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{{short description|Viral disease}}
{{Infobox medical condition
| name =
| image = Crimean-Congo Hemorrhagic Fever.jpg
| caption = Male diagnosed with Crimean–Congo hemorrhagic fever, 1969
| image_size =
| pronounce =
| field = [[Infectious disease (medical specialty)|Infectious disease]]
| symptoms = [[Fever]], muscle pains, [[headache]], vomiting, [[diarrhea]], [[petechiae|bleeding into the skin]]<ref name=WHO2013/>
| complications = [[Liver failure]]<ref name=WHO2013/>
| onset = Rapid<ref name=WHO2013/>
| duration = Two weeks<ref name=WHO2013/>
| types =
| causes =
| risks =
| diagnosis = Detecting [[antibodies]], the virus's [[RNA]], or the virus itself<ref name=WHO2013/>
| differential = [[Dengue fever]], [[Q fever]],<ref name=Gid2017/> [[Ebola|Ebola virus disease]]<ref>{{cite web|title=Ebola virus infection - Differentials {{!}} BMJ Best Practice|url=http://bestpractice.bmj.com/topics/en-gb/1210/differentials|website=bestpractice.bmj.com|access-date=21 May 2018|archive-date=13 August 2020|archive-url=https://web.archive.org/web/20200813062919/https://bestpractice.bmj.com/topics/en-gb/1210/differentials|url-status=live}}</ref>
| prevention =
| treatment = [[Supportive care]], [[ribavirin]]<ref name=WHO2013/>
| medication =
| prognosis = Risk of death ~25%<ref name=WHO2013/>
| frequency =
| deaths =
}}
<!-- Definition and symptoms -->
'''Crimean–Congo hemorrhagic fever''' ('''CCHF''') is a [[viral disease]].<ref name=WHO2013>{{cite web|title=Crimean-Congo haemorrhagic fever|url=http://www.who.int/mediacentre/factsheets/fs208/en/|website=World Health Organization|access-date=18 July 2017|date=January 2013|url-status=live|archive-url=https://web.archive.org/web/20170713160035/http://www.who.int/mediacentre/factsheets/fs208/en/|archive-date=13 July 2017}}</ref> Symptoms of CCHF may include [[fever]], [[Myalgia|muscle pains]], [[headache]], vomiting, [[diarrhea]], and [[petechiae|bleeding into the skin]].<ref name=WHO2013/> Onset of symptoms is less than two weeks following exposure.<ref name=WHO2013/> Complications may include [[liver failure]].<ref name=WHO2013/> In those who survive, recovery generally occurs around two weeks after onset.<ref name=WHO2013/>
<!-- Cause and diagnosis -->
The CCHF virus is typically spread by [[tick]] bites or contact with [[livestock]] carrying the disease.<ref name=WHO2013/> Groups that are at high risk of infection are [[farmers]] and those who work in [[slaughterhouses]].<ref name=WHO2013/> The virus can also spread between people via [[body fluids]].<ref name=WHO2013/> Diagnosis is by detecting [[antibodies]], the virus's [[RNA]], or the virus itself.<ref name=WHO2013/> It is a type of [[viral hemorrhagic fever]].<ref name=WHO2013/>
<!-- Prevention and treatment -->
Prevention involves avoiding tick bites.<ref name=WHO2013/> A [[vaccine]] is not commercially available.<ref name=WHO2013/> Treatment is typically with [[supportive care]].<ref name=WHO2013/> The medication [[ribavirin]] may also help.<ref name=WHO2013/>
<!-- Epidemiology and history -->
It occurs in Africa, the [[Balkans]], the Middle East, and Asia.<ref name=WHO2013/> Often it occurs in [[outbreaks]].<ref name=WHO2013/> In 2013 [[Iran]], Russia, [[Turkey]], and [[Uzbekistan]] documented more than fifty cases.<ref name=Gid2017>{{cite book | last1 = Berger | first1= Stephen |title=Crimean-Congo Hemorrhagic Fever: Global Status: 2017 edition|date=2017|publisher=GIDEON Informatics Inc|isbn=9781498815567|page=7|url=https://books.google.com/books?id=GEcWDgAAQBAJ&pg=PA7|language=en|url-status=live|archive-url=https://web.archive.org/web/20170910163841/https://books.google.ca/books?id=GEcWDgAAQBAJ&pg=PA7|archive-date=2017-09-10}}</ref> The risk of death among those affected is between 10 and 40%.<ref name=WHO2013/> It was first detected in the 1940s.<ref>{{cite book |last1=Magill |first1=Alan J. |title=Hunter's Tropical Medicine and Emerging Infectious Disease, Expert Consult - Online and Print,9: Hunter's Tropical Medicine and Emerging Infectious Disease|date=2013|publisher=Elsevier Health Sciences|isbn=978-1416043904|page=334|url=https://books.google.com/books?id=UgvdM8WRld4C&pg=PA334|language=en|url-status=live|archive-url=https://web.archive.org/web/20170804113952/https://books.google.ca/books?id=UgvdM8WRld4C&pg=PA334|archive-date=2017-08-04}}</ref>
{{TOC limit|3}}
==Signs and symptoms==
The illness in humans is a severe form of [[hemorrhagic fever]].<ref name="auto">{{Cite web |title=Crimean-Congo haemorrhagic fever, Fact sheet N°208 |work=WHO |date=January 2013 |access-date=2015-05-19 |url=http://www.who.int/mediacentre/factsheets/fs208/en/ |url-status=live |archive-url=https://web.archive.org/web/20150520204344/http://www.who.int/mediacentre/factsheets/fs208/en/ |archive-date=2015-05-20 }}</ref> Typically, after a 1–3 day [[incubation period]] following a tick bite or 5–6 days after exposure to infected blood or tissues, [[Influenza|flu]]-like symptoms appear, which may resolve after one week.In up to 75% of cases, signs of [[hemorrhage|bleeding]] can appear within 3–5 days of the onset of illness in case of bad containment of the first symptoms: [[mood swing|mood instability]], [[wikt:restlessness|agitation]], [[mental confusion]] and throat [[petechia]]e; and soon after nosebleeds, vomiting, and black stools. The [[liver]] becomes swollen and painful. [[Disseminated intravascular coagulation]] may occur, as well as acute [[renal failure|kidney failure]], [[Shock (circulatory)|shock]], and sometimes [[acute respiratory distress syndrome]].People usually begin to recover 9–10 days after first symptoms appear. Up to 30% of infected people die by the end of the second week of illness.<ref>{{cite web |title=Signs and Symptoms {{!}} Crimean-Congo Hemorrhagic Fever (CCHF) {{!}} CDC |url=https://www.cdc.gov/vhf/crimean-congo/symptoms/index.html |website=www.cdc.gov |accessdate=19 March 2022 |language=en-us |date=27 February 2019 |archive-date=14 March 2022 |archive-url=https://web.archive.org/web/20220314215456/https://www.cdc.gov/vhf/crimean-congo/symptoms/index.html |url-status=live }}</ref><ref>{{cite web |title=Crimean-Congo haemorrhagic fever - Symptoms, diagnosis and treatment {{!}} BMJ Best Practice |url=https://bestpractice.bmj.com/topics/en-gb/1606 |website=bestpractice.bmj.com |accessdate=19 March 2022 |archive-date=11 May 2021 |archive-url=https://web.archive.org/web/20210511094749/https://bestpractice.bmj.com/topics/en-gb/1606 |url-status=live }}</ref><ref>{{cite journal |last1=Grossi-Soyster |first1=Elysse N. |last2=LaBeaud |first2=A. Desiree |title=Rift Valley Fever: Important Considerations for Risk Mitigation and Future Outbreaks |journal=Tropical Medicine and Infectious Disease |date=2 June 2020 |volume=5 |issue=2 |pages=89 |doi=10.3390/tropicalmed5020089 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345646/ |accessdate=21 March 2022 |issn=2414-6366 |archive-date=30 January 2022 |archive-url=https://web.archive.org/web/20220130194551/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345646/ |url-status=live }}</ref>{{clarify}}
==Cause==
===Virology===
{{Virusbox
| image =
| image_alt =
| image_caption =
| parent = Orthonairovirus
| species = Crimean-Congo hemorrhagic fever orthonairovirus
| synonyms =
| synonyms_ref =
}}
[[File:PMC4848600 viruses-08-00106-g001.png|upright=1.3|thumb|Crimean-Congo hemorrhagic fever virus (CCHFV) virion and replication cycle.]]
The ''Crimean-Congo hemorrhagic fever orthonairovirus'' (CCHFV) is a member of the genus ''[[Orthonairovirus]]'', family ''[[Nairoviridae]]'' of [[RNA virus]]es.<ref name=ICTV>Virus Taxonomy: 2018 Release, EC 50, Washington, DC, July 2018, Email ratification October 2018 (MSL #33) https://talk.ictvonline.org/taxonomy/ {{Webarchive|url=https://web.archive.org/web/20200320103754/https://talk.ictvonline.org/taxonomy |date=2020-03-20 }}</ref>
The virions are 80–120 [[nanometer]]s (nm) in diameter and are [[pleomorphism (cytology)|pleomorphic]]. There are no host ribosomes within the virion. Each virion contains three copies of the genome. The envelope is single layered and is formed from a lipid bilayer 5 nm thick. It has no protrusions. The envelope proteins form small projections ~5–10 nm long. The nucleocapsids are filamentous and circular with a length of 200–3000 nm.<ref name=carter>{{cite journal | vauthors = Carter SD, Surtees R, Walter CT, Ariza A, Bergeron É, Nichol ST, Hiscox JA, Edwards TA, Barr JN | display-authors = 6 | title = Structure, function, and evolution of the Crimean-Congo hemorrhagic fever virus nucleocapsid protein | journal = Journal of Virology | volume = 86 | issue = 20 | pages = 10914–23 | date = October 2012 | pmid = 22875964 | pmc = 3457148 | doi = 10.1128/JVI.01555-12 | df = }}</ref>
The virus might enter a cell using the cell surface protein [[nucleolin]].<ref name=Xiao2011>{{cite journal | vauthors = Xiao X, Feng Y, Zhu Z, Dimitrov DS | title = Identification of a putative Crimean-Congo hemorrhagic fever virus entry factor | journal = Biochemical and Biophysical Research Communications | volume = 411 | issue = 2 | pages = 253–8 | date = July 2011 | pmid = 21723257 | pmc = 3155881 | doi = 10.1016/j.bbrc.2011.06.109 }}</ref>
====Molecular biology====
The genome is circular, negative sense [[RNA]] in three parts – Small (S), Medium (M) and Large (L). The L segment is 11–14.4 kilobases in length while the M and S segments are 4.4–6.3 and 1.7–2.1 kilobases long respectively. The L segment encodes the [[RNA polymerase]], the M segment encodes the envelope [[glycoproteins]] (Gc and Gn), and the S segment encodes the nucleocapsid protein.<ref name=carter/> The mutation rates for the three parts of the genome were estimated to be: 1.09{{e|−4}}, 1.52{{e|−4}} and 0.58{{e|−4}} substitutions/site/year for the S, M, and L segments respectively.<ref name=Carroll2010/>
====Population genetics====
CCHFV is the most genetically diverse of the [[arbovirus]]es: Its nucleotide sequences frequently differ between different strains, ranging from a 20% variability for the viral S segment to 31% for the M segment.<ref name=Bente2013>{{cite journal | vauthors = Bente DA, Forrester NL, Watts DM, McAuley AJ, Whitehouse CA, Bray M | title = Crimean-Congo hemorrhagic fever: history, epidemiology, pathogenesis, clinical syndrome and genetic diversity | journal = Antiviral Research | volume = 100 | issue = 1 | pages = 159–89 | date = October 2013 | pmid = 23906741 | doi = 10.1016/j.antiviral.2013.07.006 | url = http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1770&context=usgsstaffpub | access-date = 2018-11-27 | archive-date = 2017-09-22 | archive-url = https://web.archive.org/web/20170922234422/http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1770&context=usgsstaffpub | url-status = live }}</ref> Viruses with diverse sequences can be found within the same geographic area; closely related viruses have been isolated from widely separated regions, suggesting that viral dispersion has occurred possibly by ticks carried on migratory birds or through international livestock trade. Reassortment among genome segments during [[coinfection]] of ticks or vertebrates seems likely to have played a role in generating diversity in this virus.<ref>{{cite journal |last1=Fajs |first1=Luka |last2=Humolli |first2=Isme |last3=Saksida |first3=Ana |last4=Knap |first4=Nataša |last5=Jelovšek |first5=Mateja |last6=Korva |first6=Miša |last7=Dedushaj |first7=Isuf |last8=Avšič-Županc |first8=Tatjana |title=Prevalence of Crimean-Congo hemorrhagic fever virus in healthy population, livestock and ticks in Kosovo |journal=PloS One |date=2014 |volume=9 |issue=11 |pages=e110982 |doi=10.1371/journal.pone.0110982 |url=https://pubmed.ncbi.nlm.nih.gov/25393542/ |accessdate=24 March 2022 |issn=1932-6203 |archive-date=25 March 2022 |archive-url=https://web.archive.org/web/20220325084601/https://pubmed.ncbi.nlm.nih.gov/25393542/ |url-status=live }}</ref>{{clarify}}
Based on the sequence data, seven genotypes of CCHFV have been recognised: Africa 1 ([[Senegal]]), Africa 2 ([[Democratic Republic of the Congo]] and South Africa), Africa 3 (southern and western Africa), Europe 1 ([[Albania]], [[Bulgaria]], [[Kosovo]], [[Russia]] and [[Turkey]]), Europe 2 ([[Greece]]), Asia 1 ([[the Middle East]], [[Iran]] and [[Pakistan]]) and Asia 2 ([[China]], [[Kazakhstan]], [[Tajikistan]] and [[Uzbekistan]]).<ref>{{cite journal |last1=Alam |first1=Muhammad Masroor |last2=Khurshid |first2=Adnan |last3=Sharif |first3=Salmaan |last4=Shaukat |first4=Shahzad |last5=Suleman |first5=Rana Muhammad |last6=Angez |first6=Mehar |last7=Zaidi |first7=Syed Sohail Zahoor |title=Crimean-Congo Hemorrhagic Fever Asia-2 Genotype, Pakistan |journal=Emerging Infectious Diseases |date=2013 |volume=19 |issue=6 |pages=1017–1019 |doi=10.3201/eid1906.120771 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713814/ |accessdate=24 March 2022 |issn=1080-6040 |archive-date=3 March 2022 |archive-url=https://web.archive.org/web/20220303174230/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713814/ |url-status=live }}</ref>
===Transmission===
[[Image:Hyalomma-m-rufipes.jpg|thumb|''Hyalomma'' tick]]
[[Tick]]s are both "environmental reservoir" and [[vector (epidemiology)|vector]] for the virus, carrying it from wild animals to domestic animals and humans. Tick species identified as infected with the virus include ''Argas reflexus'', ''Hyalomma anatolicum'', ''Hyalomma detritum'', ''[[Hyalomma marginatum|Hyalomma marginatum marginatum]]'' and ''[[Rhipicephalus sanguineus]]''.<ref>{{cite web |title=Transmission {{!}} Crimean-Congo Hemorrhagic Fever (CCHF) {{!}} CDC |url=https://www.cdc.gov/vhf/crimean-congo/transmission/index.html |website=www.cdc.gov |accessdate=19 March 2022 |language=en-us |date=27 February 2019 |archive-date=28 April 2014 |archive-url=https://web.archive.org/web/20140428000848/http://www.cdc.gov/vhf/crimean-congo/transmission/index.html |url-status=live }}</ref><ref name="pap">{{cite journal |last1=Papa |first1=Anna |last2=Tsergouli |first2=Katerina |last3=Tsioka |first3=Katerina |last4=Mirazimi |first4=Ali |title=Crimean-Congo Hemorrhagic Fever: Tick-Host-Virus Interactions |journal=Frontiers in Cellular and Infection Microbiology |date=2017 |volume=7 |pages=213 |doi=10.3389/fcimb.2017.00213 |url=https://pubmed.ncbi.nlm.nih.gov/28603698/ |accessdate=26 March 2022 |issn=2235-2988 |archive-date=22 October 2021 |archive-url=https://web.archive.org/web/20211022090035/https://pubmed.ncbi.nlm.nih.gov/28603698/ |url-status=live }}</ref>{{clarify}}
At least 31 different species of ticks from the genera ''[[Haemaphysalis]]'' and ''Hyalomma'' in southeastern Iran have been found to carry the virus.<ref name=Mehravaran2012>{{cite journal | vauthors = Mehravaran A, Moradi M, Telmadarraiy Z, Mostafavi E, Moradi AR, Khakifirouz S, Shah-Hosseini N, Varaie FS, Jalali T, Hekmat S, Ghiasi SM, Chinikar S | display-authors = 6 | title = Molecular detection of Crimean-Congo haemorrhagic fever (CCHF) virus in ticks from southeastern Iran | journal = Ticks and Tick-Borne Diseases | volume = 4 | issue = 1–2 | pages = 35–8 | date = February 2013 | pmid = 23238248 | doi = 10.1016/j.ttbdis.2012.06.006 }}</ref>Wild animals and small mammals, particularly [[European hare]], Middle-African [[hedgehog]]s and [[mastomys|multimammate rats]] are the "amplifying hosts" of the virus. Birds are generally resistant to CCHF, with the exception of [[ostrich]]es. Domestic animals like sheep, goats and cattle can develop high titers of virus in their blood, but tend not to fall ill.<ref name="erg">{{cite journal | vauthors = Ergönül O, Celikbaş A, Dokuzoguz B, Eren S, Baykam N, Esener H | title = Characteristics of patients with Crimean-Congo hemorrhagic fever in a recent outbreak in Turkey and impact of oral ribavirin therapy | journal = Clinical Infectious Diseases | volume = 39 | issue = 2 | pages = 284–7 | date = July 2004 | pmid = 15307042 | doi = 10.1086/422000 | url = http://www.journals.uchicago.edu/cgi-bin/resolve?CID32782 | doi-access = free | access-date = 2008-07-26 | archive-date = 2020-08-01 | archive-url = https://web.archive.org/web/20200801084108/https://www.journals.uchicago.edu/cgi-bin/resolve?CID32782 | url-status = live }}</ref>The "sporadic infection" of humans is usually caused by a ''Hyalomma'' tick bite. Animals can transmit the virus to humans, but this would usually be as part of a disease cluster. When clusters of illness occur, it is typically after people treat, butcher or eat infected livestock, particularly [[ruminant]]s and [[ostrich]]es. Outbreaks have occurred in [[slaughterhouse|abattoir]]s and other places where workers have been exposed to infected human or animal blood and [[fomite]]s <ref name=pap/><ref name=erg/>{{clarify}}
Humans can infect humans and outbreaks also occur in clinical facilities through infected blood and unclean medical instruments.<ref name="ref">{{Cite web|url=https://www.cdc.gov/vhf/crimean-congo/transmission/index.html|archive-url=https://web.archive.org/web/20140428000848/http://www.cdc.gov/vhf/crimean-congo/transmission/index.html|url-status=live|archive-date=April 28, 2014|title=Crimean-Congo Hemorrhagic Fever (CCHF) Transmission|last=Division of High-Consequence Pathogens and Pathology|first=Viral Special Pathogens Branch|date=March 5, 2014|website=CDC}}</ref>
