Yellow Fever


Yellow fever, also known as sylvatic fever and viral hemorrhagic fever or VHF, is a severe infectious disease caused by a type of virus called a flavivirus. This flavivirus can cause outbreaks of epidemic proportions throughout Africa and tropical America. It is endemic in 33 countries in Africa and 11 countries in South America.


The first written evidence of a yellow fever epidemic occurred in the Yucatan (Mexico) in 1648. Since that time, much has been learned about the transmission patterns of this illness. It is thought that the disease originated in Africa and spread to the Americas in the seventeenth and eighteenth centuries through trading ships. The flavivirus that causes yellow fever was first identified in West Africa, in 1928, and the first vaccine (17D) to fight against the disease was produced by South African-born American microbiologist Max Theiler (1899–1972) at the Rockefeller Institute in New York City in 1937. Based on work from American pathologist and physician Ernest Goodpasture (1886–1960), Theiler used chicken eggs to culture the virus. He won a Nobel Prize in 1951 for his work. Over 400 million doses of vaccine 17D have been used throughout the years.

Many common illnesses in the United States (including the common cold, many viral causes of diarrhea, and influenza) are spread by direct passage of the causative virus between human beings. Yellow fever, however, cannot be passed directly from one infected human to another. Instead, the virus responsible for yellow fever requires an intermediate vector. A vector is an organism that can carry a particular disease-causing agent (such as a virus or bacteria) without actually developing the disease. In the case of yellow fever, a mosquito is the vector that carries the virus from one host to another.

A host is an animal that can be infected with a particular disease. The hosts of yellow fever include both humans and monkeys. The cycle of yellow fever transmission begins when a tree-hole breeding mosquito bites an infected monkey. This mosquito acquires the virus and can pass the virus to any number of other monkeys that it may bite. This form of yellow fever is known as sylvatic yellow fever, and usually affects humans only incidentally. When an infected mosquito bites a human, the human may acquire the virus. In the case of South American yellow fever, the infected human may return to the city, where an urban mosquito (Aedes aegypti) serves as a viral vector, spreading the infection rapidly by biting humans. This form of the disease is known as urban yellow fever or epidemic yellow fever.

Yellow fever epidemics also may occur after flooding caused by earthquakes and other natural disasters. They result from a combination of new habitats available for the vectors of the disease and changes in human behavior (spending more time outdoors and neglecting sanitation precautions).

Cases of yellow fever are uncommon in the United States and Canada. The last reported case of a U.S. citizen dying of yellow fever concerned a man who contracted yellow fever after visiting Venezuela in 1999. The man had not been vaccinated against yellow fever. The last epidemic in the United States occurred in New Orleans, Louisiana, in 1905.

Risk factors

The major risk factor for contracting yellow fever is residing in or traveling to an area where mosquitoes carry the virus. These areas include South America and sub-Saharan Africa. To provide protection from yellow fever, a vaccination is recommended for anyone traveling to affected areas at least ten to 14 days before the departure date.

Top left hand corner, Walter Reed, top right hand corner, Aristedes Agramonte, bottom left, Jesse Lazear, bottom right, James Carroll. Walter Reed, (1851-1902) was a U.S.

Top left hand corner, Walter Reed, top right hand corner, Aristedes Agramonte, bottom left, Jesse Lazear, bottom right, James Carroll. Walter Reed, (1851-1902) was a U.S. Army physician who in 1900 led the team that postulated and confirmed the theory that yellow fever is transmitted by a particular mosquito species, rather than by direct contact. Aristides Agramonte (1868-1931) was an American physician, pathologist and bacteriologist with expertise in tropical medicine. Jesse William Lazear (1866-1900) was an American physician. Major James Carroll (854-1907) was a U.S. Army physician. He and Lazear, subjected themselves to the bite of infectious mosquitoes, to test the theory that mosquitoes were carriers of yellow fever. The infection he contracted eventually killed him.
(NLM/Science Source)


Anyone can get yellow fever; however, older people are more at risk than younger ones. Yellow fever is found most commonly in men between the ages of 15 and 45 years who work outdoors and live in fever-endemic areas. Race has not been shown to be a factor in contraction or transmission. Between 1970 and 2015, only ten cases of yellow fever were reported in travelers from the United States and Europe. All cases were found in unimmunized travelers who had visited South America or West Africa. Eight of the cases were fatal.

