Yellow Fever

Introduction

Disease History, Characteristics, and Transmission

Impacts and Issues

Primary Source Connection

BIBLIOGRAPHY

Introduction

Yellow fever is an acute viral disease that is spread by mosquitoes and occurs in Africa and South America. Although a vaccine is available to prevent the disease, the incidence of yellow fever is growing, especially in South America. In this article, the virologist Jack Woodall discusses yellow fever and relates his first-hand experience in studying the disease. Woodall is the director of the Nucleus for the Investigation of Emerging Infectious Diseases at the Federal University of Rio de Janeiro in Brazil.

Disease History, Characteristics, and Transmission

From the seventeenth to the beginning of the twentieth century, the major ports of the United States suffered from periodic epidemics of yellow fever. New York was afflicted in 1668, Boston in 1691, and Philadelphia in 1793, where one in ten of its inhabitants died. Work on digging the Panama Canal was stalled because of the huge toll of yellow fever and malaria on the workers. The U.S. Army decided to do something about this. It set up a Yellow Fever Commission in Cuba, which was having an epidemic, and was at the time under U.S. control.

Jesse Lazear was a handsome young U.S. Army physician with a Vandyke beard, stationed in Baltimore at the start of the twentieth century. He and a colleague joined the Commission, and both volunteered to test a new theory, that the disease was transmitted by mosquitoes. They allowed themselves to be bitten by local mosquitoes; both came down with yellow fever, but only one survived; Jesse died of it.

Other soldiers, whose names have not gone down in history, volunteered to sleep in the sheets stained by the blood and vomit of yellow fever victims. Those who did so in mosquito-proofed huts did not get the disease, whereas others sleeping in clean sheets, but without mosquito netting became ill and some died. So without even knowing that yellow fever was caused by a virus, a control program could be put in place. U.S. Army General William C. Gorgas, who had himself survived yellow fever he caught in Texas, implemented mosquito control, and eradicated yellow fever from Havana, Cuba, and the Brazilian ports of Rio de Janeiro and Santos, and the Panama Canal was completed.

Before the isolation of the yellow fever virus, no vaccine could be made, and before the advent of the vaccine, yellow fever research was a hazardous undertaking. The International Health Division of the Rockefeller Foundation established yellow fever research laboratories in East and West Africa and South America to try to delimit the areas endemic (areas where the disease naturally occurs) for the disease. Six of their scientists died of yellow fever.

There are some basic things you need to know about yellow fever. First, it is the classic viral hemorrhagic fever, with sudden onset of fever, chills, headache, backache, nausea and vomiting, causing damage to the liver, kidneys and heart, and hemorrhage, with a death rate of 20–50 percent in severe cases. The liver damage produces the yellow jaundice that gives the disease its name. It is endemic in the jungles of Africa and South America, but every so often breaks out in the cities, especially in West Africa, for example in Nigeria between 1986 and 1991. The World Health Organization estimates that it still causes around 200 thousand cases with 30 thousand deaths every year.

Second, as it is a virus disease, antibiotics have no effect on it. The antiviral drug ribavirin, given within the first five days of infection, improved survival in hamsters, so might do the same for humans. Otherwise, there is only supportive treatment, and you either recover or you don't. Laboratory diagnosis is done by isolation of the virus in tissue culture from blood taken within the first five days of illness; this test takes a few days to produce a result. Rapid tests for specific components of the virus in blood samples take only hours. If these tests fail, diagnosis can still be made by finding specific antibodies in the serum later in the course of the illness. In Brazil in the days before these tests were available, a small block of tissue was removed from the liver of a victim's corpse using a steel punch to pierce the abdomen. The specimen was placed in formalin to preserve it and examined at the lab, often after days of canoe travel down the Amazon, under the microscope for characteristic stained spots inside the cells called Councilman bodies. Nowadays, we know that some other jungle viruses also produce Councilman bodies, but certainly in the majority of cases their presence proved that the victim had died of yellow fever.

Following the example of General Gorgas, other great public health figures such as Fred Soper of the Rockefeller Foundation, Cuba's Carlos Finlay and Brazil's Oswaldo Cruz spread the gospel, and by the end of 1924 yellow fever had been eradicated from the cities of Mexico, Central America, and Ecuador. In fact, there was hope that it could be eradicated from the Americas altogether, until researchers made the unwelcome discovery of an outbreak in a rural area of Brazil where the urban vector mosquito, Aedes aegypti, did not exist. The virus was cycling between monkeys and tree-top mosquito species, and infecting people who ventured into the forest to hunt, collect timber, or cut it down to make plantations.

This discovery ended the hope of continent-wide eradication. Even if you could kill every monkey in the jungle—and who would want to do that?—the virus would survive because it has been found that it is passed down by mosquitoes through their eggs, generation after generation. Some people have dreamed of replacing the vector (transmitter) mosquitoes in nature with the same species genetically engineered to be resistant to the virus, but the probability that this could be done is around zero. So in rural areas, yellow fever only gets into a human by accident, when an infected mosquito mistakes him for a monkey. But when it does, he goes back to his hut, runs a fever, and infects the Aedes aegypti there. After a few days incubation, the infected mosquitoes then transmit yellow fever to his family and neighbors.

