Evidence of vascular endothelial damage in Crimean-Congo hemorrhagic fever.
BACKGROUND
Endothelial infection has an important role in the pathogenesis of Crimean-Congo hemorrhagic fever (CCHF). In this study, we investigated the causes of vascular endothelial damage in patients with CCHF.


METHODS
This prospective case-controlled study was carried out at Ankara Numune Education and Research Hospital between April and September 2007. Seventy-five patients with a laboratory-confirmed diagnosis of CCHF and 88 healthy controls were enrolled in the study. Serum levels of soluble cell adhesion molecules (sICAM-1, sVCAM-1, sE-selectin, sP-selectin, sL-selectin), vascular endothelial growth factor (VEGF), and macrophage migration inhibitory factor (MIF) were investigated in these patients by quantitative sandwich ELISA technique.


RESULTS
In the patient group, serum levels of sVCAM-1, sL-selectin and MIF were significantly higher than in the control group; serum levels of sICAM-1, sP-selectin, sE-selectin, and VEGF were significantly lower than in the control group. Serum levels of sVCAM-1 and sICAM-1 were significantly higher in severe cases than in non-severe cases, whereas the serum level of VEGF was significantly lower. sVCAM-1 was significantly higher in non-survivors than in survivors, while serum VEGF was significantly lower in non-survivors. The optimum cut-offs of sVCAM-1 and VEGF for the prediction of mortality were 205 ng/ml and 125 ng/ml, respectively. At these cut-offs, sVCAM-1 and VEGF had a sensitivity of 100% and specificity of 42.5% and 54.5%, respectively, in identifying CCHF patients who would die from the disease. The positive predictive values were 19% and 23%, respectively; negative predictive values were 100% for both.


CONCLUSIONS
Endothelial activation can affect the course of CCHF, and vascular endothelial damage is probably indirect. Further studies are needed for general conclusions to be drawn.
Bodur
Hürrem
H
Department of Infectious Diseases and Clinical Microbiology, Ankara Numune Education and Research Hospital, Samanpazari, Ankara, Turkey. hurrembodur@gmail.com
Akinci
Esragül
E
Ongürü
Pinar
P
Uyar
Yavuz
Y
Baştürk
Bilkay
B
Gözel
Mustafa Gökhan
MG
Kayaaslan
Bircan Unal
BU
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000097:blood*; D004730:Endothelium, Vascular / Q000503:physiopathology* / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D003225:Hemorrhagic Fever Virus, Crimean-Congo / Q000472:pathogenicity*; D006479:Hemorrhagic Fever, Crimean / Q000401:mortality / Q000503:physiopathology* / Q000821:virology; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000097:blood*; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D014421:Turkey; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D055815:Young Adult
D015815:Cell Adhesion Molecules; D008263:Macrophage Migration-Inhibitory Factors; D042461:Vascular Endothelial Growth Factor A; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human