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Ticks and Tick-borne Diseases
journal homepage: www.elsevier.com/locate/ttbdis
Original article
Hitit Index to distinguish patients with and without Crimean-Congo
hemorrhagic fever
Huseyin Kayadibi
a,
⁎
, Derya Yapar
b
, Ozlem Akdogan
b
, Nuray N Ulusu
c
, Nurcan Baykam
b
a
Hitit University School of Medicine, Department of Medical Biochemistry, Corum, Turkey
b
Hitit University School of Medicine, Department of Infectious Diseases and Clinical Microbiology, Corum, Turkey
c
Koc University School of Medicine, Department of Medical Biochemistry, Istanbul, Turkey
ARTICLE INFO
Keywords:
Crimean-Congo hemorrhagic fever
Early diagnosis
Hitit Index
ABSTRACT
Crimean-Congo hemorrhagic fever (CCHF) is fatal. Therefore, it is very important to use an inexpensive, easily
accessible, quick and accurate screening index based on clinical signs and laboratory parameters to identify
patients suspected of having CCHF.
Laboratory test results on the day of hospitalization for 268 inpatients suspected of having CCHF were used to
calculate the laboratory section of the Hitit Index, while 65 of these were also monitored daily during their
hospital stay to develop the clinical section of the Hitit Index. Two-hundred CCHF-negative outpatients were also
evaluated.
One-hundred and forty-nine inpatients were CCHF-positive and 119 inpatients were CCHF-negative. The Hitit
Index is 5.6 - (5.3*lymphocyte) - (0.02*fibrinogen) - (12*direct bilirubin) + (0.04*AST) + (0.32*hema-
tocrit) - (0.5*neutrophil) - (0.07*CKD-EPI) - (0.001*CK) ± conjunctival hyperemia (+1.5 in conjunctival
hyperemia presence and -1.5 in conjunctival hyperemia absence). In 65 inpatients monitored daily, Hitit Index
results for CCHF-positive and negative inpatients were 6.10(1.90–12.30) and -5.35(-8.83– -1.95), while
CCHF-negative outpatients were -10.99(-15.64– -6.95) (P < 0.001), respectively. On hospitalization day,
just one inpatient was false-negative in 27 CCHF-positive inpatients, while four were false-positive among 38
CCHF-negative inpatients using the Hitit Index. After 24 h, just one inpatient was diagnosed falsely among 27
CCHF-positive and 38 CCHF-negative inpatients, and there was no change after 48 h.
Management of patients living in endemic regions suspected of having CCHF could be achieved within
minutes using the Hitit Index. Patients with Hitit Index less than zero can be monitored as outpatients, while
patients with Hitit Index results above zero must be hospitalized in infectious diseases wards.
This study was not registered since it was retrospective.
1. Introduction
Crimean-Congo hemorrhagic fever virus (CCHFV), which is a
member of the Orthonairovirus genus in the Nairoviridae family, causes
Crimean-Congo hemorrhagic fever (CCHF) with an average mortality
rate of 3–30% in humans. CCHFV is widespread in many regions of
Africa, the Middle East and Eastern Europe to Russia (in more than 30
countries). It is usually transmitted to humans via ticks of the genus
Hyalomma or by exposure to the blood or other body fluids of an in-
fected animal or CCHF patient. CCHF in humans has clinical symptoms
of fever, conjunctival hyperemia, facial hyperemia, headache, myalgia,
dizziness, nausea, vomiting, and diarrhea and may affect every site of
the body during the hemorrhagic period (Ergonul, 2006; Swanepoel
et al., 1989).
The distinguishing medical biochemistry laboratory features of
CCHF are elevated liver and muscle enzymes such as alanine amino-
transferase (ALT), aspartate aminotransferase (AST), lactate dehy-
drogenase (LDH) and creatine kinase (CK); coagulation disorders such
as thrombocytopenia, hypofibrinogenemia, prolonged activated partial
thromboplastin time (aPTT) and prothrombin time (PT) or international
normalized ratio (INR); and suppressed complete blood count in-
flammatory parameters such as leukocyte, lymphocyte, neutrophil and
monocyte. Bilirubin may also be an essential biomarker in CCHF due to
anti-inflammatory and anti-oxidative effects (Ergonul, 2006; Zhu et al.,
2010; Ergonul et al., 2004).
CCHF infection has four distinct phases in humans: an incubation
period, prehemorrhagic phase, hemorrhagic phase and the con-
valescence phase (Ergonul, 2006; Ergonul et al., 2017). In this study,
https://doi.org/10.1016/j.ttbdis.2019.05.010
Received 14 December 2018; Received in revised form 20 April 2019; Accepted 25 May 2019
⁎
Corresponding author at: Hitit University School of Medicine, Department of Medical Biochemistry, Corum, Turkey.
E-mail address: mdkayadibi@yahoo.com (H. Kayadibi).
Ticks and Tick-borne Diseases xxx (xxxx) xxx–xxx
1877-959X/ © 2019 Elsevier GmbH. All rights reserved.
Please cite this article as: Huseyin Kayadibi, et al., Ticks and Tick-borne Diseases, https://doi.org/10.1016/j.ttbdis.2019.05.010