The next thing that happens is that one of the people who falls ill in the village seeks hospital care in the nearest town. There he infects the local A. aegypti and starts an urban epidemic. Infected townspeople in turn carry the yellow fever to the country's capital and major ports. In the days of sailing ships, fresh water was carried on deck in open barrels, in which the mosquito bred. Passengers and crew coming on board after having been bitten by infected mosquitoes ashore would fall ill at sea, and the water-barrel mosquitoes would start an epidemic that would continue until the ship reached the U.S., Canada (Halifax in 1861), even Europe—Spain, France, England and Italy in the 1800s. There, it would be taken ashore by disembarking passengers, crew and mosquitoes, to start an epidemic.

The last outbreak of yellow fever in the United States was in 1905, when New Orleans and other Southern ports were affected. But since the demise of sailing ships, the last urban yellow fever epidemic in the western hemisphere occurred in Trinidad, West Indies, in 1954, unless you count some more recent cases on the outskirts of the town of Santa Cruz, Bolivia, which could actually have been contracted in the countryside.

A puzzling question is, why has yellow fever never spread to Asia? Its cities are full of dengue, which is carried there by the same mosquito species as in Africa and the Americas, and their jungles and temples are full of monkeys that are highly susceptible to it—the virus was first isolated by injecting the blood of a sick African into an Asian rhesus macaque. Passengers incubating the disease have jetted home from the jungles of Africa or South America to fall ill in the USA and Europe, where fortunately they did not spread the disease—but the same could occur with passengers to India or China; what a mess that would create. There is not enough vaccine in the world to cope with a wide-spread epidemic in either of those countries.

Explanations for Asia's exemption are not convincing. There is a theory that immunity against dengue, which is endemic in Asia, and related viruses, cross-protects against yellow fever. But there is plenty of dengue and related viruses in South America and Africa, and it doesn't seem to cross-protecton those continents. It was thought that the Asian strains of A. aegypti might not be as efficient in carrying the virus, but lab experiments have proved that they are.

So, yellow fever cannot be eradicated, and there is no cure. Fortunately, there is a vaccine, possibly the most successful vaccine ever developed; one painless shot and you are protected for life, although it is best to get a booster every ten years. I was privileged to know the vaccine's developer, Max Theiler, a long-faced South African with bruised-looking eyes who worked at the Rockefeller Foundation Virus Laboratory on New York City's Upper East Side, and was an ardent baseball fan. He passed the yellow fever virus through lab animals and then embryonated chicken eggs until it lost the ability to attack the nervous system. The attenuated strain, code-named 17D, was field-tested in Brazil in 1937, and had since protected many millions of people, saving countless lives. It won him the Nobel Prize many years later. The French also developed a vaccine in the brains of mice, which had side effects, but did protect millions in their West African colonies. Theiler's 17D vaccine or derivatives are now routinely incorporated in the childhood vaccination schedule of many endemic countries.

Impacts and Issues

Where are we now, at the start of a new century? The big cities of Brazil suffer dengue outbreaks every year, which as mentioned above is spread by the same mosquito that carries yellow fever. Mosquito control has not been successful, since it is not pursued as rigorously as in the days of Oswaldo Cruz, 100 years earlier.

Since the A. aegypti mosquito breeds in domestic and peridomestic containers holding water—water jars, rain-water barrels, drums, discarded tires, cans and plastic containers, drinking vessels for domestic animals, flower vases—getting rid of those should be easy. All you have to do is to throw out those that you can, empty out the water from those you cannot, or change the water in your pet's dish and flower vases every three days, before any mosquito larvae in there can turn into adults. But in places where trash collection is intermittent or non-existent, and the public is apathetic, this just doesn't happen. People like to see trucks and sanitary agents going through the streets with insecticide fogging machines, but all that does is knock out that day's mosquitoes—plenty more will hatch tomorrow.

At the end of 1999, hundreds of Brazilian tourists went to celebrate the New Year at a popular resort at the edge of the jungle called Chapada de Veadeiros. Not all had been vaccinated against yellow fever. Some were bitten by infected jungle mosquitoes and returned home only to be hospitalized with the disease in the major cities of Rio de Janeiro, Sao Paulo, Brasilia, and Goiania. By some miracle, there was no epidemic, but we might not be so lucky next time.

So even if you have no plans to travel outside the cities of countries in the yellow fever belts of Africa or South America, it is prudent to get vaccinated, no matter what it costs. The only exceptions would be infants less than nine months old, pregnant women, those with egg allergy (since the vaccine is made in eggs), and people who are immunosuppressed for any reason (for example, those undergoing cancer therapy or organ transplants, carriers of HIV). Also if you are over 65 you should consult your doctor before getting the shot, because you are at higher risk of rare side effects of the vaccine. He or she will probably tell you not to have it if you promise to stay in the cities, and if an epidemic breaks out to come straight home, where, if you should get a fever within two weeks of returning, you should inform your doctor that you may have been exposed to yellow fever.

But I really worry about Asia.

WORDS TO KNOW

ATTENUATED STRAIN: A bacterium or virus that has been weakened, often used as the basis of a vaccine against the specific disease caused by the bacterium or virus.