==Mechanism==
In terms of the pathogenesis of Crimean-Congo hemorrhagic fever, due to a variety of factors, it is not well understood. What is known of this virus mechanism is that [[endothelial cells]] and [[immune cells]] play a large role; the occupation of viral antigens in endothelial cells, is an indication that the endothelium is a important target of the virus.<ref>{{cite journal |last1=Akıncı |first1=Esragül |last2=Bodur |first2=Hürrem |last3=Leblebicioglu |first3=Hakan |title=Pathogenesis of Crimean-Congo hemorrhagic fever |journal=Vector Borne and Zoonotic Diseases (Larchmont, N.Y.) |date=July 2013 |volume=13 |issue=7 |pages=429–437 |doi=10.1089/vbz.2012.1061 |url=https://pubmed.ncbi.nlm.nih.gov/23663164/ |accessdate=22 March 2022 |issn=1557-7759 |archive-date=8 March 2022 |archive-url=https://web.archive.org/web/20220308015752/https://pubmed.ncbi.nlm.nih.gov/23663164/ |url-status=live }}</ref>
==Diagnosis==
[[File:Thermal cycler for PCR.jpg|thumb|right|150px|Thermal cycler/PCR]]
The diagnosis of Crimean-Congo Hemorrhagic Fever (CCHF) can be done via the following:<ref>{{cite web |title=Diagnosis {{!}} Crimean-Congo Hemorrhagic Fever (CCHF) {{!}} CDC |url=https://www.cdc.gov/vhf/crimean-congo/diagnosis/index.html |website=www.cdc.gov |accessdate=19 March 2022 |language=en-us |date=27 February 2019 |archive-date=18 March 2022 |archive-url=https://web.archive.org/web/20220318101811/https://www.cdc.gov/vhf/crimean-congo/diagnosis/index.html |url-status=live }}</ref>
*Antigen-Capture enzyme-Linked Immunosorbent Assay ([[ELISA]])
*Real time polymerase chain reaction ([[RT-PCR]])
*Virus isolation attempts
*[[Immunohistochemical staining]]
==Prevention==
{{Main|Prevention of viral hemorrhagic fever}}
Where mammalian tick infection is common, agricultural regulations require de-ticking farm animals before transportation or delivery for slaughter. Personal tick avoidance measures are recommended, such as use of insect repellents, adequate clothing, and body inspection for adherent ticks.When [[fever]]ish patients with evidence of bleeding require [[cardiopulmonary resuscitation|resuscitation]] or [[intensive care medicine|intensive care]], [[body substance isolation]] precautions should be taken.<ref>{{cite web |title=Prevention {{!}} Crimean-Congo Hemorrhagic Fever (CCHF) {{!}} CDC |url=https://www.cdc.gov/vhf/crimean-congo/prevention/index.html |website=www.cdc.gov |accessdate=19 March 2022 |language=en-us |date=27 February 2019 |archive-date=20 March 2021 |archive-url=https://web.archive.org/web/20210320071551/https://www.cdc.gov/vhf/crimean-congo/prevention/index.html |url-status=live }}</ref><ref>{{cite book|title=Infection Control for Viral Haemorrhagic Fevers in the African Health Care Setting|date=December 1998|publisher=World Health Organization and Centers for Disease Control and Prevention|url=https://www.cdc.gov/vhf/abroad/pdf/african-healthcare-setting-vhf.pdf|accessdate=20 October 2014|archive-date=8 July 2017|archive-url=https://web.archive.org/web/20170708093022/https://www.cdc.gov/vhf/abroad/pdf/african-healthcare-setting-vhf.pdf|url-status=live}}</ref> {{clarify}}
===Vaccine===
Since the 1970s, several vaccine trials around the world against CCHF have been terminated due to high toxicity.<ref name="auto1">{{cite journal | vauthors = Keshtkar-Jahromi M, Kuhn JH, Christova I, Bradfute SB, Jahrling PB, Bavari S | title = Crimean-Congo hemorrhagic fever: current and future prospects of vaccines and therapies | journal = Antiviral Research | volume = 90 | issue = 2 | pages = 85–92 | date = May 2011 | pmid = 21362441 | doi = 10.1016/j.antiviral.2011.02.010 | url = https://zenodo.org/record/1258736 | access-date = 2018-09-22 | archive-date = 2020-07-29 | archive-url = https://web.archive.org/web/20200729030327/https://zenodo.org/record/1258736 | url-status = live }}</ref>
{{As of| March 2011}}, the only available and probably somewhat efficacious CCHF vaccine has been an inactivated antigen preparation then used in Bulgaria.<ref name="auto1"/> No publication in the scientific literature related to this vaccine exists, which a Turkish virologist called suspicious both because antiquated technology and [[mouse brain]] were used to manufacture it.<ref name=gundem>{{cite web|url=http://gundem.milliyet.com.tr/keneye-asi-mujdesi/gundem/gundemdetay/25.05.2012/1545014/default.htm|title=Keneye aşı müjdesi|first=milliyet.com.tr Türkiye'nin lider haber|last=sitesi|url-status=live|archive-url=https://web.archive.org/web/20131219044119/http://gundem.milliyet.com.tr/keneye-asi-mujdesi/gundem/gundemdetay/25.05.2012/1545014/default.htm|archive-date=2013-12-19}}</ref>
More vaccines are under development, but the sporadic nature of the disease, even in endemic countries, suggests that large trials of vaccine efficacy will be difficult to perform. Finding volunteers may prove challenging, given growing [[anti-vaccination]] sentiment and resistance of populations to vaccination against contagious diseases. The number of people to be vaccinated, and the length of time they would have to be followed to confirm protection would have to be carefully defined. Alternatively, many scientists appear to believe that treatment of CCHF with [[ribavirin]] is more practical than prevention, but some recently conducted clinical trials appear to counter assumptions of drug efficacy.<ref name="auto1"/>
In 2011, a [[Turkey|Turkish]] research team led by [[Erciyes University]] successfully developed the first non-toxic preventive vaccine, which passed clinical trials. As of 2012, the vaccine was pending approval by the US FDA.<ref name=gundem/>
Since the Ebola epidemic, the WHO jumpstarted a "Blueprint for Research and Development preparedness" on [[Emerging infectious disease|emerging pathogen]]s with epidemic potential, against which there are no medical treatments.<ref name=sablog>{{cite web|last1=Kieny|first1=Marie-Paule |title=After Ebola, a Blueprint Emerges to Jump-Start R&D|url=https://blogs.scientificamerican.com/guest-blog/after-ebola-a-blueprint-emerges-to-jump-start-r-d/|website=Scientific American Blog Network|date=20 May 2015|access-date=13 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161220134725/https://blogs.scientificamerican.com/guest-blog/after-ebola-a-blueprint-emerges-to-jump-start-r-d/|archive-date=20 December 2016}}</ref> CCHF was the top priority on the initial list from December 2015, and is second as of January 2017.<ref name=WHOlist>{{cite web|title=R&D Blueprint. List of Blueprint priority diseases|url=http://www.who.int/blueprint/priority-diseases/en/|website=World Health Organization|date=January 2017|access-date=13 July 2017|url-status=live|archive-url=https://web.archive.org/web/20170910163841/http://www.who.int/blueprint/priority-diseases/en/|archive-date=10 September 2017}}</ref>
==Treatment==
[[File:Ribavirin-skeletal.svg|thumb|Ribavirin]]
Treatment is mostly [[supportive care|supportive]]. [[Ribavirin]] is used in treatment of this virus via both oral and intravenous formulations which seem effective.<ref name="auto"/>
{{As of |2011}} the use of [[Immunoglobulin]] preparations has remained unproven and antibody engineering, which raised hopes for [[monoclonal antibody]] therapy, has remained in its infancy.<ref name="auto1"/>
==Epidemiology==
CCHD occurs most frequently among agricultural workers, following the bite of an infected tick, and to a lesser extent among slaughterhouse workers exposed to the blood and tissues of infected livestock, and medical personnel through contact with the body fluids of infected persons.<ref name=Bente2013/>
===Geographic distribution===
In 2008, more than 50 cases/year were reported from only 4 countries: Turkey, Iran, Russia and Uzbekistan. 5-49 cases/year were present in South Africa, Central Asia including Pakistan and Afghanistan (but sparing Turkmenistan), in the Middle East only the UAE and the Balkan countries limited to Romania, Bulgaria, Serbia, Montenegro and Kosovo-Albania.<ref name=map/>
{{As of|2013}} the northern limit of CCHF has been 50 degrees northern latitude, north of which the ''[[Hyalomma]]'' ticks have not been found.<ref name="auto"/>
Per a WHO map from 2008, Hyalomma ticks occurred south of this latitude across all of the Eurasian continent and Africa, sparing only the islands of Sri Lanka, Indonesia and Japan.<ref name=map>{{cite web|url=http://www.who.int/csr/disease/crimean_congoHF/Global_CCHFRisk_20080918.png?ua=1|title=Geographic distribution of Crimean-Congo haemorrhagic fever (CCHF)| publisher=WHO|year=2008|url-status=live|archive-url=https://web.archive.org/web/20160513175948/http://www.who.int/csr/disease/crimean_congoHF/Global_CCHFRisk_20080918.png?ua=1|archive-date=2016-05-13}}</ref>
Serological or virological evidence of CCHF was widespread in Asia, Eastern Europe, the Middle East (except Israel, Lebanon and Jordan), central Africa, Western Africa, South Africa and Madagascar.<ref name=map/>
In 2014 the CDC indicated endemic areas largely unchanged in Africa and the Middle East, but different for the Balkan, including all countries of the former Yugoslavia, and also Greece, but no longer Romania. India's Northwestern regions of Rajastan and Gujarat saw their first cases.<ref name=ref/>
===Outbreaks===
The following are the many outbreaks of Crimean–Congo hemorrhagic fever:
[[File:Yozgat in Turkey.svg|thumb|right|370px|Yozgat province, turkey]]
* From 1995 to 2013, 228 cases of CCHF were reported in the Republic of Kosovo, with a case-fatality rate of 25.5%.<ref name=Kosovo>{{cite journal | vauthors = Fajs L, Jakupi X, Ahmeti S, Humolli I, Dedushaj I, Avšič-Županc T | title = Molecular epidemiology of Crimean-Congo hemorrhagic fever virus in Kosovo | journal = PLOS Neglected Tropical Diseases | volume = 8 | issue = 1 | pages = e2647 | year = 2014 | pmid = 24416468 | pmc = 3886908 | doi = 10.1371/journal.pntd.0002647 }}</ref>
* Between 2002–2008 the Ministry of Health of Turkey reported 3,128 CCHF cases, with a 5% death rate. In July 2005, authorities reported 41 cases of CCHF in central Turkey's [[Yozgat Province]], with one death. As of August 2008, a total of 50 deaths were reported for the year in various cities in Turkey due to CCHF.<ref>{{cite journal |last1=Leblebicioglu |first1=Hakan |last2=Ozaras |first2=Resat |last3=Irmak |first3=Hasan |last4=Sencan |first4=Irfan |title=Crimean-Congo hemorrhagic fever in Turkey: Current status and future challenges |journal=Antiviral Research |date=February 2016 |volume=126 |pages=21–34 |doi=10.1016/j.antiviral.2015.12.003 |url=https://pubmed.ncbi.nlm.nih.gov/26695860/ |accessdate=21 March 2022 |issn=1872-9096 |archive-date=5 March 2022 |archive-url=https://web.archive.org/web/20220305221257/https://pubmed.ncbi.nlm.nih.gov/26695860/ |url-status=live }}</ref><ref>{{cite web |title=Epidemiology of Crimean–Congo haemorrhagic fever virus: Albania, Bulgaria, Greece, Islamic Republic of Iran, Kosovo, Russian Federation, Turkey. 1st October 2008 |url=http://www.episouth.org/Episouth_CCHF_01_10_2008_final0024.pdf?&id=9062#:~:text=Crimean%E2%80%93Congo%20haemorrhagic%20fever%20%28CCHF%29%20virus%20is%20%E2%80%A2%20present,circulating%20with%20particular%20intensity%20in%202008%20in%20Turkey%2C |website=episouth.org |access-date=27 March 2022 |archive-date=27 March 2022 |archive-url=https://web.archive.org/web/20220327224607/http://www.episouth.org/Episouth_CCHF_01_10_2008_final0024.pdf?id=9062#:~:text=Crimean%E2%80%93Congo%20haemorrhagic%20fever%20%28CCHF%29%20virus%20is%20%E2%80%A2%20present,circulating%20with%20particular%20intensity%20in%202008%20in%20Turkey%2C |url-status=live }}</ref>
* In September 2010, an outbreak was reported in Pakistan's [[Khyber Pakhtunkhwa]] province. Poor diagnosis and record keeping caused the extent of the outbreak to be uncertain, though some reports indicated over 100 cases, with a case-fatality rate above 10%.<ref>{{cite journal |last1=Ijaz |first1=Muhammad |last2=Rahim |first2=Afaq |last3=Ali |first3=Iftikhar |title=Crimean-Congo Hemorrhagic Fever Virus in Pakistan |journal=Infectious Disorders Drug Targets |date=2017 |volume=17 |issue=2 |pages=143–145 |doi=10.2174/1871526517666170117125733 |url=https://pubmed.ncbi.nlm.nih.gov/28124602/ |accessdate=28 March 2022 |issn=2212-3989 |archive-date=20 October 2021 |archive-url=https://web.archive.org/web/20211020192800/https://pubmed.ncbi.nlm.nih.gov/28124602/ |url-status=live }}</ref><ref>{{cite journal |last1=Yousaf |first1=Muhammad Zubair |last2=Ashfaq |first2=Usman Ali |last3=Anjum |first3=Khalid Mahmood |last4=Fatima |first4=Shaista |title=Crimean-Congo Hemorrhagic Fever (CCHF) in Pakistan: The "Bell" is Ringing Silently |journal=Critical Reviews in Eukaryotic Gene Expression |date=2018 |volume=28 |issue=2 |pages=93–100 |doi=10.1615/CritRevEukaryotGeneExpr.2018020593 |url=https://pubmed.ncbi.nlm.nih.gov/30055534/ |accessdate=21 March 2022 |issn=1045-4403 |archive-date=21 March 2022 |archive-url=https://web.archive.org/web/20220321174826/https://pubmed.ncbi.nlm.nih.gov/30055534/ |url-status=live }}</ref>
* January 2011, the first human cases of CCHF in India was reported in [[Sanand]], Gujarat, India, with 4 reported deaths, which included the [[index patient]], treating physician and nurse.<ref>Syed Khalique Ahmed, Tanvir A Siddiqui, Anuradha Mascarenhas, Anuradha Mascarenhas, Tanvir A Siddiqui, Syed Khalique Ahmed : Pune, Ahmedabad [http://www.indianexpress.com/news/deadly-virus-makes-first-appearance-in-india-kills-three-in-gujarat/739292/ Deadly virus-makes first appearance in india kills three in gujarat] {{webarchive|url=https://web.archive.org/web/20110304153316/http://www.indianexpress.com/news/deadly-virus-makes-first-appearance-in-india-kills-three-in-gujarat/739292/ |date=2011-03-04 }} indianexpress.com, 19 January 2011</ref>
* {{As of|May 2012}}, 71 people were reported to have contracted the disease in Iran, resulting in 8 fatalities.<ref>{{cite web |url=http://edition.presstv.ir/detail/105532.html |title=Archived copy |access-date=2012-05-19 |url-status=dead |archive-url=https://web.archive.org/web/20160305050638/http://edition.presstv.ir/detail/105532.html |archive-date=2016-03-05 }}</ref>
* In October 2012, a British man died from the disease at the [[Royal Free Hospital]] in London. He had earlier been admitted to [[Gartnavel General Hospital]] in [[Glasgow]], after returning on a flight from [[Kabul]] in [[Afghanistan]].<ref>{{cite news|url=https://www.bbc.co.uk/news/uk-scotland-glasgow-west-19856504|title=Congo Fever: Patient dies in hospital|date=6 October 2012|via=www.bbc.co.uk|url-status=live|archive-url=https://web.archive.org/web/20121007200124/http://www.bbc.co.uk/news/uk-scotland-glasgow-west-19856504|archive-date=7 October 2012|work=BBC News}}</ref>
* In July 2013, seven persons died due to CCHF in Kariyana village in Babra [[taluka]], [[Amreli district]], Gujarat, India.<ref name="indiatvnews 2013">{{cite web | publisher = Indiatvnews | title=Congo Fever: Seven Die In Amreli In A Week Mobile Site | work =IndiaTv | date=2013-07-15 | url=http://m.indiatvnews.com/news/india/congo-fever-seven-die-in-amreli-in-a-week-25097.html | access-date=2015-03-28 | url-status=live | archive-url=https://web.archive.org/web/20160304055508/http://m.indiatvnews.com/news/india/congo-fever-seven-die-in-amreli-in-a-week-25097.html | archive-date=2016-03-04 }}</ref><ref>{{cite web|url=http://articles.timesofindia.indiatimes.com/2013-07-15/rajkot/40589464_1_amreli-village-cchf-congo-fever|title=Congo fever confirmed in Amreli village|publisher=Times of India|access-date=2013-08-08|archive-date=2013-09-23|archive-url=https://web.archive.org/web/20130923071304/http://articles.timesofindia.indiatimes.com/2013-07-15/rajkot/40589464_1_amreli-village-cchf-congo-fever|url-status=dead}}</ref>
* In August 2013, a farmer from [[Agago]], Uganda was treated at [[Kalongo Hospital]] for a confirmed CCHF infection. The deaths of three other individuals in the [[Northern Region, Uganda|northern region]] were suspected to have been caused by the virus.<ref>{{cite news|last=Biryabarema|first=Elias |date=17 August 2013|agency=Reuters|title=Three die in Uganda from Ebola-like fever: Health Ministry|url=https://news.yahoo.com/three-die-uganda-ebola-fever-health-ministry-122947530.html|publisher=Yahoo News|access-date=16 August 2013|url-status=live|archive-url=https://web.archive.org/web/20130820115319/http://news.yahoo.com/three-die-uganda-ebola-fever-health-ministry-122947530.html|archive-date=20 August 2013}}</ref> Another unrelated CCHF patient was admitted to [[Mulago Hospital]] on the same day. The [[Ministry of Health]] announced on the 19th that the outbreak was under control, but the second patient, a 27-year-old woman from [[Nansana]], died on the 21st. She is believed to have contracted the virus from her husband, who returned to Kampala after being treated for CCHF in [[Juba]], [[South Sudan]].<ref name=Otto>{{cite news|last=Otto|first=Alex |title=High Alert Over Crimean Fever|url=http://www.observer.ug/index.php?option=com_content&id=27116:high-alert-over-crimean-fever&catid=34:news&Itemid=114|access-date=26 August 2013|newspaper=The Observer|date=22 August 2013|location=Kampala|url-status=live|archive-url=https://web.archive.org/web/20140714151600/http://www.observer.ug/index.php?option=com_content&id=27116%3Ahigh-alert-over-crimean-fever&catid=34%3Anews&Itemid=114|archive-date=14 July 2014}}</ref>
