Fever and multisystem organ failure associated with 17D-204 yellow fever vaccination: a report of four cases

Lancet. 2001 Jul 14;358(9276):98-104. doi: 10.1016/s0140-6736(01)05327-2.


Background: In 1998, the US Centers for Disease Control and Prevention was notified of three patients who developed severe illnesses days after yellow fever vaccination. A similar case occurred in 1996. All four patients were more than 63 years old.

Methods: Vaccine strains of yellow fever virus, isolated from the plasma of two patients and the cerebrospinal fluid of one, were characterised by genomic sequencing. Clinical samples were subjected to neutralisation assays, and an immunohistochemical analysis was done on one sample of liver obtained at biopsy.

Findings: The clinical presentations were characterised by fever, myalgia, headache, and confusion, followed by severe multisystemic illnesses. Three patients died. Vaccine-related variants of yellow fever virus were found in plasma and cerebrospinal fluid of one vaccinee. The convalescent serum samples of two vaccinees showed antibody responses of at least 1:10240. Immunohistochemical assay of liver tissue showed yellow fever antigen in the Kuppfer cells of the liver sample.

Interpretation: The clinical features, their temporal association with vaccination, recovery of vaccine-related virus, antibody responses, and immunohistochemical assay collectively suggest a possible causal relation between the illnesses and yellow fever vaccination. Yellow fever remains an important cause of illness and death in South America and Africa; hence, vaccination should be maintained until the frequency of these events is quantified.

Publication types

  • Case Reports

MeSH terms

  • Adverse Drug Reaction Reporting Systems
  • Aged
  • Base Sequence
  • Biopsy
  • DNA, Viral / genetics
  • Fatal Outcome
  • Female
  • Fever / epidemiology
  • Fever / etiology*
  • Fever / metabolism
  • Fever / pathology
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Multiple Organ Failure / epidemiology
  • Multiple Organ Failure / etiology*
  • Multiple Organ Failure / metabolism
  • Multiple Organ Failure / pathology
  • Time Factors
  • United States / epidemiology
  • Vaccines, Attenuated / adverse effects
  • Yellow Fever Vaccine / adverse effects*
  • Yellow fever virus / genetics


  • DNA, Viral
  • Vaccines, Attenuated
  • Yellow Fever Vaccine