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Crimean–Congo Haemorrhagic Fever (CCHF): a Zoonoses Int.J.Curr.Microbiol.App.Sci (2020) 9(9): 3201-3210 International Journal of Current Microbiology and Applied Sciences ISSN: 2319-7706 Volume 9 Number 9 (2020) Journal homepage: http://www.ijcmas.com Review Article https://doi.org/10.20546/ijcmas.2020.909.396 Crimean–Congo Haemorrhagic Fever (CCHF): A Zoonoses Sharanagouda Patil1*, Pinaki Panigrahi2, Mahendra P Yadav3 and Bramhadev Pattnaik4 1Virology Section, ICAR-National Institute of Veterinary Epidemiology and Disease informatics (ICAR-NIVEDI), Yelahanka, Bengaluru, Karnataka, India 560064 2Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Georgetown University Medical Center, Washington, D.C, USA 20007 3SVP University of Agriculture & Technology, Meerut, India 4One Health Center for surveillance and disease dynamics, AIPH University, Bhubaneswar, Odisha & Former Director, ICAR- Directorate of Foot and Mouth Disease, Mukteswar, India *Corresponding author ABSTRACT K e yw or ds Crimean-Congo haemorrhagic fever (CCHF), a serious human disease with short incubation period, is the most wide spread tick-borne viral infection of man. It is caused CCHF, CCHF by a negative-sense RNA virus (Nairovirus genus) in the Nairoviridae family within the virus, CCHF zoonosis, Human, Bunyavirales order. The CCHF virus (CCHFV) is transmitted mainly by ticks of India, Livestock, Hyalomma spp. The disease is zoonotic and was first described in humans in 1940s in former Soviet Union. The disease was reported in India in 2011 with involvement of Zoonotic Hyalomma anatolicum ticks. Antibodies to CCHFV have been demonstrated in livestock Article Info including bovines, sheep and goat. A detailed review is being presented on CCHF including its epidemiology, pathogenesis, diagnosis, prevention and control measures. Accepted: Humans are infected by tick bites, contact with animal blood, and also during handling of 20 August 2020 infected/ sick animals. The infection can also be nosocomial. Biosafety and Biosecurity Available Online: measures including sanitation and control of ticks would be of much help in bringing 10 September 2020 CCHF under control. Introduction outbreak of a disease as a Crimean haemorrhagic fever was described in 1944– Crimean-Congo haemorrhagic fever (CCHF), 1945, when military personnel in former is a serious tick-borne viral infection of man. Soviet Union were infected in Crimea region. It occurs over larger parts of XinJiang region The Crimean haemorrhagic fever virus and of China, Middle East region, Southern Congo virus (isolated in Congo in 1956) Russia, Africa, Asia, Southern and Eastern shared antigenic similarity. Therefore, the Europe including the Iberian region disease was subsequently renamed as (Leblebicioglu, 2010; Dowall et al., 2017; Crimean-Congo haemorrhagic fever (CCHF) Hawman and Feldman, 2018). The first and the virus as Crimean-Congo 3201 Int.J.Curr.Microbiol.App.Sci (2020) 9(9): 3201-3210 haemorrhagic fever virus (CCHFV) (Ergonul, disease pathogenesis, efficacy of treatments 2006; Peyrefitte et al., 2015). CCHF is a and transmission dynamics of the virus via severe haemorrhagic fever caused by CCHF ticks (Logan et al., 1989; Tignor and virus of the genus Nairovirus (family Hanham, 1993). STAT-1 and IFNAR−/− Nairoviridae within Order Bunyavirales). knockout mice have both recently been used Several genera of Ixodid ticks act as vector as lethal models of CCHF disease (Zivcec et and reservoir for CCHFV. However, al., 2013). Hyalomma spp ticks play an important role in the transmission of this virus (Whitehouse, The Virus 2008). The natural reservoir and vector for CCHFV are mostly Hyalomma ticks; Role of The CCHF virus is widely distributed in other ticks such as Rhipicephalus, Boophilus, Africa, Southern and Eastern Europe, the Ixodes and Dermacentor species acting as Middle East and Asia’ (Hawman and vectors cannot be ruled out (Bente et al., Feldmann, 2018). The virus was first isolated 2013; Leblebicioglu et al., 2016). CCHFV in 1968 and is a lethal one (Dowall et al., usually circulates in an enzootic tick- 2017). The CCHFV is a negative-sense RNA vertebrate-tick cycle. The virus amplifies in virus in the Nairoviridae family within the various mammalian species that remain Bunyavirales order (ICTV taxonomy, 2018 asymptomatic. Ticks get infected at any stage release),the name is derived from Nairobi of life-cycle during feeding on viraemic sheep disease which causes Nairobi sheep animals. Humans are infected by tick bites disease orthonairovirus (ICTV, 9th Report, and other contact means. 