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Yellow fever

yellow fever
Classification & external resources
ICD-10 A95.
ICD-9 060
eMedicine med/2432  emerg/645
Yellow fever virus

TEM micrograph: Multiple yellow fever virions (234,000x magnification).
Virus classification
Group: Group IV ((+)ssRNA)
Family: Flaviviridae
Genus: Flavivirus
Species: Yellow fever virus

Yellow fever (also called yellow jack, black vomit or vomito negro, or sometimes American Plague) is an acute viral disease.[1] It is an important cause of hemorrhagic illness in many African and South American countries despite existence of an effective vaccine. The yellow refers to the jaundice symptoms that affect some patients.[2]

Yellow fever has been a source of several devastating epidemics. French soldiers were attacked by yellow fever during the 1802 Haitian Revolution; more than half of the army perished due to the disease.[3] Outbreaks followed by thousands of deaths occurred periodically in other Western Hemisphere locations until research, which included human volunteers (some of whom died), led to an understanding of the method of transmission to humans (primarily by mosquitos) and development of a vaccine and other preventative efforts in the early 20th century.

Despite the costly and sacrificial breakthrough research by Cuban physician Carlos Finlay, American physician Walter Reed, and many others over 100 years ago, unvaccinated populations in many developing nations in Africa and Central and South America continue to be at risk.[4] As of 2001, the World Health Organization (WHO) estimates that yellow fever causes 200,000 illnesses and 30,000 deaths every year in unvaccinated populations.[5]



  Yellow fever is caused by an arbovirus of the family Flaviviridae, a positive single-stranded RNA virus. Human infection begins after deposition of viral particles through the skin in infected arthropod saliva. The mosquitos involved are Aedes simpsaloni, A. africanus, and A. aegypti in Africa, the Haemagogus genus in South America,[5] and the Sasbethes genera in France.

Yellow fever is frequently severe but more moderate cases may occur as the result of previous infection by another flavivirus. After infection the virus first replicates locally, followed by transportation to the rest of the body via the lymphatic system.[6] Following systemic lymphatic infection the virus proceeds to establish itself throughout organ systems, including the heart, kidneys, adrenal glands, and the parenchyma of the liver; high viral loads are also present in the blood.[1] Necrotic masses (Councilman bodies) appear in the cytoplasm of hepatocytes.[6],[7]

There is a difference between disease outbreaks in rural or forest areas and in towns. Disease outbreaks in towns and non-native people may be more serious because of higher densities of mosquito vectors and higher population densities.[8]


The virus remains silent in the body during an incubation period of three to six days. There are then two disease phases. While some infections have no symptoms the first, acute phase is normally characterized by fever, muscle pain (with prominent backache), headache, shivers, loss of appetite, and nausea or vomiting. The high fever is often paradoxically associated with a slow pulse (known as Faget's sign). After three or four days most patients improve and their symptoms disappear.

Fifteen percent of patients, however, enter a toxic phase within 24 hours. Fever reappears and several body systems are affected. The patient rapidly develops jaundice and complains of abdominal pain with vomiting. Bleeding can occur from the mouth, nose, eyes, and stomach. Once this happens, blood appears in the vomit and feces. Kidney function deteriorates; this can range from abnormal protein levels in the urine (proteinuria) to complete kidney failure with no urine production (anuria). Half of the patients in the "toxic phase" die within fourteen days. The remainder recover without significant organ damage.

Yellow fever is difficult to recognize, especially during the early stages. It can easily be confused with malaria, typhoid, rickettsial diseases, haemorrhagic viral fevers (e.g. Lassa), arboviral infections (e.g. dengue), leptospirosis, viral hepatitis and poisoning (e.g. carbon tetrachloride). A laboratory analysis is required to confirm a suspect case. Blood tests (serology assays) can detect yellow fever antibodies that are produced in response to the infection. Several other techniques are used to identify the virus itself in blood specimens or liver tissue collected after death. These tests require highly trained laboratory staff using specialized equipment and materials.