* In June 2014, cases were diagnosed in Kazakhstan. Ten people, including an ambulance crew, were admitted on to hospital in southern Kazakhstan with suspected CCHF. In July 2014 an 8th person was found to be infected with CCHF at Hayatabad Medical Complex (HMC), Pakistan. The eight patients, including a nurse and 6 Afghan nationals, died between April and July 2014.<ref>{{cite web|last1=Khan|first1=Hidayat |title=Stemming outbreaks: Eighth patient dies of Congo hemorrhagic fever at HMC|url=http://tribune.com.pk/story/734275/stemming-outbreaks-eighth-patient-dies-of-congo-hemorrhagic-fever-at-hmc/|access-date=13 July 2014|url-status=live|archive-url=https://web.archive.org/web/20140713125529/http://tribune.com.pk/story/734275/stemming-outbreaks-eighth-patient-dies-of-congo-hemorrhagic-fever-at-hmc/|archive-date=13 July 2014|date=2014-07-11}}</ref>{{clarify}}
* {{As of|2015}}, sporadic confirmed cases have been reported from [[Bhuj]], Amreli, Sanand, [[Idar]] and [[Vadnagar]] in Gujarat, India. In November 2014, a doctor and a labourer in north Gujarat tested positive for the disease. In the following weeks, three more people died from CCHF.<ref name="The Times of India Mobile Site 2015">{{cite web| title=Health officials confirm congo fever death of Jaisalmer man| website=The Times of India Mobile Site| date=26 January 2015| url=http://m.timesofindia.com/city/jaipur/Health-officials-confirm-congo-fever-death-of-Jaisalmer-man/articleshow/46017452.cms| access-date=30 March 2015| url-status=live| archive-url=https://web.archive.org/web/20150402102143/http://m.timesofindia.com/city/jaipur/Health-officials-confirm-congo-fever-death-of-Jaisalmer-man/articleshow/46017452.cms| archive-date=2 April 2015}}</ref> In March 2015, one more person died of CCHF in Gujarat.<ref name="Cities2015">{{cite web | title=Kutch resident dies of Confo fever | website=The Indian Express | date=March 29, 2015 | url=http://indianexpress.com/article/india/gujarat/kutch-resident-dies-of-confo-fever/ | access-date=March 29, 2015 | url-status=live | archive-url=https://web.archive.org/web/20150403090229/http://indianexpress.com/article/india/gujarat/kutch-resident-dies-of-confo-fever/ | archive-date=April 3, 2015 }}</ref>As of 2015, among livestock, CCHF was recognized as "widespread" in India, only 4 years after the first human case had been diagnosed.<ref>{{cite web|url=http://outbreaknewstoday.com/crimean-congo-hemorrhagic-fever-spreads-across-india-82283/|title=Crimean-Congo hemorrhagic fever spreads across India - Outbreak News Today|date=9 October 2015|url-status=live|archive-url=https://web.archive.org/web/20151220080259/http://outbreaknewstoday.com/crimean-congo-hemorrhagic-fever-spreads-across-india-82283/|archive-date=20 December 2015}}</ref>
* In August 2016, the first local case of CCHF in Western Europe occurred in Western Spain. A 62-year-old man, who had been bitten by a tick in Spain died on August 25, having infected a nurse.<ref>{{Cite web|url=http://www.scientificamerican.com/article/first-local-case-of-tick-borne-disease-kills-man-in-spain/|title=First Local Case of Tick-Borne Disease Kills Man in Spain|access-date=2016-09-03|date=n.d.|publisher=Scientif American|url-status=live|archive-url=https://web.archive.org/web/20160902144044/http://www.scientificamerican.com/article/first-local-case-of-tick-borne-disease-kills-man-in-spain/|archive-date=2016-09-02}}</ref> The tick bite occurred in the [[province of Ávila]], 300 km away from the [[province of Cáceres]], where CCHF viral RNA from ticks was amplified in 2010.<ref name="nejmspain">{{cite journal | vauthors = Negredo A, de la Calle-Prieto F, Palencia-Herrejón E, Mora-Rillo M, Astray-Mochales J, Sánchez-Seco MP, Bermejo Lopez E, Menárguez J, Fernández-Cruz A, Sánchez-Artola B, Keough-Delgado E, Ramírez de Arellano E, Lasala F, Milla J, Fraile JL, Ordobás Gavín M, Martinez de la Gándara A, López Perez L, Diaz-Diaz D, López-García MA, Delgado-Jimenez P, Martín-Quirós A, Trigo E, Figueira JC, Manzanares J, Rodriguez-Baena E, Garcia-Comas L, Rodríguez-Fraga O, García-Arenzana N, Fernández-Díaz MV, Cornejo VM, Emmerich P, Schmidt-Chanasit J, Arribas JR | display-authors = 6 | title = Autochthonous Crimean-Congo Hemorrhagic Fever in Spain | journal = The New England Journal of Medicine | volume = 377 | issue = 2 | pages = 154–161 | date = July 2017 | pmid = 28700843 | doi = 10.1056/NEJMoa1615162 | doi-access = free }}</ref>{{As of|July 2017}} it was unclear what specific ecology led to the Spanish cases.<ref name=spain>{{cite journal | vauthors = Spengler JR, Bente DA | title = Crimean-Congo Hemorrhagic Fever in Spain - New Arrival or Silent Resident? | journal = The New England Journal of Medicine | volume = 377 | issue = 2 | pages = 106–108 | date = July 2017 | pmid = 28700846 | pmc = 5922251 | doi = 10.1056/NEJMp1707436 }}</ref>
* In August 2016, a number of Pakistani news sources raised concerns regarding the disease.<ref>{{cite web|url=http://tribune.com.pk/story/1164812/congo-virus-doctors-warn-outbreak-disease|title=Congo virus: Doctors warn against outbreak of disease|date=17 August 2016|publisher=The Express Tribune|url-status=live|archive-url=https://web.archive.org/web/20160906235102/http://tribune.com.pk/story/1164812/congo-virus-doctors-warn-outbreak-disease/|archive-date=6 September 2016}}</ref><ref>{{cite web|url=http://dunyanews.tv/en/Pakistan/351274-Karachi-Congo-virus-claims-another-life|title=Karachi: Congo virus claims another life - Pakistan - Dunya News|url-status=live|archive-url=https://web.archive.org/web/20160904100756/http://dunyanews.tv/en/Pakistan/351274-Karachi-Congo-virus-claims-another-life|archive-date=2016-09-04}}</ref> Between January and October 2016, CCHF outbreaks in Pakistan were reported with highest numbers of cases and deaths during August 2016, just before the festival of [[Eid-al-Adha]] (held on September 13–15 in 2016). It was hypothesized that the festival could play an important part as people could come into contact with domestic or imported animals potentially infected with CCHF virus.<ref name=statefair>{{cite journal | vauthors = Karim AM, Hussain I, Lee JH, Park KS, Lee SH | title = Surveillance of Crimean-Congo haemorrhagic fever in Pakistan | journal = The Lancet. Infectious Diseases | volume = 17 | issue = 4 | pages = 367–368 | date = April 2017 | pmid = 28346174 | doi = 10.1016/S1473-3099(17)30119-6 | url = http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(17)30119-6/abstract | doi-access = free }}</ref> The Pakistani NIH showed there was no correlation, and that CCHF cases have coincided with the peak tick proliferation during the preceding 8–10 years.<ref>{{cite journal | vauthors = Alam MM, Khurshid A, Rana MS, Aamir UB, Salman M, Ahmad M | title = Surveillance of Crimean-Congo haemorrhagic fever in Pakistan | journal = The Lancet. Infectious Diseases | volume = 17 | issue = 8 | pages = 806 | date = August 2017 | pmid = 28741546 | doi = 10.1016/S1473-3099(17)30403-6 | doi-access = free }}</ref>
* On February 5, 2020, an outbreak occurred in the central region of Mali. The infected are from Douentza and Mopti region. <ref>{{cite web |title=7 dead in Congo fever outbreak in Mali |url=https://medicalxpress.com/news/2020-02-dead-congo-fever-outbreak-mali.html |website=medicalxpress.com |access-date=8 February 2020 |language=en-us |archive-date=29 July 2020 |archive-url=https://web.archive.org/web/20200729000001/https://medicalxpress.com/news/2020-02-dead-congo-fever-outbreak-mali.html |url-status=live }}</ref><ref>{{cite web |title=Crimean-Congo hemorrhagic fever: 7 deaths in Mali village |url=http://outbreaknewstoday.com/crimean-congo-hemorrhagic-fever-7-deaths-in-mali-village-63526/ |website=Outbreak news |accessdate=25 March 2022 |archive-date=31 January 2022 |archive-url=https://web.archive.org/web/20220131072319/http://outbreaknewstoday.com/crimean-congo-hemorrhagic-fever-7-deaths-in-mali-village-63526/ |url-status=live }}</ref>
==History==
[[File:JPWoodallatICEID1998.jpg|thumb|right|150px|Jack Woodall, Virologist]]
The virus may have evolved around 1500–1100 BC. It is thought that changing climate and agricultural practices around this time could be behind its evolution.<ref name=Carroll2010>{{cite journal | vauthors = Carroll SA, Bird BH, Rollin PE, Nichol ST | title = Ancient common ancestry of Crimean-Congo hemorrhagic fever virus | journal = Molecular Phylogenetics and Evolution | volume = 55 | issue = 3 | pages = 1103–10 | date = June 2010 | pmid = 20074652 | doi = 10.1016/j.ympev.2010.01.006 }}</ref>In the 12th century a case of a hemorrhagic disease reported from what is now [[Tajikistan]] may have been the first known case of Crimean–Congo hemorrhagic fever.<ref>{{cite web |title=Crimean-Congo Hemorrhagic Fever Virus: Biology and Pathogenesis |url=https://www.medscape.com/viewarticle/729785#:~:text=In%20the%2012th%20century%20a%20hemorrhagic%20disease%2C%20today,in%20a%20region%20that%20now%20corresponds%20to%20Tadzhikistan. |website=Medscape |accessdate=29 March 2022 |language=en |archive-date=11 June 2017 |archive-url=https://web.archive.org/web/20170611202947/http://www.medscape.com/viewarticle/729785#:~:text=In%20the%2012th%20century%20a%20hemorrhagic%20disease%2C%20today,in%20a%20region%20that%20now%20corresponds%20to%20Tadzhikistan. |url-status=live }}</ref>
During the [[Crimean War]], the disease was known as "Crimean fever" and contracted by many, including [[Florence Nightingale]].<ref>Cromwell, Judith Lissauer, Florence Nightingale, Feminist, McFarland, 2013, p.149</ref>
In 1944, Soviet scientists first identified the disease they called Crimean hemorrhagic fever in [[Crimea]].<ref>{{cite web|title=Природная очаговость зоонозных инфекций в Крыму|url=http://zooeco.com/nauc-st17-2.html|website=Мир Животных|url-status=live|archive-url=https://web.archive.org/web/20160923044225/http://zooeco.com/nauc-st17-2.html|archive-date=2016-09-23}}</ref> In February 1967, virologists [[John "Jack" P. Woodall|Jack Woodall]], David Simpson, Ghislaine Courtois and others published initial reports on a virus they called the Congo virus.<ref>{{cite journal | vauthors = Simpson DI, Knight EM, Courtois G, Williams MC, Weinbren MP, Kibukamusoke JW | title = Congo virus: a hitherto undescribed virus occurring in Africa. I. Human isolations--clinical notes | journal = East African Medical Journal | volume = 44 | issue = 2 | pages = 86–92 | date = February 1967 | pmid = 6040759 }}</ref><ref>{{cite journal | vauthors = Woodall JP, Williams MC, Simpson DI | title = Congo virus: a hitherto undescribed virus occurring in Africa. II. Identification studies | journal = East African Medical Journal | volume = 44 | issue = 2 | pages = 93–8 | date = February 1967 | pmid = 6068614 }}</ref> In 1956, the Congo virus had first been isolated by physician Ghislaine Courtois, head of the Provincial Medical Laboratory, [[Kisangani|Stanleyville]], in the [[Belgian Congo]]. Strain V3010, isolated by Courtois, was sent to the [[Rockefeller Foundation]] Virus Laboratory (RFVL) in New York City and found to be identical to another strain from [[Uganda]], but to no other named virus at that time.<ref>{{cite journal |last1=Uyar |first1=Yavuz |last2=Christova |first2=Iva |last3=Papa |first3=Anna |title=Current situation of Crimean Congo hemorrhagic fever (CCHF) in Anatolia and Balkan Peninsula |journal=Turkish Bulletin of Hygiene and Experimental Biology |date=2011 |volume=68 |issue=3 |pages=139–151 |doi=10.5505/TurkHijyen.2011.60352 |url=https://jag.journalagent.com/turkhijyen/pdfs/THDBD_68_3_139_151.pdf |accessdate=29 March 2022 |archive-date=21 January 2022 |archive-url=https://web.archive.org/web/20220121001526/https://jag.journalagent.com/turkhijyen/pdfs/THDBD_68_3_139_151.pdf |url-status=live }}</ref><ref>{{cite journal |last1=Ergönül |first1=Önder |title=Crimean-Congo haemorrhagic fever |journal=The Lancet. Infectious Diseases |date=2006 |volume=6 |issue=4 |pages=203–214 |doi=10.1016/S1473-3099(06)70435-2 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185836/ |accessdate=30 March 2022 |issn=1473-3099}}</ref>{{clarify}}
In June 1967, Soviet virologist [[Mikhail Chumakov]] registered an isolate from a fatal case that occurred in [[Samarkand]] in the Catalogue of Arthropod-borne Viruses.<ref>{{cite journal | vauthors = Chumakov MP, Butenko AM, Shalunova NV, Mart'ianova LI, Smirnova SE, ((Bashkirtsev Iu)), Zavodova TI, Rubin SG, Tkachenko EA, Karmysheva VI, Reĭngol'd VN, Popov GV, Savinov AP | display-authors = 6 | title = [New data on the viral agent of Crimean hemorrhagic fever] | language = Russian | journal = Voprosy Virusologii | volume = 13 | issue = 3 | pages = 377 | date = May–June 1968 | pmid = 4235803 }}</ref>
In 1969, the Russian strain, which Chumakov had sent to the RFVL, was published to be identical to the Congo virus.<ref>{{cite journal | vauthors = Casals J | title = Antigenic similarity between the virus causing Crimean hemorrhagic fever and Congo virus | journal = Proceedings of the Society for Experimental Biology and Medicine | volume = 131 | issue = 1 | pages = 233–6 | date = May 1969 | pmid = 5770109 | doi = 10.3181/00379727-131-33847 }}
</ref>
The [[International Committee on Taxonomy of Viruses]] proposed the name ''Congo–Crimean hemorrhagic fever virus'', but the Soviets insisted on ''Crimean–Congo hemorrhagic fever virus''. In 1973, against all principles of scientific nomenclature based on priority of publication, it was adopted as the official name, in possibly the first instance of a virus losing its name to politics and the [[Cold War]].<ref>{{cite book | last1 = Ergönül | first1 = Onder | last2 = Whitehouse | first2 = Charles A. | title = Congo Hemorrhagic Fever: A Global Perspective | url = https://archive.org/details/crimeancongohemo00ergo | url-access = limited | place = Netherlands | publisher = Springer | year = 2007 | chapter = Personal Reflections, Jack Woodall | page = [https://archive.org/details/crimeancongohemo00ergo/page/n41 23] | isbn = 978-1-4020-6105-9 }}</ref>
These reports include records of the occurrence of the virus or antibodies to the virus from Greece, Portugal, South Africa, [[Madagascar]] (the first isolation from there), the [[Maghreb]], [[Dubai]], [[Saudi Arabia]], [[Kuwait]] and [[Iraq]].<ref>{{cite journal | vauthors = Crowcroft NS, Morgan D, Brown D | title = Viral haemorrhagic fevers in Europe--effective control requires a co-ordinated response | journal = Euro Surveillance | volume = 7 | issue = 3 | pages = 31–2 | date = March 2002 | pmid = 12631941 | doi = 10.2807/esm.07.03.00343-en | doi-access = free }}</ref><ref name=BullWHO>{{cite journal | vauthors = Al-Tikriti SK, Al-Ani F, Jurji FJ, Tantawi H, Al-Moslih M, Al-Janabi N, Mahmud MI, Al-Bana A, Habib H, Al-Munthri H, Al-Janabi S, AL-Jawahry K, Yonan M, Hassan F, Simpson DI | display-authors = 6 | title = Congo/Crimean haemorrhagic fever in Iraq | journal = Bulletin of the World Health Organization | volume = 59 | issue = 1 | pages = 85–90 | year = 1981 | pmid = 6790183 | pmc = 2396030 }}</ref><ref name=vector>{{cite journal | vauthors = Okorie TG | title = Comparative studies on the vector capacity of the different stages of Amblyomma variegatum Fabricius and Hyalomma rufipes Koch for Congo virus, after intracoelomic inoculation | journal = Veterinary Parasitology | volume = 38 | issue = 2–3 | pages = 215–23 | date = March 1991 | pmid = 1907050 | doi = 10.1016/0304-4017(91)90131-e }}</ref>
== References ==
{{Reflist}}
== External links ==
{{Medical resources
| ICD10 = {{ICD10|A|98|0|a|90}}
| ICD9 = {{ICD9|065.0}}
| ICDO =
| OMIM =
| DiseasesDB = 31969
| MedlinePlus = article
| eMedicineSubj = 830594
| eMedicineTopic =
}}
* [http://www.who.int/mediacentre/factsheets/fs208/en/ World Health Organization Fact Sheet] {{Webarchive|url=https://web.archive.org/web/20170713160035/http://www.who.int/mediacentre/factsheets/fs208/en/ |date=2017-07-13 }}
{{Zoonotic viral diseases}}
{{Tick-borne diseases}}
{{Taxonbar|from=Q29002571|from2=Q1788951|from3=Q24757193}}
{{DEFAULTSORT:Crimean-Congo Hemorrhagic Fever}}
[[Category:Arthropod-borne viral fevers and viral haemorrhagic fevers]]
[[Category:Hemorrhagic fevers]]
[[Category:Nairoviridae]]
[[Category:Tick-borne diseases]]
[[Category:RTT]]
[[Category:RTTID]]' |
Unified diff of changes made by edit (edit_diff ) | '@@ -1,0 +1,179 @@
+
+{{short description|Viral disease}}
+{{Infobox medical condition
+| name =
+| image = Crimean-Congo Hemorrhagic Fever.jpg
+| caption = Male diagnosed with Crimean–Congo hemorrhagic fever, 1969
+| image_size =
+| pronounce =
+| field = [[Infectious disease (medical specialty)|Infectious disease]]
+| symptoms = [[Fever]], muscle pains, [[headache]], vomiting, [[diarrhea]], [[petechiae|bleeding into the skin]]<ref name=WHO2013/>
+| complications = [[Liver failure]]<ref name=WHO2013/>
+| onset = Rapid<ref name=WHO2013/>
+| duration = Two weeks<ref name=WHO2013/>
+| types =
+| causes =
+| risks =
+| diagnosis = Detecting [[antibodies]], the virus's [[RNA]], or the virus itself<ref name=WHO2013/>