ENDEMIC: Present in a particular area or among a particular group of people.

HEMORRHAGIC FEVER: A hemorrhagic fever is caused by viral infection and features a high fever and a high volume of (copious) bleeding. The bleeding is caused by the formation of tiny blood clots throughout the bloodstream. These blood clots—also called microthrombi—deplete platelets and fibrinogen in the bloodstream. When bleeding begins, the factors needed for the clotting of the blood are scarce. Thus, uncontrolled bleeding (hemorrhage) ensues.

VECTOR: Any agent, living or otherwise, that carries and transmits parasites and diseases. Also, an organism or chemical used to transport a gene into a new host cell.

Primary Source Connection

Dr. Carlos Finlay began studying yellow fever in the 1870s and in 1881 was the first to assert that the Aedes mosquito was the vector of disease for yellow fever. Finlay's research was largely ignored for decades until a team of United States researchers posited a substantially similar theory in 1900. The following article from the New York Times discusses the scientific community's belated recognition of Finlay's contributions to yellow fever research.

Dr. Finlay Gets Full Credit Now

HAVANA PHYSICIAN WHO SOLVED THE YELLOW FEVER PROBLEM IS EXTOLLED HERE AND ABROAD

Said Mosquitos Carried It

And Allowed a Contaminated Insect to Sting Him to Prove It—Theory Ridiculed at First Reversing the usual order of things, scientists are determined that the rest of the world shall recognize in his lifetime the inestimable boon that Dr. Charles (or Carlos) J. Finlay of Havana conferred upon mankind when he formed the correct idea of how yellow fever is transmitted, proved his theory by self-inoculation, and forced it upon enlightened physicians and sanitarians after it had been rejected by contemporaries who regarded him as a nuisance.

Thousands of physicians who are well acquainted with the experiments of Reed, Carroll, and Lazear, who lost their lives in yellow fever investigations, never heard of Finlay. And yet he was their inspiration, and his experiments antedated theirs by a score of years. They succumbed, willing martyrs to the great cause; but he still lives and labors, revered by those working in the higher plains of science, regarded with something akin to awe by those who hear of him casually for the first time, and now, it seems, about to receive full credit, belated though it is, from the wide world.

It is now just thirty years and two weeks since Dr. Finlay read a paper before the Royal Academy of Havana, in which he propounded the novel theory that yellow fever was propagated by through the agency of mosquitos. And it is just six weeks ago that a physician in Edinburgh, commenting on Dr. Finlay and his discover, in the course of a letter wrote:

“Considering the times, it will eventually be considered one of the most wonderful pieces of constructive work in the history of medicine, but, like every other advance, it was rejected by contemporaries. Unlike nearly all other great medical discoverers, however, he has lived to see the acceptance of his facts and has not had to die of a broken heart; but it has been enough to break any one's heart to see himself so utterly ignored while the world has been singing the praises of the men upon whom he forced his ideas.”

Further along the same physician writes:

“No doubt Reed himself, if alive, would blush at the methods used, and would continue to insist upon giving Finlay full credit for the great conception. Too high praise cannot be given also to Lazear and Carroll for their bravery, but Finlay did the self-same inoculation twenty years earlier. Finlay, indeed, used these Americans as one would a tool, and he had to force them, for they, too, laughed at him.

“It seems to me that the credit for initiating the experiments confirming Finlay's discovery is due to Leonard Wood, who, as Governor, forced the matter along in the very city where Spanish generals had positively prohibited such work.”

History of the Discovery The Medical Record, which has all the facts in its possession, has undertaken to establish the brilliant work of Dr. Finlay in such a manner that all may know of it. The editor has written an article embodying the history of the discovery. After relating that Dr. Finlay's theory, was received with incredulity and more or less good-natured ridicule, he says;

“Nothing daunted, however, with true grit he continued his observations on the remarkable coincidence between the prevalence of yellow fever and the temporary increase in the number of mosquitos—studied the anatomy, the manner of breeding, and the habits of the mosquitos, and also continued his inoculation experiments. These were begun in July, 1881, at which time he obtained a well-marked attack of yellow fever following a bite by a contaminated mosquito.

“In a paper published in The American Journal of the Medical Sciences in October, 1886, Finlay describes the mosquito which he regarded as the agent in the spread of yellow fever. It had a dark-colored body with ventral surface coated thick skin and marked with gray or white rings; on each side of the abdomen was a double row of white spots; its most striking feature was five white rings on the hind legs, present but less marked on the anterior and middle legs; white spots were visible on the side of the thorax and front of the head, while the corselet presented a combination of white lines in the figure of a two-stringed lyre; the wings when closed did not cover the body.”

Dr. Finlay made further close observations of this mosquito, which is now known to science as Stegomyia calopus (the yellow-fever mosquito,) finding that it did its flying and biting between between 9 and 10 o'clock in the morning.

“In the same article,” continues the writer, “Finlay argues with much acuteness in support of his theory, and he concludes with the passage, which we quote at length, since it sets forth so clearly the views as to the spread of yellow fever that are universally held to-day.

Dr. Finlay's Argument “From the evidence adduced in the preceding pages,’ he writes, ‘I conclude that while yellow fever is incapable of propagation by its own unaided efforts, it might be artificially communicated by inoculation, and only becomes epidemic when such inoculation can be verified by some external natural agent, such as the mosquito’”.

