Background In 1998, the US Centers for Disease Control and Prevention was n
otified 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 geno
mic sequencing. Clinical samples were subjected to neutralisation assays, a
nd an immunohistochemical analysis was done on one sample of liver obtained
Findings The clinical presentations were characterised by fever, myalgia, h
eadache, and confusion, followed by severe multisystemic illnesses. Three p
atients died. Vaccine-related variants of yellow fever virus were found in
plasma and cerebrospinal fluid of one vaccinee. The convalescent serum samp
les of two vaccinees showed antibody responses of at least 1:10 240. Immuno
histochemical assay of liver tissue showed yellow fever antigen in the Kupp
fer cells of the liver sample.
Interpretation The clinical features, their temporal association with vacci
nation. recovery of vaccine-related virus, antibody responses, and immunohi
stochemical assay collectively suggest a possible causal relation between t
he illnesses and yellow fever vaccination. Yellow fever remains an importan
t cause of illness and death in South America and Africa; hence, vaccinatio
n should be maintained until the frequency of these events is quantified.