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

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 at biopsy. 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.