iğdır üniv. fen bil enst. der. Journal of the Institute of Science and Technology 2536-4618 Iğdır Üniversitesi 10.21597/jist.1412021 Virology Viroloji Crimean-Congo Haemorrhagic Fever Virus: From Genomic Insights to Control Strategies https://orcid.org/0000-0002-7955-086X Keşkek Türk Yonca University of Leeds, Faculty of Medicine and Health https://orcid.org/0000-0003-3745-8173 Kacı Fatma Necmiye University of Leeds, Faculty of Medicine and Health 06 01 2024 14 2 650 667 12 30 2023 03 13 2024 Copyright © 2011, Iğdır Üniversitesi Fen Bilimleri Enstitüsü Dergisi 2011 Iğdır Üniversitesi Fen Bilimleri Enstitüsü Dergisi

Crimean-Congo hemorrhagic fever virus (CCHFV) is a life-threatening arthropod-borne virus transmitted by tick bites or contact with blood or tissues of viraemic individuals and animals. CCHFV continues its existence in a broad region with sporadic cases or outbreaks. CCHFV infection is observed frequently as an asymptomatic, but sudden severe disease characterised by haemorrhagic can occur. Diagnostic methods employ enzyme-linked immunosorbent assay (ELISA) and real-time reverse transcription-polymerase chain reaction (RT-PCR). Although ribavirin has been recommended in treatment besides supportive therapy approaches, no antiviral or vaccine for CCHF is currently approved. This review demonstrates general knowledge of CCHFV, summarising its molecular biology, pathogenesis, diagnosis, epidemiology, sustaining and transmission, treatment and prevention strategies, including vaccine candidates.

 Crimean-Congo haemorrhagic fever (CCHFV) Viral haemorrhagic fevers Tick-borne Zoonosis One Health Adamu, A. M., Onoja, A. B., Ugbodu, V. E., Bala, R. S., Maina, M., Salisu, U. S., … Adegboye, O. (2024). Investigating Crimean-Congo Haemorrhagic Fever Virus Seropositivity in Camels and Human Behavioural Risks in an Abattoir in Nigeria. Epidemiology and Infection, 1, 1–8. https://doi.org/10.1017/S0950268824000189 Ahata, B., & Akçapınar, G. B. (2023). CCHFV vaccine development, current challenges, limitations, and future directions. Frontiers in Immunology, 14(September), 1–18. https://doi.org/10.3389/fimmu.2023.1238882 Ahmeti, S., Berisha, L., Halili, B., Ahmeti, F., von Possel, R., Thomé-Bolduan, C., … Emmerich, P. (2019). Crimean-congo hemorrhagic fever, Kosovo, 2013–2016. Emerging Infectious Diseases, 25(2), 321–324. https://doi.org/10.3201/eid2502.171999 Akuffo, R., Brandful, J. A. M., Zayed, A., Adjei, A., Watany, N., Fahmy, N. T., … Dueger, E. (2016). Crimean-Congo hemorrhagic fever virus in livestock ticks and animal handler seroprevalence at an abattoir in Ghana. BMC Infectious Diseases, 16(1), 1–5. https://doi.org/10.1186/s12879-016-1660-6 Al-Abri, S. S., Hewson, R., Al-Kindi, H., Al-Abaidani, I., Al-Jardani, A., Al-Maani, A., … Beeching, N. J. (2019). Clinical and molecular epidemiology of Crimean-Congo hemorrhagic fever in Oman. PLoS Neglected Tropical Diseases, 13(4), 1–15. https://doi.org/10.1371/journal.pntd.0007100 Albayrak, H., Ozan, E., & Kurt, M. (2012). Serosurvey and molecular detection of Crimean-Congo hemorrhagic fever virus (CCHFV) in northern Turkey. Tropical Animal Health and Production, 44(7), 1667–1671. https://doi.org/10.1007/s11250-012-0122-4 Antoniadis, A., Alexiou-Daniel, S., Malissiovas, N., Doutsos, J., Polyzoni, T., LeDue, J. W., … Saviolakis, G. (1991). Seroepidemiological survey for antibodies to arboviruses in Greece. Hemorrhagic Fever with Renal Syndrome, Tick-and Mosquito-Borne Viruses, 277–285. Springer. Arteaga, L. M., Bellido, J. L. M., Lista, M. C. V., Santiago, M. B. V., Soto, P. F., Bas, I., … Muro, A. (2020). Crimean-Congo haemorrhagic fever (CCHF) virusspecific antibody detection in blood donors, Castile-León, Spain, summer 2017 and 2018. Eurosurveillance, 25(10), 1–7. https://doi.org/10.2807/1560-7917.ES.2020.25.10.1900507 Atwan, Z., Alhilfi, R., Mousa, A. K., Rawaf, S., Torre, J. D. L., Hashim, A. R., … Tabche, C. (2024). Alarming update on incidence of Crimean-Congo hemorrhagic fever in Iraq in 2023. IJID Regions, 10(November 2023), 75–79. https://doi.org/10.1016/j.ijregi.2023.11.018 Barnwal, B., Karlberg, H., Mirazimi, A., & Tan, Y. J. (2016). The non-structural protein of Crimean-Congo hemorrhagic fever virus disrupts the mitochondrial membrane potential and induces apoptosis. Journal of Biological Chemistry, 291(2), 582–592. https://doi.org/10.1074/jbc.M115.667436 Bartolini, B., Gruber, C. E. M., Koopmans, M., Avšič, T., Bino, S., Christova, I., … Di Caro, A. (2019). Laboratory management