According to the World Health Organization (WHO), as of 2011, about 200,000 cases of yellow fever occur annually around the world (mostly in tropical endemic areas of Africa and the Americas), with approximately 30,000 deaths caused by the disease. Thirty-three countries are at risk of yellow fever in Africa and in the Americas; several Caribbean islands and nine South American countries (including Bolivia, Brazil, Columbia, Ecuador, and Peru) are also at risk. Up to 50% of severely affected persons without treatment die from yellow fever. The number of yellow fever cases has increased over the past several decades primarily due to fewer people becoming immune to it and fewer immunizations, along with environmental factors such as urbanization, deforestation, global climate change, and population movements into areas more prone to the virus. The vaccine for yellow fever protects humans for 30 to 35 years. About 95% of people vaccinated are immune to the disease within one week of the vaccination.

Causes and symptoms

Once a mosquito passes the yellow fever virus to a human, the chance of disease developing ranges from 5% to 20%. Infection may be fought off by the host's immune system or may be so mild that it is never identified.

In human hosts who develop the disease yellow fever, there are five distinct stages through which the infection evolves. These have been termed the periods of incubation, invasion, remission, intoxication, and convalescence.

Yellow fever's incubation period (the amount of time between the introduction of the virus into the host and the development of symptoms) is three to six days. During this time, there are generally no symptoms identifiable to the host.


Wilbur Augustus Sawyer was born in Appleton, Wisconsin, on August 7, 1879, to Minnie Edmea (Birge) and Wesley Caleb Sawyer. The Sawyers moved to Oshkosh, Wisconsin, and finally to Stockton, California in 1888. Sawyer spent two years at the University of California and then entered Harvard College where he earned his A.B. degree in 1902. In 1906, Sawyer graduated from Harvard Medical School and began a private practice, which lasted until he started his internship at Massachusetts General Hospital. Sawyer returned to California in 1908 in order to obtain a position at the University of California as a medical examiner. He then worked with the California State Board of Health from 1910 until 1918. In 1911, Sawyer married Margaret Henderson. The couple had three children.

Sawyer's first publication (1913) dealt with his research into poliomyelitis. His discovery, in 1915, that examination of an individual's stool could lead to detection of the disease was later regarded as very significant. In 1918 and 1919, Sawyer worked to control venereal disease while employed by the Army Medical Corps. In 1926 and 1927, while director of the West African Yellow Fever Commission, Sawyer succeeded in isolating the yellow fever virus. He ultimately returned to the United States, where he and Wray Lloyd devised an immunization against yellow fever (1931).

In 1944, Sawyer became director of health for the United Nations Relief and Rehabilitation Administration, a position he held for three years. He retired to Berkeley, California, where he died on November 12, 1951. The company he built with his brother still thrives today.

The next phase is the period of remission. The fever falls, and symptoms decrease in severity for several hours to several days. In some patients, this signals the end of the disease; in other patients, this is the calm before the storm.

The period of intoxication represents the most severe and potentially fatal phase of the illness. During this time, lasting three to nine days, a type of degeneration of the internal organs (specifically the kidneys, liver, and heart) occurs. This fatty degeneration results in what is considered the classic triad of yellow fever symptoms: jaundice, black vomit, and the dumping of protein into the urine. Jaundice causes the whites of the patient's eyes and the patient's skin to take on a distinctive yellow color. This is due to liver damage, and the accumulation of a substance called bilirubin, which is normally processed by a healthy liver. The liver damage also results in a tendency toward bleeding; the patient's vomit appears black due to the presence of blood. Protein, which is normally kept out of the urine by healthy, intact kidneys, appears in the urine due to disruption of the kidney's healthy functioning.

Patients who survive the period of intoxication enter into a relatively short period of convalescence. They recover with no long-term effects related to the yellow fever infection. Surviving an infection with the yellow fever virus results in lifelong immunity against repeated infection by the virus.

The course of yellow fever is complicated in some patients by secondary bacterial infections.


Diagnosis for yellow fever includes examination, testing, and procedures.


A diagnosis of yellow fever may be suspected during a physical examination when the classic triad of symptoms are present. These include:


Diagnosis of yellow fever depends on the examination of blood by various techniques in order to demonstrate either yellow fever viral antigens (the part of the virus that stimulates the patient's immune system to respond) or specific antibodies (specific cells produced by the patient's immune system that are directed against the yellow fever virus). The most common method of diagnosis, as of 2015, was accomplished by the testing of serum to detect virus-specific IgM and neutralizing antibodies.


Typically, the only procedure required for diagnosis is a blood draw so that the blood can be evaluated for signs of yellow fever.


Treatment for yellow fever includes traditional approaches, along with the use of drugs.

