What is yellow fever?

Causes and Symptoms

Yellow fever is a viral disease of humans spread by infected mosquitoes. The infectious agent is a flavivirus. Yellow fever is primarily a disease of tropical and pantropical areas of South America and sub-Saharan Africa. The absence of yellow fever from Asia is curious but may be explained by the lack of suitable reservoirs. Three types of yellow fever are recognized, sylvan yellow fever, intermediate yellow fever, and urban yellow fever.

All three types are highly communicable, but none are directly transmitted via personal contact between humans. The method of transmission was reported by physician Walter Reed in 1901 after extensive studies. A human contracts the disease through the bite of an infected mosquito that, in turn, has taken a blood meal from an infected monkey or other human. The viral incubation period within the mosquito is nine to twelve days. The virus then appears in the saliva and can be transmitted during the mosquito’s next blood meal. Thereafter, the mosquito carries the virus throughout its life.

Sylvan yellow fever is also known as jungle yellow fever. Forest monkeys are its primary reservoir, but marmosets and marsupials may also harbor the disease. Sylvan yellow fever is spread from monkey to monkey by the bite of infected Sabethes or Haemagogus mosquitoes, which breed in water-filled tree holes.

People who visit or work in rain forest environs, such as miners, engineers, wildlife biologists, and foresters, are at risk of contracting the disease. Sylvan yellow fever is rare or nonexistent outside tropical rain forests, but cases are reported every year in areas where it is endemic. The intermediate, or savannah, cycle of yellow fever is transmitted from an infected mosquito to a human living or working near an area that borders the rain forest. This cycle of the virus can also be transmitted from monkey to human, or from human to human, via the infected mosquito.

Urban yellow fever is spread by the Aedes aegypti mosquito, which is the main reservoir of the disease, along with humans. Aedes commonly lives and breeds in trash dumps and waste places around human habitations. Urban yellow fever often results in thousands of cases and high fatality rates.

In humans, the first symptoms of yellow fever typically appear from three to six days following the bite of an infected mosquito. Symptoms vary widely; the mildest cases may pass unnoticed, but in more severe cases the patient shows a number of flulike symptoms, such as muscle aches, backaches, headache, high fever, chills, nausea, and vomiting. Liver damage may occur as early as the fourth or fifth day of the illness, leading to progressive and extensive jaundice. In the most severe cases, periods of nausea, vomiting, renal failure, and extensive bleeding (hemorrhage) may prove fatal. The fatality rate may range from as low as 5 percent in indigenous populations to 50 percent or more when untreated or during severe epidemics. Higher fatality rates are typically seen in nonindigenous people.

Clinical diagnosis of yellow fever is aided by isolation of the virus in mice, by microscopic examination of liver tissue for necrotic lesions that characterize this disease, by detection of the yellow fever viral antigen in blood or liver tissue fluid of the infected patient, or by detection of the viral genome in liver tissue. Diagnosis can also be determined serologically through the detection of specific antibodies.

Treatment and Therapy

There is no specific antiviral drug for yellow fever, so treatment goals include providing symptom relief, such as oxygen support, medications to reduce fever and pain, and the administration of vitamin K and replacement fluids. Dialysis may be required for patients suffering from kidney failure. Complete recovery may take several weeks, after which the individual has a lifelong immunity to yellow fever. The yellow fever vaccine is used to prevent infection among those likely to be exposed to the virus.

Perspective and Prospects

Yellow fever has long been a dreaded tropical and subtropical disease of humans. Throughout the centuries of exploration, yellow fever epidemics occurred with alarming regularity, and high fatality rates were seen among nonindigenous visitors and settlers in regions where the disease is endemic. The presence of yellow fever on a ship was indicated by flying the fever flag or yellow jack. Before the transmission of yellow fever was understood, the disease was one of the deadliest infections known, with outbreaks such as the Great Yellow Fever Epidemic of 1878 in the Mississippi valley causing great losses of life. Physician Walter Reed was the first to describe the epidemiology of yellow fever and to recognize the importance of the mosquito vector in its spread. His research elucidated control and eradication measures that provide containment during epidemics, including the successful total suppression of yellow fever in the United States. In 1937 microbiologist Max Thieler developed a treatment for yellow fever, with research leading to the 17D vaccine. These breakthroughs led to the widespread eradication of the disease from urban areas.

Despite modern medical advances, yellow fever remains a problem in many areas—the disease is endemic to forty-four countries in Africa and South America. The Centers for Disease Control (CDC) reports five other African nations as at low risk for exposure. Many of these countries require proof of vaccination for visitors. Small numbers of cases of sylvan yellow fever occur every year in certain areas of Amazonia and northern South American countries, including Peru and Bolivia. In central Africa, the yellow fever belt extends from Ethiopia westward through Senegal, Sudan, and Ghana. Both occasional cases and epidemics occur irregularly. Between 1986 and 1988, for example, thirty thousand cases of yellow fever were reported in Nigeria, and ten thousand people died. The World Health Organization (WHO) estimates that there are 200,000 cases of yellow fever worldwide each year, which cause approximately 30,000 deaths. 90 percent of those cases are found in Africa. The CDC estimates that the risk of infection among travelers is 50 per 100,000 in West Africa and 5 per 100,000 in South America, while the risk of death from yellow fever is 10 per 100,000 in West Africa and 1 per 100,000 in South America. Since the 1990s the incidence of the disease has increased due to factors including climate change, deforestation and population movement in endemic areas, and decreasing levels of immunity among human populations.

The traditional and still most effective method of preventing urban yellow fever is the eradication of the Aedes aegypti mosquito vector. Control measures involve a combination of insecticide spraying and the cleanup or removal of potential breeding sites. The prevention of yellow fever can also be achieved through the vaccination of all people within the endemic regions. A single vaccination with an attenuated strain of virus grown in chick embryos has been shown to be effective for thirty or more years, but revaccination is recommended every ten years.

The elimination of sylvan yellow fever is probably impossible because of the difficulty of eradicating jungle populations of Sabethes and Haemagogus mosquitoes. Prevention must therefore be achieved through defensive measures for people who work in or visit jungle areas, including immunization and the use of protective clothing, netting, and mosquito repellents.

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