of Crimean-Congo haemorrhagic fever virus infections: Perspectives from two European networks. Eurosurveillance, 24(5), 1–14. https://doi.org/10.2807/1560-7917.ES.2019.24.5.1800093 Bente, D. A., Forrester, N. L., Watts, D. M., McAuley, A. J., Whitehouse, C. A., & Bray, M. (2013). Crimean-Congo hemorrhagic fever: History, epidemiology, pathogenesis, clinical syndrome and genetic diversity. Antiviral Research, 100(1), 159–189. https://doi.org/10.1016/j.antiviral.2013.07.006 Bergeron, É., Albariño, C. G., Khristova, M. L., & Nichol, S. T. (2010). Crimean-Congo Hemorrhagic Fever Virus-Encoded Ovarian Tumor Protease Activity Is Dispensable for Virus RNA Polymerase Function. Journal of Virology, 84(1), 216–226. https://doi.org/10.1128/jvi.01859-09 Bernard, C., Holzmuller, P., Bah, M. T., Bastien, M., Combes, B., Jori, F., … Vial, L. (2022). Systematic Review on Crimean–Congo Hemorrhagic Fever Enzootic Cycle and Factors Favoring Virus Transmission: Special Focus on France, an Apparently Free-Disease Area in Europe. Frontiers in Veterinary Science, 9(July), 1–17. https://doi.org/10.3389/fvets.2022.932304 Bernard, C., Joly Kukla, C., Rakotoarivony, I., Duhayon, M., Stachurski, F., Huber, K., … Vial, L. (2024). Detection of Crimean-Congo haemorrhagic fever virus in Hyalomma marginatum ticks, southern France, May 2022 and April 2023. Euro Surveillance : Bulletin Europeen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin, 29(6), 1–6. https://doi.org/10.2807/1560-7917.ES.2024.29.6.2400023 Bertolotti-Ciarlet, A., Smith, J., Strecker, K., Paragas, J., Altamura, L. A., McFalls, J. M., … Doms, R. W. (2005). Cellular Localization and Antigenic Characterization of Crimean-Congo Hemorrhagic Fever Virus Glycoproteins. Journal of Virology, 79(10), 6152–6161. https://doi.org/10.1128/jvi.79.10.6152-6161.2005 Blair, P. W., Kuhn, J. H., Pecor, D. B., Apanaskevich, D. A., Kortepeter, M. G., Cardile, A. P., … Keshtkar-Jahromi, M. (2019). An emerging biothreat: Crimean-Congo hemorrhagic fever virus in southern and western Asia. American Journal of Tropical Medicine and Hygiene, 100(1), 16–23. https://doi.org/10.4269/ajtmh.18-0553 Bodur, H., Akinci, E., Ascioglu, S., Öngürü, P., & Uyar, Y. (2012). Subclinical infections with Crimean-Congo hemorrhagic fever virus, Turkey. Emerging Infectious Diseases, 18(4), 640–642. https://doi.org/10.3201/eid1804.111374 Body, M. H. H., Abdulmajeed, H. Al., Hammad, M. H., Mohamed, S. A., Saif, S. Alh., Salim, A.-M., … Rajamony, S. (2016). Cross-sectional survey of Crimean-Congo hemorrhagic fever virus in the sultanate of Oman. Journal of Veterinary Medicine and Animal Health, 8(6), 44–49. Bonnet, S. I., Bertagnoli, S., Falchi, A., Figoni, J., Fite, J., Hoch, T., … Vial, L. (2023). An Update of Evidence for Pathogen Transmission by Ticks of the Genus Hyalomma. Pathogens, 12(4), 1–19. https://doi.org/10.3390/pathogens12040513 Bonnet, S. I., Vourc’h, G., Raffetin, A., Falchi, A., Figoni, J., Fite, J., … Quillery, E. (2022). The control of Hyalomma ticks, vectors of the Crimean–Congo hemorrhagic fever virus: Where are we now and where are we going? PLoS Neglected Tropical Diseases, 16(11), 1–23. https://doi.org/10.1371/journal.pntd.0010846 Bonney, L. C., Watson, R. J., Afrough, B., Mullojonova, M., Dzhuraeva, V., Tishkova, F., & Hewson, R. (2017). A recombinase polymerase amplification assay for rapid detection of Crimean-Congo Haemorrhagic fever Virus infection. PLOS Neglected Tropical Diseases, 11(10), e0006013. https://doi.org/10.1371/journal.pntd.0006013 Bouaicha, F., Eisenbarth, A., Elati, K., Schulz, A., Ben Smida, B., Bouajila, M., … Khamassi Khbou, M. (2021). Epidemiological investigation of Crimean-Congo haemorrhagic fever virus infection among the one-humped camels (Camelus dromedarius) in southern Tunisia. Ticks and Tick-Borne Diseases, 12(1). https://doi.org/10.1016/j.ttbdis.2020.101601 Burney, M. I., Ghafoor, A., Webb, P. A., Saleen, M., & Casals, J. (1980). Nosocomial Outbrak of Viral Hemorrhagic Fever Caused by Crimean Hemorrhagic Fever-Congo Virus in Pakistan, January 1976 *. The American Journal of Tropical Medicine and Hygiene, 29(5), 941–947. https://doi.org/10.4269/ajtmh.1980.29.941 Burt, F. J., Leman, P. A., Smith, J. F., & Swanepoel, R. (1998). The use of a reverse transcription-polymerase chain reaction for the detection of viral nucleic acid in the diagnosis of Crimean-Congo haemorrhagic fever. Journal of Virological Methods, 70(2), 129–137. https://doi.org/10.1016/S0166-0934(97)00182-1 Casals, J. (1969). Antigenic