+| differential = [[Dengue fever]], [[Q fever]],<ref name=Gid2017/> [[Ebola|Ebola virus disease]]<ref>{{cite web|title=Ebola virus infection - Differentials {{!}} BMJ Best Practice|url=http://bestpractice.bmj.com/topics/en-gb/1210/differentials|website=bestpractice.bmj.com|access-date=21 May 2018|archive-date=13 August 2020|archive-url=https://web.archive.org/web/20200813062919/https://bestpractice.bmj.com/topics/en-gb/1210/differentials|url-status=live}}</ref>
+| prevention =
+| treatment = [[Supportive care]], [[ribavirin]]<ref name=WHO2013/>
+| medication =
+| prognosis = Risk of death ~25%<ref name=WHO2013/>
+| frequency =
+| deaths =
+}}
+<!-- Definition and symptoms -->
+'''Crimean–Congo hemorrhagic fever''' ('''CCHF''') is a [[viral disease]].<ref name=WHO2013>{{cite web|title=Crimean-Congo haemorrhagic fever|url=http://www.who.int/mediacentre/factsheets/fs208/en/|website=World Health Organization|access-date=18 July 2017|date=January 2013|url-status=live|archive-url=https://web.archive.org/web/20170713160035/http://www.who.int/mediacentre/factsheets/fs208/en/|archive-date=13 July 2017}}</ref> Symptoms of CCHF may include [[fever]], [[Myalgia|muscle pains]], [[headache]], vomiting, [[diarrhea]], and [[petechiae|bleeding into the skin]].<ref name=WHO2013/> Onset of symptoms is less than two weeks following exposure.<ref name=WHO2013/> Complications may include [[liver failure]].<ref name=WHO2013/> In those who survive, recovery generally occurs around two weeks after onset.<ref name=WHO2013/>
+
+<!-- Cause and diagnosis -->
+The CCHF virus is typically spread by [[tick]] bites or contact with [[livestock]] carrying the disease.<ref name=WHO2013/> Groups that are at high risk of infection are [[farmers]] and those who work in [[slaughterhouses]].<ref name=WHO2013/> The virus can also spread between people via [[body fluids]].<ref name=WHO2013/> Diagnosis is by detecting [[antibodies]], the virus's [[RNA]], or the virus itself.<ref name=WHO2013/> It is a type of [[viral hemorrhagic fever]].<ref name=WHO2013/>
+
+<!-- Prevention and treatment -->
+Prevention involves avoiding tick bites.<ref name=WHO2013/> A [[vaccine]] is not commercially available.<ref name=WHO2013/> Treatment is typically with [[supportive care]].<ref name=WHO2013/> The medication [[ribavirin]] may also help.<ref name=WHO2013/>
+
+<!-- Epidemiology and history -->
+It occurs in Africa, the [[Balkans]], the Middle East, and Asia.<ref name=WHO2013/> Often it occurs in [[outbreaks]].<ref name=WHO2013/> In 2013 [[Iran]], Russia, [[Turkey]], and [[Uzbekistan]] documented more than fifty cases.<ref name=Gid2017>{{cite book | last1 = Berger | first1= Stephen |title=Crimean-Congo Hemorrhagic Fever: Global Status: 2017 edition|date=2017|publisher=GIDEON Informatics Inc|isbn=9781498815567|page=7|url=https://books.google.com/books?id=GEcWDgAAQBAJ&pg=PA7|language=en|url-status=live|archive-url=https://web.archive.org/web/20170910163841/https://books.google.ca/books?id=GEcWDgAAQBAJ&pg=PA7|archive-date=2017-09-10}}</ref> The risk of death among those affected is between 10 and 40%.<ref name=WHO2013/> It was first detected in the 1940s.<ref>{{cite book |last1=Magill |first1=Alan J. |title=Hunter's Tropical Medicine and Emerging Infectious Disease, Expert Consult - Online and Print,9: Hunter's Tropical Medicine and Emerging Infectious Disease|date=2013|publisher=Elsevier Health Sciences|isbn=978-1416043904|page=334|url=https://books.google.com/books?id=UgvdM8WRld4C&pg=PA334|language=en|url-status=live|archive-url=https://web.archive.org/web/20170804113952/https://books.google.ca/books?id=UgvdM8WRld4C&pg=PA334|archive-date=2017-08-04}}</ref>
+{{TOC limit|3}}
+
+==Signs and symptoms==
+The illness in humans is a severe form of [[hemorrhagic fever]].<ref name="auto">{{Cite web |title=Crimean-Congo haemorrhagic fever, Fact sheet N°208 |work=WHO |date=January 2013 |access-date=2015-05-19 |url=http://www.who.int/mediacentre/factsheets/fs208/en/ |url-status=live |archive-url=https://web.archive.org/web/20150520204344/http://www.who.int/mediacentre/factsheets/fs208/en/ |archive-date=2015-05-20 }}</ref> Typically, after a 1–3 day [[incubation period]] following a tick bite or 5–6 days after exposure to infected blood or tissues, [[Influenza|flu]]-like symptoms appear, which may resolve after one week.In up to 75% of cases, signs of [[hemorrhage|bleeding]] can appear within 3–5 days of the onset of illness in case of bad containment of the first symptoms: [[mood swing|mood instability]], [[wikt:restlessness|agitation]], [[mental confusion]] and throat [[petechia]]e; and soon after nosebleeds, vomiting, and black stools. The [[liver]] becomes swollen and painful. [[Disseminated intravascular coagulation]] may occur, as well as acute [[renal failure|kidney failure]], [[Shock (circulatory)|shock]], and sometimes [[acute respiratory distress syndrome]].People usually begin to recover 9–10 days after first symptoms appear. Up to 30% of infected people die by the end of the second week of illness.<ref>{{cite web |title=Signs and Symptoms {{!}} Crimean-Congo Hemorrhagic Fever (CCHF) {{!}} CDC |url=https://www.cdc.gov/vhf/crimean-congo/symptoms/index.html |website=www.cdc.gov |accessdate=19 March 2022 |language=en-us |date=27 February 2019 |archive-date=14 March 2022 |archive-url=https://web.archive.org/web/20220314215456/https://www.cdc.gov/vhf/crimean-congo/symptoms/index.html |url-status=live }}</ref><ref>{{cite web |title=Crimean-Congo haemorrhagic fever - Symptoms, diagnosis and treatment {{!}} BMJ Best Practice |url=https://bestpractice.bmj.com/topics/en-gb/1606 |website=bestpractice.bmj.com |accessdate=19 March 2022 |archive-date=11 May 2021 |archive-url=https://web.archive.org/web/20210511094749/https://bestpractice.bmj.com/topics/en-gb/1606 |url-status=live }}</ref><ref>{{cite journal |last1=Grossi-Soyster |first1=Elysse N. |last2=LaBeaud |first2=A. Desiree |title=Rift Valley Fever: Important Considerations for Risk Mitigation and Future Outbreaks |journal=Tropical Medicine and Infectious Disease |date=2 June 2020 |volume=5 |issue=2 |pages=89 |doi=10.3390/tropicalmed5020089 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345646/ |accessdate=21 March 2022 |issn=2414-6366 |archive-date=30 January 2022 |archive-url=https://web.archive.org/web/20220130194551/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345646/ |url-status=live }}</ref>{{clarify}}
+
+==Cause==
+===Virology===
+{{Virusbox
+| image =
+| image_alt =
+| image_caption =
+| parent = Orthonairovirus
+| species = Crimean-Congo hemorrhagic fever orthonairovirus
+| synonyms =
+| synonyms_ref =
+}}
+[[File:PMC4848600 viruses-08-00106-g001.png|upright=1.3|thumb|Crimean-Congo hemorrhagic fever virus (CCHFV) virion and replication cycle.]]
+The ''Crimean-Congo hemorrhagic fever orthonairovirus'' (CCHFV) is a member of the genus ''[[Orthonairovirus]]'', family ''[[Nairoviridae]]'' of [[RNA virus]]es.<ref name=ICTV>Virus Taxonomy: 2018 Release, EC 50, Washington, DC, July 2018, Email ratification October 2018 (MSL #33) https://talk.ictvonline.org/taxonomy/ {{Webarchive|url=https://web.archive.org/web/20200320103754/https://talk.ictvonline.org/taxonomy |date=2020-03-20 }}</ref>
+
+The virions are 80–120 [[nanometer]]s (nm) in diameter and are [[pleomorphism (cytology)|pleomorphic]]. There are no host ribosomes within the virion. Each virion contains three copies of the genome. The envelope is single layered and is formed from a lipid bilayer 5 nm thick. It has no protrusions. The envelope proteins form small projections ~5–10 nm long. The nucleocapsids are filamentous and circular with a length of 200–3000 nm.<ref name=carter>{{cite journal | vauthors = Carter SD, Surtees R, Walter CT, Ariza A, Bergeron É, Nichol ST, Hiscox JA, Edwards TA, Barr JN | display-authors = 6 | title = Structure, function, and evolution of the Crimean-Congo hemorrhagic fever virus nucleocapsid protein | journal = Journal of Virology | volume = 86 | issue = 20 | pages = 10914–23 | date = October 2012 | pmid = 22875964 | pmc = 3457148 | doi = 10.1128/JVI.01555-12 | df = }}</ref>
+The virus might enter a cell using the cell surface protein [[nucleolin]].<ref name=Xiao2011>{{cite journal | vauthors = Xiao X, Feng Y, Zhu Z, Dimitrov DS | title = Identification of a putative Crimean-Congo hemorrhagic fever virus entry factor | journal = Biochemical and Biophysical Research Communications | volume = 411 | issue = 2 | pages = 253–8 | date = July 2011 | pmid = 21723257 | pmc = 3155881 | doi = 10.1016/j.bbrc.2011.06.109 }}</ref>
+
+====Molecular biology====
+The genome is circular, negative sense [[RNA]] in three parts – Small (S), Medium (M) and Large (L). The L segment is 11–14.4 kilobases in length while the M and S segments are 4.4–6.3 and 1.7–2.1 kilobases long respectively. The L segment encodes the [[RNA polymerase]], the M segment encodes the envelope [[glycoproteins]] (Gc and Gn), and the S segment encodes the nucleocapsid protein.<ref name=carter/> The mutation rates for the three parts of the genome were estimated to be: 1.09{{e|−4}}, 1.52{{e|−4}} and 0.58{{e|−4}} substitutions/site/year for the S, M, and L segments respectively.<ref name=Carroll2010/>
+
+====Population genetics====
+CCHFV is the most genetically diverse of the [[arbovirus]]es: Its nucleotide sequences frequently differ between different strains, ranging from a 20% variability for the viral S segment to 31% for the M segment.<ref name=Bente2013>{{cite journal | vauthors = Bente DA, Forrester NL, Watts DM, McAuley AJ, Whitehouse CA, Bray M | title = Crimean-Congo hemorrhagic fever: history, epidemiology, pathogenesis, clinical syndrome and genetic diversity | journal = Antiviral Research | volume = 100 | issue = 1 | pages = 159–89 | date = October 2013 | pmid = 23906741 | doi = 10.1016/j.antiviral.2013.07.006 | url = http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1770&context=usgsstaffpub | access-date = 2018-11-27 | archive-date = 2017-09-22 | archive-url = https://web.archive.org/web/20170922234422/http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1770&context=usgsstaffpub | url-status = live }}</ref> Viruses with diverse sequences can be found within the same geographic area; closely related viruses have been isolated from widely separated regions, suggesting that viral dispersion has occurred possibly by ticks carried on migratory birds or through international livestock trade. Reassortment among genome segments during [[coinfection]] of ticks or vertebrates seems likely to have played a role in generating diversity in this virus.<ref>{{cite journal |last1=Fajs |first1=Luka |last2=Humolli |first2=Isme |last3=Saksida |first3=Ana |last4=Knap |first4=Nataša |last5=Jelovšek |first5=Mateja |last6=Korva |first6=Miša |last7=Dedushaj |first7=Isuf |last8=Avšič-Županc |first8=Tatjana |title=Prevalence of Crimean-Congo hemorrhagic fever virus in healthy population, livestock and ticks in Kosovo |journal=PloS One |date=2014 |volume=9 |issue=11 |pages=e110982 |doi=10.1371/journal.pone.0110982 |url=https://pubmed.ncbi.nlm.nih.gov/25393542/ |accessdate=24 March 2022 |issn=1932-6203 |archive-date=25 March 2022 |archive-url=https://web.archive.org/web/20220325084601/https://pubmed.ncbi.nlm.nih.gov/25393542/ |url-status=live }}</ref>{{clarify}}
+
+Based on the sequence data, seven genotypes of CCHFV have been recognised: Africa 1 ([[Senegal]]), Africa 2 ([[Democratic Republic of the Congo]] and South Africa), Africa 3 (southern and western Africa), Europe 1 ([[Albania]], [[Bulgaria]], [[Kosovo]], [[Russia]] and [[Turkey]]), Europe 2 ([[Greece]]), Asia 1 ([[the Middle East]], [[Iran]] and [[Pakistan]]) and Asia 2 ([[China]], [[Kazakhstan]], [[Tajikistan]] and [[Uzbekistan]]).<ref>{{cite journal |last1=Alam |first1=Muhammad Masroor |last2=Khurshid |first2=Adnan |last3=Sharif |first3=Salmaan |last4=Shaukat |first4=Shahzad |last5=Suleman |first5=Rana Muhammad |last6=Angez |first6=Mehar |last7=Zaidi |first7=Syed Sohail Zahoor |title=Crimean-Congo Hemorrhagic Fever Asia-2 Genotype, Pakistan |journal=Emerging Infectious Diseases |date=2013 |volume=19 |issue=6 |pages=1017–1019 |doi=10.3201/eid1906.120771 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713814/ |accessdate=24 March 2022 |issn=1080-6040 |archive-date=3 March 2022 |archive-url=https://web.archive.org/web/20220303174230/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713814/ |url-status=live }}</ref>
+
+===Transmission===
+[[Image:Hyalomma-m-rufipes.jpg|thumb|''Hyalomma'' tick]]
+
+[[Tick]]s are both "environmental reservoir" and [[vector (epidemiology)|vector]] for the virus, carrying it from wild animals to domestic animals and humans. Tick species identified as infected with the virus include ''Argas reflexus'', ''Hyalomma anatolicum'', ''Hyalomma detritum'', ''[[Hyalomma marginatum|Hyalomma marginatum marginatum]]'' and ''[[Rhipicephalus sanguineus]]''.<ref>{{cite web |title=Transmission {{!}} Crimean-Congo Hemorrhagic Fever (CCHF) {{!}} CDC |url=https://www.cdc.gov/vhf/crimean-congo/transmission/index.html |website=www.cdc.gov |accessdate=19 March 2022 |language=en-us |date=27 February 2019 |archive-date=28 April 2014 |archive-url=https://web.archive.org/web/20140428000848/http://www.cdc.gov/vhf/crimean-congo/transmission/index.html |url-status=live }}</ref><ref name="pap">{{cite journal |last1=Papa |first1=Anna |last2=Tsergouli |first2=Katerina |last3=Tsioka |first3=Katerina |last4=Mirazimi |first4=Ali |title=Crimean-Congo Hemorrhagic Fever: Tick-Host-Virus Interactions |journal=Frontiers in Cellular and Infection Microbiology |date=2017 |volume=7 |pages=213 |doi=10.3389/fcimb.2017.00213 |url=https://pubmed.ncbi.nlm.nih.gov/28603698/ |accessdate=26 March 2022 |issn=2235-2988 |archive-date=22 October 2021 |archive-url=https://web.archive.org/web/20211022090035/https://pubmed.ncbi.nlm.nih.gov/28603698/ |url-status=live }}</ref>{{clarify}}
+
+At least 31 different species of ticks from the genera ''[[Haemaphysalis]]'' and ''Hyalomma'' in southeastern Iran have been found to carry the virus.<ref name=Mehravaran2012>{{cite journal | vauthors = Mehravaran A, Moradi M, Telmadarraiy Z, Mostafavi E, Moradi AR, Khakifirouz S, Shah-Hosseini N, Varaie FS, Jalali T, Hekmat S, Ghiasi SM, Chinikar S | display-authors = 6 | title = Molecular detection of Crimean-Congo haemorrhagic fever (CCHF) virus in ticks from southeastern Iran | journal = Ticks and Tick-Borne Diseases | volume = 4 | issue = 1–2 | pages = 35–8 | date = February 2013 | pmid = 23238248 | doi = 10.1016/j.ttbdis.2012.06.006 }}</ref>Wild animals and small mammals, particularly [[European hare]], Middle-African [[hedgehog]]s and [[mastomys|multimammate rats]] are the "amplifying hosts" of the virus. Birds are generally resistant to CCHF, with the exception of [[ostrich]]es. Domestic animals like sheep, goats and cattle can develop high titers of virus in their blood, but tend not to fall ill.<ref name="erg">{{cite journal | vauthors = Ergönül O, Celikbaş A, Dokuzoguz B, Eren S, Baykam N, Esener H | title = Characteristics of patients with Crimean-Congo hemorrhagic fever in a recent outbreak in Turkey and impact of oral ribavirin therapy | journal = Clinical Infectious Diseases | volume = 39 | issue = 2 | pages = 284–7 | date = July 2004 | pmid = 15307042 | doi = 10.1086/422000 | url = http://www.journals.uchicago.edu/cgi-bin/resolve?CID32782 | doi-access = free | access-date = 2008-07-26 | archive-date = 2020-08-01 | archive-url = https://web.archive.org/web/20200801084108/https://www.journals.uchicago.edu/cgi-bin/resolve?CID32782 | url-status = live }}</ref>The "sporadic infection" of humans is usually caused by a ''Hyalomma'' tick bite. Animals can transmit the virus to humans, but this would usually be as part of a disease cluster. When clusters of illness occur, it is typically after people treat, butcher or eat infected livestock, particularly [[ruminant]]s and [[ostrich]]es. Outbreaks have occurred in [[slaughterhouse|abattoir]]s and other places where workers have been exposed to infected human or animal blood and [[fomite]]s <ref name=pap/><ref name=erg/>{{clarify}}
+
+Humans can infect humans and outbreaks also occur in clinical facilities through infected blood and unclean medical instruments.<ref name="ref">{{Cite web|url=https://www.cdc.gov/vhf/crimean-congo/transmission/index.html|archive-url=https://web.archive.org/web/20140428000848/http://www.cdc.gov/vhf/crimean-congo/transmission/index.html|url-status=live|archive-date=April 28, 2014|title=Crimean-Congo Hemorrhagic Fever (CCHF) Transmission|last=Division of High-Consequence Pathogens and Pathology|first=Viral Special Pathogens Branch|date=March 5, 2014|website=CDC}}</ref>
+
+==Mechanism==
+In terms of the pathogenesis of Crimean-Congo hemorrhagic fever, due to a variety of factors, it is not well understood. What is known of this virus mechanism is that [[endothelial cells]] and [[immune cells]] play a large role; the occupation of viral antigens in endothelial cells, is an indication that the endothelium is a important target of the virus.<ref>{{cite journal |last1=Akıncı |first1=Esragül |last2=Bodur |first2=Hürrem |last3=Leblebicioglu |first3=Hakan |title=Pathogenesis of Crimean-Congo hemorrhagic fever |journal=Vector Borne and Zoonotic Diseases (Larchmont, N.Y.) |date=July 2013 |volume=13 |issue=7 |pages=429–437 |doi=10.1089/vbz.2012.1061 |url=https://pubmed.ncbi.nlm.nih.gov/23663164/ |accessdate=22 March 2022 |issn=1557-7759 |archive-date=8 March 2022 |archive-url=https://web.archive.org/web/20220308015752/https://pubmed.ncbi.nlm.nih.gov/23663164/ |url-status=live }}</ref>
