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Yellow fever vaccine is a
vaccine A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified.
that protects against
yellow fever Yellow fever is a viral disease of typically short duration. In most cases, symptoms include fever, chills, loss of appetite, nausea, muscle pains – particularly in the back – and headaches. Symptoms typically improve within five days. ...
. Yellow fever is a viral infection that occurs in
Africa Africa is the world's second-largest and second-most populous continent, after Asia in both cases. At about 30.3 million km2 (11.7 million square miles) including adjacent islands, it covers 6% of Earth's total surface area ...
and
South America South America is a continent entirely in the Western Hemisphere and mostly in the Southern Hemisphere, with a relatively small portion in the Northern Hemisphere at the northern tip of the continent. It can also be described as the sou ...
. Most people begin to develop immunity within ten days of vaccination and 99 percent are protected within one month, and this appears to be lifelong. The vaccine can be used to control outbreaks of disease. It is given either by injection into a muscle or just under the skin. The
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...
(WHO) recommends routine immunization in all countries where the disease is common. This should typically occur between nine and twelve months of age. Those traveling to areas where the disease occurs should also be immunized. Additional doses after the first are generally not needed. The yellow fever vaccine is generally safe. This includes in those with
HIV infection Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ma ...
but without symptoms. Mild side effects may include
headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...
, muscle pains, pain at the injection site,
fever Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...
, and rash. Severe allergies occur in about eight per million doses, serious neurological problems occur in about four per million doses, and
organ failure Organ dysfunction is a condition where an organ does not perform its expected function. Organ failure is organ dysfunction to such a degree that normal homeostasis cannot be maintained without external clinical intervention. It is not a diagnosis ...
occurs in about three per million doses. It appears to be safe in
pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...
and is therefore recommended among those who will be potentially exposed. It should not be given to those with very poor immune function. Yellow fever vaccine came into use in 1938. It is on the
World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...
. The vaccine is made from weakened yellow fever virus. Some countries require a yellow fever vaccination certificate before entry from a country where the disease is common.


Medical uses

People most at risk of contracting the virus should be vaccinated. Woodcutters working in tropical areas should be particularly targeted for vaccination.
Insecticide Insecticides are substances used to kill insects. They include ovicides and larvicides used against insect eggs and larvae, respectively. Insecticides are used in agriculture, medicine, industry and by consumers. Insecticides are claimed t ...
s, protective clothing, and screening of houses are helpful, but not always sufficient for mosquito control; people should always use an insecticide spray while in certain areas. In affected areas, mosquito control methods have proven effective in decreasing the number of cases. Travellers should have the vaccine ten days prior to being in an endemic area. On 17 May 2013, the World Health Organization (WHO)
Strategic Advisory Group of Experts on immunization The Strategic Advisory Group of Experts (SAGE) is the principal advisory group to World Health Organization (WHO) for vaccines and immunization. Established in 1999 through the merging of two previous committees, notably the Scientific Advisory Grou ...
(SAGE) announced that a 'booster' dose of yellow fever (YF) vaccine, ten years after a primary dose, is not necessary. Since yellow fever vaccination began in the 1930s, only 12 known cases of yellow fever post-vaccination have been identified, after 600 million doses have been dispensed. Evidence showed that among this small number of "vaccine failures", all cases developed the disease within five years of vaccination. This demonstrates that immunity does not decrease with time.


Schedule

The World Health Organization recommends the vaccine between the ages of 9 and 12 months in areas where the disease is common. Anyone over the age of nine months who has not been previously immunized and either lives in or is traveling to an area where the disease occurs should also be immunized.