similarity between the virus causing Crimean hemorrhagic fever and Congo virus. Proceedings of the Society for Experimental Biology and Medicine, 131(1), 233–236. https://doi.org/https://doi.org/10.3181/00379727-131-33847 Chinikar, S., Ghiasi, S. M., Naddaf, S., Piazak, N., Moradi, M., Razavi, M. R., … Ataei, B. (2012). Serological evaluation of Crimean-Congo hemorrhagic fever in humans with high-risk professions living in enzootic regions of Isfahan Province of Iran and genetic analysis of circulating strains. Vector-Borne and Zoonotic Diseases, 12(9), 733–738. Chinikar, S., Shayesteh, M., Khakifirouz, S., Jalali, T., Rasi Varaie, F. S., Rafigh, M., … Shah-Hosseini, N. (2013). Nosocomial infection of Crimean-Congo haemorrhagic fever in eastern Iran: Case report. Travel Medicine and Infectious Disease, 11(4), 252–255. https://doi.org/10.1016/j.tmaid.2012.11.009 Conger, N. G., Paolino, K. M., Osborn, E. C., Rusnak, J. M., Günther, S., Pool, J., … Rieger, T. (2015). Health care response to CCHF in US soldier and nosocomial transmission to health care providers, Germany, 2009. Emerging Infectious Diseases, 21(1), 23. Cooper, R. G., Horbanczuk, J. O., & Fujihara, N. (2004). Viral diseases of the Ostrich (Struthio camelus var. domesticus). Animal Science Journal, 75(2), 89–95. https://doi.org/10.1111/j.1740-0929.2004.00161.x D’Addiego, J., Elaldi, N., Wand, N., Osman, K., Bagci, B. K., Kennedy, E., … Hewson, R. (2023). Investigating the effect of ribavirin treatment on genetic mutations in Crimean–Congo haemorrhagic fever virus (CCHFV) through next-generation sequencing. Journal of Medical Virology, 95(2). https://doi.org/10.1002/jmv.28548 de la Fuente, J., & Contreras, M. (2022). Additional considerations for anti-tick vaccine research. Expert Review of Vaccines, 21(8), 1019–1021. https://doi.org/10.1080/14760584.2022.2071704 Dowall, S. D., Richards, K. S., Graham, V. A., Chamberlain, J., & Hewson, R. (2012). Development of an indirect ELISA method for the parallel measurement of IgG and IgM antibodies against Crimean-Congo haemorrhagic fever (CCHF) virus using recombinant nucleoprotein as antigen. Journal of Virological Methods, 179(2), 335–341. https://doi.org/10.1016/j.jviromet.2011.11.020 Drosten, C., Göttig, S., Schilling, S., Asper, M., Panning, M., Schmitz, H., & Günther, S. (2002). Rapid detection and quantification of RNA of Ebola and Marburg viruses, Lassa virus, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus, dengue virus, and yellow fever virus by real-time reverse transcription-PCR. Journal of Clinical Microbiology, 40(7), 2323–2330. https://doi.org/10.1128/JCM.40.7.2323-2330.2002 Drosten, C., Kümmerer, B. M., Schmitz, H., & Günther, S. (2003). Molecular diagnostics of viral hemorrhagic fevers. Antiviral Research, 57(1–2), 61–87. https://doi.org/10.1016/S0166-3542(02)00201-2 Duh, D., Saksida, A., Petrovec, M., Dedushaj, I., & Avšič-ŽUpanc, T. (2006). Novel one-step real-time RT-PCR assay for rapid and specific diagnosis of Crimean-Congo hemorrhagic fever encountered in the Balkans. Journal of Virological Methods, 133(2), 175–179. https://doi.org/10.1016/j.jviromet.2005.11.006 Emmerich, P., Mika, A., von Possel, R., Rackow, A., Liu, Y., Schmitz, H., … Deschermeier, C. (2018). Sensitive and specific detection of Crimean-Congo Hemorrhagic Fever Virus (CCHFV)—Specific IgM and IgG antibodies in human sera using recombinant CCHFV nucleoprotein as antigen in μ-capture and IgG immune complex (IC) ELISA tests. PLoS Neglected Tropical Diseases, 12(3), 1–24. https://doi.org/10.1371/journal.pntd.0006366 Emmerich, P., von Possel, R., Deschermeier, C., Ahmeti, S., Berisha, L., Halili, B., … Borchardt-Lohölter, V. (2021). Comparison of diagnostic performances of ten different immunoassays detecting anti-CCHFVIgM and IgG antibodies from acute to subsided phases of Crimean-Congo hemorrhagic fever. PLoS Neglected Tropical Diseases, 15(3), 1–15. https://doi.org/10.1371/journal.pntd.0009280 Ergönül, Ö. (2006). Crimean-Congo haemorrhagic fever. The Lancet Infectious Diseases, 6(4), 203–214. https://doi.org/10.1016/S1473-3099(06)70435-2 Ergonul, O., Celikbas, A., Baykam, N., Eren, S., & Dokuzoguz, B. (2006). Analysis of risk-factors among patients with Crimean-Congo haemorrhagic fever virus infection: severity criteria revisited. Clinical Microbiology and Infection, 12(6), 551–554. https://doi.org/10.1111/j.1469-0691.2006.01445.x Ergönül, Ö., Çelikbaş, A., Dokuzoǧuz, B., Eren, Ş., Baykam, N., & Esener, H. (2004). Characteristics