Crimean-Congo Hemorrhagic Fever

Year 2014, Volume: 4 Issue: 5, 1 - 9, 01.06.2014

N Elaldi Safak Kaya

https://doi.org/10.5799/ahinjs.02.2014.S1.0135

Cited By: 4

Abstract

Crimean-Congo hemorrhagic fever (CCHF), a tick-borne viral hemorrhagic fever, is a zoonotic infection that caused by CCHF virus (CCHFV) of the family Bunyaviridae, genus Nairovirus. Transmission occurs mainly by Hyalomma m. marginatum tick exposure. Blood and bloody excretions of the patients are highly infectious and contact of skin and mucous membrane may lead to CCHF transmission. CCHF was described firstly in the Crimean peninsula in 1944, in former Soviet Union and in Kelkit Valley in 2002 in Turkey. By the year 2013, it has been notified in more than 30 countries of Asia, the Middle East, Southeastern part of Europe and Africa. The disease is characterized by fever and thrombocytopenia, in severe cases, hemorrhage and shock. Although, the case fatality rate for the infection is generally ranged from 10 to 50%, it was reported as 5% for Turkey. Main targets of CCHFV are immune cells and endothelium. Both innate and adaptive immunity are important for fighting against CCHFV in the host. Headache, fever, fatigue and muscle, joint pain, conjunctival injection, facial hyperemia, thrombocytopenia, elevated liver enzymes, hepatomegaly and splenomegaly are the main symptoms and findings for CCHF. Hemorrhagic manifestations including ecchymosis, melena, hematochezia, hematemesis, and epistaxis are commonly seen in severe cases. Supportive treatment is essential and nowadays neither a special drug, nor safe vaccine for humans is available for the treatment and prevention of CCHF. In case of penetrating injury with contaminated material, the oral ribavirin prophylaxis may be offered after the area being washed with soapy water and ethanol.

Keywords

Crimean-Congo hemorrhagic fever (CCHF), CCHF virus, epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment, prevention

Crimean-Congo Hemorrhagic Fever

Abstract

Kırım-Kongo kanamalı ateşi (KKKA) Bunyaviridae ailesi, Nairovirüs cinsine mensup KKKA virüsü (CCHFV) tarafından oluşturulan kene kaynaklı bir viral hemorajik ateş ve zoonotik bir enfeksiyon hastalığıdır. Bulaş başlıca Hyalomma m. marginatum keneleri ile temas sonucu oluşur. Hastalara ait kan ve kanlı vücut çıkartıları son derece bulaştırıcı ve cilt ve mukoza temasıyla KKKA bulaşı olabilir. KKKA ilk olarak eski Sovyetler Birliği’nde 1944 yılında Kırım yarımadasında, Türkiye’de Kelkit Vadisi’nde 2002 yılında ilk olarak tarif edilmiştir. KKKA 2013 yılı itibarıyla Güneydoğu Asya, Orta Doğu, Avrupa ve Afrika’da 30’dan fazla ülkede bildirilmiştir. Hastalık ateş, trombositopeni ve ciddi vakalarda kanama ve şok ile karakterizedir. Vaka-ölüm oranı genellikle %10-%50 arasında değişmekle birlikte Türkiye için %5 olarak bildirilmiştir. CCHFV’nin konak dokuda ana hedefleri bağışıklık hücreleri ve endotel olup, CCHFV’ye karşı korunmada konakta hem doğal ve hem de özgül bağışıklık önemlidir. Baş ağrısı, ateş, halsizlik, kas ve eklem ağrısı, konjuktiva ve yüzde kızarıklık, trombositopeni, karaciğer enzimlerinde yükselme, hepatomegali ve splenomegali KKKA için önemli belirti ve bulgulardır. Ekimoz, melena, hematokezia, hematemez ve burun kanaması gibi kanama bulgular ağır vakalarda görülür. Destek tedavisi esas tedavi olup günümüzde insanlarda kullanılan KKKA’ya özgül ne bir ilaç ne de güvenli bir aşı bulunmamaktadır. Penetran yaralanma durumunda yaralanan bölgenin sabunlu su ve etanol ile yıkanmasından sonra oral ribavirin profilaksisi verilebilir

Keywords

Kırım-Kongo kanamalı ateşi (KKKA), CCHFV, epidemiyoloji, patogenez, klinik belirtiler, tanı, tedavi, korunma

