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Review Article *Corresponding author Sachin Kumar, Department of Science and Technology, Science and Engineering Research Board (SERB), India, Crimean Congo Hemorrhagic Email: Submitted: 03 April 2017 (CCHF) – A Chronicle of Accepted: 17 July 2017 Published: 26 July 2017 ISSN: 2475-9430 Human, and Animal Copyright Snehil Gupta1, VijayKumar Jawalagatti2, Devender Harkal3, and © 2017 Sachin Kumar et al. Sachin Kumar4* OPEN ACCESS 1Department of Veterinary Parasitology, Lala Lajpat Rai University of Veterinary and Animal Sciences, India Keywords 2Division of Parasitology, ICAR-Indian Veterinary Research Institute, India • Crimean-Congo hemorrhagic fever 3Division of Public Health and Epidemiology, ICAR-Indian Veterinary Research • Hyalomma anatolicum Institute, India • Tick and tick borne disease 4Department of Science and Technology, Science and Engineering Research Board • Human infection (SERB), India

Abstract Crimean-Congo Hemorrhagic Fever (CCHF) is a tick borne zoonotic with case fatality ranging from 9-50% and endemic in Africa, Asia, Eastern Europe, and the Middle East. The virus propagates in a silent enzootic tick-vertebrate-tick cycle, which on external interventions leads to outbreak like situation. The regular mode of infection in humans are tick bites, nosocomial infection, crushing of infected , direct contact with CCHF virus infected blood or tissue as during slaughtering infected animals. In a short span of 6 years, India witnessed several outbreaks, which begins from Gujarat to the recent Uttar Pradesh incidence. India being a tropical country and niche for more than 106 species of ticks, CCHFV poses significant threat to health of livestock owners, farmers, veterinarians and abbatoir workers. In India, Hyalomma anatolicum is mainly accredited for transmission of CCHF virus, however, in the recent studies, all the major tick genera are found to be infected with CCHF virus. The present review on CCHF will focus on discussing the update information on the disease pattern which is quiet necessary after CCHF outbreaks reported from India. The information provided might be helpful in designing future control strategy and may help to answer the questions raised in the minds about this disease.

INTRODUCTION emergence of CCHF in human cycle, including global warming, habitat fragmentation, changes in land use patterns, livestock Ticks are one of the most successful creatures trade and movements and migratory birds [13-15]. Being a accredited next to the mosquito as of human diseases [1]. Out of 914 globally known ticks, 106 are reported from India. and seasonal, typically subtropical climate, with mountains and Ticks serve as vector of several human diseases such as KFD, riversvector andborne a widely disease, distributed the occurrence rich diversity of CCHF of is wild region animal specific and CCHF, Indian tick typhus, , human babesiosis and so on. Amongst the various tick borne diseases, outbreaks of oC (subtropical climate) CCHF in last 6 years generates alarming situation in India and favoredtick species tick favorsactivity the and amplification multiplication. of virus. Moreover, 75-80% strict measures should be carried out to keep a check on the re- humidity and temperature around 28 emergance of the disease. CCHF disease in human was noticed for CCHF virus propagates via enzootic tick-vertebrate-tick cycle in latent form of infection. Wild life animal serve as tick time from a febrile patient in Belgian Congo in the year 1956 and reservoir for livestock animals and often results in failure of thusthe first named time as in CCHF Crimea virus in 1944, in 1973 the by virus International was isolated Committee for the first on any tick control strategy [16]. In midst of tick-animal interface, human get accidental infestation with ticks. Amongst ticks, their Hyalomma ticks and peak mortality also recorded collaborating bionomics plays an important role in disease transmission and withTaxonomy Hyalomma on Viruses spp. [2]. dominant The virus season, was first thus time biologist isolated initially from for transmission of any disease through saliva, an attachment accredited Hyalomma spp. as sole transmitting agent of CCHFv. Ergonul in 2006 reported that CCHFv has been found in more suffered from tick bites in CCHF clinical cases and the case fatality than 31 countries across Africa, Balkans, Asia, southeast Europe, of 48-72 hrs is required. Humans are quiet often reported to be and the Middle East, closely approximating the known global to its bionomics, biting nature, quick movements and localization lies in the range 10-50% in case of tick–human interface [17]. Due distribution of Hyalomma spp. Ticks. In the last decade CCHF of cases in Hyalomma prone area and Hyalomma predominant virus has been recognized as a growing problem in Europe and Asia with an upsurge of cases in Kosovo [3] and the emergence isolation of CCHFv from Hyalomma sp ticks, Hyalomma is of human clinical cases in Greece [4], Turkey [5], and Georgia [6- predominantlyseasons [18], accused and moreover for transmitting initial successfulthe infection attempts to human. in 12]. Biologists have laid down several hypotheses for the sudden In addition, another most common way of infection in human