Side effects

The yellow fever 17D vaccine is considered safe, with over 500 million doses given and very few documented cases of vaccine associated illness (62 confirmed cases and 35 deaths as of January 2019). In no case of vaccine-related illness has there been evidence of the virus reverting to a virulent phenotype. The majority of adverse reactions to the 17D vaccine result from allergic reaction to the eggs in which the vaccine is grown. Persons with known
egg allergy Egg allergy is an immune hypersensitivity to proteins found in chicken eggs, and possibly goose, duck, or turkey eggs. Symptoms can be either rapid or gradual in onset. The latter can take hours to days to appear. The former may include anap ...
should discuss this with their physician prior to vaccination. In addition, there is a small risk of
neurologic disease A neurological disorder is any disorder of the nervous system. Structural, biochemical or electrical abnormalities in the brain, spinal cord or other nerves can result in a range of symptoms. Examples of symptoms include paralysis, muscle weakne ...
and
encephalitis Encephalitis is inflammation of the brain. The severity can be variable with symptoms including reduction or alteration in consciousness, headache, fever, confusion, a stiff neck, and vomiting. Complications may include seizures, hallucinations ...
, particularly in individuals with compromised
immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
s and very young children. The 17D vaccine is
contraindicated In medicine, a contraindication is a condition that serves as a reason not to take a certain medical treatment due to the harm that it would cause the patient. Contraindication is the opposite of indication, which is a reason to use a certain tre ...
in (among others) infants between zero and six months or adults over 59 years of age, people with
thymus The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, thymus cell lymphocytes or '' T cells'' mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders ...
disorders associated with abnormal immune cell function, people with primary immunodeficiencies, and anyone with a diminished immune capacity including those taking
immunosuppressant drugs Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system. Classification Immunosuppressive drugs can be classified into ...
. There is a small risk of more severe yellow fever-like disease associated with the vaccine. This reaction, known as yellow fever vaccine-associated acute viscerotropic disease (YEL-AVD), causes a fairly severe disease closely resembling yellow fever caused by virulent strains of the virus. The risk factors for YEL-AVD are not known, although it has been suggested that it may be genetic. The 2'-5'-oligoadenylate synthase (OAS) component of the
innate immune response The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the ...
has been shown to be particularly important in protection from Flavivirus infection. Another reaction to the yellow fever vaccine is known as yellow fever vaccine-associated acute neurotropic disease (YEL-AND). The Canadian Medical Association published a 2001 CMAJ article entitled "Yellow fever vaccination: be sure the patient needs it". The article begins by stating that of the seven people who developed system failure within two to five days of the vaccine in 1996–2001, six died "including 2 who were vaccinated even though they were planning to travel to countries where yellow fever has never been reported." The article cites that "3 demonstrated histopatholic changes consistent with wild yellow fever virus." The author recommends vaccination for only non-contraindicated travelers (see the articles list) and those travelers going where yellow fever activity is reported or in the endemic zone which can be found mapped at the CDC website cited below. In addition, the 2010 online edition of the Center for Disease Control Traveler's Health Yellow Book states that between 1970 and 2002 only "nine cases of yellow fever were reported in unvaccinated travelers from the United States and Europe who traveled" to West Africa and South America, and 8 of the 9 died. However, it goes on to cite "only 1 documented case of yellow fever in a vaccinated traveler. This nonfatal case occurred in a traveler from Spain who visited several West African countries in 1988".