References

• Le Guenno B. Emerging viruses. Sci Am 1995;273:56-64.
• Johnson KM. Viral hemorrhagic fevers: a comparative ap- praisal. In: Richman D, Whitley R, Hayden F, eds. Clinical Virology. Washington DC: ASM Press, 2002:135-144.
• Geisbert TW, Jahrling PB. Exotic emerging viral diseases: progress and challenges. Nat Med 2004;10:110-121.
• Anonymous. Management of patients with suspected viral hemorrhagic fever, MMWR 1988;37:1-16.
• Mertens M, Schmidt K, Ozkul A, Groschup MH. The impact of Crimean-Congo hemorrhagic fever virus on public health. Antiviral Res 2013;98:248-260.
• Yilmaz GR, Buzgan T, Irmak H, et al. The epidemiology of Crimean-Congo hemorrhagic fever in Turkey, 2002—2007. Int J Infect Dis 2009;13:380-386.
• Wallace MR, Hale BR, Utz GC, et al. Endemic infectious dis- eases of Afghanistan. Clin Infect Dis 2002;34:171-207.
• Whitehouse CA. Crimean-Congo hemorrhagic fever. Antiviral Res 2004;64:145-160.
• Elaldi N, Bodur H, Ascioglu S, et al. Efficacy of oral ribavirin treatment in Crimean-Congo haemorrhagic fever: a quasi- experimental study from Turkey. J Infect 2009;58:238-244.
• Ergonul O. Crimean-Congo hemorrhagic fever. Lancet Infect Dis 2006;6:203-214.
• Bakir M, Ugurlu M, Dokuzoguz B, et al. Crimean-Congo hemorrhagic fever outbreak in Middle Anatolia: a multicentre study of clinical features and outcome measures. J Med Mi- crobiol 2005;54:1-5.
• Simon M, Falk KI, Lundkvist A, Mirazimi A. Exogenous nitric oxide inhibits Crimean Congo hemorrhagic fever virus. Virus Res 2006;120(1-2):184-190.
• Estrada-Peña A, Ayllón N, de la Fuente J. Impact of climate trends on tick-borne pathogen transmission. Front Physiol 2012;3:64.
• LeDue JW: Epidemiology of hemorrhagic fever viruses, Rev Infect Dis 1989;11(Suppl 11):730-735.
• Koksal I, Yilmaz G, Iskender S, et al. The first Crimean-Con- go hemorrhagic fever case in the winter season from Turkey. Intervirology 2011;54:144-145.
• Gunes T, Poyraz O, Vatansever Z. Crimean-Congo hemor- rhagic fever virus in ticks collected from humans, livestock, and picnic sites in the hyperendemic region of Turkey. Vector Borne Zoonotic Dis 2011;11:1411-1416.
• Swanepoel R, Leman PA, Burt FJ, et al. Experimental in- fection of ostriches with Crimean-Congo haemorrhagic fever virus. Epidemiol Infect 1998;121:427-432.
• Ergonul O, Celikbas A, Yildirim U, et al. Pregnancy and Crimean-Congo haemorrhagic fever. Clin Microbiol Infect 2010;16:647-650.
• Elaldi N. Kırım-Kongo hemorajik ateşi epidemiyolojisi. Klimik Derg 2004;17:151-155. (In Turkish)
• Van Eeden PJ, Joubert JR, van de Wal BW, et al. A noso- comial outbreak of Crimean-Congo haemorrhagic fever at Tygerberg Hospital. Part I. Clinical features. S Afr Med J 1985;10:711-717.
• Van de Wal BW, Joubert JR, Van Eeden PJ, King JB. A noso- comial outbreak of Crimean-Congo haemorrhagic fever at Tygerberg Hospital. Part IV. Preventive and prophylactic measures. S Afr Med J 1985;10:729-732.
• Xiao X, Feng Y, Zhu Z, Dimitrov DS. Identification of a pu- tative Crimean-Congo hemorrhagic fever virus entry factor. Biochem Biophys Res Commun 2011;411:253-258.
• Bray M. Pathogenesis of viral hemorrhagic fever. Curr Opin Immunol 2005;17:399-403.
• Zivcec M, Safronetz D, Scott D, et al. Lethal Crimean-Congo hemorrhagic fever virus infection in interferon α/β recep- tor knockout mice is associated with high viral loads, pro- inflammatory responses and coagulopathy. J Infect Dis 2013;207:1909-1921.
• Engin A, Arslan S, Kizildag S, et al. Toll-like receptor 8 and 9 polymorphisms in Crimean-Congo hemorrhagic fever. Mi- crobes Infect 2010(12-13):1071-1078.
