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Table of Contents
Year : 2021  |  Volume : 58  |  Issue : 4  |  Page : 383-385

Biosensor-based methods for Crimean-Congo hemorrhagic fever virus detection

1 Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
2 Department of Biochemistry, Faculty of Sciences, Payame Noor University; Virology Department, Pasteur Institute of Tehran, Tehran, Iran
3 Microbial Biotechnology Research Center, Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
4 Neuroscience and Addiction Studies Department, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
5 Department of Microbiology, School of Medicine, Abadan University of Medical Sciences, Abadan, Iran

Date of Submission09-Mar-2021
Date of Acceptance03-Sep-2021
Date of Web Publication25-Mar-2022

Correspondence Address:
Samaneh Abbasi
Department of Microbiology, School of Medicine, Abadan University of Medical Sciences, Abadan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0972-9062.328976

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Crimean-Congo hemorrhagic fever is a tick-borne disease with high fatality rate that is endemic in some parts of Asia, Africa and Europe. Rapid diagnostics of Crimean-Congo hemorrhagic fever (CCHF) is necessary for appropriate clinical management of this disease and also can be useful in preventing of secondary spread from human-to-human, though, common tests which are used to diagnose Crimean-Congo hemorrhagic fever have some limitations. Here we review 1) common diagnostic tests for CCHF, 2) limitations in laboratories methods of CCHF and 3) biosensor researches for detection of CCHF. It is necessary to design and develop an effective, rapid, and also low-cost tool such as biosensor to detect Crimean-Congo hemorrhagic fever. Based on the key role of rapid detection of CCHF in the control of infection, development of a biosensor as a rapid tool seems very major in the diagnosis of CCHF, though, there are limited studies on this field and more researches are needed in this issue.

Keywords: Crimean-Congo hemorrhagic fever virus; diagnostic; biosensor

How to cite this article:
Zandi M, Rasooli A, Soltani S, Teymouri S, Mohammadi S, Abbasi S. Biosensor-based methods for Crimean-Congo hemorrhagic fever virus detection. J Vector Borne Dis 2021;58:383-5

How to cite this URL:
Zandi M, Rasooli A, Soltani S, Teymouri S, Mohammadi S, Abbasi S. Biosensor-based methods for Crimean-Congo hemorrhagic fever virus detection. J Vector Borne Dis [serial online] 2021 [cited 2022 May 21];58:383-5. Available from: https://www.jvbd.org/text.asp?2021/58/4/383/328976

  Introduction Top

Crimean-Congo hemorrhagic fever virus (CCHFV) is an enveloped negative sense ssRNA virus which belongs to Orthonairovirus genus of the Nairoviridae family[1] . It causes Crimean-Congo hemorrhagic fever disease which is a potentially serious tick-borne viral disease. CCHFV is transmitted to human by bite of infected ticks or from body fluids of infectious animals or individuals[2]. The common symptoms of CCHF including headache, chills, tiredness, generalized muscle pain, however, laboratory findings such as enhanced liver enzymes, raised duration of bleeding and thrombocytopenia are reported in infected individual with CCHF[3]. The treatment of CCHF is principally supportive, while the early use of ribavirin is helpful. Favipiravir was shown to be an efficient antiviral for the cure of advanced CCHF acting in vitro synergistically with ribavirin[4].

CCHF has been reported in the Balkans, Eastern Europe, central Asia, turkey, china, Middle East, and Africa[5],[6],[7],[8],[9]. CCHF has an average case mortality rate of 5-30%[10]. Due to high fatality rates associated with this infection, vast pathogenicity and facility of spread from human to human, a rapid and valid diagnosis method can prevent further spread of the disease.

Owing to the lack of special treatment choices or vaccines, and a high mortality rate, recognition of CCHF disease at primary stage will be helpful for the survival of patients. Currently, biosensors are considered as suitable analytical devices to detect infectious diseases and analysis of a variety of microorganism in biomedicine, food quality control, and pharmaceutical industry[11],[12],[13]. This review aims to present a quick, inexpensive, and applied detection method for CCHF disease that may lead to more effective diagnostic in both developed and underdeveloped countries.