Cite this article: Gupta S, VijayKumar J, Harkal D, Kumar S (2017) Crimean Congo Hemorrhagic Fever (CCHF) – A Chronicle of Human, Tick and Animal. Ann Clin Cytol Pathol 3(6): 1073. Sachin Kumar et al. (2017) Email:

Central Bringing Excellence in Open Access is by contact with infected blood or other tissues of livestock. loss of hepatotropism and neurotropism of virus after treatment Human to human transmission can be encountered in case of with ribavirin, however, persistence of viremia was noticed by close contact with infected blood, secretions, organs or other ROLE OF ANIMALS IN CCHF OUTBREAKS due to due to improper autoclave of instruments, reuse of the researchers [28]. needlesbody fluids and ofcontamination infected persons. of medical Nosocomial supplies infection and in suchcan occurcases CCHF virus, similar to other zoonotic agents, appears to produce little or no disease in its natural hosts but causes severe and recording of the tick fauna and the associated pathogens are disease in humans. CCHF virus infection has been detected in importantmotality rate for maythe control hike up of to tick 80% and [19]. tick-borne The regular diseases. monitoring In India, numerous domestic and wild vertebrates through virus isolation the enlisting of Indian ticks followed by Ghosh et al. [20], which and majority by sero-epidemiological survey to detect presented the tick distribution in various states of India. There to CCHF virus. Hares, hedgehogs, cattle, sheep, goats, horses, yaks is no commercially available vaccine against CCHFv for humans and swine were reported as the main natural hosts of the CCHF and animals. The information of population dynamics of ticks and virus. Birds were considered resistant to CCHFV infection until tick borne disease are important for successfully laid down of the mankind witnessed death of a worker slaughtering ostriches strategies related to CCHF virus control, and this requires further on a farm in Cape Province of . Later on low titer of inter-sectoral collaboration under the supervision of health virus was recorded from guinea fowl also but it was concluded authorities. that birds are asymptomatic carrier of infection [29]. Migratory birds are often transport the ticks and their associated pathogens EPIDEMIOLOGY AND PHYLOGENETIC DIVERSITY across the barriers such as rivers, deserts and mountains, oceans OF CCHF VIRUS and continents. In domestic animals, the infection is usually sub- Crimean-Congo hemorrhagic fever (CCHF) which is clinical and lasts from a few days to a few weeks. So, shepherds, characterised by by a sudden onset of high fever, , severe campers, agricultural workers, veterinarians, abattoir workers, headache, dizziness, back, and abdominal pains is a tick-borne and other persons in close contact with livestock and ticks are at disease caused by arbovirus Crimean-Congo hemorrhagic fever risk of infection [30]. virus (CCHFv), which is a member of the Bunyaviridae family ROLE OF TICKS IN TRANSMISSION OF CCHF biosafety level IV pathogen due to its pathogenicity and high (upto Invariably most of the literature accredited Hyalomma of viruses, of the genusCCHFv Nairovirus is an enveloped [21,22]. virus It ishaving considered negative as isolation in 1960s from adult ticks [31]. In India, CCHF virus has species for the transmission of CCHF in Pakistan since its first 50%)(nucleocapsid), case fatality. M (membrane glycoprotein), and L (polymerase) been isolated from the Hyalomma anatolicum genomepolarity single segments, stranded respectively RNA genome [23]. constituting The structuretripartite viz. and S Hyalomma viz. H.anatolicum, H.detritum, for the first time replication strategy of CCHF virus is indistinguishable from any H.dromedarii, H.brevipunctata, H.issaci, H.hussaini, H.kumari [7]. In India, 8 species of other member of Bunyaviridae [24]. The advances in molecular and H.turanicum were found to be distributed in 24 states of and biochemical analyses showed CCHFV encodes larger protein India [32]. There is no such report of any attempt of isolation of CCHFV from other species of ticks in India. However, with the advent of molecular detection in ticks, biologists have reported with different post translational modifications as compared to involvement of more than 31 species of ticks, which includes both basedother members on geographical of Bunyaviridae. ground Phylogenetic and grouped analyses diverse of isolates S-RNA hard tick and soft tick in transmission of CCHF virus. The fatal viral intoand seven L-RNA different segment clades. of CCHFV However, revealed the phylogenetic significant divergence grouping infection had reported from about 30 countries, including India. Although the outbreaks have been recorded in peak Hyalomma seasons, the virus was also isolated from ticks of other genera based on M-RNA segment sequences significantly differ from such as spp., spp., Haemaphysalis virusS-RNA genome and L-RNA from segments India, livestockindicating and high tick frequency virus was of genetic found spp., spp. and Argas spp. both transovarially as well as reassortment in M-RNA segment [25]. On sequencing of CCHF transstadially [33]; Turell, 2007 [34]; Tahmasebi et al. [35]. In the Asian/Middle East lineage IV [7]. Even being an arbovirus, a study at Turkey, 165 ticks were examined by RT-PCR for the similar to Tajikistan strain (TAJ/H08966), which belongs in CCHF virus [36]. In an another study on highly CCHF endemic, presence of the CCHFV, of which 27% were found positive for countries)CCHFV showed geographical significantly distribution. high genomic plasticity allowing it Tokat province of Turkey, 7 species of ticks viz. Haemaphysalis to adapt diversified environments resulting in its widespread (30 concinna, Hyalomma anatolicum, Hyalomma detritum, Hyalomma The virus is distributed over much of Asia, extending from marginatum, Hyalomma turanicum, Rhipicephalus bursa and China to the Middle East and Southern Russia and focal endemic Rhiphicephalus turanicus ticks were found positive for CCHF virus areas in Africa and southern Europe, including Kosovo and using qPCR [37]. In 2013, a survey conducted in Iran provide Turkey [26]. Yearly epidemics, as well as sporadic cases of CCHF molecular evidences of CCHV in Hyalomma sp. and Haemaphysalis are seen in some of these areas, often with high case fatality (5 to variation of the virus, transmission route, and/or different sp. ticks via quantitative PCR and found 4.3% ticks positive for treatment60%). The facilities. fatality rate The differencesvirus replication may beis inhibited due to phylogenetic by ribavirin HUMANS-CCHF virus in Zehadan THE district ULTIMATE of Iran [38]. VICTIM OF THE CHRONICLE cells post treatment [27]. In vivo experimentation showed the Humans are the only known hosts of CCHFV where it resulting in significantly low titer in experimentally infected vero