of patients with crimean-congo heniorrhagic fever in a recent outbreak in Turkey and impact of oral ribavirin therapy. Clinical Infectious Diseases, 39(2), 284–287. https://doi.org/10.1086/422000 Ergönül, Ö., Keske, Ş., Çeldir, M. G., Kara, İ. A., Pshenichnaya, N., Abuova, G., … Gönen, M. (2018). Systematic review and meta-analysis of postexposure prophylaxis for crimean-congo hemorrhagic fever virus among healthcare workers. Emerging Infectious Diseases, 24(9), 1642–1648. https://doi.org/10.3201/eid2409.171709 Ergonul, Onder. (2008). Treatment of Crimean-Congo hemorrhagic fever. Antiviral Research, 78(1), 125–131. https://doi.org/10.1016/j.antiviral.2007.11.002 Ergonul, Onder. (2012). Crimean-Congo hemorrhagic fever virus: New outbreaks, new discoveries. Current Opinion in Virology, 2(2), 215–220. https://doi.org/10.1016/j.coviro.2012.03.001 Espunyes, J., Cabezón, O., Pailler-García, L., Dias-Alves, A., Lobato-Bailón, L., Marco, I., … Napp, S. (2021). Hotspot of Crimean-congo hemorrhagic fever virus seropositivity in wildlife, northeastern Spain. Emerging Infectious Diseases, 27(9), 2480–2484. https://doi.org/10.3201/eid2709.211105 Estrada-Peña, A., Palomar, A. M., Santibáñez, P., Sánchez, N., Habela, M. A., Portillo, A., … Oteo, J. A. (2012). Crimean-Congo Hemorrhagic Fever Virus in Ticks, Southwestern Europe, 2010. Emerging Infectious Diseases, 18(1), 179–180. https://doi.org/10.3201/eid1801.111040 Estrada, D. F., & De Guzman, R. N. (2011). Structural Characterization of the Crimean-Congo Hemorrhagic Fever Virus Gn Tail Provides Insight into Virus Assembly. Journal of Biological Chemistry, 286(24), 21678–21686. https://doi.org/10.1074/jbc.M110.216515 Febrer-Sendra, B., Fernández-Soto, P., García-Bernalt Diego, J., Crego-Vicente, B., Negredo, A., Muñor-Bellido, J. L., … Muro, A. (2023). A Novel RT-LAMP for the Detection of Different Genotypes of Crimean–Congo Haemorrhagic Fever Virus in Patients from Spain. International Journal of Molecular Sciences, 24(7). https://doi.org/10.3390/ijms24076411 Fels, J. M., Maurer, D. P., Herbert, A. S., Wirchnianski, A. S., Vergnolle, O., Cross, R. W., … Laura, M. (2022). HHS Public Access. 184(13), 3486–3501. https://doi.org/10.1016/j.cell.2021.05.001.Protective Fillâtre, P., Revest, M., & Tattevin, P. (2019). Crimean-Congo hemorrhagic fever: An update. Medecine et Maladies Infectieuses, 49(8), 574–585. https://doi.org/10.1016/j.medmal.2019.09.005 Fletcher, T. E., Gulzhan, A., Ahmeti, S., Al-Abri, S. S., Asik, Z., Atilla, A., … Leblebicioglu, H. (2017). Infection prevention and control practice for Crimean-Congo hemorrhagic fever - A multi-center cross-sectional survey in Eurasia. PLoS ONE, 12(9), 1–10. https://doi.org/10.1371/journal.pone.0182315 Freitas, N., Enguehard, M., Denolly, S., Levy, C., Neveu, G., Lerolle, S., … Cosset, F. L. (2020). The interplays between crimean-congo hemorrhagic fever virus (cchfv) m segment-encoded accessory proteins and structural proteins promote virus assembly and infectivity. PLoS Pathogens, 16(9), 1–29. https://doi.org/10.1371/journal.ppat.1008850 García Rada, A. (2016). First outbreak of Crimean-Congo haemorrhagic fever in western Europe kills one man in Spain. BMJ, 354(September), i4891. https://doi.org/10.1136/bmj.i4891 Gargili, A., Estrada-Peña, A., Spengler, J. R., Lukashev, A., Nuttall, P. A., & Bente, D. A. (2017). The role of ticks in the maintenance and transmission of Crimean-Congo hemorrhagic fever virus: A review of published field and laboratory studies. Antiviral Research, 144, 93–119. https://doi.org/10.1016/j.antiviral.2017.05.010 Garrison, A. R., Alkhovsky [Альховский Сергей Владимирович], S. V., Avšič-Županc, T., Bente, D. A., Bergeron, É., Burt, F., … Consortium, I. R. (2020). ICTV Virus Taxonomy Profile: Nairoviridae. Journal of General Virology, 101(8), 798–799. https://doi.org/10.1099/jgv.0.001485 Goedhals, D., Paweska, J. T., & Burt, F. J. (2017). Long-lived CD8+ T cell responses following Crimean-Congo haemorrhagic fever virus infection. PLoS Neglected Tropical Diseases, 11(12), 1–12. https://doi.org/10.1371/journal.pntd.0006149 Graci, J. D., & Cameron, C. E. (2006). Mechanisms of action of ribavirin against distinct viruses. Reviews in Medical Virology, 16(1), 37–48. https://doi.org/10.1002/rmv.483 Grandi, G., Chitimia-dobler, L., Choklikitumnuey, P., Strube, C., Springer, A., Albihn, A., … Omazic, A. (2020). First records of adult Hyalomma marginatum and H. rufipes ticks (Acari: Ixodidae) in Sweden. Ticks and Tick-Borne Diseases, 11(3), 