+
+==Diagnosis==
+[[File:Thermal cycler for PCR.jpg|thumb|right|150px|Thermal cycler/PCR]]
+The diagnosis of Crimean-Congo Hemorrhagic Fever (CCHF) can be done via the following:<ref>{{cite web |title=Diagnosis {{!}} Crimean-Congo Hemorrhagic Fever (CCHF) {{!}} CDC |url=https://www.cdc.gov/vhf/crimean-congo/diagnosis/index.html |website=www.cdc.gov |accessdate=19 March 2022 |language=en-us |date=27 February 2019 |archive-date=18 March 2022 |archive-url=https://web.archive.org/web/20220318101811/https://www.cdc.gov/vhf/crimean-congo/diagnosis/index.html |url-status=live }}</ref>
+*Antigen-Capture enzyme-Linked Immunosorbent Assay ([[ELISA]])
+*Real time polymerase chain reaction ([[RT-PCR]])
+*Virus isolation attempts
+*[[Immunohistochemical staining]]
+
+==Prevention==
+{{Main|Prevention of viral hemorrhagic fever}}
+Where mammalian tick infection is common, agricultural regulations require de-ticking farm animals before transportation or delivery for slaughter. Personal tick avoidance measures are recommended, such as use of insect repellents, adequate clothing, and body inspection for adherent ticks.When [[fever]]ish patients with evidence of bleeding require [[cardiopulmonary resuscitation|resuscitation]] or [[intensive care medicine|intensive care]], [[body substance isolation]] precautions should be taken.<ref>{{cite web |title=Prevention {{!}} Crimean-Congo Hemorrhagic Fever (CCHF) {{!}} CDC |url=https://www.cdc.gov/vhf/crimean-congo/prevention/index.html |website=www.cdc.gov |accessdate=19 March 2022 |language=en-us |date=27 February 2019 |archive-date=20 March 2021 |archive-url=https://web.archive.org/web/20210320071551/https://www.cdc.gov/vhf/crimean-congo/prevention/index.html |url-status=live }}</ref><ref>{{cite book|title=Infection Control for Viral Haemorrhagic Fevers in the African Health Care Setting|date=December 1998|publisher=World Health Organization and Centers for Disease Control and Prevention|url=https://www.cdc.gov/vhf/abroad/pdf/african-healthcare-setting-vhf.pdf|accessdate=20 October 2014|archive-date=8 July 2017|archive-url=https://web.archive.org/web/20170708093022/https://www.cdc.gov/vhf/abroad/pdf/african-healthcare-setting-vhf.pdf|url-status=live}}</ref> {{clarify}}
+
+===Vaccine===
+Since the 1970s, several vaccine trials around the world against CCHF have been terminated due to high toxicity.<ref name="auto1">{{cite journal | vauthors = Keshtkar-Jahromi M, Kuhn JH, Christova I, Bradfute SB, Jahrling PB, Bavari S | title = Crimean-Congo hemorrhagic fever: current and future prospects of vaccines and therapies | journal = Antiviral Research | volume = 90 | issue = 2 | pages = 85–92 | date = May 2011 | pmid = 21362441 | doi = 10.1016/j.antiviral.2011.02.010 | url = https://zenodo.org/record/1258736 | access-date = 2018-09-22 | archive-date = 2020-07-29 | archive-url = https://web.archive.org/web/20200729030327/https://zenodo.org/record/1258736 | url-status = live }}</ref>
+
+{{As of| March 2011}}, the only available and probably somewhat efficacious CCHF vaccine has been an inactivated antigen preparation then used in Bulgaria.<ref name="auto1"/> No publication in the scientific literature related to this vaccine exists, which a Turkish virologist called suspicious both because antiquated technology and [[mouse brain]] were used to manufacture it.<ref name=gundem>{{cite web|url=http://gundem.milliyet.com.tr/keneye-asi-mujdesi/gundem/gundemdetay/25.05.2012/1545014/default.htm|title=Keneye aşı müjdesi|first=milliyet.com.tr Türkiye'nin lider haber|last=sitesi|url-status=live|archive-url=https://web.archive.org/web/20131219044119/http://gundem.milliyet.com.tr/keneye-asi-mujdesi/gundem/gundemdetay/25.05.2012/1545014/default.htm|archive-date=2013-12-19}}</ref>
+More vaccines are under development, but the sporadic nature of the disease, even in endemic countries, suggests that large trials of vaccine efficacy will be difficult to perform. Finding volunteers may prove challenging, given growing [[anti-vaccination]] sentiment and resistance of populations to vaccination against contagious diseases. The number of people to be vaccinated, and the length of time they would have to be followed to confirm protection would have to be carefully defined. Alternatively, many scientists appear to believe that treatment of CCHF with [[ribavirin]] is more practical than prevention, but some recently conducted clinical trials appear to counter assumptions of drug efficacy.<ref name="auto1"/>
+In 2011, a [[Turkey|Turkish]] research team led by [[Erciyes University]] successfully developed the first non-toxic preventive vaccine, which passed clinical trials. As of 2012, the vaccine was pending approval by the US FDA.<ref name=gundem/>
+
+Since the Ebola epidemic, the WHO jumpstarted a "Blueprint for Research and Development preparedness" on [[Emerging infectious disease|emerging pathogen]]s with epidemic potential, against which there are no medical treatments.<ref name=sablog>{{cite web|last1=Kieny|first1=Marie-Paule |title=After Ebola, a Blueprint Emerges to Jump-Start R&D|url=https://blogs.scientificamerican.com/guest-blog/after-ebola-a-blueprint-emerges-to-jump-start-r-d/|website=Scientific American Blog Network|date=20 May 2015|access-date=13 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161220134725/https://blogs.scientificamerican.com/guest-blog/after-ebola-a-blueprint-emerges-to-jump-start-r-d/|archive-date=20 December 2016}}</ref> CCHF was the top priority on the initial list from December 2015, and is second as of January 2017.<ref name=WHOlist>{{cite web|title=R&D Blueprint. List of Blueprint priority diseases|url=http://www.who.int/blueprint/priority-diseases/en/|website=World Health Organization|date=January 2017|access-date=13 July 2017|url-status=live|archive-url=https://web.archive.org/web/20170910163841/http://www.who.int/blueprint/priority-diseases/en/|archive-date=10 September 2017}}</ref>
+
+==Treatment==
+
+[[File:Ribavirin-skeletal.svg|thumb|Ribavirin]]
+Treatment is mostly [[supportive care|supportive]]. [[Ribavirin]] is used in treatment of this virus via both oral and intravenous formulations which seem effective.<ref name="auto"/>
+
+{{As of |2011}} the use of [[Immunoglobulin]] preparations has remained unproven and antibody engineering, which raised hopes for [[monoclonal antibody]] therapy, has remained in its infancy.<ref name="auto1"/>
+
+==Epidemiology==
+CCHD occurs most frequently among agricultural workers, following the bite of an infected tick, and to a lesser extent among slaughterhouse workers exposed to the blood and tissues of infected livestock, and medical personnel through contact with the body fluids of infected persons.<ref name=Bente2013/>
+
+===Geographic distribution===
+
+In 2008, more than 50 cases/year were reported from only 4 countries: Turkey, Iran, Russia and Uzbekistan. 5-49 cases/year were present in South Africa, Central Asia including Pakistan and Afghanistan (but sparing Turkmenistan), in the Middle East only the UAE and the Balkan countries limited to Romania, Bulgaria, Serbia, Montenegro and Kosovo-Albania.<ref name=map/>
+
+{{As of|2013}} the northern limit of CCHF has been 50 degrees northern latitude, north of which the ''[[Hyalomma]]'' ticks have not been found.<ref name="auto"/>
+Per a WHO map from 2008, Hyalomma ticks occurred south of this latitude across all of the Eurasian continent and Africa, sparing only the islands of Sri Lanka, Indonesia and Japan.<ref name=map>{{cite web|url=http://www.who.int/csr/disease/crimean_congoHF/Global_CCHFRisk_20080918.png?ua=1|title=Geographic distribution of Crimean-Congo haemorrhagic fever (CCHF)| publisher=WHO|year=2008|url-status=live|archive-url=https://web.archive.org/web/20160513175948/http://www.who.int/csr/disease/crimean_congoHF/Global_CCHFRisk_20080918.png?ua=1|archive-date=2016-05-13}}</ref>
+Serological or virological evidence of CCHF was widespread in Asia, Eastern Europe, the Middle East (except Israel, Lebanon and Jordan), central Africa, Western Africa, South Africa and Madagascar.<ref name=map/>
+
+In 2014 the CDC indicated endemic areas largely unchanged in Africa and the Middle East, but different for the Balkan, including all countries of the former Yugoslavia, and also Greece, but no longer Romania. India's Northwestern regions of Rajastan and Gujarat saw their first cases.<ref name=ref/>
+
+===Outbreaks===
+The following are the many outbreaks of Crimean–Congo hemorrhagic fever:
+[[File:Yozgat in Turkey.svg|thumb|right|370px|Yozgat province, turkey]]
+* From 1995 to 2013, 228 cases of CCHF were reported in the Republic of Kosovo, with a case-fatality rate of 25.5%.<ref name=Kosovo>{{cite journal | vauthors = Fajs L, Jakupi X, Ahmeti S, Humolli I, Dedushaj I, Avšič-Županc T | title = Molecular epidemiology of Crimean-Congo hemorrhagic fever virus in Kosovo | journal = PLOS Neglected Tropical Diseases | volume = 8 | issue = 1 | pages = e2647 | year = 2014 | pmid = 24416468 | pmc = 3886908 | doi = 10.1371/journal.pntd.0002647 }}</ref>
+* Between 2002–2008 the Ministry of Health of Turkey reported 3,128 CCHF cases, with a 5% death rate. In July 2005, authorities reported 41 cases of CCHF in central Turkey's [[Yozgat Province]], with one death. As of August 2008, a total of 50 deaths were reported for the year in various cities in Turkey due to CCHF.<ref>{{cite journal |last1=Leblebicioglu |first1=Hakan |last2=Ozaras |first2=Resat |last3=Irmak |first3=Hasan |last4=Sencan |first4=Irfan |title=Crimean-Congo hemorrhagic fever in Turkey: Current status and future challenges |journal=Antiviral Research |date=February 2016 |volume=126 |pages=21–34 |doi=10.1016/j.antiviral.2015.12.003 |url=https://pubmed.ncbi.nlm.nih.gov/26695860/ |accessdate=21 March 2022 |issn=1872-9096 |archive-date=5 March 2022 |archive-url=https://web.archive.org/web/20220305221257/https://pubmed.ncbi.nlm.nih.gov/26695860/ |url-status=live }}</ref><ref>{{cite web |title=Epidemiology of Crimean–Congo haemorrhagic fever virus: Albania, Bulgaria, Greece, Islamic Republic of Iran, Kosovo, Russian Federation, Turkey. 1st October 2008 |url=http://www.episouth.org/Episouth_CCHF_01_10_2008_final0024.pdf?&id=9062#:~:text=Crimean%E2%80%93Congo%20haemorrhagic%20fever%20%28CCHF%29%20virus%20is%20%E2%80%A2%20present,circulating%20with%20particular%20intensity%20in%202008%20in%20Turkey%2C |website=episouth.org |access-date=27 March 2022 |archive-date=27 March 2022 |archive-url=https://web.archive.org/web/20220327224607/http://www.episouth.org/Episouth_CCHF_01_10_2008_final0024.pdf?id=9062#:~:text=Crimean%E2%80%93Congo%20haemorrhagic%20fever%20%28CCHF%29%20virus%20is%20%E2%80%A2%20present,circulating%20with%20particular%20intensity%20in%202008%20in%20Turkey%2C |url-status=live }}</ref>
+* In September 2010, an outbreak was reported in Pakistan's [[Khyber Pakhtunkhwa]] province. Poor diagnosis and record keeping caused the extent of the outbreak to be uncertain, though some reports indicated over 100 cases, with a case-fatality rate above 10%.<ref>{{cite journal |last1=Ijaz |first1=Muhammad |last2=Rahim |first2=Afaq |last3=Ali |first3=Iftikhar |title=Crimean-Congo Hemorrhagic Fever Virus in Pakistan |journal=Infectious Disorders Drug Targets |date=2017 |volume=17 |issue=2 |pages=143–145 |doi=10.2174/1871526517666170117125733 |url=https://pubmed.ncbi.nlm.nih.gov/28124602/ |accessdate=28 March 2022 |issn=2212-3989 |archive-date=20 October 2021 |archive-url=https://web.archive.org/web/20211020192800/https://pubmed.ncbi.nlm.nih.gov/28124602/ |url-status=live }}</ref><ref>{{cite journal |last1=Yousaf |first1=Muhammad Zubair |last2=Ashfaq |first2=Usman Ali |last3=Anjum |first3=Khalid Mahmood |last4=Fatima |first4=Shaista |title=Crimean-Congo Hemorrhagic Fever (CCHF) in Pakistan: The "Bell" is Ringing Silently |journal=Critical Reviews in Eukaryotic Gene Expression |date=2018 |volume=28 |issue=2 |pages=93–100 |doi=10.1615/CritRevEukaryotGeneExpr.2018020593 |url=https://pubmed.ncbi.nlm.nih.gov/30055534/ |accessdate=21 March 2022 |issn=1045-4403 |archive-date=21 March 2022 |archive-url=https://web.archive.org/web/20220321174826/https://pubmed.ncbi.nlm.nih.gov/30055534/ |url-status=live }}</ref>
+* January 2011, the first human cases of CCHF in India was reported in [[Sanand]], Gujarat, India, with 4 reported deaths, which included the [[index patient]], treating physician and nurse.<ref>Syed Khalique Ahmed, Tanvir A Siddiqui, Anuradha Mascarenhas, Anuradha Mascarenhas, Tanvir A Siddiqui, Syed Khalique Ahmed : Pune, Ahmedabad [http://www.indianexpress.com/news/deadly-virus-makes-first-appearance-in-india-kills-three-in-gujarat/739292/ Deadly virus-makes first appearance in india kills three in gujarat] {{webarchive|url=https://web.archive.org/web/20110304153316/http://www.indianexpress.com/news/deadly-virus-makes-first-appearance-in-india-kills-three-in-gujarat/739292/ |date=2011-03-04 }} indianexpress.com, 19 January 2011</ref>
+* {{As of|May 2012}}, 71 people were reported to have contracted the disease in Iran, resulting in 8 fatalities.<ref>{{cite web |url=http://edition.presstv.ir/detail/105532.html |title=Archived copy |access-date=2012-05-19 |url-status=dead |archive-url=https://web.archive.org/web/20160305050638/http://edition.presstv.ir/detail/105532.html |archive-date=2016-03-05 }}</ref>
+* In October 2012, a British man died from the disease at the [[Royal Free Hospital]] in London. He had earlier been admitted to [[Gartnavel General Hospital]] in [[Glasgow]], after returning on a flight from [[Kabul]] in [[Afghanistan]].<ref>{{cite news|url=https://www.bbc.co.uk/news/uk-scotland-glasgow-west-19856504|title=Congo Fever: Patient dies in hospital|date=6 October 2012|via=www.bbc.co.uk|url-status=live|archive-url=https://web.archive.org/web/20121007200124/http://www.bbc.co.uk/news/uk-scotland-glasgow-west-19856504|archive-date=7 October 2012|work=BBC News}}</ref>
+* In July 2013, seven persons died due to CCHF in Kariyana village in Babra [[taluka]], [[Amreli district]], Gujarat, India.<ref name="indiatvnews 2013">{{cite web | publisher = Indiatvnews | title=Congo Fever: Seven Die In Amreli In A Week Mobile Site | work =IndiaTv | date=2013-07-15 | url=http://m.indiatvnews.com/news/india/congo-fever-seven-die-in-amreli-in-a-week-25097.html | access-date=2015-03-28 | url-status=live | archive-url=https://web.archive.org/web/20160304055508/http://m.indiatvnews.com/news/india/congo-fever-seven-die-in-amreli-in-a-week-25097.html | archive-date=2016-03-04 }}</ref><ref>{{cite web|url=http://articles.timesofindia.indiatimes.com/2013-07-15/rajkot/40589464_1_amreli-village-cchf-congo-fever|title=Congo fever confirmed in Amreli village|publisher=Times of India|access-date=2013-08-08|archive-date=2013-09-23|archive-url=https://web.archive.org/web/20130923071304/http://articles.timesofindia.indiatimes.com/2013-07-15/rajkot/40589464_1_amreli-village-cchf-congo-fever|url-status=dead}}</ref>
+* In August 2013, a farmer from [[Agago]], Uganda was treated at [[Kalongo Hospital]] for a confirmed CCHF infection. The deaths of three other individuals in the [[Northern Region, Uganda|northern region]] were suspected to have been caused by the virus.<ref>{{cite news|last=Biryabarema|first=Elias |date=17 August 2013|agency=Reuters|title=Three die in Uganda from Ebola-like fever: Health Ministry|url=https://news.yahoo.com/three-die-uganda-ebola-fever-health-ministry-122947530.html|publisher=Yahoo News|access-date=16 August 2013|url-status=live|archive-url=https://web.archive.org/web/20130820115319/http://news.yahoo.com/three-die-uganda-ebola-fever-health-ministry-122947530.html|archive-date=20 August 2013}}</ref> Another unrelated CCHF patient was admitted to [[Mulago Hospital]] on the same day. The [[Ministry of Health]] announced on the 19th that the outbreak was under control, but the second patient, a 27-year-old woman from [[Nansana]], died on the 21st. She is believed to have contracted the virus from her husband, who returned to Kampala after being treated for CCHF in [[Juba]], [[South Sudan]].<ref name=Otto>{{cite news|last=Otto|first=Alex |title=High Alert Over Crimean Fever|url=http://www.observer.ug/index.php?option=com_content&id=27116:high-alert-over-crimean-fever&catid=34:news&Itemid=114|access-date=26 August 2013|newspaper=The Observer|date=22 August 2013|location=Kampala|url-status=live|archive-url=https://web.archive.org/web/20140714151600/http://www.observer.ug/index.php?option=com_content&id=27116%3Ahigh-alert-over-crimean-fever&catid=34%3Anews&Itemid=114|archive-date=14 July 2014}}</ref>
+* In June 2014, cases were diagnosed in Kazakhstan. Ten people, including an ambulance crew, were admitted on to hospital in southern Kazakhstan with suspected CCHF. In July 2014 an 8th person was found to be infected with CCHF at Hayatabad Medical Complex (HMC), Pakistan. The eight patients, including a nurse and 6 Afghan nationals, died between April and July 2014.<ref>{{cite web|last1=Khan|first1=Hidayat |title=Stemming outbreaks: Eighth patient dies of Congo hemorrhagic fever at HMC|url=http://tribune.com.pk/story/734275/stemming-outbreaks-eighth-patient-dies-of-congo-hemorrhagic-fever-at-hmc/|access-date=13 July 2014|url-status=live|archive-url=https://web.archive.org/web/20140713125529/http://tribune.com.pk/story/734275/stemming-outbreaks-eighth-patient-dies-of-congo-hemorrhagic-fever-at-hmc/|archive-date=13 July 2014|date=2014-07-11}}</ref>{{clarify}}