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Central Bringing Excellence in Open Access manifests a clinical condition depicting a distant evolutionary CONCLUSION pattern of virus from human. Disease in vernacular languages

in tick system either by molecular or cell culture technique in bleeding) and Karakhalak (Black death) in different parts of the Pocket studies had been conducted on identification of virus world.are also In known humans, as Khungribta(bloodCCHF is characterized taking), by acuteKhumYmuny febrile illness(Nose India. A 106 tick species are reported from India, thus a systematic leading to a fatal hemorrhagic syndrome. Humans can become planned study is emphasized here to identify the tick vector responsible for CCHF in India, thereby a control strategy can be haemolymph as while crushing infected ticks, direct or indirect laid down to check the re-emergance of disease in India. Although contactinfected with by tick a CCHF bites, patient, contact or with by contacttick fluids with such blood as salivaor tissues and ticks are major vector of CCSF but nosocomial infection cannot be left aside while designing any control strategy. Seroprevalence major culprit for CCHF outbreaks in world [39]. CCHF in humans studies shows animals are key reservoir, majority ticks are the passesof infected through animal the [26]. 4 phases, Nosocomial viz. incubation, transmission pre-hemorrhagic, is reported as potential vectors and humans are the most susceptible victims hemorrhagic, and convalescence periods [26]. Incubation period for CCHF virus. Thus shepherds, campers, agricultural and abattoir workers, veterinarians, and other high-risk persons phase having should protect themselves from direct contact with virus- ofon 39-41an averageoC. In lieshemorrhagic for 3-7days phase, followed individual by pre may –hemorrhagic manifest contaminated tissues or blood and against tick bites. To control hematemesis, flumelena, like symptoms gingival and with vaginal temperature bleeding, in hematuriathe range the CCHF in endemic region, organize a suitable public awareness and menometrorrhagia or dark coffee coloured urine and tar programme about its spread, symptoms, and prevention. like faeces leading to DIC and failure of liver, kidney and lung. ACKNOWLEDGEMENTS In certain unusual cases, incubation period upto 53 days is also reported [40]. Mortality in clinical outbreak may ranges upto 30- We grateful acknowledge the Department of Science and Technology, Science and Engineering Research Board (SERB), and loss of memory may be noticed. Laboratory examination reveals50% [21,41,42]. elevated Inlevel convalescent of ALT, AST, phase, CPK, xerostomia, LDH and prolonged polyneuritis PT New Delhi, India for funding through National Post Doctoral and activated Partial Thromboplastin Time (aPTT), leucopenia FellowshipREFERENCES Project No. DST/NPDF/000312/2016. and [43,44]. 1. Jongejan F, Uilenberg G. The global importance of ticks. Parasitology. Diagnosis of CCHFV can be made using blood, serum, tissue 2004; 129 : S3-S14. or urine samples but requires BSL-4 facility for processing of 2. samples. Cell lines such as Vero and BHK-21 provides high yields and easily accessible to the researchers. Serological diagnosis Chumakov MP, Butenko AM, Shalunova NV, Mart’ianova LI, Smirnova can be made upto 4months targeting IgM and upto 5years on SE, Bashkirtsev IuN, et al. [New data on the viral agent of Crimean 3. Jameson LJ, Morgan PJ, Medlock JM, Watola G, Vaux AG. Importation of targeting IgG. Other diagnostic techniques such as IgM captured hemorrhagic fever]. Vopr Virusol. 