• Burt FJ, Swanepoel R, Shieh WJ, et al. Immunohistochemical and in situ localization of Crimean-Congo hemorrhagic fever (CCHF) virus in human tissues and implications for CCHF pathogenesis. Arch Pathol Lab Med 1997;121:839-846.
• Connolly-Andersen AM, Moll G, Andersson C, et al.Crimean- Congo hemorrhagic fever virus activates endothelial cells. J Virol 2011;85:7766-7774.
• Kumar P, Shen Q, Pivetti CD, et al. Molecular mechanisms of endothelial hyperpermeability: implications in inflammation. Expert Rev Mol Med 2009;11:e19.
• Ozsurekci Y, Arasli M, Karadag Oncel E, et al. Can the mild clinical course of crimean-congo hemorrhagic fever in children be explained by cytokine responses? J Med Virol 2013;85:1955-1959.
• Papa A, Bino S, Velo E, et al. Cytokine levels in Crimean- Congo hemorrhagic fever. J Clin Virol 2006;36:272-276.
• Ergonul O, Tuncbilek S, Baykam N, et al. Evaluation of serum levels of interleukin (IL)-6, IL-10, and tumor necrosis factor- alpha in patients with Crimean-Congo hemorrhagic fever. J Infect Dis 2006;193:941-944.
• Akıncı E, Bodur H, Leblebicioglu H. Pathogenesis of Crime- an-Congo hemorrhagic Fever. Vector Borne Zoonotic Dis 2013;13:429-437.
• Geisbert TW, Young HA, Jahrling PB, et al. Mechanisms underlying coagulation abnormalities in ebola hemorrhagic fever: overexpression of tissue factor in primate monocytes/ macrophages is a key event. J Infect Dis 2003;188:1618- 1629.
• Bente DA, Forrester NL, Watts DM, et al. Crimean-Con- go hemorrhagic fever: History, epidemiology, pathogen- esis, clinical syndrome and genetic diversity. Antiviral Res 2013;100:159-189.
• Saksida A, Duh D, Wraber B, et al. Interacting roles of im- mune mechanisms and viral load in the pathogenesis of Crimean-Congo hemorrhagic fever. Clin Vaccine Immunol 2010;17:1086-1093.
• Swanepoel R, Gill DE, Shepherd AJ, et al. The clinical pa- thology of Crimean-Congo Hemorrhagic fever. Rev Infect Dis 1989;11:794-800.
• Kaya A, Engin A, Guven AS, et al. Crimean-Congo hemor- rhagic fever disease due to tick bite with very long incubation periods. Int J Infect Dis 2011;15:e449-452.
• Ergonul O, Celikbas A, Baykam N, et al. Analysis of risk- factors among patients with Crimean-Congo haemorrhagic fever virus infection: severity criteria revisited. Clin Microbiol Infect 2006;12:551-554.
• Swanepoel R, Shepherd AJ, Leman PA, et l. Epidemiologic and clinical features of Crimean-Congo hemorrhagic fever in Southern Africa. Am J Trop Med Hyg 1987;36:120-132.
• Borio L, Inglesby T, Peters CJ, et al. Hemorrhagic fever vi- ruses as biological weapons: Medical and public health man- agement. JAMA 2002;287:2391-2405.
• Schwarz TF, Nsanze H, Ameen AM. Clinical features of Crimean-Congo hemorrhagic fever in the United Arab Emir- ates. Infect 1997;25:364-367.
• Van Eeden PJ, Van Eeden SF, et al. A nosocomial outbreak of Crimean-Congo haemorrhagic fever at Tygerberg Hospital. Part II. Management of patients. S Afr Med J 1985;68:718- 721.
• Leblebicioglu H, Bodur H, Dokuzoguz B, et al. Case man- agement and supportive treatment for patients with Crime- an-Congo hemorrhagic fever. Vector Borne Zoonotic Dis 2012;12:805-811.
• Burt FJ, Leman PA, Abbott JC, Swanepoel R. Serodiagno- sis of Crimean- Congo haemorrhagic fever. Epidemiol Infect 1994;113:551-562.
• Zeller H. Laboratory diagnosis of Crimean-Congo hemor- rhagic fever. In: Ergonul O, Whitehouse CA, Dordrecht NL, eds. Crimean-Congo hemorrhagic fever: A global perspec- tive. Springer; 2007:233-243.
• Mardani M, Keshtkar-Jahromi M. Crimean-Congo hemor- rhagic fever. Arch Iran Med 2007;10:204-214.
• Drosten C, Gottig S, Schilling S, et al. 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. J Clin Microbiol 2002;:2323- 2330.
