Risk groups for yellow fever vaccine-associated viscerotropic disease (YEL-AVD)

Vaccine. 2014 Oct 7;32(44):5769-75. doi: 10.1016/j.vaccine.2014.08.051. Epub 2014 Sep 3.


Although previously considered as the safest of the live virus vaccines, reports published since 2001 indicate that live yellow fever virus vaccine can cause a severe, often fatal, multisystemic illness, yellow fever vaccine-associated viscerotropic disease (YEL-AVD), that resembles the disease it was designed to prevent. This review was prompted by the availability of a listing of the cumulative cases of YEL-AVD, insights from a statistical method for analyzing risk factors and re-evaluation of previously published data. The purpose of this review is to identify and analyze risk groups based on gender, age, outcome and predisposing illnesses. Using a passive surveillance system in the US, the incidence was reported as 0.3 to 0.4 cases per 100,000. However, other estimates range from 0 to 12 per 100,000. Identified and potential risk groups for YEL-AVD include elderly males, women between the ages of 19 and 34, people with a variety of autoimmune diseases, individuals who have been thymectomized because of thymoma, and infants and children ≤11 years old. All but the last group are supported by statistical analysis. The confirmed risk groups account for 77% (49/64) of known cases and 76% (32/42) of the deaths. The overall case fatality rate is 66% (42/64) with a rate of 80% (12/15) in young women, in contrast to 50% (13/26) in men ≥56 years old. Recognition of YEL-AVD raises the possibility that similar reactions to live chimeric flavivirus vaccines that contain a yellow fever virus vaccine backbone could occur in susceptible individuals. Delineation of risk groups focuses the search for genetic mutations resulting in immune defects associated with a given risk group. Lastly, identification of risk groups encourages concentration on measures to decrease both the incidence and the severity of YEL-AVD.

Keywords: Risk groups; Vaccine; Viscerotropic; Yellow fever.

Publication types

  • Review

MeSH terms

  • Adult
  • Adverse Drug Reaction Reporting Systems
  • Autoimmune Diseases / complications
  • Child
  • Child, Preschool
  • Drug-Related Side Effects and Adverse Reactions
  • Female
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Odds Ratio
  • Risk Factors
  • Thymus Gland / physiopathology
  • Yellow Fever Vaccine / adverse effects*
  • Young Adult


  • Yellow Fever Vaccine