BACKGROUND : Rift Valley fever (RVF) is a mosquito-borne viral zoonosis affecting domestic and wild ruminants,
camels and humans. Outbreaks of RVF are characterized by a sudden onset of abortions and high mortality
amongst domestic ruminants. Humans develop disease ranging from a mild flu-like illness to more severe
complications including hemorrhagic syndrome, ocular and neurological lesions and death. During the RVF
outbreak in South Africa in 2010/11, a total of 278 human cases were laboratory confirmed, including 25 deaths.
The role of the host inflammatory response to RVF pathogenesis is not completely understood.
METHODS : Virus load in serum from human fatal and non-fatal cases was determined by standard tissue culture
infective dose 50 (TCID50) titration on Vero cells. Patient serum concentration of chemokines and cytokines involved
in inflammatory responses (IL-8, RANTES, CXCL9, MCP-1, IP-10, IL-1β, IL-6, IL-10, TNF and IL-12p70) was determined
using cytometric bead assays and flow cytometry.
RESULTS : Fatal cases had a 1-log10 higher TCID50/ml serum concentration of RVF virus (RVFV) than survivors (p < 0.05).
There were no significant sequence differences between isolates recovered from fatal and non-fatal cases. Chemokines
and pro- and anti-inflammatory cytokines were detected at significantly increased (IL-8, CXCL9, MCP-1, IP-10, IL-10) or
decreased (RANTES) levels when comparing fatal cases to infected survivors and uninfected controls, or when
comparing combined infected patients to uninfected controls.
CONCLUSIONS : The results suggest that regulation of the host inflammatory responses plays an important role in the
outcome of RVFV infection in humans. Dysregulation of the inflammatory response contributes to a fatal outcome. The
cytokines and chemokines identified in this study that correlate with fatal outcomes warrant further investigation as
markers for disease severity.