“The history and etiology of yellow fever exclude from our consideration as possibly agents of transmission other blood-sucking insects such as fleas &c., the habits and geographical distribution of which in no wise agree with the course of that disease; whereas a careful study of the habits and a natural history of the mosquito shows a remarkable agreement with the circumstances that favor or impede the transmission of yellow fever.”

“So far as my information goes this disease appears incapable of propagation wherever tropical do not or are not likely to exist, ceasing to be epidemic at the time limits of temperature and altitude which are incompatible with the functional activity of these insects; while, on the other hand, it spreads readily wherever they abound. From these considerations, taken in connection with my successful attempts in producing experimental yellow fever by means of the mosquito's sting, it is to be inferred that these insects are the habitual agents of transmission.”

In an article running through several numbers of The Edinburgh Medical Journal in 1894, Dr. Finlay again set forth his mosquito theory, and once more in The Medical Record, on May 27, 1899, before the United States Army Commission had proved its correctness in such a manner that there could be no denial. In the latter article he asks:

“Why should not the houses in yellow fever countries be provided with mosquito blinds, such as are used in the United States as a matter of comfort, while here it might be a question of life or death?”

He next went on to tell how the larvae might be destroyed and the mosquitos exterminated, and described ideal sanitary measures and hospital construction. In brief, he foreshadowed conditions which afterward became realities and converted hot-beds of yellow fever into delightful health resorts.

“There can be not doubt that yellow fever might be stamped out from Cuba and Puerto Rico,” he said, “and malaria reduced to a minimum. It would then be the business of the port and quarantine officers to prevent the introduction of fresh germs.”

His Dreams Realized “When the United States Army occupied Havana,” the writer continues, “Finlay saw his opportunity, and went to the sanitary authorities with his mosquito and his theory, and urged them to investigate the subject and prove the theory which he knew to be a fact. He was received with polite toleration, but without great enthusiasm. He persisted, nevertheless, in season and out of season, and in fact made such a nuisance of himself that an investigation was finally decided upon, his confidence arousing a suspicion that he might, after all, be on the right track.

“The results of this investigation are well known. Major Reed and his associates, Agramonte, Carroll, and Lazear, took Finlay's mosquito and his data and by a series of experiments, the equal of any in the annals of scientific investigation, established beyond cavil the mosquito doctrine of yellow fever transmission.

“Some of his views were found to be erroneous, which is not surprising when one considers the disadvantages under which he labored single-handed, but his basic idea was found to be absolutely correct. Making a practical application of this doctrine and perfecting the measures outlines by Finlay in his Medical Record article, the genius of Gorgas converted the two notorious pestholes, Havana and Panama, into health resorts.

“This is all ancient history, but for that very reason it is in danger of being forgotten. Even such a master of medical history as Osler forgot it in an address on the transmission of disease through the agency of blood-sucking insects, which he delivered before the London School of Tropical Medicine last Spring. In this address he omitted all mention of Finlay's work, and only when he was reminded of it by a letter from Guiteras of Havana in The Lancet did her apparently recall the great part which this pioneer has taken in the establishment of the mosquito doctrine.”

Dr. Finlay was born in Cuba and has devoted his life to the inhabitants of that island, although his work has extended to a wide sphere, but the Scotch really claim and are justly proud of him and his achievements.

“DR. FINLAY GETS FULL CREDIT NOW: HAVANA PHYSICIAN WHO SOLVED THE YELLOW FEVER PROBLEM IS EXTOLLED HERE AND ABROAD,” NEW YORK TIMES, SEPTEMBER 3, 1911.

See AlsoArthropod-borne Disease; Hemorrhagic Fevers; Host and Vector; Tropical Infectious Diseases.

BIBLIOGRAPHY

Books

Dickerson, James L. Yellow Fever: A Deadly Disease Poised to Kill Again. New York: Prometheus, 2006.

Periodicals

Woodall, Jack. “Why Mosquitoes Trump Birds.” The Scientist. (January 2006).

Web Sites

Centers for Disease Control and Prevention (CDC). “Yellow Fever - Disease and Vaccine.” <http://www.cdc.gov/ncidod/dvbid/yellowfever/index.htm> (accessed June 13, 2007).

World Health Organization. “Togo: Yellow Fever Vaccination Campaign Protects 1.3 Million People.” <http://www.who.int/features/2007/yellow_fever/en/index.html> (accessed June 13, 2007).

Jack Woodall

Yellow Fever

Definition

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.

Description

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.

WILBUR AUGUSTUS SAWYER (1879–1951)

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 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 of poliomyelitis. His discovery, in 1915, that examination of the 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 would ultimately return to the United States, where he and Wray Lloyd would devise 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 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.

Symptoms

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

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.

Treatment

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).

Prognosis

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.

Prevention

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).

KEY TERMS

Epidemic— A situation in which a particular disease spreads rapidly 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.

Host— The organism (such as a monkey or human) in which another organism (such as a virus or bacteria) is living.

Sylvatic— 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.

Vector— A carrier organism (such as a fly or mosquito) which serves to deliver a virus (or other agent of infection) to a host.