In 1937, Max Theiler, working at the Rockefeller Foundation, developed a vaccine for yellow fever that gives a ten-year or more immunity from the disease and effectively protects people traveling to affected areas, while at the same time being a means to control the disease. According to the travel clinic at the University of Utah Hospital, the vaccine presents a significantly increased risk of severe allergic reaction in adults aged 60 and older, with the risk increasing again after age 65, and again after age 70. The reaction is capable of producing multiple organ failure and should be evaluated carefully by a qualified health professional before being administered to the elderly.

Woodcutters working in tropical areas should be particularly targeted for vaccination. Insecticides, 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.[9]

Recent studies have noted the increase in the number of areas affected by mosquito-borne viral infections and have called for further research and funding for vaccines.[10],[11]


There is no true cure for yellow fever, therefore vaccination is important. Treatment is symptomatic and supportive only. Fluid replacement, fighting hypotension and transfusion of blood derivates is generally needed only in severe cases. In cases that result in acute renal failure, dialysis may be necessary. A fever victim needs to get a lot of rest, fresh air, and drink plenty of fluids.

Current research

In the hamster model of yellow fever, early administration of the antiviral ribavirin is an effective early treatment of many pathological features of the disease.[12] Ribavirin treatment during the first five days after virus infection improved survival rates, reduced tissue damage in target organs (liver and spleen), prevented hepatocellular steatosis, and normalized alanine aminotransferase (a liver damage marker) levels. The results of this study suggest that ribavirin may be effective in the early treatment of yellow fever, and that its mechanism of action in reducing liver pathology in yellow fever virus infection may be similar to that observed with ribavirin in the treatment of hepatitis C, a virus related to yellow fever.[12] Because ribavirin had failed to improve survival in a virulent primate (rhesus) model of yellow fever infection, it had been previously discounted as a possible therapy.[13]

In 2007, the World Community Grid launched a project where by computer modeling of the yellow fever virus (and related viruses) thousands of small molecules are screened for their potential anti-viral properties in fighting yellow fever. This is the first project to utilize computer simulations in seeking out medicines to directly attack the virus once a person is infected. This is a distributed process project similar to SETI@Home where the general public downloads the World Community Grid agent and the program (along with thousands of other users) screens thousands of molecules while their computer would be otherwise idle. If the user needs to use the computer the program sleeps. There are several different projects running, including a similar one screening for anti-AIDS drugs. The project covering yellow fever is called "Discovering Dengue Drugs – Together." The software and information about the project can be found at:

  • World Community Grid web site


Historical reports have claimed a mortality rate of between 1 in 17 (5.8%) and 1 in 3 (33%).[14] The WHO factsheet on yellow fever, updated in 2001, states that 15% of patients enter a "toxic phase" and that half of that number die within ten to fourteen days, with the other half recovering.[15]


    Yellow fever occurs only in Africa, South and Central America, and the Caribbean.[16] Most outbreaks in South America are to people who work within the tropical rain forests and have direct contact with the organisms within the rainforest.

The disease can remain locally unknown in humans for long periods of time and then suddenly break out in an epidemic fashion. In Central America and Trinidad, such epidemics have been due to a form of the disease (jungle yellow fever) that is kept alive in Red Howler monkey populations and transmitted by Haemagogus mosquito species which live only in the canopy of rain forests. The virus is passed to humans when the tall rainforest trees are cut down. Infected woodcutters can then pass on the disease to others via species of Aedes mosquitoes that typically live at low altitudes, thus triggering an epidemic.[17]


  Yellow fever has had an important role in the history of Africa, the Americas, Europe, and the Caribbean.

Europe 541-549

Fragile after the fall of Rome, Europe was further weakened by "Yellow Plague" (yellow fever). The Byzantine Empire suffered as well.[18]

Cuba: 1762-1763

British and American colonial troops died by the thousands in Havana between 1762-1763. Epidemics struck coastal and island communities throughout the area during the next 140 years.

