Abstract
BackgroundAlthough there have been a number of studies on the pathogenesis of Crimean-Congo hemorrhagic fever (CCHF) recently, knowledge on this topic is still insufficient. This study aims to reveal the kinetics of serum CCHF virus (CCHFV) titers, serum levels of anti-CCHFV immunoglobulin (Ig)G, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and interferon (IFN)-γ in CCHF patients.MethodsIn total, 31 CCHF cases (11 fatal) were studied. Serum samples were obtained daily from all patients from the time of admission and continued for a 7-day hospitalization period for serologic (ELISA), virologic (real-time PCR), and cytokine (ELISA) analysis.ResultsThe mean serum CCHFV titer at admission was 5.5E + 09 copies/mL in fatal cases and 5.7E + 08 copies/mL in survivors (p < 0.001). Compared to survivors, both the mean serum levels of IL-6 and TNF-α at admission were found to be significantly increased in fatal cases. The serum levels of IL-6, TNF-α and serum CCHFV titer at admission were significantly and positively correlated with disseminated intravascular coagulation (DIC) scores (r = 0.626, p = 0.0002; r = 0.461, p = 0.009; and r = 0.625, p = 0.003, respectively). When the data obtained from the sequential determination of CCHFV titer and levels of anti-CCHFV IgG, IL-6, TNF-α, IL-10 and IFN-γ were grouped according to the days of illness, the initial serum CCHFV titer of a fatal patient was 5.5E + 09 (copies/mL) and it was 6.1E + 09 (copies/mL) in a survivor on the 2 day of illness. While significant alterations were observed in all cytokines during the monitoring period, IL-6 levels remained consistently higher in fatal cases and TNF-α levels increased in both in fatal and non-fatal CCHF cases.ConclusionsThe increased CCHFV load and higher concentrations of IL-6 and TNF-α, the presence of DIC, and the absence of CCHFV specific immunity are strongly associated with death in CCHF.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-416) contains supplementary material, which is available to authorized users.
Highlights
There have been a number of studies on the pathogenesis of Crimean-Congo hemorrhagic fever (CCHF) recently, knowledge on this topic is still insufficient
Crimean-Congo hemorrhagic fever (CCHF) is a viral hemorrhagic fever (VHF) which is caused by an RNA virus, the CCHF virus (CCHFV), belonging to the Nairovirus genus of the Bunyaviridae family
Previous studies revealed that serum pro-inflammatory and anti-inflammatory cytokines including tumor necrosis factor (TNF)-α, IL-6, IL-10, IL-12, and IFN-γ were increased in patients with CCHF and levels of some cytokines were higher in the fatal cases than those were in survivors [9,10,11]
Summary
There have been a number of studies on the pathogenesis of Crimean-Congo hemorrhagic fever (CCHF) recently, knowledge on this topic is still insufficient. When human cells are exposed to VHF agents in vitro, they may produce many of these inflammatory mediators Such inflammatory mediators play an important role in fatal cases with fulminant progression and in the development of shock [5]. Previous studies revealed that serum pro-inflammatory and anti-inflammatory cytokines including TNF-α, IL-6, IL-10, IL-12, and IFN-γ were increased in patients with CCHF and levels of some cytokines were higher in the fatal cases than those were in survivors [9,10,11]. This study aims to reveal the kinetics of serum CCHFV load, anti-CCHFV IgG titers and cytokines including TNF-α, IL-6, IL-10, and IFN-γ by daily simultaneous sequential estimation in patients with CCHF and analyze their contribution to the pathogenesis of this disease
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