+* {{As of|2015}}, sporadic confirmed cases have been reported from [[Bhuj]], Amreli, Sanand, [[Idar]] and [[Vadnagar]] in Gujarat, India. In November 2014, a doctor and a labourer in north Gujarat tested positive for the disease. In the following weeks, three more people died from CCHF.<ref name="The Times of India Mobile Site 2015">{{cite web| title=Health officials confirm congo fever death of Jaisalmer man| website=The Times of India Mobile Site| date=26 January 2015| url=http://m.timesofindia.com/city/jaipur/Health-officials-confirm-congo-fever-death-of-Jaisalmer-man/articleshow/46017452.cms| access-date=30 March 2015| url-status=live| archive-url=https://web.archive.org/web/20150402102143/http://m.timesofindia.com/city/jaipur/Health-officials-confirm-congo-fever-death-of-Jaisalmer-man/articleshow/46017452.cms| archive-date=2 April 2015}}</ref> In March 2015, one more person died of CCHF in Gujarat.<ref name="Cities2015">{{cite web | title=Kutch resident dies of Confo fever | website=The Indian Express | date=March 29, 2015 | url=http://indianexpress.com/article/india/gujarat/kutch-resident-dies-of-confo-fever/ | access-date=March 29, 2015 | url-status=live | archive-url=https://web.archive.org/web/20150403090229/http://indianexpress.com/article/india/gujarat/kutch-resident-dies-of-confo-fever/ | archive-date=April 3, 2015 }}</ref>As of 2015, among livestock, CCHF was recognized as "widespread" in India, only 4 years after the first human case had been diagnosed.<ref>{{cite web|url=http://outbreaknewstoday.com/crimean-congo-hemorrhagic-fever-spreads-across-india-82283/|title=Crimean-Congo hemorrhagic fever spreads across India - Outbreak News Today|date=9 October 2015|url-status=live|archive-url=https://web.archive.org/web/20151220080259/http://outbreaknewstoday.com/crimean-congo-hemorrhagic-fever-spreads-across-india-82283/|archive-date=20 December 2015}}</ref>
+* In August 2016, the first local case of CCHF in Western Europe occurred in Western Spain. A 62-year-old man, who had been bitten by a tick in Spain died on August 25, having infected a nurse.<ref>{{Cite web|url=http://www.scientificamerican.com/article/first-local-case-of-tick-borne-disease-kills-man-in-spain/|title=First Local Case of Tick-Borne Disease Kills Man in Spain|access-date=2016-09-03|date=n.d.|publisher=Scientif American|url-status=live|archive-url=https://web.archive.org/web/20160902144044/http://www.scientificamerican.com/article/first-local-case-of-tick-borne-disease-kills-man-in-spain/|archive-date=2016-09-02}}</ref> The tick bite occurred in the [[province of Ávila]], 300 km away from the [[province of Cáceres]], where CCHF viral RNA from ticks was amplified in 2010.<ref name="nejmspain">{{cite journal | vauthors = Negredo A, de la Calle-Prieto F, Palencia-Herrejón E, Mora-Rillo M, Astray-Mochales J, Sánchez-Seco MP, Bermejo Lopez E, Menárguez J, Fernández-Cruz A, Sánchez-Artola B, Keough-Delgado E, Ramírez de Arellano E, Lasala F, Milla J, Fraile JL, Ordobás Gavín M, Martinez de la Gándara A, López Perez L, Diaz-Diaz D, López-García MA, Delgado-Jimenez P, Martín-Quirós A, Trigo E, Figueira JC, Manzanares J, Rodriguez-Baena E, Garcia-Comas L, Rodríguez-Fraga O, García-Arenzana N, Fernández-Díaz MV, Cornejo VM, Emmerich P, Schmidt-Chanasit J, Arribas JR | display-authors = 6 | title = Autochthonous Crimean-Congo Hemorrhagic Fever in Spain | journal = The New England Journal of Medicine | volume = 377 | issue = 2 | pages = 154–161 | date = July 2017 | pmid = 28700843 | doi = 10.1056/NEJMoa1615162 | doi-access = free }}</ref>{{As of|July 2017}} it was unclear what specific ecology led to the Spanish cases.<ref name=spain>{{cite journal | vauthors = Spengler JR, Bente DA | title = Crimean-Congo Hemorrhagic Fever in Spain - New Arrival or Silent Resident? | journal = The New England Journal of Medicine | volume = 377 | issue = 2 | pages = 106–108 | date = July 2017 | pmid = 28700846 | pmc = 5922251 | doi = 10.1056/NEJMp1707436 }}</ref>
+* In August 2016, a number of Pakistani news sources raised concerns regarding the disease.<ref>{{cite web|url=http://tribune.com.pk/story/1164812/congo-virus-doctors-warn-outbreak-disease|title=Congo virus: Doctors warn against outbreak of disease|date=17 August 2016|publisher=The Express Tribune|url-status=live|archive-url=https://web.archive.org/web/20160906235102/http://tribune.com.pk/story/1164812/congo-virus-doctors-warn-outbreak-disease/|archive-date=6 September 2016}}</ref><ref>{{cite web|url=http://dunyanews.tv/en/Pakistan/351274-Karachi-Congo-virus-claims-another-life|title=Karachi: Congo virus claims another life - Pakistan - Dunya News|url-status=live|archive-url=https://web.archive.org/web/20160904100756/http://dunyanews.tv/en/Pakistan/351274-Karachi-Congo-virus-claims-another-life|archive-date=2016-09-04}}</ref> Between January and October 2016, CCHF outbreaks in Pakistan were reported with highest numbers of cases and deaths during August 2016, just before the festival of [[Eid-al-Adha]] (held on September 13–15 in 2016). It was hypothesized that the festival could play an important part as people could come into contact with domestic or imported animals potentially infected with CCHF virus.<ref name=statefair>{{cite journal | vauthors = Karim AM, Hussain I, Lee JH, Park KS, Lee SH | title = Surveillance of Crimean-Congo haemorrhagic fever in Pakistan | journal = The Lancet. Infectious Diseases | volume = 17 | issue = 4 | pages = 367–368 | date = April 2017 | pmid = 28346174 | doi = 10.1016/S1473-3099(17)30119-6 | url = http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(17)30119-6/abstract | doi-access = free }}</ref> The Pakistani NIH showed there was no correlation, and that CCHF cases have coincided with the peak tick proliferation during the preceding 8–10 years.<ref>{{cite journal | vauthors = Alam MM, Khurshid A, Rana MS, Aamir UB, Salman M, Ahmad M | title = Surveillance of Crimean-Congo haemorrhagic fever in Pakistan | journal = The Lancet. Infectious Diseases | volume = 17 | issue = 8 | pages = 806 | date = August 2017 | pmid = 28741546 | doi = 10.1016/S1473-3099(17)30403-6 | doi-access = free }}</ref>
+* On February 5, 2020, an outbreak occurred in the central region of Mali. The infected are from Douentza and Mopti region. <ref>{{cite web |title=7 dead in Congo fever outbreak in Mali |url=https://medicalxpress.com/news/2020-02-dead-congo-fever-outbreak-mali.html |website=medicalxpress.com |access-date=8 February 2020 |language=en-us |archive-date=29 July 2020 |archive-url=https://web.archive.org/web/20200729000001/https://medicalxpress.com/news/2020-02-dead-congo-fever-outbreak-mali.html |url-status=live }}</ref><ref>{{cite web |title=Crimean-Congo hemorrhagic fever: 7 deaths in Mali village |url=http://outbreaknewstoday.com/crimean-congo-hemorrhagic-fever-7-deaths-in-mali-village-63526/ |website=Outbreak news |accessdate=25 March 2022 |archive-date=31 January 2022 |archive-url=https://web.archive.org/web/20220131072319/http://outbreaknewstoday.com/crimean-congo-hemorrhagic-fever-7-deaths-in-mali-village-63526/ |url-status=live }}</ref>
+
+==History==
+[[File:JPWoodallatICEID1998.jpg|thumb|right|150px|Jack Woodall, Virologist]]
+The virus may have evolved around 1500–1100 BC. It is thought that changing climate and agricultural practices around this time could be behind its evolution.<ref name=Carroll2010>{{cite journal | vauthors = Carroll SA, Bird BH, Rollin PE, Nichol ST | title = Ancient common ancestry of Crimean-Congo hemorrhagic fever virus | journal = Molecular Phylogenetics and Evolution | volume = 55 | issue = 3 | pages = 1103–10 | date = June 2010 | pmid = 20074652 | doi = 10.1016/j.ympev.2010.01.006 }}</ref>In the 12th century a case of a hemorrhagic disease reported from what is now [[Tajikistan]] may have been the first known case of Crimean–Congo hemorrhagic fever.<ref>{{cite web |title=Crimean-Congo Hemorrhagic Fever Virus: Biology and Pathogenesis |url=https://www.medscape.com/viewarticle/729785#:~:text=In%20the%2012th%20century%20a%20hemorrhagic%20disease%2C%20today,in%20a%20region%20that%20now%20corresponds%20to%20Tadzhikistan. |website=Medscape |accessdate=29 March 2022 |language=en |archive-date=11 June 2017 |archive-url=https://web.archive.org/web/20170611202947/http://www.medscape.com/viewarticle/729785#:~:text=In%20the%2012th%20century%20a%20hemorrhagic%20disease%2C%20today,in%20a%20region%20that%20now%20corresponds%20to%20Tadzhikistan. |url-status=live }}</ref>
+During the [[Crimean War]], the disease was known as "Crimean fever" and contracted by many, including [[Florence Nightingale]].<ref>Cromwell, Judith Lissauer, Florence Nightingale, Feminist, McFarland, 2013, p.149</ref>
+
+In 1944, Soviet scientists first identified the disease they called Crimean hemorrhagic fever in [[Crimea]].<ref>{{cite web|title=Природная очаговость зоонозных инфекций в Крыму|url=http://zooeco.com/nauc-st17-2.html|website=Мир Животных|url-status=live|archive-url=https://web.archive.org/web/20160923044225/http://zooeco.com/nauc-st17-2.html|archive-date=2016-09-23}}</ref> In February 1967, virologists [[John "Jack" P. Woodall|Jack Woodall]], David Simpson, Ghislaine Courtois and others published initial reports on a virus they called the Congo virus.<ref>{{cite journal | vauthors = Simpson DI, Knight EM, Courtois G, Williams MC, Weinbren MP, Kibukamusoke JW | title = Congo virus: a hitherto undescribed virus occurring in Africa. I. Human isolations--clinical notes | journal = East African Medical Journal | volume = 44 | issue = 2 | pages = 86–92 | date = February 1967 | pmid = 6040759 }}</ref><ref>{{cite journal | vauthors = Woodall JP, Williams MC, Simpson DI | title = Congo virus: a hitherto undescribed virus occurring in Africa. II. Identification studies | journal = East African Medical Journal | volume = 44 | issue = 2 | pages = 93–8 | date = February 1967 | pmid = 6068614 }}</ref> In 1956, the Congo virus had first been isolated by physician Ghislaine Courtois, head of the Provincial Medical Laboratory, [[Kisangani|Stanleyville]], in the [[Belgian Congo]]. Strain V3010, isolated by Courtois, was sent to the [[Rockefeller Foundation]] Virus Laboratory (RFVL) in New York City and found to be identical to another strain from [[Uganda]], but to no other named virus at that time.<ref>{{cite journal |last1=Uyar |first1=Yavuz |last2=Christova |first2=Iva |last3=Papa |first3=Anna |title=Current situation of Crimean Congo hemorrhagic fever (CCHF) in Anatolia and Balkan Peninsula |journal=Turkish Bulletin of Hygiene and Experimental Biology |date=2011 |volume=68 |issue=3 |pages=139–151 |doi=10.5505/TurkHijyen.2011.60352 |url=https://jag.journalagent.com/turkhijyen/pdfs/THDBD_68_3_139_151.pdf |accessdate=29 March 2022 |archive-date=21 January 2022 |archive-url=https://web.archive.org/web/20220121001526/https://jag.journalagent.com/turkhijyen/pdfs/THDBD_68_3_139_151.pdf |url-status=live }}</ref><ref>{{cite journal |last1=Ergönül |first1=Önder |title=Crimean-Congo haemorrhagic fever |journal=The Lancet. Infectious Diseases |date=2006 |volume=6 |issue=4 |pages=203–214 |doi=10.1016/S1473-3099(06)70435-2 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185836/ |accessdate=30 March 2022 |issn=1473-3099}}</ref>{{clarify}}
+
+In June 1967, Soviet virologist [[Mikhail Chumakov]] registered an isolate from a fatal case that occurred in [[Samarkand]] in the Catalogue of Arthropod-borne Viruses.<ref>{{cite journal | vauthors = Chumakov MP, Butenko AM, Shalunova NV, Mart'ianova LI, Smirnova SE, ((Bashkirtsev Iu)), Zavodova TI, Rubin SG, Tkachenko EA, Karmysheva VI, Reĭngol'd VN, Popov GV, Savinov AP | display-authors = 6 | title = [New data on the viral agent of Crimean hemorrhagic fever] | language = Russian | journal = Voprosy Virusologii | volume = 13 | issue = 3 | pages = 377 | date = May–June 1968 | pmid = 4235803 }}</ref>
+In 1969, the Russian strain, which Chumakov had sent to the RFVL, was published to be identical to the Congo virus.<ref>{{cite journal | vauthors = Casals J | title = Antigenic similarity between the virus causing Crimean hemorrhagic fever and Congo virus | journal = Proceedings of the Society for Experimental Biology and Medicine | volume = 131 | issue = 1 | pages = 233–6 | date = May 1969 | pmid = 5770109 | doi = 10.3181/00379727-131-33847 }}
+</ref>
+
+The [[International Committee on Taxonomy of Viruses]] proposed the name ''Congo–Crimean hemorrhagic fever virus'', but the Soviets insisted on ''Crimean–Congo hemorrhagic fever virus''. In 1973, against all principles of scientific nomenclature based on priority of publication, it was adopted as the official name, in possibly the first instance of a virus losing its name to politics and the [[Cold War]].<ref>{{cite book | last1 = Ergönül | first1 = Onder | last2 = Whitehouse | first2 = Charles A. | title = Congo Hemorrhagic Fever: A Global Perspective | url = https://archive.org/details/crimeancongohemo00ergo | url-access = limited | place = Netherlands | publisher = Springer | year = 2007 | chapter = Personal Reflections, Jack Woodall | page = [https://archive.org/details/crimeancongohemo00ergo/page/n41 23] | isbn = 978-1-4020-6105-9 }}</ref>
+
+These reports include records of the occurrence of the virus or antibodies to the virus from Greece, Portugal, South Africa, [[Madagascar]] (the first isolation from there), the [[Maghreb]], [[Dubai]], [[Saudi Arabia]], [[Kuwait]] and [[Iraq]].<ref>{{cite journal | vauthors = Crowcroft NS, Morgan D, Brown D | title = Viral haemorrhagic fevers in Europe--effective control requires a co-ordinated response | journal = Euro Surveillance | volume = 7 | issue = 3 | pages = 31–2 | date = March 2002 | pmid = 12631941 | doi = 10.2807/esm.07.03.00343-en | doi-access = free }}</ref><ref name=BullWHO>{{cite journal | vauthors = Al-Tikriti SK, Al-Ani F, Jurji FJ, Tantawi H, Al-Moslih M, Al-Janabi N, Mahmud MI, Al-Bana A, Habib H, Al-Munthri H, Al-Janabi S, AL-Jawahry K, Yonan M, Hassan F, Simpson DI | display-authors = 6 | title = Congo/Crimean haemorrhagic fever in Iraq | journal = Bulletin of the World Health Organization | volume = 59 | issue = 1 | pages = 85–90 | year = 1981 | pmid = 6790183 | pmc = 2396030 }}</ref><ref name=vector>{{cite journal | vauthors = Okorie TG | title = Comparative studies on the vector capacity of the different stages of Amblyomma variegatum Fabricius and Hyalomma rufipes Koch for Congo virus, after intracoelomic inoculation | journal = Veterinary Parasitology | volume = 38 | issue = 2–3 | pages = 215–23 | date = March 1991 | pmid = 1907050 | doi = 10.1016/0304-4017(91)90131-e }}</ref>
+
+== References ==
+
+{{Reflist}}
+
+== External links ==
+{{Medical resources
+| ICD10 = {{ICD10|A|98|0|a|90}}
+| ICD9 = {{ICD9|065.0}}
+| ICDO =
+| OMIM =
+| DiseasesDB = 31969
+| MedlinePlus = article
+| eMedicineSubj = 830594
+| eMedicineTopic =
+}}
+* [http://www.who.int/mediacentre/factsheets/fs208/en/ World Health Organization Fact Sheet] {{Webarchive|url=https://web.archive.org/web/20170713160035/http://www.who.int/mediacentre/factsheets/fs208/en/ |date=2017-07-13 }}
+
+{{Zoonotic viral diseases}}
+{{Tick-borne diseases}}
+{{Taxonbar|from=Q29002571|from2=Q1788951|from3=Q24757193}}
+
+{{DEFAULTSORT:Crimean-Congo Hemorrhagic Fever}}
+[[Category:Arthropod-borne viral fevers and viral haemorrhagic fevers]]
+[[Category:Hemorrhagic fevers]]
+[[Category:Nairoviridae]]
+[[Category:Tick-borne diseases]]
+[[Category:RTT]]
+[[Category:RTTID]]
' |
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0 => '',
1 => '{{short description|Viral disease}}',
2 => '{{Infobox medical condition',
3 => '| name =',
4 => '| image = Crimean-Congo Hemorrhagic Fever.jpg',
5 => '| caption = Male diagnosed with Crimean–Congo hemorrhagic fever, 1969',
6 => '| image_size =',
7 => '| pronounce =',
8 => '| field = [[Infectious disease (medical specialty)|Infectious disease]]',
9 => '| symptoms = [[Fever]], muscle pains, [[headache]], vomiting, [[diarrhea]], [[petechiae|bleeding into the skin]]<ref name=WHO2013/>',
10 => '| complications = [[Liver failure]]<ref name=WHO2013/>',
11 => '| onset = Rapid<ref name=WHO2013/>',
12 => '| duration = Two weeks<ref name=WHO2013/>',
13 => '| types =',
14 => '| causes =',
15 => '| risks =',
16 => '| diagnosis = Detecting [[antibodies]], the virus's [[RNA]], or the virus itself<ref name=WHO2013/>',
17 => '| differential = [[Dengue fever]], [[Q fever]],<ref name=Gid2017/> [[Ebola|Ebola virus disease]]<ref>{{cite web|title=Ebola virus infection - Differentials {{!}} BMJ Best Practice|url=http://bestpractice.bmj.com/topics/en-gb/1210/differentials|website=bestpractice.bmj.com|access-date=21 May 2018|archive-date=13 August 2020|archive-url=https://web.archive.org/web/20200813062919/https://bestpractice.bmj.com/topics/en-gb/1210/differentials|url-status=live}}</ref>',
18 => '| prevention =',
19 => '| treatment = [[Supportive care]], [[ribavirin]]<ref name=WHO2013/>',
20 => '| medication =',
21 => '| prognosis = Risk of death ~25%<ref name=WHO2013/>',
22 => '| frequency =',
23 => '| deaths =',
24 => '}}',