• Yapar M, Aydogan H, Pahsa A, et al. Rapid and quantitative detection of Crimean-Congo hemorrhagic fever virus by one- step real-time reverse transcriptase-PCR. Jpn J Infect Dis 2005;58:358-362.
• Knust P, Rollin PE. Viral hemorrhagic fevers. Traveler’s health. Infectious diseases related to travel. Center for Dis- ease Control and Prevention. URL-http://wwwnc.cdc.gov/ travel/yellowbook/2012/chapter-3-infectious-diseases-relat- ed-to-travel/viral-hemorrhagic-fevers.htm (12 Apr 2014)
• Paragas J, Whitehouse CA, Endy TP, Bray M. A simple as- say for determining antiviral activity against Crimean-Congo hemorrhagic fever virus. Antiviral Res 2004;62:21-25.
• Tignor GH and Hanham CA. Ribavirin efficacy in an in vivo model of Crimean/Congo hemorrhagic fever virus (CCHF) infection. Antiviral Res 1993;22:309-325.
• World Health Organization 2003. Communicable Disease profile Iraq. Updated 19 March 2003. Communicable Dis- ease Working Group on Emergencies, HQ Division of Com- municable Disease Control, EMRO WHO Office, Baghdad.
• Fisher-Hoch SP, Khan JA, Rehman S, et al. Crimean Con- go-haemorrhagic fever treated with oral ribavirin. Lancet 1995;346(8973):472-475.
• Mardani M, Keshtkar Jahromi M, Naieni KH, Zeinali M. The efficacy of oral ribavirin in the treatment of Crimean-Congo hemorrhagic fever in Iran. Clin Infect Dis 2003;36:1613-1618.
• Alavi-Naini R, Moghtaderi A, Koohpayeh H-R, et al. Crimean- Congo hemorrhagic fever in Southeast of Iran. J of Infect 2005;52:378-382.
• Ergonul O, Celikbas A, Dokuzoguz B, et al. Charactheristics of patients with Crimean-Congo hemorrhagic fever in a re- cent outbreak in Turkey and impact of oral ribavirin therapy. Clin Infect Dis 2004;39:284-287.
• Z Kiki I, Erol S, et al. Crimean-Congo Hemorrhagic fever in Eastern Turkey: clinical features, risk factors and efficacy of ribavirin therapy. J Infect 2006;52:207-215.
• Cevik MA, Elaldi N, Akinci E, et al. A preliminary study to evaluate the effect of intravenous ribavirin treatment on sur- vival rates in Crimean-Congo hemorrhagic fever. J Infect 2008;57:350-351.
• Metanat M, Sharifi-Mood B, Salehi M. A comparative study of the efficacy of oral ribavirin for Crimean-Congo haemor- rhagic fever in patients treated during the initial 5 days vs af- ter 5 days of disease, Southeast Iran. Int J Antimicrob Agents 2005;85. (Poster presentation)
• Koksal I, Yilmaz G, Aksoy F, et al. The efficacy of ribavirin in the treatment of Crimean-Congo hemorrhagic fever in East- ern Black Sea region in Turkey. J Clin Virol 2010;47:65-68.
• Hoogstraal H. The epidemiology of tick-borne Crimean/ Congo hemorrhagic fever in Asia, Europe, and Africa. J Med Entomol 1979;15:307-417.
• Vassilenko SM, Vassilev TL, Bozadjiev LG, et al. Specific intravenous immunoglobulin for Crimean-Congo haemor- rhagic fever. Lancet 1990;335:791-792.
• Kubar A, Haciomeroglu M, Ozkul A, et al. Prompt adminis- tration of Crimean-Congo hemorrhagic fever (CCHF) virus hyperimmunoglobulin in patients diagnosed with CCHF and viral load monitorization by reverse transcriptase-PCR. Jpn J Infect Dis 2011;64:439-443.
• Recommended precaution procedures protect healthcare workers from Crimean-Congo hemorrhagic fever virus. Int J Infect Dis 2013; 17:e1046-1050.
• Anonymous. CDC. Crimean Congo hemorrhagic fever. URL- http://www.cdc.gov/vhf/crimean-congo/prevention/index. html (12 Apr 2014)
• Spik K, Shurtleff A, McElroy AK, et al. Immunogenicity of combination DNA vaccines for Rift Valley fever virus, tick- borne encephalitis virus, Hantaan virus, and Crimean Congo hemorrhagic fever virus. Vaccine 2006;24:4657-4666.