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% (1).

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 second day, becomes disproportionately 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, profound albuminuria, and epigastric tenderness with hematemesis often occur together after 5 days of illness. There may be oliguria, renal insufficiency, 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. Malignant yellow fever occurs in approximately 15% of people (2).

Bacterial superinfections, particularly pneumonia, may occur during recovery.

• Viral culture, reverse transcription–polymerase chain reaction (RT-PCR), or serologic testing for IgM and neutralizing antibodies

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 (20 kg/m³); 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, or RT-PCR (1). If diagnosis is not established before death, yellow fever is confirmed by identification of characteristic midzonal hepatocyte necrosis at autopsy.

RT-PCR is most useful within 7 days from illness onset. The patient's history of yellow fever vaccination should be obtained to interpret results of serological testing. IgM antibodies to the yellow fever vaccine virus can persist several years following vaccination and serological testing cannot differentiate between recent infection and vaccination (RT-PCR is most useful within 7 days from illness onset. The patient's history of yellow fever vaccination should be obtained to interpret results of serological testing. IgM antibodies to the yellow fever vaccine virus can persist several years following vaccination and serological testing cannot differentiate between recent infection and vaccination (2).

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

• Supportive care

Treatment of yellow fever is mainly supportive (1). 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 in patients requiring hospitalization. There is no available specific antiviral treatment.). 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 in patients requiring hospitalization. There is no available specific antiviral treatment.

Suspected or confirmed cases must be quarantined.

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. The occurrence of death in monkeys due to yellow fever often indicates that jungle outbreaks are occurring with the risk of spillover to people. Unvaccinated individuals in these regions 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 (by using diethyltoluamide (DEET), mosquito netting, and protective attire. The occurrence of death in monkeys due to yellow fever often indicates that jungle outbreaks are occurring with the risk of spillover to people. Unvaccinated individuals in these regions 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 (1).

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%. This 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%. Thisyellow fever vaccine is appropriate for individuals ≥ 9 months of age. A single dose of yellow fever vaccine provides long-lasting protection. Booster doses are not recommended by the World Health Organization, although individual countries may have different requirements for entry. In the United States, the vaccine is given only at U. S. Public Health Service–authorized Yellow Fever Vaccination Centers (2).

Yellow fever vaccine booster doses can be considered in the following populations (Yellow fever vaccine booster doses can be considered in the following populations (3, 4):

• Women who were pregnant, regardless of trimester, when first vaccinated

• People who received a hematopoietic stem cell transplant following their last dose of the yellow fever vaccine

• People with asymptomatic human immunodeficiency virus (HIV) infection

• Laboratory workers who handle wild-type yellow fever virus

• Travelers who will be in higher risk locations and received their yellow fever vaccine ≥ 10 years previously

The yellow fever vaccine is contraindicated in patients who have:The yellow fever vaccine is contraindicated in patients who have:

• An allergy to vaccine components

• Age ≤ 6 months

• Uncontrolled HIV infection or a CD4 count < 200/mm³

• Thymus disorder with associated abnormal immune function

• Primary immunodeficiencies

• Malignancy

• Received a solid organ transplant

• Immunosuppressive conditions or are on immunomodulatory therapies

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. Pregnancy or breastfeeding is not a contraindication to receiving the yellow fever vaccine, though data are limited and discussion with a healthcare professional is indicated. 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. Pregnancy or breastfeeding is not a contraindication to receiving the yellow fever vaccine, though data are limited and discussion with a healthcare professional is indicated.

Administration of the yellow fever vaccine needs to be coordinated with the administration of other live attenuated viral vaccines. When possible, live attenuated vaccines should be administered simultaneously. If simultaneous administration is not possible, live attenuated vaccines should be given at least 30 days apart to avoid impairment of immune response to the vaccine. Administration of the yellow fever vaccine needs to be coordinated with the administration of other live attenuated viral vaccines. When possible, live attenuated vaccines should be administered simultaneously. If simultaneous administration is not possible, live attenuated vaccines should be given at least 30 days apart to avoid impairment of immune response to the vaccine.

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