Immune response during adverse events after 17D-derived yellow fever vaccination in Europe

Background. In 1999-2000, reports of fatalities after vaccination with 17D-derived yellow fever vaccine (YEL) focused mainly on cases of YEL-associated adverse events (YEL-AEs) and YEL-associated viscerotropic disease (YEL-AVD). Here, we investigated 6 recent European cases to provide insight regarding immune response involvement and to identify potential risk factors. Methods. Clinical, microbiological, molecular biological, and immunological assays were performed on serum from 6 patients with YEL-AEs, including 5 with YEL-AVD and 1 with YEL-associated neurotropic disease (YEL-AND). Results. The levels of 3 liver enzymes associated with infection were clearly increased in all patients with YEL-AVD, but no elevations were observed in the patient with YEL-AND. In the patients with severe YEL-AVD, platelet counts were markedly reduced (< 100,000 cells/mu L). The only patient with fatal YEL-AVD exhibited a cytokine profile comparable to that seen in YF: high levels of interleukin (IL)-6, IL-8, monocyte chemotactic protein (MCP)-1, monokine induced by interferon-gamma, and growth-related oncogene (GRO). The other patients with YEL-AVD exhibited similar but less severe cytokine profiles. The patient with YEL-AND exhibited a cytokine profile similar to that found in vaccinees without YEL-AEs: elevated levels of RANTES and low levels of GRO, MCP-1, transforming growth factor-beta(1), and tumor necrosis factor-beta. Conclusions. On the basis of these results, we conclude that elevations in cytokine levels and reductions in platelet counts are suitable surrogate markers for patients likely to experience severe adverse reactions to YEL.