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Yellow Fever


Thomas M. Yuill

, PhD, University of Wisconsin-Madison

Last full review/revision Aug 2021| Content last modified Aug 2021
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Yellow fever is a mosquito-borne flavivirus infection Overview of Arbovirus, Arenavirus, and Filovirus Infections Arbovirus (arthropod-borne virus) applies to any virus that is transmitted to humans and/or other vertebrates by certain species of blood-feeding arthropods, chiefly insects (flies and mosquitoes)... read more 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-polymerase chain reaction (RT-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 weeks previously by feeding on a person with viremia. In jungle (sylvatic) yellow fever, the virus is transmitted by Haemagogus and Sabethes forest canopy mosquitoes that acquire the virus from wild primates. Incidence is highest during months of peak rainfall, humidity, and temperature in tropical South America and during the late rainy and early dry seasons in Africa.

Symptoms and Signs of Yellow Fever

Infection ranges from asymptomatic (in 5 to 50% of cases) to a hemorrhagic fever with a case fatality rate of up to 50%. 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 week 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.

Diagnosis of Yellow Fever

  • Viral culture, reverse transcription–polymerase chain reaction (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.

Complete blood count, urinalysis, liver tests, coagulation tests, viral blood culture, and serologic tests should be done. Leukopenia with relative neutropenia is common, as are thrombocytopenia, delayed clotting, and increased prothrombin time (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 Overview of Acute Viral Hepatitis Acute viral hepatitis is diffuse liver inflammation caused by specific hepatotropic viruses that have diverse modes of transmission and epidemiologies. A nonspecific viral prodrome is followed... read more . In malignant yellow fever, hypoglycemia Hypoglycemia Hypoglycemia unrelated to exogenous insulin therapy is an uncommon clinical syndrome characterized by low plasma glucose level, symptomatic sympathetic nervous system stimulation, and central... read more and hyperkalemia Hyperkalemia Hyperkalemia is a serum potassium concentration > 5.5 mEq/L (> 5.5 mmol/L), usually resulting from decreased renal potassium excretion or abnormal movement of potassium out of cells. There are... read more may occur terminally.

Diagnosis of yellow fever 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.

Treatment of Yellow Fever

  • Supportive care

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

Treatment of yellow fever 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 gastrointestinal bleeding and can be used in all patients ill enough to require hospitalization.

Suspected or confirmed cases must be quarantined.

Prevention of Yellow Fever

Preventive measures include

  • Mosquito avoidance

  • Vaccination

The most effective way to prevent yellow fever outbreaks is

  • To maintain ≥ 80% vaccination coverage of the population in areas at risk of yellow fever

It is also helpful 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. 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 subcutaneously) ≥ 10 days before traveling is indicated; the vaccine is effective in 95%. Although a single dose of yellow fever vaccine provides long-lasting protection and the World Health Organization and the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices no longer recommend a booster dose every 10 years for most travelers, not all points of entry into countries may be aware that this requirement has been suspended. Thus, it is probably more practical for those vaccinated > 10 years previously to get the booster and its accompanying official certificate and not risk being denied entry. A recent study showed that in infants vaccinated when 9 to 12 months of age, neutralizing antibodies may decline to undetectable levels in as little as 2 to 3 years, suggesting a loss of protection (1 Prevention reference 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... read more ) and possible necessity for a booster. In the US, the vaccine is given only at US Public Health Service–authorized Yellow Fever Vaccination Centers (Centers for Disease Control and Prevention: Yellow Fever Vaccination Centers).

The yellow fever vaccine is contraindicated in the following:

  • Pregnant women

  • Infants < 6 months

  • People with compromised immunity

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

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

Prevention reference

  • 1. Domingo C, Fraissinet J, Ansah PO, et al: Long-term immunity against yellow fever in children vaccinated during infancy: a longitudinal cohort study. The Lancet 19:1363-70, 2019. doi: 10.1016/S1473-3099(19)30323-8

Key Points

  • Yellow fever is a mosquito-borne viral disease endemic in South America and Africa.

  • Mild cases are often unrecognized; others cause fever, headache, myalgias, and prostration.

  • Severe cases result in jaundice, delirium, and sometimes often fatal hemorrhagic fever with seizures, coma, multiple organ failure, and death (in up to 50%).

  • Quarantine patients with suspected or confirmed yellow fever.

  • Treat supportively (including using vitamin K to treat bleeding and an H2 blocker or a proton pump inhibitor and sucralfate to prevent bleeding).

  • An effective vaccine is available; a single dose provides adequate lifetime protection.

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