Open Access Highly Accessed Research article

Sequential determination of serum viral titers, virus-specific IgG antibodies, and TNF-α, IL-6, IL-10, and IFN-γ levels in patients with Crimean-Congo hemorrhagic fever

Safak Kaya1*, Nazif Elaldi2, Ayhan Kubar3, Nevcihan Gursoy4, Meral Yilmaz5, Gulderen Karakus5, Turabi Gunes5, Zubeyde Polat6, Mustafa Gokhan Gozel2, Aynur Engin2, Ilyas Dokmetas2, Mehmet Bakir2, Neziha Yilmaz7 and Mehmet Sencan8

Author Affiliations

1 Department of Infectious Diseases and Clinical Bacteriology, Training and Research Hospital, Diyarbakir, Turkey

2 Department of Infectious Diseases and Clinical Bacteriology, Faculty of Medicine, Cumhuriyet University, Sivas, Turkey

3 Department of Clinical Microbiology, Section of Clinical Virology, Gulhane Military Medicine Academy, Ankara, Turkey

4 Department of Food Engineering, Faculty of Engineering, Cumhuriyet University, Sivas, Turkey

5 Cumhuriyet University Medical Faculty Research Center (CUTFAM), Cumhuriyet University, Sivas, Turkey

6 Cumhuriyet University Vocabulary School, Cumhuriyet University, Sivas, Turkey

7 Department of Virology, Refik Saydam Hifzissiha Institute, Turkish Ministry of Health, Ankara, Turkey

8 Department of Internal Medicine, Section of Haematology, Faculty of Medicine, Cumhuriyet University, Sivas, Turkey

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BMC Infectious Diseases 2014, 14:416  doi:10.1186/1471-2334-14-416

Published: 28 July 2014

Abstract

Background

Although 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.

Methods

In 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.

Results

The 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.

Conclusions

The 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.

Keywords:
CCHF; CCHFV titer; Specific IgG; TNF-α; IL-6; IL-10; IFN-γ; DIC; Mortality