Diagnosis methods of CCHF and limitation

Finding rapid diagnostic methods for CCHFV is an important strategy for rapid recovery of patient and protection of healthy individuals. There are several laboratory tests such as antigen-capture enzyme-linked immunosorbent assay (ELISA) and solid-phase radioimmunoassay technique (SPRIA), real-time polymerase chain reaction (RT-PCR), virus isolation (tissue culture or using mouse model). ELISA and SPRIA are the latest sensitive, rapid and reproducible techniques for diagnosis of viral antigen and antibodies even in the low level of infecting virus in short time (~5-6 h). PCR and Real-Time PCR are molecular methods that detect the viral genome. For detection of IgG and IgM antibodies in the serum (from Day 6) and in blood (up to four months for IgM and up to five years for IgG), laboratory method such as immunofluorescence (IF) and ELISA can be used[14],[15],[16].

Although all these laboratory methods are reliable and sensitive, there are some limitations such as need of special equipment, laboratories with high level of biosafety and good laboratory practice by laboratory staff handling materials from suspected CCHF cases. Thus, some of these detection techniques are not suitable in underdeveloped countries and are dangerous due to the potential transmission (sample-to-person, or indirect transmission)[17],[18].

In recent years, biosensor technology as a stable and economical system is used for quick diagnosis of infectious agents[19]. Biosensors are transportable analytical devices which comprise of a bioreceptor, transducer, analyze, and measurable signal[20]. This device demands an efficient immobilization of antibodies, aptamers, peptides, or nucleic acids on the surface of a transducer that can analysis recognition[11].

Biosensors for the detection of CCHFV

Biosensor platform for CCHFV can be considered in three main steps: (1) detection of various biorecognition elements such as nucleic acid or proteins of CCHFV, human immunoglobulins and human microRNA (miRNA), (2) use of an immobilized bioreceptor including DNA probe, antibody/antigen, ligand, aptamer and enzyme on a transducer, and (3) hybridization detection methods including electrochemical, piezoelectric, fluorescent, colorimetric, magnetic and acoustic technologies[18].

Researchers designed a fiber-optic biosensor for the detection produced IgG antibodies against of CCHF. They presented that the sensitivity of fiber-optic biosensor is 10 times more than colorimetric ELISA and both individuals infected with CCHFV with high and low levels of IgG antibodies were detected by fiber-optic biosensor[21]. Jalili et al. 2021 suggests that the aptamer-antibody ELISA test antibody could be used to diagnose CCHF-induced viral infections. This test has a rapid detection with a 100% sensitivity that can rapidly detect the nucleoprotein (NP) of the CCHF virus (CCHFV) in human serum[22].

Recently, for detecting four different viruses related to hemorrhagic fever in humans including hantavirus, dengue virus, Ebola virus and chikungunya fever virus, Zhao et al, developed lateral flow biosensor according to strand-displacement amplification and magnetic beads. They used various rapid methods, including LFB-based DNA detection and antibody-free enrichment of a specific virus[23].

  Conclusion Top

Today’s diagnostic methods in laboratories or diagnostic centers require expensive equipment or trained individuals for operation, however, CCHF-endemic areas are mostly rural and these diagnostic services are limited in such areas. Because of high pathogenicity of CCHFV and the high risk in transmission of CCHFV from human-to-human, developing biosensors as quick, reliable, safe and high sensitivity diagnostics tools can be very significant in the diagnosis of CCHF, however, more studies are needed in this field.

Conflict of interest: None

Ethical Statement

Ethical statement: The ethics committee of the Abadan University of Medical Sciences approved the study protocol (Ethics registration code: IR.ABADANUMS. REC.1399.217).