101403. https://doi.org/https://doi.org/10.1016/j.ttbdis.2020.101403 Grard, G., Drexler, J. F., Fair, J., Muyembe, J. J., Wolfe, N. D., Drosten, C., & Leroy, E. M. (2011). Re-Emergence of Crimean-Congo hemorrhagic fever virus in central Africa. PLoS Neglected Tropical Diseases, 5(10), 4–6. https://doi.org/10.1371/journal.pntd.0001350 Guglielmone, A. A., Robbins, R. G., Apanaskevich, D. A., Petney, T. N., Estrada Peña, A., Horak, I. G., … Barker, S. C. (2010). The Argasidae, Ixodidae and Nuttalliellidae (Acari: Ixodida) of the world: a list of valid species names. Hawman, D. W., & Feldmann, H. (2023). Crimean–Congo haemorrhagic fever virus. Nature Reviews Microbiology, 21(7), 463–477. https://doi.org/10.1038/s41579-023-00871-9 Hawman, D. W., Haddock, E., Meade-White, K., Williamson, B., Hanley, P. W., Rosenke, K., … Feldmann, H. (2018). Favipiravir (T-705) but not ribavirin is effective against two distinct strains of Crimean-Congo hemorrhagic fever virus in mice. Antiviral Research, 157(June), 18–26. https://doi.org/10.1016/j.antiviral.2018.06.013 Hema, M., & Konakalla, N. C. (2021). Recent developments in detection and diagnosis of plant viruses. Recent Developments in Applied Microbiology and Biochemistry, 163–180. Hoogstraal, H. (1979). Review Article: The Epidemiology of Tick-Borne Crimean-Congo Hemorrhagic Fever in Asia, Europe, and Africa. Journal of Medical Entomology, 15(4), 307–417. https://doi.org/10.1093/jmedent/15.4.307 Hulswit, R. J. G., Paesen, G. C., Bowden, T. A., & Shi, X. (2021). Recent advances in bunyavirus glycoprotein research: Precursor processing, receptor binding and structure. Viruses, 13(2), 1–30. https://doi.org/10.3390/v13020353 Ibrahim, A. S., Ibrahim, K. S., Mohammed, M. O., Al-Shaikhani, M. A., Barzanji, A. A., Saeed, S. J., … Bhnam, M. N. (2014). Crimean Congo hemorrhagic fever management in Erbil during 2010-2011. European Scientific Journal, 10(24). Jalali, T., Salehi-Vaziri, M., Pouriayevali, M. H., & Gargari, S. L. M. (2021). Aptamer based diagnosis of crimean-congo hemorrhagic fever from clinical specimens. Scientific Reports, 11(1), 12639. https://doi.org/10.1038/s41598-021-91826-8 Johnson, S., Henschke, N., Maayan, N., Mills, I., Buckley, B. S., Kakourou, A., & Marshall, R. (2018). Ribavirin for treating Crimean Congo haemorrhagic fever. Cochrane Database of Systematic Reviews, 2018(6). https://doi.org/10.1002/14651858.CD012713.pub2 Kadanali, A., Erol, S., Özkurt, Z., & Özden, K. (2009). Epidemiological risk factors for Crimean-Congo hemorrhagic fever patients. Turkish Journal of Medical Sciences, 39(6), 829–832. https://doi.org/10.3906/sag-0904-49 Kamboj, A., Pateriya, A. K., Mishra, A., Ranaware, P., Kulkarni, D. D., & Raut, A. A. (2014). Novel molecular beacon probe-based real-time RT-PCR assay for diagnosis of Crimean-Congo hemorrhagic fever encountered in India. BioMed Research International, 2014, 5–8. https://doi.org/10.1155/2014/496219 Karti, S. S., Odabasi, Z., Korten, V., Yilmaz, M., Sonmez, M., Caylan, R., … Ksiazek, T. G. (2004). Crimean-Congo hemorrhagic fever in Turkey. Emerging Infectious Diseases, 10(8), 1379–1384. https://doi.org/10.3201/eid1008.030928 Keshtkar-Jahromi, M., Kuhn, J. H., Christova, I., Bradfute, S. B., Jahrling, P. B., & Bavari, S. (2011). Crimean-Congo hemorrhagic fever: Current and future prospects of vaccines and therapies. Antiviral Research, 90(2), 85–92. https://doi.org/10.1016/j.antiviral.2011.02.010 Khan, A. S., Maupin, G. O., Rollin, P. E., Noor, A. M., Shurie, H. H., Shalabi, A. G., … Ijaz, K. (1997). An outbreak of Crimean-Congo hemorrhagic fever in the United Arab Emirates, 1994-1995. The American Journal of Tropical Medicine and Hygiene, 57(5), 519–525. Komut, S., Çorakyer, N., Kaplan, G., & Baykam, N. (2023). An Evaluation of the Hitit Index in Differential Diagnosis of Crimean-Congo Hemorrhagic Fever in the Emergency Department. Medicina, 59(10), 1796. https://doi.org/10.3390/medicina59101796 Kubar, A., Haciomeroglu, M., Ozkul, A., Bagriacik, U., Akinci, E., Sener, K., & Bodur, H. (2011). Prompt administration of crimean-congo hemorrhagic fever (CCHF) virus hyperimmunoglobulin in patients diagnosed with CCHF and viral load monitorization by reverse transcriptase-PCR. Japanese Journal of Infectious Diseases, 64(5), 439–443. https://doi.org/10.7883/yoken.64.439 Kumar, B., Manjunathachar, H. V., & Ghosh, S. (2020). A review on Hyalomma species infestations on human and animals and progress on management strategies. Heliyon, 6(12), e05675. https://doi.org/10.1016/j.heliyon.2020.e05675 Leblebicioglu, H. (2010). Crimean-Congo haemorrhagic fever in Eurasia. International Journal of Antimicrobial Agents, 36(SUPPL. 