History

African tropical cultures had adopted burial traditions in which the deceased were buried near their habitation, including those who died of Yellow fever. This ensured that people within these cultures gained immunity through a childhood case of "endemic" yellow fever through acquired immunity. This led to a lasting misperception first by colonial authorities and foreign medical experts that Africans have a "natural immunity" to the illness. In the nineteenth century health provisioners forced abandonment of these traditional burial traditions, leading to local populations dying of yellow fever as frequently as those without such burial customs such as settler populations. The first modern attempts to develop a yellow fever vaccine followed the opening of the
Panama Canal The Panama Canal ( es, Canal de Panamá, link=no) is an artificial waterway in Panama that connects the Atlantic Ocean with the Pacific Ocean and divides North and South America. The canal cuts across the Isthmus of Panama and is a condui ...
in 1912, which increased global exposure to the disease. The Japanese bacteriologist
Hideyo Noguchi , also known as , was a prominent Japanese bacteriologist who in 1911 discovered the agent of syphilis as the cause of progressive paralytic disease. Early life Noguchi Hideyo whose childhood name was Seisaku Noguchi was born to a family of farme ...
led investigations for the
Rockefeller Foundation The Rockefeller Foundation is an American private foundation and philanthropy, philanthropic medical research and arts funding organization based at 420 Fifth Avenue, New York City. The second-oldest major philanthropic institution in America, aft ...
in
Ecuador Ecuador ( ; ; Quechua: ''Ikwayur''; Shuar: ''Ecuador'' or ''Ekuatur''), officially the Republic of Ecuador ( es, República del Ecuador, which literally translates as "Republic of the Equator"; Quechua: ''Ikwadur Ripuwlika''; Shuar: ' ...
that resulted in a vaccine based on his theory that the disease was caused by a leptospiral bacterium. However, other investigators could not duplicate his results and the ineffective vaccine was eventually abandoned. Another vaccine was developed from the "French strain" of the virus, obtained by
Pasteur Institute The Pasteur Institute (french: Institut Pasteur) is a French non-profit private foundation dedicated to the study of biology, micro-organisms, diseases, and vaccines. It is named after Louis Pasteur, who invented pasteurization and vacc ...
scientists from a man in Dakar, Senegal, who survived his bout with the disease. This vaccine could be administered by
scarification Scarification involves scratching, etching, burning/branding, or superficially cutting designs, pictures, or words into the skin as a permanent body modification or body art. The body modification can take roughly 6–12 months to heal. In the ...
, like the
smallpox vaccine The smallpox vaccine is the first vaccine to be developed against a contagious disease. In 1796, British physician Edward Jenner demonstrated that an infection with the relatively mild cowpox virus conferred immunity against the deadly smallpox ...
, and was given in combination to produce immunity to both diseases, but it also had severe systemic and neurologic complications in a few cases. Attempts to attenuate the virus used in the vaccine failed. Scientists at the Rockefeller Foundation developed another vaccine derived from the serum of an African named Asibi in 1927, the first isolation of the virus from a human. It was safer but involved the use of large amounts of human serum, which limited widespread use. Both vaccines were in use for several years, the Rockefeller vaccine in the Western hemisphere and England, and the Pasteur Institute vaccine in France and its African colonies. In 1937,
Max Theiler Max Theiler (30 January 1899 – 11 August 1972) was a South African-American virologist and physician. He was awarded the Nobel Prize in Physiology or Medicine in 1951 for developing a vaccine against yellow fever in 1937, becoming the first ...
, working with Hugh Smith and Eugen Haagen at the
Rockefeller Foundation The Rockefeller Foundation is an American private foundation and philanthropy, philanthropic medical research and arts funding organization based at 420 Fifth Avenue, New York City. The second-oldest major philanthropic institution in America, aft ...
to improve the vaccine from the "Asibi" strain, discovered that a favorable chance mutation in the attenuated virus had produced a highly effective strain that was named 17D. Following the work of
Ernest Goodpasture Ernest William Goodpasture (October 17, 1886 – September 20, 1960) was an American pathologist and physician. Goodpasture advanced the scientific understanding of the pathogenesis of infectious diseases, parasitism, and a variety of ricketts ...
, Theiler used chicken eggs to culture the virus. After field trials in Brazil, over one million people were vaccinated by 1939, without severe complications. This vaccine was widely used by the U.S. Army during World War II. For his work on the yellow fever vaccine, Theiler received the 1951 Nobel Prize in Physiology or Medicine. Only the 17D vaccine remains in use today. Theiler's vaccine was responsible for the largest outbreak of
Hepatitis B Hepatitis B is an infectious disease caused by the '' Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. ...
in history: infecting 330,000 soldiers and giving 50,000 jaundice between 1941 and 1942. At the time, chronic infectious hepatitis was not known, so when human serum was used in vaccine preparation, serum drawn from a chronic Hepatitis B Virus (HBV) carrier would contaminate the Yellow Fever Vaccine. In 1941, researchers at Rocky Mountain Laboratories developed a safer alternative, an "aqueous-base" version of the 17D vaccine using distilled water combined with the virus grown in chicken eggs. Since 1971, screening technology for HBV has been available and is routinely used in situations where HBV contamination is possible including vaccine preparation. Also in the 1930s, a French team developed the French neurotropic vaccine (FNV), which was extracted from
mouse brain The mouse brain refers to the brain of Mus musculus. Various brain atlases exist. For reasons of reproducibility, genetically characterized, stable strains like C57BL/6 were chosen to produce high-resolution images and databases. Well known o ...
tissue. Since this vaccine was associated with a higher incidence of
encephalitis Encephalitis is inflammation of the brain. The severity can be variable with symptoms including reduction or alteration in consciousness, headache, fever, confusion, a stiff neck, and vomiting. Complications may include seizures, hallucinations ...
, FNV was not recommended after 1961. Vaccine 17D is still in use, and more than 400 million doses have been distributed. Little research has been done to develop new vaccines. Newer vaccines, based on vero cells, are in development (as of 2018)..


