yellow fever

Yellow fever, which is 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.

The first written evidence of such an epidemic occurred in the Yucatan in 1648. Since that time, much has been learned about the interesting transmission patterns of this devastating illness. It is thought that the disease originated in Africa and spread to the Americas in the 17th and 18th centuries through trading ships. The flavivirus that causes yellow fever was first identified in 1928 and the first vaccine against the disease was produced at the Rockefeller Institute in New York in 1937.

In order to understand how yellow fever is passed, several terms need to be defined. The word "host" refers to an animal that can be infected with a particular disease. The term "vector" refers to an organism which can carry a particular disease-causing agent (such as a virus or bacteria) without actually developing the disease. The vector can then pass the virus or bacterium on to a new host.

Many of the common illnesses in the United States (including the common cold, many viral causes of diarrhea, and influenza or "flu") are spread via direct passage of the causative virus between human beings. Yellow fever, however, cannot be passed directly from one infected human being to another. Instead, the virus responsible for yellow fever requires an intermediate vector, a mosquito, which carries the virus from one host to another.

The hosts of yellow fever include both humans and monkeys. The cycle of yellow fever transmission occurs as follows: an infected monkey is bitten by a tree-hole breeding mosquito. This mosquito acquires the virus, and can pass the virus on 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 a human is bitten by an infected mosquito, however, 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 may also 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 as of 2004. The last reported case in an American citizen concerned a man who contracted yellow fever in Brazil in 1996. The last epidemic in the United States occurred in New Orleans in 1905.

Once a mosquito has passed the yellow fever virus to a human, the chance of disease developing is about 5-20%. 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.

The period of invasion lasts two to five days, and begins with an abrupt onset of symptoms, including fever and chills, intense headache and lower backache, muscle aches, nausea, and extreme exhaustion. The patient's tongue shows a characteristic white, furry coating in the center, surrounded by a swollen, reddened margin. While most other infections that cause a high fever also cause an increased heart rate, yellow fever results in an unusual finding, called Faget's sign. This is the simultaneous occurrence of a high fever with a slowed heart rate. Throughout the period of invasion, there are still live viruses circulating in the patient's blood stream. Therefore, a mosquito can bite the ill patient, acquire the virus, and continue passing it on to others.

The next phase is called 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 proves only to be 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. Further, infection with the yellow fever virus results in lifelong immunity against repeated infection with the virus.

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

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 which are directed against the yellow fever virus). The most rapid method of diagnosis as of 2004 is capture enzyme immunoassay. The diagnosis can be strongly suspected when Faget's sign is present. When the classic triad of symptoms is noted yellow fever is strongly suspected.

There are no antiviral treatments available as of 2004 to combat the yellow fever virus, although researchers at the University of Texas are studying ribavirin (Virazole, Rebetol), a drug that is given by mouth to treat hepatitis C, as a potential treatment for liver damage caused by yellow fever. 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 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).

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. Twenty to fifty percent of these patients die of the infection. Death may occur due to massive bleeding (hemorrhage), often following a lapse into a comatose state.

A very safe and very effective yellow fever vaccine exists. The Arilvax vaccine is made from a live attenuated 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 in which humans are working, along with programs to vaccinate all people living in such areas, are necessary to avoid massive yellow fever outbreaks.

Persons planning to travel to countries where yellow fever in endemic may obtain up-to-date information on yellow fever vaccination from the Centers for Disease Control and Prevention by telephone (404-332-4559) or fax (404-332-4265).

Beers, Mark H., MD, and Robert Berkow, MD., editors. "Viral Diseases." Section 13, Chapter 162 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2002.

Barrett, A. D. "Current Status of the Arilvax Yellow Fever Vaccine." Expert Review of Vaccines 3 (August 2004): 413-420.

Lo Re, V., III, and S. J. Gluckman. "Travel Immunizations." American Family Physician 70 (July 1, 2004): 89-99.

Reeder, G. David, MD, and Theodore E. Woodward, MD. "Yellow Fever." eMedicine February 25, 2002. http://www.emedicine.com/med/topic2432.htm.

Sbrana, E., S. Y. Xiao, H. Guzman, et al. "Efficacy of Post-Exposure Treatment of Yellow Fever with Ribavirin in a Hamster Model of the Disease." American Journal of Tropical Medicine and Hygiene 71 (September 2004): 306-312.

Centers for Disease Control and Prevention (CDC). 1600 Clifton Rd., NE, Atlanta, GA 30333. (800) 311-3435, (404) 639-3311. http://www.cdc.gov.

Infectious Diseases Society of America (IDSA). 66 Canal Center Plaza, Suite 600, Alexandria, VA 22314. (703) 299-0200. Fax: (703) 299-0204. http://www.idsociety.org.

World Health Organization (WHO). http://www.who.int/en/.

World Health Organization Fact Sheet. "Flooding and Communicable Diseases Fact Sheet: Risk Assessment and Preventive Measures." December 2004. http://www.who.int/hac/techguidance/ems/flood_cds/en/index.html.

1. the color produced by stimulation by light waves of wavelength of 571.5 to 578.5 mμ.

2. a color between orange and green, produced by energy of wavelengths between 570 and 590 nm.

3. a dye or stain with this color.

yellow fever an acute infectious type of hemorrhagic fever, transmitted by the female of certain species of mosquitoes, and characterized by fever, jaundice due to necrosis of the liver, and albuminuria. It is less rampant today than previously, largely because of vaccination and better control of the mosquitoes, but it is still a danger in most tropical countries. Among native inhabitants who contract the disease there is a mortality rate of about 5 per cent. In visitors from other climates, fatalities once ran as high as 40 per cent but are now much lower. With proper immunization precautions, a visitor from a temperate country today takes only a minimal risk.



The mosquito that transmits classic yellow fever is Aedes aegypti. In the jungles of Brazil and in parts of Africa, in the absence of Aedes aegypti, the disease may be carried by a different mosquito species that lives in treetops. These forest mosquitoes can communicate the disease to forest workers and also to certain animals, such as monkeys and marmosets, which then serve as virus reservoirs and as sources of reinfection for humans. This form of the disease is called jungle or sylvan yellow fever, and it is difficult to control because of the virtual impossibility of eradicating the tree-inhabiting mosquitoes.

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