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-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 or mild symptoms in most people to a hemorrhagic fever with a case fatality rate of 30 to 60% (Centers for Disease Control and Prevention [CDC]: Yellow Fever; Symptoms, Diagnosis, & Treatment).
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. In malignant yellow fever, hypoglycemia and hyperkalemia 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
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
1) and possible necessity for a booster. In the United States, 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).
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 clinician 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 30 to 60%).
Quarantine patients with suspected or confirmed yellow fever.
An effective vaccine is available; a single dose provides adequate lifetime protection.