1), 43–46. https://doi.org/10.1016/j.ijantimicag.2010.06.020 Leblebicioglu, H., Ozaras, R., Irmak, H., & Sencan, I. (2016). Crimean-Congo hemorrhagic fever in Turkey: Current status and future challenges. Antiviral Research, 126, 21–34. https://doi.org/10.1016/j.antiviral.2015.12.003 Liu, D., Li, Y., Zhao, J., Deng, F., Duan, X., Kou, C., … Sun, S. (2014). Fine Epitope Mapping of the Central Immunodominant Region of Nucleoprotein from Crimean-Congo Hemorrhagic Fever Virus (CCHFV). PLoS ONE, 9(11), e108419. https://doi.org/10.1371/journal.pone.0108419 Maltezou, H. C., Papa, A., Tsiodras, S., Dalla, V., Maltezos, E., & Antoniadis, A. (2009). Crimean-Congo hemorrhagic fever in Greece: a public health perspective. International Journal of Infectious Diseases, 13(6), 713–716. https://doi.org/10.1016/j.ijid.2008.11.011 Mardani, M., Jahromi, M. K., Naieni, K. H., & Zeinali, M. (2003). The Efficacy of Oral Ribavirin in the Treatment of Crimean-Congo Hemorrhagic Fever in Iran. Clinical Infectious Diseases, 36(12), 1613–1618. https://doi.org/10.1086/375058 Messina, J. P., Pigott, D. M., Golding, N., Duda, K. A., Brownstein, J. S., Weiss, D. J., … Hay, S. I. (2015). The global distribution of Crimean-Congo hemorrhagic fever. (July), 503–513. https://doi.org/10.1093/trstmh/trv050 Mofleh, J., & Ahmad, A. Z. (2012). Crimean–Congo haemorrhagic fever outbreak investigation in the Western Region of Afghanistan in 2008. Eastern Mediterranean Health Journal, 18(5), 522–526. https://doi.org/10.26719/2012.18.5.522 Moshref, Z. S., Jalali, T., Rezaei Adriani, R., Soltati, E., & Mousavi Gargari, S. L. (2023). Aptamer-based diagnosis of various SARS-CoV2 strains isolated from clinical specimens. Heliyon, 9(6), e16458. https://doi.org/10.1016/j.heliyon.2023.e16458 Mousavi-Jazi, M., Karlberg, H., Papa, A., Christova, I., & Mirazimi, A. (2012). Healthy individuals’ immune response to the Bulgarian Crimean-Congo hemorrhagic fever virus vaccine. Vaccine, 30(44), 6225–6229. https://doi.org/10.1016/j.vaccine.2012.08.003 Mustafa, M. L., Ayazi, E., Mohareb, E., Yingst, S., Zayed, A., Rossi, C. A., … Leslie, T. (2011). Crimean-Congo Hemorrhagic Fever, Afghanistan, 2009. Emerging Infectious Diseases, 17(10), 1940–1941. https://doi.org/10.3201/eid1710.110061 Negredo, A., de la Calle-Prieto, F., Palencia-Herrejón, E., Mora-Rillo, M., Astray-Mochales, J., Sánchez-Seco, M. P., … Arribas, J. R. (2017). Autochthonous Crimean–Congo Hemorrhagic Fever in Spain. New England Journal of Medicine, 377(2), 154–161. https://doi.org/10.1056/nejmoa1615162 Nekliudov, M. (1952). A case of hemorrhagic fever (Crimean). Savremenna Medicina, 5, 92–95. Oestereich, L., Rieger, T., Neumann, M., Bernreuther, C., Lehmann, M., Krasemann, S., … Günther, S. (2014). Evaluation of Antiviral Efficacy of Ribavirin, Arbidol, and T-705 (Favipiravir) in a Mouse Model for Crimean-Congo Hemorrhagic Fever. PLoS Neglected Tropical Diseases, 8(5). https://doi.org/10.1371/journal.pntd.0002804 Omoga, D. C. A., Tchouassi, D. P., Venter, M., Ogola, E. O., Osalla, J., Kopp, A., … Sang, R. (2023). Transmission Dynamics of Crimean–Congo Haemorrhagic Fever Virus (CCHFV): Evidence of Circulation in Humans, Livestock, and Rodents in Diverse Ecologies in Kenya. Viruses, 15(9), 1–17. https://doi.org/10.3390/v15091891 Ozdarendeli, A. (2023). Crimean–Congo Hemorrhagic Fever Virus: Progress in Vaccine Development. Diagnostics, 13(16), 1–29. https://doi.org/10.3390/diagnostics13162708 Ozkaya, E., Dincer, E., Carhan, A., Uyar, Y., Ertek, M., Whitehouse, C. A., & Ozkul, A. (2010). Molecular epidemiology of Crimean-Congo hemorrhagic fever virus in Turkey: Occurrence of local topotype. Virus Research, 149(1), 64–70. https://doi.org/10.1016/j.virusres.2009.12.014 Palomar, A. M., Portillo, A., Santibáñez, P., Mazuelas, D., Arizaga, J., Crespo, A., … Oteo, J. A. (2013). Crimean-congo hemorrhagic fever virus in ticks from migratory birds, Morocco. Emerging Infectious Diseases, 19(2), 260–263. https://doi.org/10.3201/eid1902.121193 Papa, Anna, Christova, I., Papadimitriou, E., & Antoniadis, A. (2004). Crimean-Congo hemorrhagic fever in Bulgaria. Emerging Infectious Diseases, 10(8), 1465–1467. https://doi.org/10.3201/eid1008.040162 Papa, Anna, Papadimitriou, E., & Christova, I. (2011). The Bulgarian vaccine Crimean-Congo haemorrhagic fever virus strain. Scandinavian Journal of