25 => '<!-- Definition and symptoms -->',
26 => ''''Crimean–Congo hemorrhagic fever''' ('''CCHF''') is a [[viral disease]].<ref name=WHO2013>{{cite web|title=Crimean-Congo haemorrhagic fever|url=http://www.who.int/mediacentre/factsheets/fs208/en/|website=World Health Organization|access-date=18 July 2017|date=January 2013|url-status=live|archive-url=https://web.archive.org/web/20170713160035/http://www.who.int/mediacentre/factsheets/fs208/en/|archive-date=13 July 2017}}</ref> Symptoms of CCHF may include [[fever]], [[Myalgia|muscle pains]], [[headache]], vomiting, [[diarrhea]], and [[petechiae|bleeding into the skin]].<ref name=WHO2013/> Onset of symptoms is less than two weeks following exposure.<ref name=WHO2013/> Complications may include [[liver failure]].<ref name=WHO2013/> In those who survive, recovery generally occurs around two weeks after onset.<ref name=WHO2013/>',
27 => '',
28 => '<!-- Cause and diagnosis -->',
29 => 'The CCHF virus is typically spread by [[tick]] bites or contact with [[livestock]] carrying the disease.<ref name=WHO2013/> Groups that are at high risk of infection are [[farmers]] and those who work in [[slaughterhouses]].<ref name=WHO2013/> The virus can also spread between people via [[body fluids]].<ref name=WHO2013/> Diagnosis is by detecting [[antibodies]], the virus's [[RNA]], or the virus itself.<ref name=WHO2013/> It is a type of [[viral hemorrhagic fever]].<ref name=WHO2013/>',
30 => '',
31 => '<!-- Prevention and treatment -->',
32 => 'Prevention involves avoiding tick bites.<ref name=WHO2013/> A [[vaccine]] is not commercially available.<ref name=WHO2013/> Treatment is typically with [[supportive care]].<ref name=WHO2013/> The medication [[ribavirin]] may also help.<ref name=WHO2013/>',
33 => '',
34 => '<!-- Epidemiology and history -->',
35 => 'It occurs in Africa, the [[Balkans]], the Middle East, and Asia.<ref name=WHO2013/> Often it occurs in [[outbreaks]].<ref name=WHO2013/> In 2013 [[Iran]], Russia, [[Turkey]], and [[Uzbekistan]] documented more than fifty cases.<ref name=Gid2017>{{cite book | last1 = Berger | first1= Stephen |title=Crimean-Congo Hemorrhagic Fever: Global Status: 2017 edition|date=2017|publisher=GIDEON Informatics Inc|isbn=9781498815567|page=7|url=https://books.google.com/books?id=GEcWDgAAQBAJ&pg=PA7|language=en|url-status=live|archive-url=https://web.archive.org/web/20170910163841/https://books.google.ca/books?id=GEcWDgAAQBAJ&pg=PA7|archive-date=2017-09-10}}</ref> The risk of death among those affected is between 10 and 40%.<ref name=WHO2013/> It was first detected in the 1940s.<ref>{{cite book |last1=Magill |first1=Alan J. |title=Hunter's Tropical Medicine and Emerging Infectious Disease, Expert Consult - Online and Print,9: Hunter's Tropical Medicine and Emerging Infectious Disease|date=2013|publisher=Elsevier Health Sciences|isbn=978-1416043904|page=334|url=https://books.google.com/books?id=UgvdM8WRld4C&pg=PA334|language=en|url-status=live|archive-url=https://web.archive.org/web/20170804113952/https://books.google.ca/books?id=UgvdM8WRld4C&pg=PA334|archive-date=2017-08-04}}</ref>',
36 => '{{TOC limit|3}}',
37 => '',
38 => '==Signs and symptoms==',
39 => 'The illness in humans is a severe form of [[hemorrhagic fever]].<ref name="auto">{{Cite web |title=Crimean-Congo haemorrhagic fever, Fact sheet N°208 |work=WHO |date=January 2013 |access-date=2015-05-19 |url=http://www.who.int/mediacentre/factsheets/fs208/en/ |url-status=live |archive-url=https://web.archive.org/web/20150520204344/http://www.who.int/mediacentre/factsheets/fs208/en/ |archive-date=2015-05-20 }}</ref> Typically, after a 1–3 day [[incubation period]] following a tick bite or 5–6 days after exposure to infected blood or tissues, [[Influenza|flu]]-like symptoms appear, which may resolve after one week.In up to 75% of cases, signs of [[hemorrhage|bleeding]] can appear within 3–5 days of the onset of illness in case of bad containment of the first symptoms: [[mood swing|mood instability]], [[wikt:restlessness|agitation]], [[mental confusion]] and throat [[petechia]]e; and soon after nosebleeds, vomiting, and black stools. The [[liver]] becomes swollen and painful. [[Disseminated intravascular coagulation]] may occur, as well as acute [[renal failure|kidney failure]], [[Shock (circulatory)|shock]], and sometimes [[acute respiratory distress syndrome]].People usually begin to recover 9–10 days after first symptoms appear. Up to 30% of infected people die by the end of the second week of illness.<ref>{{cite web |title=Signs and Symptoms {{!}} Crimean-Congo Hemorrhagic Fever (CCHF) {{!}} CDC |url=https://www.cdc.gov/vhf/crimean-congo/symptoms/index.html |website=www.cdc.gov |accessdate=19 March 2022 |language=en-us |date=27 February 2019 |archive-date=14 March 2022 |archive-url=https://web.archive.org/web/20220314215456/https://www.cdc.gov/vhf/crimean-congo/symptoms/index.html |url-status=live }}</ref><ref>{{cite web |title=Crimean-Congo haemorrhagic fever - Symptoms, diagnosis and treatment {{!}} BMJ Best Practice |url=https://bestpractice.bmj.com/topics/en-gb/1606 |website=bestpractice.bmj.com |accessdate=19 March 2022 |archive-date=11 May 2021 |archive-url=https://web.archive.org/web/20210511094749/https://bestpractice.bmj.com/topics/en-gb/1606 |url-status=live }}</ref><ref>{{cite journal |last1=Grossi-Soyster |first1=Elysse N. |last2=LaBeaud |first2=A. Desiree |title=Rift Valley Fever: Important Considerations for Risk Mitigation and Future Outbreaks |journal=Tropical Medicine and Infectious Disease |date=2 June 2020 |volume=5 |issue=2 |pages=89 |doi=10.3390/tropicalmed5020089 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345646/ |accessdate=21 March 2022 |issn=2414-6366 |archive-date=30 January 2022 |archive-url=https://web.archive.org/web/20220130194551/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345646/ |url-status=live }}</ref>{{clarify}}',
40 => '',
41 => '==Cause==',
42 => '===Virology===',
43 => '{{Virusbox',
44 => '| image =',
45 => '| image_alt =',
46 => '| image_caption =',
47 => '| parent = Orthonairovirus',
48 => '| species = Crimean-Congo hemorrhagic fever orthonairovirus',
49 => '| synonyms =',
50 => '| synonyms_ref =',
51 => '}}',
52 => '[[File:PMC4848600 viruses-08-00106-g001.png|upright=1.3|thumb|Crimean-Congo hemorrhagic fever virus (CCHFV) virion and replication cycle.]]',
53 => 'The ''Crimean-Congo hemorrhagic fever orthonairovirus'' (CCHFV) is a member of the genus ''[[Orthonairovirus]]'', family ''[[Nairoviridae]]'' of [[RNA virus]]es.<ref name=ICTV>Virus Taxonomy: 2018 Release, EC 50, Washington, DC, July 2018, Email ratification October 2018 (MSL #33) https://talk.ictvonline.org/taxonomy/ {{Webarchive|url=https://web.archive.org/web/20200320103754/https://talk.ictvonline.org/taxonomy |date=2020-03-20 }}</ref>',
54 => '',
55 => 'The virions are 80–120 [[nanometer]]s (nm) in diameter and are [[pleomorphism (cytology)|pleomorphic]]. There are no host ribosomes within the virion. Each virion contains three copies of the genome. The envelope is single layered and is formed from a lipid bilayer 5 nm thick. It has no protrusions. The envelope proteins form small projections ~5–10 nm long. The nucleocapsids are filamentous and circular with a length of 200–3000 nm.<ref name=carter>{{cite journal | vauthors = Carter SD, Surtees R, Walter CT, Ariza A, Bergeron É, Nichol ST, Hiscox JA, Edwards TA, Barr JN | display-authors = 6 | title = Structure, function, and evolution of the Crimean-Congo hemorrhagic fever virus nucleocapsid protein | journal = Journal of Virology | volume = 86 | issue = 20 | pages = 10914–23 | date = October 2012 | pmid = 22875964 | pmc = 3457148 | doi = 10.1128/JVI.01555-12 | df = }}</ref>',
56 => 'The virus might enter a cell using the cell surface protein [[nucleolin]].<ref name=Xiao2011>{{cite journal | vauthors = Xiao X, Feng Y, Zhu Z, Dimitrov DS | title = Identification of a putative Crimean-Congo hemorrhagic fever virus entry factor | journal = Biochemical and Biophysical Research Communications | volume = 411 | issue = 2 | pages = 253–8 | date = July 2011 | pmid = 21723257 | pmc = 3155881 | doi = 10.1016/j.bbrc.2011.06.109 }}</ref>',
57 => '',
58 => '====Molecular biology====',
59 => 'The genome is circular, negative sense [[RNA]] in three parts – Small (S), Medium (M) and Large (L). The L segment is 11–14.4 kilobases in length while the M and S segments are 4.4–6.3 and 1.7–2.1 kilobases long respectively. The L segment encodes the [[RNA polymerase]], the M segment encodes the envelope [[glycoproteins]] (Gc and Gn), and the S segment encodes the nucleocapsid protein.<ref name=carter/> The mutation rates for the three parts of the genome were estimated to be: 1.09{{e|−4}}, 1.52{{e|−4}} and 0.58{{e|−4}} substitutions/site/year for the S, M, and L segments respectively.<ref name=Carroll2010/>',
60 => '',
61 => '====Population genetics====',
62 => 'CCHFV is the most genetically diverse of the [[arbovirus]]es: Its nucleotide sequences frequently differ between different strains, ranging from a 20% variability for the viral S segment to 31% for the M segment.<ref name=Bente2013>{{cite journal | vauthors = Bente DA, Forrester NL, Watts DM, McAuley AJ, Whitehouse CA, Bray M | title = Crimean-Congo hemorrhagic fever: history, epidemiology, pathogenesis, clinical syndrome and genetic diversity | journal = Antiviral Research | volume = 100 | issue = 1 | pages = 159–89 | date = October 2013 | pmid = 23906741 | doi = 10.1016/j.antiviral.2013.07.006 | url = http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1770&context=usgsstaffpub | access-date = 2018-11-27 | archive-date = 2017-09-22 | archive-url = https://web.archive.org/web/20170922234422/http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1770&context=usgsstaffpub | url-status = live }}</ref> Viruses with diverse sequences can be found within the same geographic area; closely related viruses have been isolated from widely separated regions, suggesting that viral dispersion has occurred possibly by ticks carried on migratory birds or through international livestock trade. Reassortment among genome segments during [[coinfection]] of ticks or vertebrates seems likely to have played a role in generating diversity in this virus.<ref>{{cite journal |last1=Fajs |first1=Luka |last2=Humolli |first2=Isme |last3=Saksida |first3=Ana |last4=Knap |first4=Nataša |last5=Jelovšek |first5=Mateja |last6=Korva |first6=Miša |last7=Dedushaj |first7=Isuf |last8=Avšič-Županc |first8=Tatjana |title=Prevalence of Crimean-Congo hemorrhagic fever virus in healthy population, livestock and ticks in Kosovo |journal=PloS One |date=2014 |volume=9 |issue=11 |pages=e110982 |doi=10.1371/journal.pone.0110982 |url=https://pubmed.ncbi.nlm.nih.gov/25393542/ |accessdate=24 March 2022 |issn=1932-6203 |archive-date=25 March 2022 |archive-url=https://web.archive.org/web/20220325084601/https://pubmed.ncbi.nlm.nih.gov/25393542/ |url-status=live }}</ref>{{clarify}}',
63 => '',
64 => 'Based on the sequence data, seven genotypes of CCHFV have been recognised: Africa 1 ([[Senegal]]), Africa 2 ([[Democratic Republic of the Congo]] and South Africa), Africa 3 (southern and western Africa), Europe 1 ([[Albania]], [[Bulgaria]], [[Kosovo]], [[Russia]] and [[Turkey]]), Europe 2 ([[Greece]]), Asia 1 ([[the Middle East]], [[Iran]] and [[Pakistan]]) and Asia 2 ([[China]], [[Kazakhstan]], [[Tajikistan]] and [[Uzbekistan]]).<ref>{{cite journal |last1=Alam |first1=Muhammad Masroor |last2=Khurshid |first2=Adnan |last3=Sharif |first3=Salmaan |last4=Shaukat |first4=Shahzad |last5=Suleman |first5=Rana Muhammad |last6=Angez |first6=Mehar |last7=Zaidi |first7=Syed Sohail Zahoor |title=Crimean-Congo Hemorrhagic Fever Asia-2 Genotype, Pakistan |journal=Emerging Infectious Diseases |date=2013 |volume=19 |issue=6 |pages=1017–1019 |doi=10.3201/eid1906.120771 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713814/ |accessdate=24 March 2022 |issn=1080-6040 |archive-date=3 March 2022 |archive-url=https://web.archive.org/web/20220303174230/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3713814/ |url-status=live }}</ref>',
65 => '',
66 => '===Transmission===',
67 => '[[Image:Hyalomma-m-rufipes.jpg|thumb|''Hyalomma'' tick]]',
68 => '',
69 => '[[Tick]]s are both "environmental reservoir" and [[vector (epidemiology)|vector]] for the virus, carrying it from wild animals to domestic animals and humans. Tick species identified as infected with the virus include ''Argas reflexus'', ''Hyalomma anatolicum'', ''Hyalomma detritum'', ''[[Hyalomma marginatum|Hyalomma marginatum marginatum]]'' and ''[[Rhipicephalus sanguineus]]''.<ref>{{cite web |title=Transmission {{!}} Crimean-Congo Hemorrhagic Fever (CCHF) {{!}} CDC |url=https://www.cdc.gov/vhf/crimean-congo/transmission/index.html |website=www.cdc.gov |accessdate=19 March 2022 |language=en-us |date=27 February 2019 |archive-date=28 April 2014 |archive-url=https://web.archive.org/web/20140428000848/http://www.cdc.gov/vhf/crimean-congo/transmission/index.html |url-status=live }}</ref><ref name="pap">{{cite journal |last1=Papa |first1=Anna |last2=Tsergouli |first2=Katerina |last3=Tsioka |first3=Katerina |last4=Mirazimi |first4=Ali |title=Crimean-Congo Hemorrhagic Fever: Tick-Host-Virus Interactions |journal=Frontiers in Cellular and Infection Microbiology |date=2017 |volume=7 |pages=213 |doi=10.3389/fcimb.2017.00213 |url=https://pubmed.ncbi.nlm.nih.gov/28603698/ |accessdate=26 March 2022 |issn=2235-2988 |archive-date=22 October 2021 |archive-url=https://web.archive.org/web/20211022090035/https://pubmed.ncbi.nlm.nih.gov/28603698/ |url-status=live }}</ref>{{clarify}}',
70 => '',
71 => 'At least 31 different species of ticks from the genera ''[[Haemaphysalis]]'' and ''Hyalomma'' in southeastern Iran have been found to carry the virus.<ref name=Mehravaran2012>{{cite journal | vauthors = Mehravaran A, Moradi M, Telmadarraiy Z, Mostafavi E, Moradi AR, Khakifirouz S, Shah-Hosseini N, Varaie FS, Jalali T, Hekmat S, Ghiasi SM, Chinikar S | display-authors = 6 | title = Molecular detection of Crimean-Congo haemorrhagic fever (CCHF) virus in ticks from southeastern Iran | journal = Ticks and Tick-Borne Diseases | volume = 4 | issue = 1–2 | pages = 35–8 | date = February 2013 | pmid = 23238248 | doi = 10.1016/j.ttbdis.2012.06.006 }}</ref>Wild animals and small mammals, particularly [[European hare]], Middle-African [[hedgehog]]s and [[mastomys|multimammate rats]] are the "amplifying hosts" of the virus. Birds are generally resistant to CCHF, with the exception of [[ostrich]]es. Domestic animals like sheep, goats and cattle can develop high titers of virus in their blood, but tend not to fall ill.<ref name="erg">{{cite journal | vauthors = Ergönül O, Celikbaş A, Dokuzoguz B, Eren S, Baykam N, Esener H | title = Characteristics of patients with Crimean-Congo hemorrhagic fever in a recent outbreak in Turkey and impact of oral ribavirin therapy | journal = Clinical Infectious Diseases | volume = 39 | issue = 2 | pages = 284–7 | date = July 2004 | pmid = 15307042 | doi = 10.1086/422000 | url = http://www.journals.uchicago.edu/cgi-bin/resolve?CID32782 | doi-access = free | access-date = 2008-07-26 | archive-date = 2020-08-01 | archive-url = https://web.archive.org/web/20200801084108/https://www.journals.uchicago.edu/cgi-bin/resolve?CID32782 | url-status = live }}</ref>The "sporadic infection" of humans is usually caused by a ''Hyalomma'' tick bite. Animals can transmit the virus to humans, but this would usually be as part of a disease cluster. When clusters of illness occur, it is typically after people treat, butcher or eat infected livestock, particularly [[ruminant]]s and [[ostrich]]es. Outbreaks have occurred in [[slaughterhouse|abattoir]]s and other places where workers have been exposed to infected human or animal blood and [[fomite]]s <ref name=pap/><ref name=erg/>{{clarify}}',
72 => '',
73 => 'Humans can infect humans and outbreaks also occur in clinical facilities through infected blood and unclean medical instruments.<ref name="ref">{{Cite web|url=https://www.cdc.gov/vhf/crimean-congo/transmission/index.html|archive-url=https://web.archive.org/web/20140428000848/http://www.cdc.gov/vhf/crimean-congo/transmission/index.html|url-status=live|archive-date=April 28, 2014|title=Crimean-Congo Hemorrhagic Fever (CCHF) Transmission|last=Division of High-Consequence Pathogens and Pathology|first=Viral Special Pathogens Branch|date=March 5, 2014|website=CDC}}</ref>',
74 => '',
75 => '==Mechanism==',
76 => 'In terms of the pathogenesis of Crimean-Congo hemorrhagic fever, due to a variety of factors, it is not well understood. What is known of this virus mechanism is that [[endothelial cells]] and [[immune cells]] play a large role; the occupation of viral antigens in endothelial cells, is an indication that the endothelium is a important target of the virus.<ref>{{cite journal |last1=Akıncı |first1=Esragül |last2=Bodur |first2=Hürrem |last3=Leblebicioglu |first3=Hakan |title=Pathogenesis of Crimean-Congo hemorrhagic fever |journal=Vector Borne and Zoonotic Diseases (Larchmont, N.Y.) |date=July 2013 |volume=13 |issue=7 |pages=429–437 |doi=10.1089/vbz.2012.1061 |url=https://pubmed.ncbi.nlm.nih.gov/23663164/ |accessdate=22 March 2022 |issn=1557-7759 |archive-date=8 March 2022 |archive-url=https://web.archive.org/web/20220308015752/https://pubmed.ncbi.nlm.nih.gov/23663164/ |url-status=live }}</ref>',