The only treatments for yellow fever are given to relieve its symptoms. Fevers and pain should be relieved with acetaminophen, not aspirin or ibuprofen, both of which could increase the already-present risk of bleeding. Dehydration (due to fluid loss, both from fever and bleeding) needs to be carefully avoided. This can be accomplished by increasing fluids. The risk of bleeding into the stomach can be decreased through the administration of antacids and other medications. Hemorrhage (heavy bleeding) may require blood transfusions. Kidney failure may require dialysis (a process that allows the work of the kidneys in clearing the blood of potentially toxic substances to be taken over by a machine, outside of the body).


To date, there are no antiviral treatments available to combat the yellow fever virus. Nonclinical research has yielded limited results.

Researchers have found that ribavirin (Virazole, Rebetol), a drug that is given by mouth to treat hepatitis C, is successful in reducing mortality from yellow fever in hamsters, but only if given within 120 hours of infection. Another drug, Interferon-alpha has also been found to reduce mortality in monkeys with yellow fever but only when administered within 24 hours of infection.

Public health role and response

The World Health Organization (WHO) recommends routine childhood vaccination to prevent yellow fever in endemic countries where epidemics are possible. Quick detection of yellow fever and fast response of governments through emergency vaccination campaigns are important in controlling outbreaks. WHO recommends that at-risk countries maintain at least one national laboratory where blood tests for yellow fever can be performed.

The organization Secretariat for the International Coordinating Group (ICG) for Yellow Fever Vaccine Provision provides an emergency stockpile of yellow fever vaccines whenever outbreaks occur in any country of the world. WHO also leads the Yellow Fever Initiative (YFI), which is a preventive vaccination effort for at-risk countries, especially 12 participating African countries where the disease is most likely to occur. The YFI recommends “including yellow fever vaccines in routine infant immunizations (starting at age 9 months), implementing mass vaccination campaigns in high-risk areas for people in all age groups aged 9 months and older, and maintaining surveillance and outbreak response capacity.”

A protein normally produced by the immune system to fight infection or rid the body of foreign material. The material that stimulates the production of antibodies is called an antigen. Specific antibodies are produced in response to each different antigen and can only inactivate that particular antigen.
Any foreign substance, usually a protein, that stimulates the body's immune system to produce antibodies.
A reddish-yellow bile pigment made by the liver.
The cleansing of the blood through use of a special machine that filters the blood. The process is performed when the kidneys are unable to filter blood properly.
A situation in which the number of cases of a particular disease exceeds the endemic or average number of cases. Infections of such diseases often spread through a population of people in a relatively short period of time.
Faget's sign—
The simultaneous occurrence of a high fever with a slowed heart rate.
The species to which the virus that causes yellow fever belongs.
Abnormal and obsessive bleeding.
The organism (such as a monkey or human) in which another organism (such as a virus or bacteria) is living.
The yellowing of the skin and whites of the eyes caused by an increased level of bilirubin in the blood.
Pertaining to or living in the woods or forested areas. The form of yellow fever transmitted by mosquitoes to rainforest monkeys is called sylvatic yellow fever.
A carrier organism (such as a fly or mosquito) that serves to deliver a virus (or other agent of infection) to a host.


Five to ten percent of all diagnosed cases of yellow fever are fatal. Jaundice occurring during a yellow fever infection is an extremely grave predictor; 20–50% of these patients die of the infection. Death may occur due to massive bleeding (hemorrhage), often following a lapse into a comatose (unconscious) state.


A very safe and very effective yellow fever vaccine exists. The Arilvax vaccine is made from a live attenuated (weakened) form of the yellow fever virus, strain 17D. In the United States, the vaccine is given only at Yellow Fever Vaccination Centers authorized by the U.S. Public Health Service. About 95% of vaccine recipients acquire long-term immunity to the yellow fever virus. Careful measures to decrease mosquito populations in both urban areas and jungle areas where humans are working, along with programs to vaccinate all people living in such areas, are necessary to avoid massive yellow fever outbreaks.

Individuals planning to travel in countries where yellow fever is endemic may obtain up-to-date information on yellow fever vaccination from the U.S. Centers for Disease Control and Prevention (CDC).

See also Traveler's health ; Tropical disease ; Vector control .



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Centers for Disease Control and Prevention, 1600 Clifton Rd., Atlanta, GA, 30333, (800) 232-4636,, .

National Institute of Allergy and Infectious Diseases, 6610 Rockledge Dr., MSC 6612, Bethesda, MD, 20892, (301) 496-5717, (866) 284-4107, Fax: (301) 402-3573, .

World Health Organization, Avenue Appia 20, Geneva, Switzerland, 1211 27, 41 22 791-2111, Fax: 41 22 791-3111, .

Rosalyn Carson-DeWitt, MD
Revised by William A. Atkins, BB, BS, MBA

  This information is not a tool for self-diagnosis or a substitute for professional care.