Philadelphia: 1793

Main article: Yellow Fever Epidemic of 1793

In 1793, the largest yellow fever epidemic in American history killed as many as 5,000 people in Philadelphia, Pennsylvania—roughly 10% of the population.[19]

Haiti: 1802

In 1802, an army of forty thousand sent by First Consul Napoleon Bonaparte of France to Haiti to suppress the Haitian Revolution was dwindled out by an epidemic of yellow fever (including the expedition's commander and Bonaparte's brother-in-law, Charles Leclerc). Some historians believe Haiti was to be a staging point for an invasion of the United States through Louisiana (then still under French control).[20]

Norfolk, Virginia: 1855

A ship carrying persons infected with the virus arrived in Hampton Roads in southeastern Virginia in June 1855 .[14] The disease spread quickly through the community, eventually killing over 3,000 people, mostly residents of Norfolk and Portsmouth. The Howard Association, a benevolent organization, was formed to help coordinate assistance in the form of funds, supplies, and medical professionals and volunteers which poured in from many other areas, particularly the Atlantic and Gulf Coast areas of the United States. See also "The Mermaids and Yellow Jack. A NorFolktale." children's historical fiction written by Norfolk Author Lisa Suhay retelling of the event and founding of the Bon Secours DePaul Hospital system in the United States in response to the epidemic.[21]

Memphis, Tennessee: 1878

Worst yellow fever epidemic in U.S. history occurred in 1878 with over 5,000 deaths in Memphis alone and 20,000 deaths in the whole of the Mississippi Valley.

Carlos Finlay and Walter Reed

  Carlos Finlay, a Cuban doctor and scientist, first proposed proofs in 1881 that yellow fever is transmitted by mosquitoes rather than direct human contact.[22] Dr.Walter Reed, M.D., (1851-1902) was an American Army surgeon who led a team that confirmed Finlay's theory. This risky but fruitful research work was done with human volunteers, including some of the medical personnel such as Clara Maass and Walter Reed Medal winner surgeon Jesse William Lazear who allowed themselves to be deliberately infected and died of the virus.[23] The acceptance of Finlay's work was one of the most important and far-reaching effects of the Walter Reed Commission of 1900.[24] Applying methods first suggested by Finlay, the elimination of yellow fever from Cuba was completed, as well as the completion of the Panama Canal. Lamentably, almost 20 years had passed before Reed's efforts were recognized while most of the scientific community ignored Finlay's methods of mosquito control.

Finlay and Reed's work was put to the test for the first time in the United States when a yellow fever epidemic struck New Orleans in 1905; according to the PBS American Experience documentary The Great Fever, houses were fumigated, cisterns for drinking water were inspected, and pools of standing water were treated with kerosene. The result was that the death toll from the epidemic was much lower than that from previous yellow fever epidemics, and that there has not been a major outbreak of the disease in the United States since. Although no cure has yet been discovered, an effective vaccine has been developed, which can prevent and help people recover from the disease.

