of yellow fever associated with their particular circumstances and the rare but potentially fatal serious adverse events associated with vaccination.

More information on yellow fever can be obtained from the U.S. Centers for Disease Control and Prevention and Wikipedia (the latter source includes a broad historical perspective).

Leo Shapiro
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