Manufacture and global supply

Increases in cases of yellow fever in endemic areas of Africa and South America in the 1980s were addressed by the WHO Yellow Fever Initiative launched in the mid-2000s. The initiative was supported by the
Gavi Alliance GAVI, officially Gavi, the Vaccine Alliance (previously the GAVI Alliance, and before that the Global Alliance for Vaccines and Immunization) is a public–private global health partnership with the goal of increasing access to immunization ...
, a collaboration of the
WHO Who or WHO may refer to: * Who (pronoun), an interrogative or relative pronoun * Who?, one of the Five Ws in journalism * World Health Organization Arts and entertainment Fictional characters * Who, a creature in the Dr. Seuss book '' Horton He ...
,
UNICEF UNICEF (), originally called the United Nations International Children's Emergency Fund in full, now officially United Nations Children's Fund, is an agency of the United Nations responsible for providing humanitarian and developmental aid to c ...
, vaccine manufacturers, and private philanthropists such as the
Bill & Melinda Gates Foundation The Bill & Melinda Gates Foundation (BMGF), a merging of the William H. Gates Foundation and the Gates Learning Foundation, is an American private foundation founded by Bill Gates and Melinda French Gates. Based in Seattle, Washington, it was ...
. Gavi-supported vaccination campaigns since 2011 have covered 88 million people in 14 countries considered at "high-risk" of a yellow fever outbreak (Angola was considered "medium risk"). As of 2013, there were four WHO-qualified manufacturers: Bio-Manguinhos in Brazil (with the
Oswaldo Cruz Foundation The Oswaldo Cruz Foundation (Portuguese ''Fundação Oswaldo Cruz'', also known as FIOCRUZ) is a scientific institution for research and development in biological sciences located in Rio de Janeiro, Brazil; it is considered one of the world's ma ...
), Institute Pasteur in Dakar, Senegal, the Federal State Unitary Enterprise of Chumakov Institute in Russia, and
Sanofi Pasteur Sanofi Pasteur is the vaccines division of the French multinational pharmaceutical company Sanofi. Sanofi Pasteur is the largest company in the world devoted entirely to vaccines. It is one of four global producers of the yellow fever vaccine. ...
, the French pharmaceutical company. Two other manufacturers supply domestic markets: Wuhan Institute of Biological Products in China and
Sanofi Pasteur Sanofi Pasteur is the vaccines division of the French multinational pharmaceutical company Sanofi. Sanofi Pasteur is the largest company in the world devoted entirely to vaccines. It is one of four global producers of the yellow fever vaccine. ...
in the United States. Demand for yellow fever vaccine for preventive campaigns has increased from about five million doses per year to a projected 62 million per year by 2014. UNICEF reported in 2013 that supplies were insufficient. Manufacturers are producing about 35 million of the 64 million doses needed per year. Demand for the yellow fever vaccine has continued to increase due to the growing number of countries implementing yellow fever vaccination as part of their routine immunization programmes. The outbreak of yellow fever in Angola and in the Democratic Republic of Congo in 2016 has raised concerns about whether the global supply of vaccine is adequate to meet the need during a large epidemic or
pandemic A pandemic () is an epidemic of an infectious disease that has spread across a large region, for instance multiple continents or worldwide, affecting a substantial number of individuals. A widespread endemic disease with a stable number of in ...
of the disease. Routine childhood immunization was suspended in other African countries to ensure an adequate supply in the vaccination campaign against the outbreak in Angola. Emergency stockpiles of vaccine diverted to Angola, which consisted of about 10 million doses at the end of March 2016, had become exhausted, but were being replenished by May 2016. However, in August it was reported that about one million doses of six million shipped in February had been sent to the wrong place or not kept cold enough to ensure efficacy, resulting in shortages to fight the spreading epidemic in DR Congo. As an emergency measure, experts suggested
fractional dose vaccination Fractional dose vaccination is a strategy to reduce the dose of a vaccine to achieve a vaccination policy goal that is more difficult to achieve with conventional vaccination approaches, including deploying a vaccine faster in a pandemic, reaching ...
, using a fractional dose (1/5 or 1/10 of the usual dose) to extend existing supplies of vaccine. Others have noted that switching manufacturing processes to modern cell-culture technology might improve vaccine supply shortfalls, as the manufacture of the current vaccine in chicken eggs is slow and laborious. On 17 June 2016, the WHO agreed to the use of 1/5 the usual dose as an emergency measure during the ongoing outbreak in Angola and the DR Congo. The fractional dose would not qualify for a yellow fever certificate of vaccination for travelers. Later studies found that the fractional dose was just as protective as the full dose, even 10 years after vaccination. As of February 2021, UNICEF reported awarded contract prices of ranging from to per dose under multi-year contracts with various suppliers.


Travel requirements

Travellers who wish to enter certain countries or territories must be vaccinated against yellow fever 10 days before crossing the border, and be able to present a vaccination record/certificate at the border checks. In most cases, this travel requirement depends on whether the country they are travelling from has been designated by the World Health Organization as being a 'country with risk of yellow fever transmission'. In a few countries, it does not matter which country the traveller comes from: everyone who wants to enter these countries must be vaccinated against yellow fever. There are exemptions for newborn children; in most cases, any child who is at least 9 months or 1 year old needs to be vaccinated.


References


External links

* * {{DEFAULTSORT:Yellow Fever Vaccine Live vaccines Vaccines World Health Organization essential medicines (vaccines) Yellow fever Wikipedia medicine articles ready to translate