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Yellow Fever

By Matthew E. Levison, MD, Adjunct Professor of Medicine; Professor School of Public Health, Drexel University College of Medicine; Drexel University

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Yellow fever is a mosquito-borne flavivirus infection endemic in tropical South America and sub-Saharan Africa. Symptoms may include sudden onset of fever, relative bradycardia, headache, and, if severe, jaundice, hemorrhage, and multiple organ failure. Diagnosis is with viral culture, reverse transcription PCR, and serologic tests. Treatment is supportive. Prevention involves vaccination and mosquito control.

In urban yellow fever, the virus is transmitted by the bite of an Aedes aegypti mosquito infected about 2 wk previously by feeding on a person with viremia. In jungle (sylvatic) yellow fever, the virus is transmitted by Haemagogus and other forest canopy mosquitoes that acquire the virus from wild primates. Incidence is highest during months of peak rainfall, humidity, and temperature in South America and during the late rainy and early dry seasons in Africa.

Symptoms and Signs

Infection ranges from asymptomatic (in 5 to 50% of cases) to a hemorrhagic fever with 50% mortality. Incubation lasts 3 to 6 days. Onset is sudden, with fever of 39 to 40° C, chills, headache, dizziness, and myalgias. The pulse is usually rapid initially but, by the 2nd day, becomes slow for the degree of fever (Faget sign). The face is flushed, and the eyes are injected. Nausea, vomiting, constipation, severe prostration, restlessness, and irritability are common.

Mild disease may resolve after 1 to 3 days. However, in moderate or severe cases, the fever falls suddenly 2 to 5 days after onset, and a remission of several hours or days ensues. The fever recurs, but the pulse remains slow. Jaundice, extreme albuminuria, and epigastric tenderness with hematemesis often occur together after 5 days of illness. There may be oliguria, petechiae, mucosal hemorrhages, confusion, and apathy.

Disease may last > 1 wk with rapid recovery and no sequelae. In the most severe form (called malignant yellow fever), delirium, intractable hiccups, seizures, coma, and multiple organ failure may occur terminally. During recovery, bacterial superinfections, particularly pneumonia, can occur.


  • Viral culture, reverse transcription PCR (RT-PCR), or serologic testing

Yellow fever is suspected in patients in endemic areas if they develop sudden fever with relative bradycardia and jaundice; mild disease often escapes diagnosis.

CBC, urinalysis, liver function tests, coagulation tests, viral blood culture, and serologic tests should be done. Leukopenia with relative neutropenia is common, as are thrombocytopenia, prolonged clotting, and increased PT. Bilirubin and aminotransferase levels may be elevated acutely and for several months. Albuminuria, which occurs in 90% of patients, may reach 20 g/L; it helps differentiate yellow fever from hepatitis. In malignant yellow fever, hypoglycemia and hyperkalemia may occur terminally.

Diagnosis is confirmed by culture, serologic tests, RT-PCR, or identification of characteristic midzonal hepatocyte necrosis at autopsy.

Needle biopsy of the liver during illness is contraindicated because hemorrhage is a risk.


  • Supportive care

Up to 10% of patients with disease severe enough to be diagnosed die.

Treatment is mainly supportive. Bleeding may be treated with vitamin K. An H2 blocker or a proton pump inhibitor and sucralfate can be helpful as prophylaxis for GI bleeding and can be used in all patients ill enough to require hospitalization.

Suspected or confirmed cases must be quarantined.


Preventive measures include

  • Mosquito avoidance

  • Vaccination

The most effective way to prevent outbreaks is to reduce the number of mosquitoes and limit mosquito bites by using diethyltoluamide (DEET), mosquito netting, and protective attire. During jungle outbreaks, people should evacuate the area until they are immunized and mosquitoes are controlled. Prompt mass yellow fever vaccination of the population is used to control an ongoing yellow fever outbreak through immunization. A single dose of vaccine can provide life-long immunity against yellow fever.

For people traveling to endemic areas, active immunization with the 17D strain of live-attenuated yellow fever vaccine (0.5 mL sc q 10 yr) is indicated and is effective in 95%. Although a single dose of yellow fever vaccine provides long-lasting protection and the WHO and the CDC's Advisory Committee on Immunization Practices no longer recommend a booster dose every 10 yr for most travelers, not all points of entry into countries may be aware that this requirement has been suspended; thus, it is probably safer to get the booster and not risk being denied entry. In the US, the vaccine is given only at US Public Health Service–authorized Yellow Fever Vaccination Centers (CDC: Yellow Fever Vaccination Centers).

The vaccine is contraindicated in the following:

  • Pregnant women

  • Infants < 6 mo

  • People with compromised immunity

If infants aged 6 to 8 mo cannot avoid travel to an endemic area, parents should discuss vaccination with their physician since the vaccine is typically not offered until age 9 mo.

To prevent further mosquito transmission, infected patients should be isolated in rooms that are well screened and sprayed with insecticides.