See also


  1. ^ a b Schmaljohn AL, McClain D. (1996 isbn= 0-9631172-1-1). Alphaviruses (Togaviridae) and Flaviviruses (Flaviviridae). In: Baron's Medical Microbiology (Baron S et al, eds.), 4th ed., Univ of Texas Medical Branch. 
  2. ^ Anker M, Schaaf D, et al (2000-01-07). WHO Report on Global Surveillance of Epidemic-prone Infectious Diseases (PDF) 11. WHO. Retrieved on 2007-06-11.
  3. ^ Bollet, AJ (2004). Plagues and Poxes: The Impact of Human History on Epidemic Disease. Demos Medical Publishing, pp. 48–9. ISBN 188879979X. 
  4. ^ Tomori O (2002). "Yellow fever in Africa: public health impact and prospects for control in the 21st century". Biomedica 22 (2): 178-210. PMID 12152484.
  5. ^ a b Yellow fever fact sheet. WHO—Yellow fever. Retrieved on 2006-04-18.
  6. ^ a b Ryan KJ; Ray CG (editors) (2004). Sherris Medical Microbiology, 4th ed., McGraw Hill. ISBN 0-8385-8529-9. 
  7. ^ Quaresma JA, Barros VL, Pagliari C, Fernandes ER, Guedes F, Takakura CF, Andrade HF Jr, Vasconcelos PF, Duarte MI (2006). "Revisiting the liver in human yellow fever: virus-induced apoptosis in hepatocytes associated with TGF-beta, TNF-alpha and NK cells activity". Virology 345 (1): 22-30. PMID 16278000.
  8. ^ Barnett, ED (March 2007). "Yellow fever: epidemiology and prevention.". Clin Infect Dis 44 (6): 850-6. Retrieved on 2007-12-05.
  9. ^ Joint Statement on Mosquito Control in the United States from the U.S. Environmental Protection Agency (EPA) and the U.S. Centers for Disease Control and Prevention (CDC) (PDF). Environmental Protection Agency (2000-05-03). Retrieved on June 25, 2006.
  10. ^ Pugachev KV, Guirakhoo F, Monath TP (2005). "New developments in flavivirus vaccines with special attention to yellow fever". Curr Opin Infect Dis 18 (5): 387-94. PMID 16148524.
  11. ^ Petersen LR, Marfin AA (2005). "Shifting epidemiology of Flaviviridae". J Travel Med 12 Suppl 1: S3-11. PubMed.
  12. ^ a b Sbrana E, Xiao SY, Guzman H, Ye M, Travassos da Rosa AP, Tesh RB (2004). "Efficacy of post-exposure treatment of yellow fever with ribavirin in a hamster model of the disease". Am J Trop Med Hyg 71 (3): 306-12. PubMed.
  13. ^ Huggins JW (1989). "Prospects for treatment of viral hemorrhagic fevers with ribavirin, a broad-spectrum antiviral drug". Rev Infect Dis 11 Suppl 4: S750-61. PubMed.
  14. ^ a b Mauer HB. Mosquito control ends fatal plague of yellow fever. Retrieved on 2007-06-11, 2006. (undated newspaper clipping)
  15. ^ WHO Yellow Fever Fact Sheet. Retrieved on 2007-02-22.
  16. ^ Yellow fever: a current threat. WHO. Retrieved on June 25, 2006.
  17. ^ Theiler, Max and Downs, W. G. (1973). The Arthropod-Borne Viruses of Vertebrates: An Account of The Rockefeller Foundation Virus Program 1951-1970. Yale University Press. ISBN 0-300-01508-9. 
  18. ^ The Yellow Plague. Oxford Journals. Retrieved on 2006-11-08.
  19. ^ Yellow Fever Attacks Philadelphia, 1793. EyeWitness to History. Retrieved on 2007-06-22.
  20. ^ Bruns, Roger (2000). Almost History: Close Calls, Plan B's, and Twists of Fate in American History. Hyperion. ISBN 0786885793. 
  21. ^ Suhay, Lisa. The Mermaids and Yellow Jack. A NorFolktale.. iParenting Media Awards. Retrieved on 2007-12-26.
  22. ^ Chaves-Carballo E (2005). "Carlos Finlay and yellow fever: triumph over adversity". Mil Med 170 (10): 881-5. PubMed.
  23. ^ General info on Major Walter Reed. Major Walter Reed, Medical Corps, U.S. Army. Retrieved on 2006-05-02.
  24. ^ Phillip S. Hench Walter Reed Yellow Fever Collection. UVA Health Sciences: Historical Collections. Retrieved on 2006-05-06.

Further reading

  • Downs, Wilbur H., et al.. "Virus diseases in the West Indies". Caribbean Medical Journal 1965 (XXVI(1-4)): –.
  • Theiler, Max and Downs, W. G. The Anthropod-Borne Viruses of Vertebrates: An Account of the Rockefeller Foundation Virus Program, 1951-1970. Yale University Press, 1973.

Historical yellow fever information

  • The Great Fever on PBS
  • PBS website on the 1793 Philadelphia yellow fever epidemic.
  • Yellow Fever in Norfolk and Portsmouth 1855 an extensive website
  • Interactive Internet article on the 1855 Yellow Fever Epidemic from Pilot Online, Hampton Roads: a detailed story with maps, slides, and quiz
  • New Orleans, 1905: Housing Conditions and the Yellow Fever: a case study
  • Yellow fever deaths in New Orleans.
  • Enzootic transmission of yellow fever virus in Peru.
  • World Health Organization report on yellow fever

Vaccine development

  • Turning Yellow - article by Christine Soares
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Yellow_fever". A list of authors is available in Wikipedia.
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