Resources

BOOKS

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.

PERIODICALS

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.

ORGANIZATIONS

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/〉.

OTHER

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〉.

Yellow Fever and Malaria

Sources

Dreaded Diseases . Yellow fever and malaria, two of the most feared diseases of the period, were often confused. Their symptoms—chills, aches, and high fever—are similar, and they tended to appear in hot weather. Neither is contagious—one person cannot catch it directly from another person—and both are transmitted by mosquitoes. In the late eighteenth century no one knew what caused these diseases; some thought there was a connection with swamp air or with summer heat. Yellow fever attacks the liver, producing the jaundice that makes the skin turn yellow, while with malaria, parasites build up rapidly in the liver, and the overworked spleen becomes enlarged as it tries to filter the parasites out. In severe cases blood vessels to the brain are blocked, causing delirium, coma, and death. The two diseases were apt to strike differently: yellow fever broke out in frightening epidemics, sometimes as far north as Philadelphia and New York City; malaria was a constant menace in hot, swampy areas of the Southeast, especially South Carolina and Georgia.

Philadelphia . The worst outbreak of yellow fever in America occurred in Philadelphia during the summer and fall of 1793. There were an estimated five thousand fatalities out of a population of forty-five thousand. A victim’s first symptoms were high fever and headache, followed a day or two later by severe vomiting of blood as the internal organs degenerated. Death often occurred within four days to a week after contracting the disease. People were so afraid of catching the disease that they avoided contact even with their friends and stopped shaking hands. Relatives were afraid to bury the victims, and a familiar sight was the death cart passing by and the cry of the grave diggers: “Bring out your dead!”

Causes. Even experienced doctors who recognized the symptoms were ignorant of the cause, although there were plenty of theories. The best-known physician of the day, Benjamin Rush, believed that the contagion may have resulted from a shipment of coffee that was rotting on a Philadelphia wharf. It was also thought possible that the air itself carried the disease. Crews on ships in the harbor were advised to burn tobacco in the hope that its smoke would cleanse the air somehow. Others, convinced it was God punishing a sinful population, noted with some satisfaction that many of the victims were from the poor sections of town, and of course the poor were more wicked than the rich. And while it was true that the poor were afflicted more than the wealthy, it was because of unsanitary conditions in their neighborhoods—stagnant water and open sewage that drew mosquitoes—and not the wrath of God. But the disease attacked the rich as well, especially those brave enough to stay in the city rather than flee to the countryside. As the rich fled, there were other kinds of victims: shops and businesses had to close, leaving thousands out of work.

Prevention and Cure . Once the epidemic had struck, health officials tried to keep the contagion from getting worse by burning tobacco to clean the air and by recommending public prayer and fasting. People tried mud baths or garlic to prevent the disease from striking. Doctors would try anything to save their patients. The most common “cure” was to administer mercury pills and extract large volumes of blood. Bleeding was the fashionable theory of the day: if enough blood were removed, it was believed, the disease would have nothing to attack. One can only imagine how many lives would have been saved if the patient had simply been left alone. Although emergency hospitals were set up, it was difficult to find people brave enough to staff them, and in any case victims had no desire to go to a hospital to die.

Government Shutdown . Philadelphia’s municipal government practically disintegrated during the epidemic. Only the work of an unofficial committee of public-spirited citizens, acting as a combined government and board of health, prevented total chaos. The U.S. capital was then at Philadelphia. It was common practice at the time to partially shut down the government during the hot summer months, so it was not unusual that President George Washington left for Mount Vernon. Secretary of State Thomas Jefferson, remaining calm in the midst of all the panic, tried to stay on, but found that his staff had evacuated the city, so he too went home to Virginia. Secretary of the Treasury Alexander Hamilton also went home, but not before contracting a mild case. As the time approached for the government officials to return, many feared for their lives. Washington decided to move the capital to Germantown, which became the temporary seat of government until November. By December the crisis had passed, and Congress was able to reconvene in Philadelphia.

Lessons Learned . Since there was no fundamental understanding of the cause of yellow fever, not many lessons emerged, although Benjamin Rush’s critics now had more examples of the ill effects of his practice of excessive bleeding. When the disease struck Philadelphia again, mildly in 1795 and 1796 and violently in 1797, the same inadequate measures were taken. Dr. Rush did, however, correctly point out that poor sanitation appeared to be a contributing factor, and his efforts to clean up Philadelphia finally resulted in the development of a public water system. It would be years before people trusted the public health conditions in Philadelphia, and more than a century before Walter Reed would prove that the female Aedes aegypti mosquito was the carrier.

Malaria . While yellow fever also reached epidemic levels in southern cities, it was malaria that was the most prevalent killer in the South. Malaria —the word comes from mala aria, an Italian phrase for “bad air”—had been a problem in the warm, wet Southeast coastal regions of America since early colonial days. Many early settlers from Europe, with no defenses against malaria, suffered and died from what they called “fever and ague.” South Carolinians were particularly susceptible to malaria because rice plants, for which large tracts of land had been cleared, grew best in shallow pools of standing water, which also formed breeding grounds for mosquitoes. Of course, at the time the mosquito was considered merely a pest, not a carrier of deadly disease.

