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Yellow fever is a viral disease that was first described in the mid-sixteenth century in Yucatan, Mexico. It is caused by the amaril virus, an arbovirus (a virus transmitted by an insect vector) isolated in 1927, simultaneously in Ghana and at the Institut Pasteur in Dakar, Senegal. The disease is currently endemic in Africa and has reemerged in South America. Some serious forms can be fatal. However, there is a safe, effective vaccine. A booster is recommended every ten years.
The yellow fever virus is transmitted to humans via bites from mosquitoes belonging to the Aedes and Haemagogus genera. It also infects forest monkeys, in a mosquito-monkey-mosquito cycle, which can occasionally also include humans.
Following a one-week incubation period, the disease typically begins with fever, chills, muscular pain and headaches. At this point, it could be confused with flu, dengue or malaria. In its serious forms, there is a temporary remission after three days, followed by the onset of a hemorrhagic syndrome with black vomit (hence the Spanish name, vomito negro), jaundice (which accounts for the name in English) and renal problems (albuminuria). Death then occurs in 50 to 80% of cases, after delirium, seizures and coma. All curable forms convey lifelong immunity.
There is no specific treatment for yellow fever. Rest, drugs to lower temperature and relieve vomiting and pain, along with rehydration therapy, are the only methods of treatment for this disease.
WHO estimates that there are 200,000 cases of yellow fever annually across the globe, with 30,000 deaths.
Large-scale epidemics affected tropical America in the 17th, 18th and 19th centuries, and it became "the most dreaded disease in the Americas".
Today, the disease is rife in the intertropical regions of America and Africa. For reasons unexplained, it has never spread to Asia.
Africa is by far the most heavily affected continent, with 95% of the world's cases. The frequency of epidemics and isolated cases has been regularly increasing over the last few years, with particularly high figures seen in Mali and Sudan in 2005. African epidemics, formerly limited to grasslands and along forest fringes, are now reaching the expanding towns and cities, which are providing new mosquito habitats (old tires or containers filled with water). The epidemics in Abidjan in the Ivory Coast in 2001 and 2008 stand testament to this.
The disease had almost disappeared from South America during the first half of the 20th century, but a dramatic increase in mosquito vector populations has caused a resurgence of the infection (most notably in Colombia in 2003).
Yellow fever is also an imported disease: unvaccinated tourists can become infected in endemic regions and develop the disease on returning from their travels. Several fatal cases have been reported over the last few years, such as in Germany (1999), the USA (1999) and Belgium (2001) in travelers returning from Ivory Coast, Venezuela and Gambia respectively.
Circulation of the yellow fever virus in Africa has been the subject of longitudinal studies carried out jointly by the Institut Pasteur in Dakar, Abidjan and Bangui and entomologists at the Institute for Research and Development.
Different mosquito species – Aedes in Africa and Haemagogus janthinomys in South America – transmit the amaril virus to monkeys. In contrast to African monkeys, New World monkeys are very susceptible to infection, and show a high case fatality rate. The virus persists in mosquito-monkey-mosquito cycles – sylvatic forest cycles that do not naturally include humans. Yellow fever is a zoonosis, in all probability dating from ancient times, which was transmitted to humans when they ventured into tropical forests.
The mosquito responsible for urban epidemics is Aedes aegypti. This mosquito is also the vector for dengue, another arbovirus that is spreading rapidly throughout the world. Global warming may accelerate the introduction of mosquitoes that can transmit these diseases into the northern hemisphere, where international trade already provides opportunities for the disease to spread.
Vaccination was made possible in 1932 by scientists at the Institut Pasteur in Dakar, using a live attenuated strain that became known as the "French neurotropic strain". Heat-resistant and administered by scarification, this vaccine put an end to yellow fever in French-speaking Africa. However, it sometimes caused neuromeningeal reactions: after 1960 its use in children under 10 was stopped, and production of the vaccine at the Institut Pasteur in Dakar ceased in 1982.
In 1937 a second vaccine (strain 17D), prepared from the attenuated virus, was developed at the Rockefeller Institute in the USA and rendered thermostable by a team at the Institut Pasteur in Paris. Its effectiveness and safety have progressively been improved, and make it one of the best viral vaccines currently available. This vaccine is now mainly produced at the Institut Pasteur in Dakar. The laboratory is approved by the World Health Organization to supply the yellow fever vaccine to Expanded Programs on Immunization in Africa. There are other manufacturers in Europe and America.
International regulations recommend yellow fever vaccinations (in a single injection) every ten years.
Yellow fever vaccination is the only mandatory vaccination for travelers to the endemic intertropical regions of Africa and South America.
Three Institut Pasteur units are particularly involved in research into yellow fever: The Flavivirus-Host Molecular Interactions Unit (led by Philippe Desprès), the Dendritic Cell Immunobiology Unit (led by Matthew Albert) and the Structural Virology Unit (led by Felix Rey).
The Flavivirus-Host Molecular Interactions Unit is working to improve understanding of the molecular basis of yellow fever virus attenuation in the 17D vaccine strain, which is still in use today. The Dendritic Cell Immunobiology and Structural Virology units study the yellow fever virus from the angles of the pathophysiology of the viral infection and the structural biology of the virus.
The virus is also the subject of research work within the Institut Pasteur International Network, and in particular the Institut Pasteur in Dakar, Senegal.
Illustration - Copyright Institut Pasteur
Caption - The yellow fever virus
> Flavivirus-Host Molecular Interactions Unit
led by Philippe Desprès
> Dentritic Cell Immunobiology Unit
led by Matthew Albert
> Viral Pathogenesis Unit
led by Fernando Arenzana-Seidedos
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