2011).In 2017, the ICTV reclassified the family Bunyaviridae as order Bunyavirales. The infection can also be nosocomial. The All five genera of the former family incubation period is short; 3-7 days. This Bunyaviridae (Hantavirus, Nairovirus, infection was considered as a threatening Orthobunyavirus, Phlebovirus, Tospovirus) emergence in humans (Fillâtre et al., 2019). are now novel viral families, viz., The CCHFV exhibits wide genetic Hantaviridae, Feraviridae, Fimoviridae, diversity.5% difference at the amino acid Jonviridae, Nairoviridae, Peribunyaviridae, level at nucleoprotein and L protein and up to Phasmaviridae, Phenuiviridae, and 25% in the glycoprotein precursor is noticed Tospoviridae. The virus contains three (Bente et al., 2013). The evaluation of genomic segments viz., small, medium, and therapeutic candidates for CCHF has been large that encode for the nucleoprotein, hindered due to the lack of an animal model glycoprotein, and RNA-dependent RNA- for CCHF in humans. Many animal models polymerase, respectively (Whitehouse, 2008). that have been evaluated so far develop The genus Nairovirus contains the Crimean- viraemia upon infection, but do not develop Congo hemorrhagic fever group (CCHFV and any clinical features of the disease. The Hazara virus) and the Nairobi sheep disease mammals lacking a fully functional immune group (Nairobi sheep disease virus -NSDV system, including neonatal mice, signal and Dugbe virus (García-Sastre and Endy, transducer and activator of transcription 1 2009). Both CCHF and NSD group viruses (STAT-1) knockout mice and interferon α/β are transmitted primarily by ticks sometimes receptor (IFNAR−/−) knockout mice upon virus has also been isolated from culicoides, CCHFV infection develop the disease flies and mosquitoes. For most Nairoviruses, (Mendoza et al., 2018). The new born mouse it is still to be explored whether they are model of CCHFV has been used to study pathogenic for humans (Whitehouse, 2008). 3202 Int.J.Curr.Microbiol.App.Sci (2020) 9(9): 3201-3210 Dugbe virus (DUGV) which is genetically replication occurs in the cytoplasm of infected close to CCHFV and mildly pathogenic virus. cells, and viral particles bud principally through the Golgi apparatus (Peyrefitte et al., The genome of Nairoviruses is much larger 2015). The viral glycoproteins contain compared to other genera members because receptor-recognition sites and influence viral of double the size of L segment (Strauss and cell tropism and the ability of the viruses to Strauss, 2008). There are seven species in this infect vertebrate and tick hosts. group with distinct names having multiple strains. The Nairobi sheep disease virus, first The viral RNA dependent RNA polymerase identified as the causative agent of the disease (L protein) binds to a promoter on each in 1917, transmitted by the tick Rhipicephalus encapsidated segment, and transcribes the appendiculatus, having symptoms of acute mRNA. The virus attaches to host receptors gastro enteritis and hemorrhagic symptoms in though Gn-Gc glycoprotein dimer, and is sheep and goats, with mortality over 90%. endocytosed into vesicles in the host cell. Humans can be infected by the virus with Transcription is terminated by a strong mild illness. The Ganjam virus present in hairpin sequence at the end of each gene, and India is closely related to this virus that the transcripts are capped by L protein during causes disease in sheep and goats which is synthesis using cap snatching process in the transmitted by the tick Haemaphysalis cytoplasm. intermedia. Members of Nairoviridae family are enveloped and spherical with diameter of Transmission and Epidemiology 80 to 120nm, and have three segments of Negative-stranded RNA linear genome; L CCHFV circulates in tick-vertebrate-tick segment is between 6.8 and 12 kb, M segment cycle which is the most widespread tick-borne between 3.2 and 4.9 kb and S segment virus on earth, and it is a matter of concern between 1 and 3 kb. The gene segments code that the geographic distribution of Hyalomma for four to six proteins. The gene fragments ticks is expanding. Migratory birds play an are covered by the copies of the important role in disseminating Hyalomma nucleoprotein. The nairovirus genome ticks into northern parts of Europe and consists of three segments of single-stranded, exposing naïve human populations to CCHFV negative-sense RNA, designated large (L), (Dowall et al., 2017). The virus is maintained medium (M) and small (S). These genome by tick-mediated transmission between segments encode four structural proteins; the several species of vertebrate including wild L segment codes for RNA-dependent RNA and domestic mammals, viz., ungulate polymerase, the M segment encodes two livestock, rabbits, mice, birds and hedgehogs structural membrane glycoproteins Gn and etc. These animals develop transient viraemia Gc, and the S segment encodes the and remain asymptomatic. Direct nucleocapsid protein N. Non-structural transmission to humans occurs during
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