Yellow fever

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200,000 cases of yellow fever annually across the globe, with 30,000 deaths

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Cause

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.

Symptoms and treatment

Following a 3 to 6 days 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 20 to 60% of cases, after delirium, seizures and coma. All curable forms convey lifelong immunity. There is no specific treatment for yellow fever. Apart from prevention by vaccination, the only way to fight the disease once it has been contracted is through rest, rehydration therapy, and drugs to lower temperature and relieve vomiting and pain.

Epidemiology

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 where vaccine coverage is poor. For reasons unexplained, it had never spread to Asia until 2016 when a few cases were reported in China due to Chinese nationals becoming infected while working in Angola and returning home with the disease.

Africa

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, and in Angola and the Democratic Republic of Congo in 2016 (where emergency vaccination campaigns were organized). 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 American continent

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 and Brazil in 2017).

Imported cases

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.

The spread of mosquito vectors

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 French Research Institute for Development.

Different mosquito species – Aedes in Africa and Haemagogus janthinomys in South America – transmit the yellow fever 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 and Zika virus, other arboviruses that are 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 diseases to spread.

Vaccination

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 a virus attenuated by Max Theiler (1951 Nobel Prize in Medicine), 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.

International regulations require yellow fever vaccinations prior to a first trip to an endemic region (documentary evidence of vaccination is requested on entry to endemic countries). A single injection provides long-term protection.

Yellow fever vaccination is the only mandatory vaccination for travelers to the endemic intertropical regions of Africa and South America.

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At the Institut Pasteur

Three Institut Pasteur units are currently involved in research into yellow fever: the Virus sensing and signaling Unit (led by Nolwenn Jouvenet), the Structural Virology Unit (led by Felix Rey) and the Arboviruses and Insect vectors Unit (led by Anna-Bella Failloux).

The Virus sensing and signaling 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 Structural Virology Unit studies the yellow fever virus from the angles of the pathophysiology of the viral infection and the structural biology of the virus. The Arboviruses and Insect vectors Unit researches interactions between the virus, the vector mosquito and the environment.

The virus is also the subject of research work within the Institut Pasteur International Network, and in particular the Institut Pasteur in Dakar, Senegal.


March 2021



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