Yellow Fever
2019 Case Definition

Background

Yellow fever virus is a mosquito-borne flavivirus that is closely related to dengue, Japanese encephalitis, West Nile, and Zika viruses. On average, only one travel-associated case of yellow fever has been identified among U.S. travelers every 10 years. However, increasing numbers of travelers to and from endemic areas and outbreaks near major urban areas have heightened concern for the possible introduction and spread of the virus in the United States. Yellow fever is preventable by a safe and effective vaccine.

Clinical Description

Most yellow fever virus infections are asymptomatic. Following an incubation period of 3–9 days, approximately one-third of infected people develop symptomatic illness characterized by fever and headache. Other clinical findings include chills, vomiting, myalgia, lumbosacral pain, and bradycardia relative to elevated body temperature. An estimated 5%–25% of patients progress to more severe disease, including jaundice, renal insufficiency, cardiovascular instability, or hemorrhage (e.g., epistaxis, hematemesis, melena, hematuria, petechiae, or ecchymoses). The case-fatality rate for severe yellow fever is 30%–60%.

Clinical Criteria

A clinically compatible case of yellow fever is defined as:

• • Acute illness with at least one of the following: fever, jaundice, or elevated total bilirubin ≥ 3 mg/dl

AND

• Absence of a more likely clinical explanation.

Laboratory Criteria For Diagnosis

Confirmatory laboratory evidence:

• Isolation of yellow fever virus from, or demonstration of yellow fever viral antigen or nucleic acid in, tissue, blood, CSF, or other body fluid.
• Four-fold or greater rise or fall in yellow fever virus-specific neutralizing antibody titers in paired sera.
• Yellow fever virus-specific IgM antibodies in CSF or serum with confirmatory virus-specific neutralizing antibodies in the same or a later specimen.

Presumptive laboratory evidence:

• Yellow fever virus-specific IgM antibodies in CSF or serum, and negative IgM results for other arboviruses endemic to the region where exposure occurred.

Epidemiologic Linkage

Epidemiologically linked to a confirmed yellow fever case, or visited or resided in an area with a risk of yellow fever in the 2 weeks before onset of illness.

Probable

A case that meets the above clinical and epidemiologic linkage criteria, and meets the following:

• Yellow fever virus-specific IgM antibodies in CSF or serum, AND negative IgM results for other arboviruses endemic to the region where exposure occurred, AND no history of yellow fever vaccination.

Confirmed

A case that meets the above clinical criteria and meets one or more of the follcowing:

• Isolation of yellow fever virus from, or demonstration of yellow fever viral antigen or nucleic acid in, tissue, blood, CSF, or other body fluid, AND no history of yellow fever vaccination within 30 days before onset of illness unless there is molecular evidence of infection with wild-type yellow fever virus.
• Four-fold or greater rise or fall in yellow fever virus-specific neutralizing antibody titers in paired sera, AND no history of yellow fever vaccination within 30 days before onset of illness.
• Yellow fever virus-specific IgM antibodies in CSF or serum with confirmatory virus-specific neutralizing antibodies in the same or a later specimen, AND no history of yellow fever vaccination.

• Yellow Fever | 1997 Case Definition