1968; 13: 377. Hyalomma marginatum, vector of Crimean-Congo haemorrhagic fever virus, into the United Kingdom by migratory birds. Ticks Tick Borne also developed but found to have very low sensitivity and Dis. 2012; 3: 95-99. reproducibility.ELISA, Immunofluroescence In contrary, qPCR assay provides (IFAT), high CFTb sensitivity and HAI and are 4. Papa A, Maltezou HC, Tsiodras S, Dalla VG, Papadimitriou T, Pierroutsakos I, et al. A case of Crimean-Congo haemorrhagic fever in specificityINDIAN SCENARIOand provides result OF CCHF within 8 hours. 5. Karti SS, Odabasi Z, Korten V, Yilmaz M, Sonmez M, Caylan R, et al. India being a developing country, poor in resources and Greece, June 2008. Euro Surveill. 2008; 13: 18952. Crimean-Congo hemorrhagic fever in Turkey. Emerg Infect Dis. 2004; laboratory facilities required to handle CCHF virus. Though the cases were reported from neighbouring countries but not clinically evident until January, 2011 outbreak in Ahmadabad 6. 10: 1379-1384. Kuchuloria T, et al. Crimean-Congo hemorrhagic fever in man, (Gujarat), there were no immediate preparation for dealing Zakhashvili K, Tsertsvadze N, Chikviladze T, Jghenti E, Bekaia M, with the situation [45]. The outbreak was followed by report of resurgence of CCHF in Amreli and Ahmedabad district of Gujarat. 7. RepublicMishra AC,of Georgia, Mehta 2009. M, MouryaEmerg Infect DT, Dis. Gandhi 2010; S.16: Crimean-Congo1326-8. animals from Sirohi district of Rajasthan. In 2013, a cluster of haemorrhagicPatel AK, Patel fever KK, in MehtaIndia. Lancet. M, Parikh 2011; TM, 378: Toshniwal 372. H, Patel K. The NIV, Pune reported the seroprevalence of CCHFV in domestic First Crimean-Congo hemorrhagic fever outbreak in India. J Assoc 8. Patan, Kutch and Amreli district of Gujarat. In 2014, three deaths human cases were reported from Karyana, Surendra Nagar, were recorded in Bayad taluka and village Madhapur of Kuch 9. PhysiciansLahariya C, India. Goel 2011;MK, Kumar 59: 585-589. A, Puri M, Sodhi A. Emergence of viral district in Gujarat, three deaths in Jaiselmer and Jodhpur district hemorrhagic : is recent outbreak of Crimean Congo Hemorrhagic of Rajasthan and one case reported from Himachal Pradesh. Seoprevalence study of domestic animals of Gujarat showed 10. FeverMourya in DT,India Yadav an indication? PD, Shete J Postgrad AM, Gurav Med. YK, 2012; Raut 58: CG, 39-46. Jadi RS, et al. that at least 15 districts are having prevalence of CCHF virus reported a clinical case of CCHF from Moradabad, Uttar Pradesh. fever virus in human, ticks and animals in Ahmadabad, India, 2010- In Jodhpur (Rajasthan), 2 male nurse died due to CCHF in 2015. Detection, isolation and confirmation of Crimean-Congo hemorrhagic In 2015, Gujarat again witnessed death due to CCHF in Ratadiya 11. 2011.Yadav PLoSPD, Cherian Negl Trop SS, Dis.Zawar 2012; D, Kokate6: e1653. P, Gunjikar R, Jadhav S, et al. village of Mundra taluka of district Kutch. Genetic characterization and molecular clock analyses of the Crimean-