  References Top

Abudurexiti, A. Taxonomy of the order Bunyavirales: update 2019. Archives of virology 2019; 164(7): 1949-1965.  Back to cited text no. 1
Dai S. Crimean-Congo Hemorrhagic Fever Virus: Current Advances and Future Prospects of Antiviral Strategies. Viruses 2021; 13(7): 1195.  Back to cited text no. 2
Kilinc, C. Examination of the specific clinical symptoms and laboratory findings of Crimean-Congo hemorrhagic fever. Journal of vector borne diseases 2016; 53(2): 162.  Back to cited text no. 3
Papa, A. Diagnostic approaches for crimean-congo hemorrhagic fever virus. Expert review of molecular diagnostics 2019; 19(6): 531-536.  Back to cited text no. 4
Ergönül, O. Zoonotic infections among veterinarians in Turkey: Crimean-Congo hemorrhagic fever and beyond. International journal of infectious diseases 2006; 10(6): 465-469.  Back to cited text no. 5
Uyar, Y. Evaluation of PCR and ELISA-IgM results in the laboratory diagnosis of Crimean-Congo haemorrhagic fever cases in 2008 in Turkey. Mikrobiyoloji bulteni 2010; 44(1): 57-64.  Back to cited text no. 6
Whitehouse, C.A. Crimean–Congo hemorrhagic fever. Antiviral research 2004; 64(3): 145-160.  Back to cited text no. 7
Aksoy, D. Characteristics of headache and its relationship with disease severity in patients with Crimean–Congo hemorrhagic fever. Agri 2018; 30(1): 12-17.  Back to cited text no. 8
Sargianou, M. and A. Papa.Epidemiological and behavioral factors associated with Crimean-Congo hemorrhagic fever virus infections in humans. Expert review of anti-infective therapy 2013; 11 (9): 897-908.  Back to cited text no. 9
Tezer, H. Crimean–Congo hemorrhagic fever in children. Journal of Clinical Virology 2010; 48(3): 184-186.  Back to cited text no. 10
Fani, M. Future developments in biosensors for field-ready SARS-CoV-2 virus diagnostics. Biotechnology and applied biochemistry 2021; 68(4): 695-699.  Back to cited text no. 11
Nguyen, H.H. Immobilized enzymes in biosensor applications. Materials 2019; 12(1): 121.  Back to cited text no. 12
Zandi, M. Biosensor as an alternative diagnostic method for rabies virus detection: A literature review. Biotechnology and Applied Biochemistry 2021.  Back to cited text no. 13
Saleem, M. Crimean-Congo hemorrhagic fever: etiology, diagnosis, management and potential alternative therapy. Asian Pacific Journal of Tropical Medicine 2020; 13(4): 143.  Back to cited text no. 14
Shahbazi, N.Seroepidemiological survey of Crimean-Congo haemorrhagic fever among high-risk groups in the west of Iran. Journal of vector borne diseases 2019; 56(2): 174.  Back to cited text no. 15
Ergonul, O.Crimean–Congo hemorrhagic fever virus: new outbreaks, new discoveries. Current opinion in virology, 2012; 2(2): 215-220.  Back to cited text no. 16
Leblebicioglu, H. Healthcare-associated Crimean-Congo haem- orrhagic fever in Turkey, 2002–2014: a multicentre retrospective cross-sectional study. Clinical Microbiology and Infection 2016; 22(4): 387. e1-387. e4.  Back to cited text no. 17
Al-Abri, S.S. Clinical and molecular epidemiology of Crimean- Congo hemorrhagic fever in Oman. PLoS neglected tropical diseases 2019; 13(4): e0007100.  Back to cited text no. 18
Justino, C.I. Recent developments in recognition elements for chemical sensors and biosensors. TrAC Trends in Analytical Chemistry 2015; 68: 2-17.  Back to cited text no. 19
Saylan, Y. Surface plasmon resonance sensors for medical diagnosis, in Nanotechnology Characterization Tools for Biosensing and Medical Diagnosis. Springer 2018; 425-458.  Back to cited text no. 20
Algaar, F. Fiber-optic immunosensor for detection of Crimean- Congo hemorrhagic fever IgG antibodies in patients. Analytical chemistry 2015; 87(16): 8394-8398.  Back to cited text no. 21
Jalali, T. Aptamer based diagnosis of crimean-congo hemorrhagic fever from clinical specimens. Scientific Reports 2021; 11 (1): 1-10.  Back to cited text no. 22
Zhao, J. A lateral flow biosensor based on gold nanoparticles detects four hemorrhagic fever viruses. Analytical Methods 2020; 12(46): 5613-5620.  Back to cited text no. 23


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