Remedies . Although malaria’s cause was unknown, it was often treated differently from yellow fever. First of all, malaria was not always life threatening, so measures such as bleeding were not considered necessary. Fevers were intermittent, and chronic fatigue was often the most debilitating effect. Second, it had been recognized from early colonial times that cinchona bark (from a South American tree) was effective in reducing the symptoms of malaria. We now know that it worked because it contains a substance similar to quinine.

Rich Versus Poor . Unlike yellow fever, which was likely to strike in the crowded cities, malaria was prevalent in the low-lying countryside (it was often called “country fever”). The wealthy landowners simply left during the hot season; in fact, some of South Carolina’s richest families spent the summer in Newport, Rhode Island. That left the poor and slaves to labor in the intensely hot and mosquito-infested rice fields. It was generally believed that African slaves were not only better able than whites to endure the intense heat of southern summers, but were also resistant to malaria. Medical studies have since proved that black Africans were, in fact, partially immune, having come from areas where malaria was prevalent, and having built up antibodies, which were not genetic, but passed from mother to child during pregnancy. This immunity is curiously tied to sickle-cell anemia, a condition that causes blood circulation problems in black children, yet helps ward off malaria. The tragic social consequence was the belief in a “natural” law that blacks’ immunity to malaria justified their slavery to work the plantations of the South while the white owners spent the hot months in safer regions. Like yellow fever, malaria was eventually reduced through improved public sanitation, quarantine of ships coming from infected regions, and (after 1900) control of mosquitoes.

Sources

Dumas Malone, Jefferson and the Ordeal of Liberty (Boston: Little, Brown, 1962);

Page Smith, The Shaping of America (New York: McGraw-Hill, 1980);

Peter H. Wood, Black Majority (New York: Norton, 1974).

Yellow Fever

What Is Yellow Fever?

Are There Different Kinds of Yellow Fever?

How Do People Know They Have Yellow Fever?

How Do Doctors Diagnose and Treat Yellow Fever?

How Can Yellow Fever Be Prevented?

Resources

Yellow fever is an infectious disease caused by a virus that is transmitted to humans by mosquitoes.

KEYWORDS

for searching the Internet and other reference sources

Aedes aegypti mosquito

Epidemic

Flavivirus

Mosquito-borne disease

Viral hemorrhagic fevers

What Is Yellow Fever?

Yellow fever is a disease caused by yellow fever virus, a member of the flavivirus (FLAY-vih-vy-rus) group of viruses. The disease gets its name because it often causes jaundice*, which tints the skin yellow, and a high fever. Yellow fever also can cause kidney failure and uncontrolled bleeding, or hemorrhaging (HEM-rij-ing). Many cases produce only mild illness, but severe cases of yellow fever can be fatal. Once someone has survived the disease, the person will have lifetime immunity* against it.

*jaundice

(JON-dis) is a yellowing of the skin, and sometimes the whites of the eyes, caused by a buildup in the body of bilirubin, a chemical produced in and released by the liver. An increase in bilirubin may indicate disease of the liver or certain blood disorders.

*immunity

(ih-MYOON-uh-tee) is the condition of being protected against an infectious disease. Immunity often develops after a germ is introduced to the body. One type of immunity occurs when the body makes special protein molecules called antibodies to fight the disease-causing germ. The next time that germ enters the body, the antibodies quickly attack it, usually preventing the germ from causing disease.

Yellow fever afflicts both humans and monkeys and has been known since at least the 1600s. The disease is not spread by person-to-person contact. It is transmitted by several different species of mosquitoes; a person can contract yellow fever only from the bite of a mosquito that has bitten an infected person or monkey.

The disease once caused epidemics in the Americas, Europe, and the Caribbean, but at the beginning of the twenty-first century the disease occurs almost exclusively in South America and Africa. Each year, outbreaks lead to an estimated 200,000 cases and 30,000 deaths worldwide. Vaccines against the virus were developed in 1928 and 1937, and mosquito-eradication programs have made great progress in controlling the disease. The last recorded outbreak of yellow fever in the United States was in New Orleans in 1905. However, lapses in prevention programs in Africa and South America have allowed yellow fever to once again become a serious public health issue on those continents.

Are There Different Kinds of Yellow Fever?

Yellow fever occurs as three subtypes: epidemic (urban), intermediate, and jungle-acquired. Epidemic yellow fever spreads in densely populated areas of Africa and South America via the bite of Aedes aegypti (a-E-deez eh-JIP-tie) mosquitoes. Intermediate yellow fever occurs in Africa as the result of mosquitoes breeding in humid flat grasslands (savannahs) during rainy seasons, then infecting both monkeys and humans. In dry seasons, the virus can remain alive in unhatched mosquito eggs that are resistant to the heat.

Jungle-acquired yellow fever occurs mainly in South America when mosquitoes pick up the virus from infected forest monkeys and then transmit the disease to humans in jungles and rainforests. People who are regional settlers, soldiers, or agricultural or forestry workers are at greatest risk for this less common form of the disease.

How Do People Know They Have Yellow Fever?