Infectious Diseases, 43(3), 225–229. https://doi.org/10.3109/00365548.2010.540036 Papa, Anna, Tsergouli, K., Tsioka, K., & Mirazimi, A. (2017). Crimean-Congo hemorrhagic fever: Tick-host-virus interactions. Frontiers in Cellular and Infection Microbiology, 7(MAY), 1–7. https://doi.org/10.3389/fcimb.2017.00213 Papa, Anna, Tzala, E., & Maltezou, H. C. (2011). Crimean-Congo Hemorrhagic Fever Virus, Northeastern Greece. Emerging Infectious Diseases, 17(1), 141–143. https://doi.org/10.3201/eid1701.100073 Papadopoulos, O. t, & Koptopoulos, G. (1980). Crimean-Congo hemorrhagic fever (CCHF) in Greece: isolation of the virus from Rhipicephalus bursa ticks and a preliminary serological survey. Zentbl Bakteriol Hyg Abt, 1(Suppl 9), 189–193. Pattyn, S. R. (1978). Ebola virus haemorrhagic fever. Proceedings of an International Colloquium on Ebola Virus Infection and Other Haemorrhagic Fevers held in Antwerp, Belgium, 6-8 December, 1977. Ebola Virus Haemorrhagic Fever. Proceedings of an International Colloquium on Ebola Virus Infection and Other Haemorrhagic Fevers Held in Antwerp, Belgium, 6-8 December, 1977. Elsevier/North-Holland Biomedical Press, 335 Jan van Galenstraat, PO Box 211 …. Rosenke, K., Feldmann, H., Westover, J. B., Hanley, P. W., Martellaro, C., Feldmann, F., … Safronetz, D. (2018). Use of favipiravir to treat lassa virus infection in Macaques. Emerging Infectious Diseases, 24(9), 1696–1699. https://doi.org/10.3201/eid2409.180233 Safronetz, D., Rosenke, K., Westover, J. B., Martellaro, C., Okumura, A., Furuta, Y., … Gowen, B. B. (2015). The broad-spectrum antiviral favipiravir protects Guinea pigs from lethal Lassa virus infection post-disease onset. Scientific Reports, 5(June), 1–11. https://doi.org/10.1038/srep14775 Saijo, M., Tang, Q., Shimayi, B., Han, L., Zhang, Y., Asiguma, M., … Morikawa, S. (2005). Recombinant nucleoprotein-based serological diagnosis of Crimean-Congo hemorrhagic fever virus infections. Journal of Medical Virology, 75(2), 295–299. https://doi.org/10.1002/jmv.20270 Salim Abadi, Y., Telmadarraiy, Z., Vatandoost, H., Chinikar, S., Oshaghi, M. A., Moradi, M., … Nasiri, A. (2010). Hard ticks on domestic ruminants and their seasonal population pynamics in Yazd Province, Iran. Iranian Journal of Arthropod-Borne Diseases, 4(1), 66–71. Sargianou, M., Panos, G., Tsatsaris, A., Gogos, C., & Papa, A. (2013). Crimean-Congo hemorrhagic fever: Seroprevalence and risk factors among humans in Achaia, western Greece. International Journal of Infectious Diseases, 17(12), e1160–e1165. https://doi.org/10.1016/j.ijid.2013.07.015 Schluederberg, A. N. N. (1965). Immune Globulins in Human Viral Infections. Nature, 205(4977), 1232–1233. https://doi.org/10.1038/2051232a0 Schwarz, T. F., Nsanze, H., Longson, M., Nitschko, H., Gilch, S., Shurie, H., … Jager, G. (1996). Polymerase chain reaction for diagnosis and identification of distinct variants of Crimean-Congo hemorrhagic fever virus in the United Arab Emirates. The American Journal of Tropical Medicine and Hygiene, 55(2), 190—196. https://doi.org/10.4269/ajtmh.1996.55.190 Shahhosseini, N., Wong, G., Babuadze, G., Camp, J. V., Ergonul, O., Kobinger, G. P., … Nowotny, N. (2021). Crimean-congo hemorrhagic fever virus in asia, africa and europe. Microorganisms, 9(9), 1–24. https://doi.org/10.3390/microorganisms9091907 Sharifi-Mood, B., Metanat, M., & Alavi-Naini, R. (2014). Prevalence of Crimean-Congo Hemorrhagic FeverAmong High Risk Human Groups. International Journal of High Risk Behaviors and Addiction, 3(1), 5–8. https://doi.org/10.5812/ijhrba.11520 Simpson, D. I. H., Knight, E. M., Courtois, G. H., Williams, M. C., Weinbren, M. P., & Kibukamusoke, J. W. (1967). Congo virus: a hitherto undescribed virus occurring in Africa. Part 1. Human isolations-clinical notes. East African Medical Journal, 44(2), 87–92. Spengler, J. R., Bente, D. A., Bray, M., Burt, F., Hewson, R., Korukluoglu, G., … Papa, A. (2018). Second International Conference on Crimean-Congo Hemorrhagic Fever. Antiviral Research, 150(November 2017), 137–147. https://doi.org/10.1016/j.antiviral.2017.11.019 Spengler, J. R., Bergeron, É., & Rollin, P. E. (2016). Seroepidemiological Studies of Crimean-Congo Hemorrhagic Fever Virus in Domestic and Wild Animals. PLoS Neglected Tropical Diseases, 10(1), 1–28. https://doi.org/10.1371/journal.pntd.0004210 Spengler, J. R., Estrada-Peña, A., Garrison, A. R., Schmaljohn, C., Spiropoulou, C. F., Bergeron, É., & Bente, D. A. (2016). A chronological review of experimental infection