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Congo hemorrhagic fever virus from human and ticks in India, 2010- 2011. Infect Genet Evol. 2013; 14: 223-231. (Nairovirus, family Bunyaviridae) infection in birds. Trans R Soc Trop 12. Yadav PD, Raut CG, Patil DY, Majumdar TD, Mourya DT. Crimean- 30. GonzalezMed Hyg. JP,1987; Camicas 81: 1004-1007. JL, Cornet JP, Wilson ML. Biological and clinical Congo hemorrhagic fever: current scenario in India. Proceedings of responses of west African sheep to Crimean-Congo haemorrhagic

the National Academy of Sciences, India Section B: Biological Sciences. 31. feverBegum virus F, Wissemanexperimental CL infection. Jr, Casals Res J. Virol. Tick-borne 1998; 149: viruses 445-455. of West 13. 2014;Ergunay 84: K, 9-18. Whitehouse CA, Ozkul A. Current status of human arboviral Pakistan. IV. Viruses similar to or identical with, Crimean hemorrhagic diseases in Turkey. Vector Borne Zoonotic Dis. 2011; 11: 731-41. fever (Congo-Semunya), Wad Medani and Pak Argas 461 isolated from ticks of the Changa Manga Forest, Lahore District, and of Hunza, Gilgit 14. Estrada-Peña A, Vatansever Z, Gargili A, Ergönul O. The trend towards Agency, W. Pakistan. Am J Epidemiol. 1970; 92: 197-202. habitat fragmentation is the key factor driving the spread of Crimean- 32. Ghosh S, Bansal GC, Gupta SC, Ray D, Khan MQ, Irshad H, et al. Status of tick distribution in Bangladesh, India and Pakistan. Parasitol Res. 15. CongoUyar Y, haemorrhagic Christova I, fever. Papa Epidemiol A. Current Infect. situation 2010; of 138: Crimean 1194-1203. Congo 2007; 101: S207-S216. hemorrhagic fever (CCHF) in Anatolia and Balkan Peninsula. Turk 33.

16. HijyenveCamicas JL, Deneysel Wilson BiyolojiML, Cornet Dergisi. JP, Digoutte 2011; 68: JP, 139-151.Calvo MA, Adam F, et al. recombinantSaijo M, Qing nucleoprotein T, Niikura M, for Maeda detection A, Ikegami of immunoglobulin T, Sakai K, et al. G Ecology of ticks as potential vectors of Crimean-Congo hemorrhagic antibodiesImmunofluorescence to Crimean-Congo technique hemorrhagic using fever HeLa virus. cells J Clin expressing Microbiol. fever virus in Senegal: epidemiological implications Arch Virol. 1990; 2002; 40: 372-375. 1: 303-322. 34. Turell M. Role of ticks in the transmission of Crimean-Congo 17. Swanepoel R, Shepherd AJ, Leman PA, Shepherd SP, McGillivray GM, hemorrhagic fever virus. In: Ergonul O, Whitehouse CA, editors. Erasmus MJ, et al. Epidemiologic and clinical features of Crimean- Crimean-Congo Hemorrhagic Fever: A Global Perspective. Springer, Congo hemorrhagic fever in southern Africa. Am J Trop Med Hyg.

35. Dordrecht, The Netherlands. 2001; 143-154. 1987;Hoogstraal 36: 120-132. H. The epidemiology of tick-borne Crimean-Congo A, et al. Molecular epidemiology of Crimean- Congo hemorrhagic hemorrhagic fever in Asia, Europe, and Africa. J Med Entomol. 1979; feverTahmasebi virus genomeF, Ghiasi isolated SM, Mostafavi from ticks E, ofMoradi Hamadan M, Piazak province N, Mozafariof Iran. J 18. 15: 307-417. Vector Borne Dis. 2010; 47: 211-216. 19. 36. Karan T, Ekici M, Tekin S, Bursali A. Crimean-Congo hemorrhagic fever Hallett AF. A nosocomial outbreak of Crimean-Congo haemorrhagic virus in Ixodid ticks in Tokat province of Turkey. J Biotechnol. 2012; feverShepherd at Tygerberg AJ, Swanepoel hospital. R, Shepherd Part 5. SP, Virological Leman PA, and Blackburn serological NK,