After an incubation* period of 3 to 6 days, the yellow fever virus begins to produce symptoms. An early phase of disease occurs, which includes fever, headache, muscle aches, and vomiting. The infected person may have a slower heartbeat than that expected with a high fever. After a few days, most of the symptoms disappear. Many people recover from yellow fever at this point without complications. However, about 15 percent of patients develop a second, toxic phase of the disease, in which fever reappears and the disease becomes more severe. Inflammation of the liver occurs, along with jaundice, stomach pains, and vomiting. The mouth, nose, eyes, and stomach can bleed uncontrollably, with blood present in vomited material and bowel movements. The kidneys may begin to fail, and patients may go into a coma (an unconscious state in which a person cannot be awakened).

*incubation

(ing-kyoo-BAY-shun) is the period of time between infection by a germ and when symptoms first appear. Depending on the germ, this period can be from hours to months.

How Do Doctors Diagnose and Treat Yellow Fever?

Early stages of yellow fever can be easily confused with other diseases such as malaria*, typhoid fever*, and other hemorrhagic (heh-muh-RAH-jik) fevers and types of viral hepatitis*. Blood tests can detect whether a patient’s body has produced yellow fever antibodies* to fight the infection. Doctors also will take a travel history to see if a patient recently has visited a country where yellow fever occurs.

*malaria

(mah-LAIR-e-uh) is a disease spread to humans by the bite of an infected mosquito.

*typhoid fever

(TIE-foyd FEE-ver) is an infection with the bacterium Salmonella typhi that causes fever, headache, confusion, and muscle aches.

*hepatitis

(heh-puh-TIE-tis) is an inflammation of the liver. Hepatitis can be caused by viruses, bacteria, and a number of other noninfectious medical conditions.

*antibodies

(AN-tih-bah-deez) are protein molecules produced by the body’s immune system to help fight specific infections caused by microorganisms, such as bacteria and viruses.

No specific treatment exists for yellow fever. Care is geared toward treating complications of the disease. In serious cases, intensive care in the hospital usually is needed. Patients may be given fluids to prevent dehydration*, and blood transfusions* may be necessary if bleeding is severe.

*dehydration

(dee-hi-DRAY-shun) is a condition in which the body is depleted of water, usually caused by excessive and unre-placed loss of body fluids, such as through sweating, vomiting, or diarrhea.

*transfusions

(trans-FYOO-zhunz) are procedures in which blood or certain parts of blood, such as specific cells, are given to a person who needs them because of illness or blood loss.

Most people who contract yellow fever recover from the early phase of the disease within a week; those who progress to the toxic phase may take several weeks or longer to recover. About half of those who develop toxic phase symptoms die within 2 weeks; the other half may recover without significant long-term problems.

How Can Yellow Fever Be Prevented?

Vaccination against yellow fever is the single most important prevention measure, and it is a must for people traveling to countries where the disease is common. Most countries in which yellow fever occurs require a certificate proving that travelers have been vaccinated before they are allowed into the country. One dose of vaccine provides at least 10 years of immunity.

Doctors recommend that infants under 6 months of age, pregnant women, people allergic to eggs (eggs are used in producing the vaccine), and people with weakened immune systems (such as people who have AIDS* or certain cancers) not receive the vaccine; these people are advised to delay visits to countries where yellow fever is endemic*.

*AIDS ,

or acquired immunodeficiency (ih-myoo-no-dih-FIH-shen-see) syndrome, is an infection that severely weakens the immune system; it is caused by the human immunodeficiency virus (HIV).

*endemic

(en-DEH-mik) describes a disease or condition that is present in a population or geographic area at all times.

Avoiding mosquito bites when traveling abroad reduces the risk of contracting yellow fever. To help prevent infection, experts suggest that travelers:

• wear long sleeves and pants
• avoid going outside when mosquitoes are active—at dawn, dusk, and early evening
• use mosquito repellent
• sleep beneath a mosquito net

See also

Dengue Fever

Hepatitis, Infectious

Malaria

West Nile Fever

Resources

Organizations

U.S. Centers for Disease Control and Prevention (CDC), 1600 Clifton Road, Atlanta, GA 30333. The CDC is the U.S. government authority for information about infectious and other diseases, including yellow fever.

Telephone 800-311-3435 http://www.cdc.gov

World Health Organization (WHO), Avenue Appia 20, 1211 Geneva 27, Switzerland. WHO provides information about yellow fever at its website.

Telephone 011-41-22-791-2111 http://www.who.int

Yellow Fever

How yellow fever is spread

Clinical course of yellow fever

Diagnosis

Treatment

Prevention

Resources

Yellow fever is a severe illness that causes outbreaks of epidemic proportions throughout Africa and tropical America. The first written evidence of such an epidemic dates back to a 1648 outbreak in the Yucatan Peninsula in Mexico. Since that time, much has been learned about the interesting transmission patterns of this devastating illness.

How yellow fever is spread

Many of the common illnesses in the United States, including the common cold, diarrhea, and influenza, are spread via direct passage of the causative virus between human beings. Yellow fever, however, cannot be passed from one human being to another. Rather, the virus responsible for yellow fever is transmitted through 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 begins when an infected monkey is bitten by a tree-hole breeding mosquito. This mosquito acquires the virus, and can pass the virus to any number of other monkeys that it bites. When a human is bitten by such a mosquito, 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) servesasaviral vector, spreading the infection between humans.