studies of the role of wild animals and livestock in the maintenance and transmission of Crimean-Congo hemorrhagic fever virus. Antiviral Research, 135, 31–47. https://doi.org/10.1016/j.antiviral.2016.09.013 Spiropoulou, C. F., & Bente, D. A. (2020). Orthohantavirus, orthonairovirus, orthobunyavirus, and phlebovirus. Fields Virology. Philadelphia, Pennsylvania: Wolters Kluwer/Lippincott Williams & Wilkins, 750–783. Stähelin-Massik, J., Zimmermann, H., & Gnehm, H. E. (2008). Tick-borne encephalitis in swiss children 2000-2004: Five-year nationwide surveillance of epidemiologic characteristics and clinical course. Pediatric Infectious Disease Journal, 27(6), 555–557. https://doi.org/10.1097/INF.0b013e318165c195 Tang, Q., Saijo, M., Zhang, Y., Asiguma, M., Tianshu, D., Han, L., … Morikawa, S. (2003). A patient with Crimean-Congo hemorrhagic fever serologically diagnosed by recombinant nucleoprotein-based antibody detection systems. Clinical and Diagnostic Laboratory Immunology, 10(3), 489–491. https://doi.org/10.1128/CDLI.10.3.489-491.2003 Tchesnokov, E. P., Bailey-Elkin, B. A., Mark, B. L., & Götte, M. (2020). Independent inhibition of the polymerase and deubiquitinase activities of the Crimean-Congo Hemorrhagic Fever Virus full-length L-protein. PLOS Neglected Tropical Diseases, 14(6), e0008283. https://doi.org/10.1371/journal.pntd.0008283 Temur, A. I., Kuhn, J. H., Pecor, D. B., Apanaskevich, D. A., & Keshtkar-Jahromi, M. (2021). Epidemiology of Crimean-Congo Hemorrhagic Fever (CCHF) in Africa—Underestimated for Decades. The American Journal of Tropical Medicine and Hygiene, 104(6), 1978–1990. https://doi.org/10.4269/ajtmh.20-1413 Tezer, H., Sucakli, I. A., Sayli, T. R., Celikel, E., Yakut, I., Kara, A., … Ergonul, O. (2010). Crimean-Congo hemorrhagic fever in children. Journal of Clinical Virology, 48(3), 184–186. https://doi.org/10.1016/j.jcv.2010.04.001 Tignor, G. H., & Hanham, C. A. (1993). Ribavirin efficacy in an in vivo model of Crimean-Congo hemorrhagic fever virus (CCHF) infection. Antiviral Research, 22(4), 309–325. Tipih, T., & Burt, F. J. (2020). Crimean–Congo hemorrhagic fever virus: advances in vaccine development. BioResearch Open Access, 9(1), 137–150. Vesenjak-Hirjan, J., Punda-Polić, V., & Dobe, M. (1991). Geographical distribution of arboviruses in Yugoslavia. Journal of Hygiene, Epidemiology, Microbiology, and Immunology, 35(2), 129–140. Vorou, R., Pierroutsakos, I. N., & Maltezou, H. C. (2007). Crimean-Congo hemorrhagic fever. Current Opinion in Infectious Diseases, 20(5), 495–500. https://doi.org/10.1097/QCO.0b013e3282a56a0a Wasfi, F., Dowall, S., Ghabbari, T., Bosworth, A., Chakroun, M., Varghese, A., … Letaief, A. (2016). Sero-epidemiological survey of Crimean-Congo hemorrhagic fever virus in Tunisia. Parasite, 23. https://doi.org/10.1051/parasite/2016010 Watts, D. M., Ksiazek, T. G., Linthicum, K. J., & Hoogstraal, H. (2019). Crimean-Congo hemorrhagic fever. The Arboviruses, 177–222. Watts, D. M., Ussery, M. A., Nash, D., & Peters, C. J. (1989). Inhibition of Crimean-Congo hemorrhagic fever viral infectivity yields in vitro by ribavirin. The American Journal of Tropical Medicine and Hygiene, 41(5), 581–585. Weidmann, M., Avsic-Zupanc, T., Bino, S., Bouloy, M., Burt, F., Chinikar, S., … Zeller, H. (2016). Biosafety standards for working with crimean-congo hemorrhagic fever virus. Journal of General Virology, 97(11), 2799–2808. https://doi.org/10.1099/jgv.0.000610 Whitehouse, C. A. (2004). Crimean-Congo hemorrhagic fever. Antiviral Research, 64(3), 145–160. https://doi.org/10.1016/j.antiviral.2004.08.001 World Health Organization (WHO). (2018). Roadmap for Research and Product Development against Crimean-Congo Haemorrhagic Fever (CCHF). 1–11. Retrieved from https://www.who.int/blueprint/priority-diseases/key-action/cchf-draft-r-and-d-roadmap.pdf?ua=1 World Health Organization (WHO). (2020). Vector-borne diseases. Retrieved from https://www.who.int/news-room/fact-sheets/detail/vector-borne-diseases World Health Organization (WHO). (2022a). Crimean-Congo haemorrhagic fever. Retrieved from https://www.who.int/news-room/fact-sheets/detail/crimean-congo-haemorrhagic-fever World Health Organization (WHO). (2022b). Crimean-Congo haemorrhagic fever. Retrieved from https://www.who.int/health-topics/crimean-congo-haemorrhagic-fever/#tab=tab_1 Zivcec, M., Scholte, F., Spiropoulou, C., Spengler, J., & Bergeron, É. (2016). Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus. Viruses, 8(4), 106. https://doi.org/10.3390/v8040106