Yellow fever

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Info bulb.pngYellow Fever was one of several factors which defeated the first attempt to produce a Panama Canal

Yellow fever virus is a small RNA virus, the animal vectors of which are Aedes spp., Sabethes spp. or Haemagogus spp. mosquitoes with monkeys as the natural host and reservor. Vaccination with an attentuated live vaccine is effective, lasting 10 years (in many much longer), but carries a small mortality of about 0.3/100,000 which is substantially greater in people with immunosuppression. The risk of such issues also increases over 60 years , being about 1.5/100,000 for those above 60 years old. The two principle serious adverse reactions to this live vaccine are systemic immune activation without control of the viraemia which has the 65% mortality or transient neurodisability from meningoencephalitis or Guillain-Barre syndrome.

Info bulb.pngMosquitoes:

Aedes have a bend in the middle with their thorax down and abdomen parallel to the host's skin as they feed. Anopheles characteristically have a head down resting position, so their back end sticks up in the air.

First isolated 1927 in Ghana its principle host species is monkeys.


Clinical Features

The diagnosis has to be clinical (serology is only usually available after recovery) and this proves challenging with any index case

Disease may then resolve or relapse after typically a day to:

Death if it occurs usually is about a week


  • Mosquito control
  • Vaccination
    • The vaccine produces severe reactions of the order of 1 in 100000.[2] Vaccine recommendations must accordingly evaluate risk.benefit accurately[3]
      • This risk as with most live vaccines is usually associated with defects in innate immunity:
        1. Young adults such as women on immunosuppressants where if a serious reaction occurs there is a high case-fatality rate
        2. The elderly, particularly men with age-related immune senescence.
      • It is possibly confined to first vaccination
      • Two severe reactions are known:
        1. viscerotropic.
        2. vaccine-associated neurologic disease
    • Two virus substrains are currently used in the production of yellow fever vaccines:
      1. 17DD, which is used in Brazil
      2. 17D-204 in all other vaccines


This is dictated by the monkey host. Essentially a risk for those in tropical Central/South Americia and Central Africia with outbreaks in man following on from outbreaks in monkeys which in a given area may be separated by many years. However WHO has recently refined the at risk area, so that much of coastal Eastern central Africa and an area from northern Peru through to Columbia is only moderate risk, with vaccination only recommended to travellers likely to spend considerable time in rural areas for example. This may bring greater consistency within national vaccination recommendations, as a considerable challenge for the international traveller has been that individual states set the rules and have for example disregarded low risk activities such as transit air passage through an airport with negligible yellow fever risk. There are three classic transmission cycles:

  • Urban cycle
  • Sylvatic forest or jungle cycle
  • Savannah intermediate cycle
    • Vectors genus Aedes in Africa and usual cause of background human disease


It has caused government and financial disruption as well as countless deaths. The yellow quarantine flag became feared in all the world's port cities in the 18th century. At its peak it was killing up to 60000 a year. It has been transmitted to man for many thousands of years but only became noticeable due to the African slave trade

  • 1600s Probable first epidemic transmission into man in Africa
  • 1647 Slave trade associated epidemic in Barbados
  • 1648 Slave trade associated epidemic in Guadalupe. Also probable outbreak Yucatan peninsula of Mexico (xekik - black vomit)
  • 1668 New York
  • 1691 Boston
  • 1699 Charleston
  • 1730 2200 die in Cadiz, Spain.
  • 1790 - 1802 Haiti outbreak kills most of British garrison
  • 1793 Philadelphia yellow fever epidemic killed about 9% of cities population and USA federal government flees city
  • 1803 Barcelona outbreak
  • 1820 200 die in Savannah, Georgia
  • 1821 Barcelona outbreak
  • 1848 Josiah Clark Nott notes a possible association with mosquitos
  • 1853 7849 die in New Orleans
  • 1855 3000 die in Norfolk and Portsmouth, Virginia
  • 1861 26 die Saint-Nazaire out of 44 who became ill
  • 1865 15 die in Swansea outbreak out of 27 who became ill when cargo of copper ore from Cuba was discharged
  • 1867 Amongst many deaths in Texas and Louisiana outbreak is a USA major general and the wife of the founder of Texas
  • 1870 1235 die in Barcelona with about 12,000 cases
  • 1878 About 20,000 died in Mississippi River Valley epidemic (eg Memphis Saffron Scourge of 1878)
  • 1881 Cuban epidemiologist Carlos Finlay proposed mosquito transmission with report of bite transmission
  • 1882–1889 French Panama Canal failure ultimately results in near collapse French financial system
  • 1898 More American solders die from disease than battle in Cuba which leads to the Reed Yellow Fever Commission
  • 1900 Walter Reed confirmed mosquito transmission resulting in organised mosquito control measures (the 30 army volunteer experiment).
  • 1905 New Orleans outbreak. Dr. William Gorgas, convinced President Theodore Roosevelt to grant funding on a 4000 man eradication effort in Panama
  • 1906 Eradication of the disease in Havana and Panama (11 November 1906)
  • 1927 Yellow fever virus isolated - first human virus to be isolated
  • 1937 Max Theiler developed live attenuated vaccine 17D still used today
  • 1950 Concern with the high rate of postvaccinal encephalitis following administration of the yellow fever vaccine to infants. The consequence decrease in vaccination is followed in the 1960s by several outbreaks
  • 1982 Formal withdrawal of French neurotropic vaccine because of risk postvaccinal encephalitis
  • 1999 Bolivia outbreak
  • 2015 Outbreak in December in Angola and Democratic Republic of Congo uses up entire world emergency stock of Theiler's vaccine
  • 2017 Outbreak in Brazil


A secondary suphonamide AP30451 is being studied in animal models