The host-vector-host cycle of yellow fever was first described by Walter Reed (1851-1902), the military surgeon for whom the Walter Reed Medical Center in Washington, D.C., is named. Reed was commissioned by the United States government to study yellow fever transmission. Reed’s discovery of the mosquito as an intermediate vector led to improved control over the spread of the disease, ultimately allowing the building of the Panama Canal in an area prone to yellow fever epidemics.

Clinical course of yellow fever

Once a mosquito has transmitted the yellow fever virus to a human, the likelihood of symptomatic disease development is about 5-20%. Some infections may be warded off by the host’s immune system; others may be sub clinical, meaning they lack the severity of symptoms that would usually result in the identification of infection.

After a human host has received the yellow fever virus, there are five distinct stages through which a classic yellow fever infection evolves. These have been termed the periods of incubation, invasion, remission, intoxication, and convalescence.

The incubation period is the amount of time between the introduction of the virus into the host and the development of symptoms. For yellow fever this period 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; it begins with an abrupt onset of symptoms, consisting of fever and chills, intense headache, lower backache, muscle aches, nausea, and extreme exhaustion. The patient’s tongue shows a characteristic white furry coating in the center, surrounded by beefy red margins. While most other infections that cause an elevation in temperature also cause an increase in heartrate, yellow fever produces an unusual symptom, called Faget’s sign—the simultaneous occurrence of a high fever with a slowed heart rate. Throughout the period of invasion, there are still viruses circulating in the patient’s blood stream, so continued viral transmission through mosquito vectors is possible.

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

The period of intoxication is the most severe and potentially fatal phase of the illness. During this time, lasting three to nine days, a type of degeneration, or tissue breakdown, 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 release of protein into the urine. Jaundice causes the skin and the whites of the patient’s eyes to take on a distinctive yellow tint. This yellow color is due to liver damage, resulting in the accumulation of bilirubin 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 partially digested blood. Protein, which is normally kept out of the urine by healthy and intact kidneys, appears in the urine due to disruption of the kidneys’ composition by fatty degeneration.

Patients who survive the period of intoxication enter into a relatively short period of convalescence, and recover with no long-term deficits related to the yellow fever infection. Further, infection with the yellow fever virus results in lifelong immunity against repeated infection with the virus.

Five to 10 percent of all diagnosed cases of yellow fever are fatal. The occurrence of jaundice during a yellow fever infection is an extremely grave predictor, with 20-50% of these persons dying from their infection. Death may occur due to hemorrhaging (massive bleeding), often following a lapse into a comatose state.

Diagnosis

the diagnosis of yellow fever is made through examining the blood using various techniques in order to demonstrate the presence of either yellow fever viral antigens (the part of the virus that initiates the patient’s immune response) or specific antibodies (the cells produced by the patient’s immune system that are specifically directed against the yellow fever virus). Yellow fever is strongly suspected when Faget’s sign is present, or when the classic triad of symptoms is noted.

Treatment

medical management of yellow fever infection is directed toward relief of symptomatology. No active anti-viral treatment currently exists. Fevers and pain should be relieved with acetaminophen; neither aspirin nor ibuprofen should be used, because either one could exacerbate the bleeding tendency already present. Dehydration, due to fluid loss both from fever and bleeding, must be carefully avoided. The risk of bleeding into the stomach can be decreased through the administration of antacids and other medications. Hemorrhages may require blood transfusions, and kidney failure may require dialysis, a process that allows the work of the kidneys in clearing the blood of potentially toxic sub stances to be taken over by a machine that is outside of the body.

Prevention

a safe, highly effective yellow fever vaccine exists, with about 95% of vaccine recipients acquiring long-term immunity to the yellow fever flavivirus. Careful measures to decrease mosquito populations in both urban areas and jungle areas in which humans are

KEY TERMS

Degeneration —Breakdown of tissue.

Faget’s sign —The simultaneous occurrence of a high fever with a slowed heart rate.

Host —The organism, such as a monkey or human, in which another organism, such as a virus or bacteria, is living.

Vector —Any agent, living or otherwise, that carries and transmits parasites and diseases.

working, along with programs to vaccinate all people living in such areas, are necessary to avoid massive yellow fever outbreaks. According to the World Health Organization, after several decades of diminishing numbers of cases, a resurgence of yellow fever is occurring in many African countries. Lapsing immunization programs where they were effective in the past is considered responsible for the re-emergence of the disease.

See also Mosquitoes.

Resources

BOOKS

Kasper, Dennis L., et al. Harrison’s Principles of Internal Medicine, 16th ed. New York: McGraw Hill, 2004.

Kobayashi, G., Patrick R. Murray, Ken Rosenthal, and Michael Pfaller. Medical Microbiology. St. Louis, MO: Mosby, 2003.

Mandell, Douglas, et al. Principles and Practice of Infectious Diseases. New York: Churchill Livingstone, 2004.

OTHER

World Health Organization. “Yellow Fever.” <http://www.who.int/csr/disease/yellowfev/en/> (accessed on November 30, 3006).

Rosalyn Carson-DeWitt