Serum levels of inflammatory cytokines in Rift Valley fever patients are indicative of severe disease
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RESEARCH
Open Access
Serum levels of inflammatory cytokines in Rift Valley fever patients are indicative of severe disease Petrus Jansen van Vuren1,2*, Sharon Shalekoff3,5, Antoinette A. Grobbelaar1, Brett N. Archer4, Juno Thomas4, Caroline T. Tiemessen3,5 and Janusz T. Paweska1,2,5
Abstract 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. Keywords: Rift Valley fever, Inflammation, Pathogenesis
Background Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa, the Arabian Peninsula and islands in the Indian ocean off the east coast of Africa [1, 2]. RVF virus (RVFV), a member of the Phlebovirus genus in the Bunyaviridae family, infects domestic * Correspondence: [email protected] 1 Centre for Emerging and Zoonotic Diseases, National Institute for Communicable Diseases division of the National Health Laboratory Service, Sandringham, South Africa 2 Department of Microbiology and Plant Pathology, University of Pretoria, Pretoria, South Africa Full list of author information is available at the end of the article
livestock, wild ruminants and humans. Humans acquire infection through the bite of infected mosquitoes or from contact with infected tissues or b
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