37. 161S: 19-48. 20. observations.Ghosh S, Bansal S AfrGC, MedGupta J. 1985;SC, Ray 68: D, 733-736. Khan MQ, Irshad H, et al. Status hemorrhagic fever virus in various ixodid tick species from a highly of tick distribution in Bangladesh, India and Pakistan. Parasitol Res. Tekin S, Bursali A, Mutluay N, Keskin A, Dundar E. Crimean-Congo 2007; 101: S207-S216. Mehravaran A, Moradi M, Telmadarraiy Z, Mostafavi E, Moradi 21. Whitehouse CA. Crimean-Congo hemorrhagic fever. Antiviral Res. endemic area. Vet Parasitol. 2012; 186: 546-552. 2004; 64: 145-160. 38. haemorrhagic fever (CCHF) virus in ticks from southeastern Iran. 22. Whitehouse CA. Crimean-Congo hemorrhagic fever virus and AR, Khakifirouz S, et al. Molecular detection of Crimean-Congo other nairoviruses. In: Mahy BWJ, Van Regenmortel MHV, editors. 39. Ticks Tick Borne Dis. 2013; 4: 35-38. fever. Curr Opin Infect Dis. 2007; 20: 495-500. Vorou R, Pierroutsakos IN, Maltezou HC. Crimean-Congo hemorrhagic 23. EncyclopediaBishop DHL. Biology of Virology. and molecular Elsevier, Oxford. biology 2008;of Bunyaviruses. 596-603. In: Elliott 40. Crimean-Congo hemorrhagic fever disease due to tick bite with very longKaya incubation A, Engin A, periods. Güven Int AS, J Infect Içağasıoğlu Dis. 2011; FD, Cevit15: e449-e452. O, Elaldı N, et al. 24. RM,Schmaljohn editor. The C, Bunyaviridae. Hooper JW. Bunyaviridae:Plenum Press, New The York. Viruses 1996; and 19-61. Their Replication, 4th ed. Lippincott Williams &Wilkins, Philadelphia, PA. 41. Hoogstraal H. The epidemiology of tick-borne Crimean-Congo 2001. hemorrhagic fever in Asia, Europe, and Africa. J Med Entomol. 1979; 25. Morikawa S, Saijo M, Kurane I. Recent progress in molecular biology 15: 307-417. of Crimean-Congo hemorrhagic fever. Comp Immunol Microbiol Infect 42. Bishop DH. Biology and molecular biology of bunyaviruses. In: Elliott

26. Ergönül O. Crimean-Congo haemorrhagic fever. Lancet Infect Dis. 61. Dis. 2007; 30: 375-389. RM, editor. The Bunyaviridae. Plenum Press, New York, NY. 1996; 19- 2006; 6: 203-214. 43. Ergun H, Ciftci E. Crimean-Congo haemorrhagic fever. Turkiye 27. Klinikleri J Pediatr Sci. 2007; 3: 23-26. hemorrhagic fever viral infectivity yields in vitro by ribavirin. Am J 44. Watts DM, Ussery MA, Nash D, Peters CJ. Inhibition of Crimean-Congo Kara A. Crimean-Congo haemorrhagic fever. Turk Arch Ped. 2008; 43: Trop Med Hyg. 1989; 41: 581-585. in vivo model of 45. Mourya DT, Yadav PD, Shete AM, Gurav YK, Raut CG, Jadi RS, et al. Crimean-Congo hemorrhagic fever virus (CCHF) infection. Antiviral 108-118. 28. Tignor GH, Hanham CA. Ribavirin efficacy in an Res. 1993; 22: 309-325. fever virus in human, ticks and animals in Ahmadabad, India, 2010- 29. Shepherd AJ, Swanepoel R, Leman PA, Shepherd SP. Field and Detection, isolation Trop and Dis. confirmation 2012; 6: e1653. of Crimean-Congo hemorrhagic laboratory investigation of Crimean-Congo haemorrhagic fever virus 2011. PLoS Negl Cite this article Gupta S, VijayKumar J, Harkal D, Kumar S (2017) Crimean Congo Hemorrhagic Fever (CCHF) – A Chronicle of Human, Tick and Animal. Ann Clin Cytol Pathol 3(6): 1073.

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