77 => '',
78 => '==Diagnosis==',
79 => '[[File:Thermal cycler for PCR.jpg|thumb|right|150px|Thermal cycler/PCR]]',
80 => 'The diagnosis of Crimean-Congo Hemorrhagic Fever (CCHF) can be done via the following:<ref>{{cite web |title=Diagnosis {{!}} Crimean-Congo Hemorrhagic Fever (CCHF) {{!}} CDC |url=https://www.cdc.gov/vhf/crimean-congo/diagnosis/index.html |website=www.cdc.gov |accessdate=19 March 2022 |language=en-us |date=27 February 2019 |archive-date=18 March 2022 |archive-url=https://web.archive.org/web/20220318101811/https://www.cdc.gov/vhf/crimean-congo/diagnosis/index.html |url-status=live }}</ref>',
81 => '*Antigen-Capture enzyme-Linked Immunosorbent Assay ([[ELISA]])',
82 => '*Real time polymerase chain reaction ([[RT-PCR]])',
83 => '*Virus isolation attempts',
84 => '*[[Immunohistochemical staining]]',
85 => '',
86 => '==Prevention==',
87 => '{{Main|Prevention of viral hemorrhagic fever}}',
88 => 'Where mammalian tick infection is common, agricultural regulations require de-ticking farm animals before transportation or delivery for slaughter. Personal tick avoidance measures are recommended, such as use of insect repellents, adequate clothing, and body inspection for adherent ticks.When [[fever]]ish patients with evidence of bleeding require [[cardiopulmonary resuscitation|resuscitation]] or [[intensive care medicine|intensive care]], [[body substance isolation]] precautions should be taken.<ref>{{cite web |title=Prevention {{!}} Crimean-Congo Hemorrhagic Fever (CCHF) {{!}} CDC |url=https://www.cdc.gov/vhf/crimean-congo/prevention/index.html |website=www.cdc.gov |accessdate=19 March 2022 |language=en-us |date=27 February 2019 |archive-date=20 March 2021 |archive-url=https://web.archive.org/web/20210320071551/https://www.cdc.gov/vhf/crimean-congo/prevention/index.html |url-status=live }}</ref><ref>{{cite book|title=Infection Control for Viral Haemorrhagic Fevers in the African Health Care Setting|date=December 1998|publisher=World Health Organization and Centers for Disease Control and Prevention|url=https://www.cdc.gov/vhf/abroad/pdf/african-healthcare-setting-vhf.pdf|accessdate=20 October 2014|archive-date=8 July 2017|archive-url=https://web.archive.org/web/20170708093022/https://www.cdc.gov/vhf/abroad/pdf/african-healthcare-setting-vhf.pdf|url-status=live}}</ref> {{clarify}}',
89 => '',
90 => '===Vaccine===',
91 => 'Since the 1970s, several vaccine trials around the world against CCHF have been terminated due to high toxicity.<ref name="auto1">{{cite journal | vauthors = Keshtkar-Jahromi M, Kuhn JH, Christova I, Bradfute SB, Jahrling PB, Bavari S | title = Crimean-Congo hemorrhagic fever: current and future prospects of vaccines and therapies | journal = Antiviral Research | volume = 90 | issue = 2 | pages = 85–92 | date = May 2011 | pmid = 21362441 | doi = 10.1016/j.antiviral.2011.02.010 | url = https://zenodo.org/record/1258736 | access-date = 2018-09-22 | archive-date = 2020-07-29 | archive-url = https://web.archive.org/web/20200729030327/https://zenodo.org/record/1258736 | url-status = live }}</ref>',
92 => '',
93 => '{{As of| March 2011}}, the only available and probably somewhat efficacious CCHF vaccine has been an inactivated antigen preparation then used in Bulgaria.<ref name="auto1"/> No publication in the scientific literature related to this vaccine exists, which a Turkish virologist called suspicious both because antiquated technology and [[mouse brain]] were used to manufacture it.<ref name=gundem>{{cite web|url=http://gundem.milliyet.com.tr/keneye-asi-mujdesi/gundem/gundemdetay/25.05.2012/1545014/default.htm|title=Keneye aşı müjdesi|first=milliyet.com.tr Türkiye'nin lider haber|last=sitesi|url-status=live|archive-url=https://web.archive.org/web/20131219044119/http://gundem.milliyet.com.tr/keneye-asi-mujdesi/gundem/gundemdetay/25.05.2012/1545014/default.htm|archive-date=2013-12-19}}</ref>',
94 => 'More vaccines are under development, but the sporadic nature of the disease, even in endemic countries, suggests that large trials of vaccine efficacy will be difficult to perform. Finding volunteers may prove challenging, given growing [[anti-vaccination]] sentiment and resistance of populations to vaccination against contagious diseases. The number of people to be vaccinated, and the length of time they would have to be followed to confirm protection would have to be carefully defined. Alternatively, many scientists appear to believe that treatment of CCHF with [[ribavirin]] is more practical than prevention, but some recently conducted clinical trials appear to counter assumptions of drug efficacy.<ref name="auto1"/>',
95 => 'In 2011, a [[Turkey|Turkish]] research team led by [[Erciyes University]] successfully developed the first non-toxic preventive vaccine, which passed clinical trials. As of 2012, the vaccine was pending approval by the US FDA.<ref name=gundem/>',
96 => '',
97 => 'Since the Ebola epidemic, the WHO jumpstarted a "Blueprint for Research and Development preparedness" on [[Emerging infectious disease|emerging pathogen]]s with epidemic potential, against which there are no medical treatments.<ref name=sablog>{{cite web|last1=Kieny|first1=Marie-Paule |title=After Ebola, a Blueprint Emerges to Jump-Start R&D|url=https://blogs.scientificamerican.com/guest-blog/after-ebola-a-blueprint-emerges-to-jump-start-r-d/|website=Scientific American Blog Network|date=20 May 2015|access-date=13 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161220134725/https://blogs.scientificamerican.com/guest-blog/after-ebola-a-blueprint-emerges-to-jump-start-r-d/|archive-date=20 December 2016}}</ref> CCHF was the top priority on the initial list from December 2015, and is second as of January 2017.<ref name=WHOlist>{{cite web|title=R&D Blueprint. List of Blueprint priority diseases|url=http://www.who.int/blueprint/priority-diseases/en/|website=World Health Organization|date=January 2017|access-date=13 July 2017|url-status=live|archive-url=https://web.archive.org/web/20170910163841/http://www.who.int/blueprint/priority-diseases/en/|archive-date=10 September 2017}}</ref>',
98 => '',
99 => '==Treatment==',
100 => '',
101 => '[[File:Ribavirin-skeletal.svg|thumb|Ribavirin]]',
102 => 'Treatment is mostly [[supportive care|supportive]]. [[Ribavirin]] is used in treatment of this virus via both oral and intravenous formulations which seem effective.<ref name="auto"/>',
103 => '',
104 => '{{As of |2011}} the use of [[Immunoglobulin]] preparations has remained unproven and antibody engineering, which raised hopes for [[monoclonal antibody]] therapy, has remained in its infancy.<ref name="auto1"/>',
105 => '',
106 => '==Epidemiology==',
107 => 'CCHD occurs most frequently among agricultural workers, following the bite of an infected tick, and to a lesser extent among slaughterhouse workers exposed to the blood and tissues of infected livestock, and medical personnel through contact with the body fluids of infected persons.<ref name=Bente2013/>',
108 => '',
109 => '===Geographic distribution===',
110 => '',
111 => 'In 2008, more than 50 cases/year were reported from only 4 countries: Turkey, Iran, Russia and Uzbekistan. 5-49 cases/year were present in South Africa, Central Asia including Pakistan and Afghanistan (but sparing Turkmenistan), in the Middle East only the UAE and the Balkan countries limited to Romania, Bulgaria, Serbia, Montenegro and Kosovo-Albania.<ref name=map/>',
112 => '',
113 => '{{As of|2013}} the northern limit of CCHF has been 50 degrees northern latitude, north of which the ''[[Hyalomma]]'' ticks have not been found.<ref name="auto"/>',
114 => 'Per a WHO map from 2008, Hyalomma ticks occurred south of this latitude across all of the Eurasian continent and Africa, sparing only the islands of Sri Lanka, Indonesia and Japan.<ref name=map>{{cite web|url=http://www.who.int/csr/disease/crimean_congoHF/Global_CCHFRisk_20080918.png?ua=1|title=Geographic distribution of Crimean-Congo haemorrhagic fever (CCHF)| publisher=WHO|year=2008|url-status=live|archive-url=https://web.archive.org/web/20160513175948/http://www.who.int/csr/disease/crimean_congoHF/Global_CCHFRisk_20080918.png?ua=1|archive-date=2016-05-13}}</ref>',
115 => 'Serological or virological evidence of CCHF was widespread in Asia, Eastern Europe, the Middle East (except Israel, Lebanon and Jordan), central Africa, Western Africa, South Africa and Madagascar.<ref name=map/>',
116 => '',
117 => 'In 2014 the CDC indicated endemic areas largely unchanged in Africa and the Middle East, but different for the Balkan, including all countries of the former Yugoslavia, and also Greece, but no longer Romania. India's Northwestern regions of Rajastan and Gujarat saw their first cases.<ref name=ref/>',
118 => '',
119 => '===Outbreaks===',
120 => 'The following are the many outbreaks of Crimean–Congo hemorrhagic fever:',
121 => '[[File:Yozgat in Turkey.svg|thumb|right|370px|Yozgat province, turkey]]',
122 => '* From 1995 to 2013, 228 cases of CCHF were reported in the Republic of Kosovo, with a case-fatality rate of 25.5%.<ref name=Kosovo>{{cite journal | vauthors = Fajs L, Jakupi X, Ahmeti S, Humolli I, Dedushaj I, Avšič-Županc T | title = Molecular epidemiology of Crimean-Congo hemorrhagic fever virus in Kosovo | journal = PLOS Neglected Tropical Diseases | volume = 8 | issue = 1 | pages = e2647 | year = 2014 | pmid = 24416468 | pmc = 3886908 | doi = 10.1371/journal.pntd.0002647 }}</ref>',
123 => '* Between 2002–2008 the Ministry of Health of Turkey reported 3,128 CCHF cases, with a 5% death rate. In July 2005, authorities reported 41 cases of CCHF in central Turkey's [[Yozgat Province]], with one death. As of August 2008, a total of 50 deaths were reported for the year in various cities in Turkey due to CCHF.<ref>{{cite journal |last1=Leblebicioglu |first1=Hakan |last2=Ozaras |first2=Resat |last3=Irmak |first3=Hasan |last4=Sencan |first4=Irfan |title=Crimean-Congo hemorrhagic fever in Turkey: Current status and future challenges |journal=Antiviral Research |date=February 2016 |volume=126 |pages=21–34 |doi=10.1016/j.antiviral.2015.12.003 |url=https://pubmed.ncbi.nlm.nih.gov/26695860/ |accessdate=21 March 2022 |issn=1872-9096 |archive-date=5 March 2022 |archive-url=https://web.archive.org/web/20220305221257/https://pubmed.ncbi.nlm.nih.gov/26695860/ |url-status=live }}</ref><ref>{{cite web |title=Epidemiology of Crimean–Congo haemorrhagic fever virus: Albania, Bulgaria, Greece, Islamic Republic of Iran, Kosovo, Russian Federation, Turkey. 1st October 2008 |url=http://www.episouth.org/Episouth_CCHF_01_10_2008_final0024.pdf?&id=9062#:~:text=Crimean%E2%80%93Congo%20haemorrhagic%20fever%20%28CCHF%29%20virus%20is%20%E2%80%A2%20present,circulating%20with%20particular%20intensity%20in%202008%20in%20Turkey%2C |website=episouth.org |access-date=27 March 2022 |archive-date=27 March 2022 |archive-url=https://web.archive.org/web/20220327224607/http://www.episouth.org/Episouth_CCHF_01_10_2008_final0024.pdf?id=9062#:~:text=Crimean%E2%80%93Congo%20haemorrhagic%20fever%20%28CCHF%29%20virus%20is%20%E2%80%A2%20present,circulating%20with%20particular%20intensity%20in%202008%20in%20Turkey%2C |url-status=live }}</ref>',
124 => '* In September 2010, an outbreak was reported in Pakistan's [[Khyber Pakhtunkhwa]] province. Poor diagnosis and record keeping caused the extent of the outbreak to be uncertain, though some reports indicated over 100 cases, with a case-fatality rate above 10%.<ref>{{cite journal |last1=Ijaz |first1=Muhammad |last2=Rahim |first2=Afaq |last3=Ali |first3=Iftikhar |title=Crimean-Congo Hemorrhagic Fever Virus in Pakistan |journal=Infectious Disorders Drug Targets |date=2017 |volume=17 |issue=2 |pages=143–145 |doi=10.2174/1871526517666170117125733 |url=https://pubmed.ncbi.nlm.nih.gov/28124602/ |accessdate=28 March 2022 |issn=2212-3989 |archive-date=20 October 2021 |archive-url=https://web.archive.org/web/20211020192800/https://pubmed.ncbi.nlm.nih.gov/28124602/ |url-status=live }}</ref><ref>{{cite journal |last1=Yousaf |first1=Muhammad Zubair |last2=Ashfaq |first2=Usman Ali |last3=Anjum |first3=Khalid Mahmood |last4=Fatima |first4=Shaista |title=Crimean-Congo Hemorrhagic Fever (CCHF) in Pakistan: The "Bell" is Ringing Silently |journal=Critical Reviews in Eukaryotic Gene Expression |date=2018 |volume=28 |issue=2 |pages=93–100 |doi=10.1615/CritRevEukaryotGeneExpr.2018020593 |url=https://pubmed.ncbi.nlm.nih.gov/30055534/ |accessdate=21 March 2022 |issn=1045-4403 |archive-date=21 March 2022 |archive-url=https://web.archive.org/web/20220321174826/https://pubmed.ncbi.nlm.nih.gov/30055534/ |url-status=live }}</ref>',
125 => '* January 2011, the first human cases of CCHF in India was reported in [[Sanand]], Gujarat, India, with 4 reported deaths, which included the [[index patient]], treating physician and nurse.<ref>Syed Khalique Ahmed, Tanvir A Siddiqui, Anuradha Mascarenhas, Anuradha Mascarenhas, Tanvir A Siddiqui, Syed Khalique Ahmed : Pune, Ahmedabad [http://www.indianexpress.com/news/deadly-virus-makes-first-appearance-in-india-kills-three-in-gujarat/739292/ Deadly virus-makes first appearance in india kills three in gujarat] {{webarchive|url=https://web.archive.org/web/20110304153316/http://www.indianexpress.com/news/deadly-virus-makes-first-appearance-in-india-kills-three-in-gujarat/739292/ |date=2011-03-04 }} indianexpress.com, 19 January 2011</ref>',
126 => '* {{As of|May 2012}}, 71 people were reported to have contracted the disease in Iran, resulting in 8 fatalities.<ref>{{cite web |url=http://edition.presstv.ir/detail/105532.html |title=Archived copy |access-date=2012-05-19 |url-status=dead |archive-url=https://web.archive.org/web/20160305050638/http://edition.presstv.ir/detail/105532.html |archive-date=2016-03-05 }}</ref>',
127 => '* In October 2012, a British man died from the disease at the [[Royal Free Hospital]] in London. He had earlier been admitted to [[Gartnavel General Hospital]] in [[Glasgow]], after returning on a flight from [[Kabul]] in [[Afghanistan]].<ref>{{cite news|url=https://www.bbc.co.uk/news/uk-scotland-glasgow-west-19856504|title=Congo Fever: Patient dies in hospital|date=6 October 2012|via=www.bbc.co.uk|url-status=live|archive-url=https://web.archive.org/web/20121007200124/http://www.bbc.co.uk/news/uk-scotland-glasgow-west-19856504|archive-date=7 October 2012|work=BBC News}}</ref>',
128 => '* In July 2013, seven persons died due to CCHF in Kariyana village in Babra [[taluka]], [[Amreli district]], Gujarat, India.<ref name="indiatvnews 2013">{{cite web | publisher = Indiatvnews | title=Congo Fever: Seven Die In Amreli In A Week Mobile Site | work =IndiaTv | date=2013-07-15 | url=http://m.indiatvnews.com/news/india/congo-fever-seven-die-in-amreli-in-a-week-25097.html | access-date=2015-03-28 | url-status=live | archive-url=https://web.archive.org/web/20160304055508/http://m.indiatvnews.com/news/india/congo-fever-seven-die-in-amreli-in-a-week-25097.html | archive-date=2016-03-04 }}</ref><ref>{{cite web|url=http://articles.timesofindia.indiatimes.com/2013-07-15/rajkot/40589464_1_amreli-village-cchf-congo-fever|title=Congo fever confirmed in Amreli village|publisher=Times of India|access-date=2013-08-08|archive-date=2013-09-23|archive-url=https://web.archive.org/web/20130923071304/http://articles.timesofindia.indiatimes.com/2013-07-15/rajkot/40589464_1_amreli-village-cchf-congo-fever|url-status=dead}}</ref>',
129 => '* In August 2013, a farmer from [[Agago]], Uganda was treated at [[Kalongo Hospital]] for a confirmed CCHF infection. The deaths of three other individuals in the [[Northern Region, Uganda|northern region]] were suspected to have been caused by the virus.<ref>{{cite news|last=Biryabarema|first=Elias |date=17 August 2013|agency=Reuters|title=Three die in Uganda from Ebola-like fever: Health Ministry|url=https://news.yahoo.com/three-die-uganda-ebola-fever-health-ministry-122947530.html|publisher=Yahoo News|access-date=16 August 2013|url-status=live|archive-url=https://web.archive.org/web/20130820115319/http://news.yahoo.com/three-die-uganda-ebola-fever-health-ministry-122947530.html|archive-date=20 August 2013}}</ref> Another unrelated CCHF patient was admitted to [[Mulago Hospital]] on the same day. The [[Ministry of Health]] announced on the 19th that the outbreak was under control, but the second patient, a 27-year-old woman from [[Nansana]], died on the 21st. She is believed to have contracted the virus from her husband, who returned to Kampala after being treated for CCHF in [[Juba]], [[South Sudan]].<ref name=Otto>{{cite news|last=Otto|first=Alex |title=High Alert Over Crimean Fever|url=http://www.observer.ug/index.php?option=com_content&id=27116:high-alert-over-crimean-fever&catid=34:news&Itemid=114|access-date=26 August 2013|newspaper=The Observer|date=22 August 2013|location=Kampala|url-status=live|archive-url=https://web.archive.org/web/20140714151600/http://www.observer.ug/index.php?option=com_content&id=27116%3Ahigh-alert-over-crimean-fever&catid=34%3Anews&Itemid=114|archive-date=14 July 2014}}</ref>',
130 => '* In June 2014, cases were diagnosed in Kazakhstan. Ten people, including an ambulance crew, were admitted on to hospital in southern Kazakhstan with suspected CCHF. In July 2014 an 8th person was found to be infected with CCHF at Hayatabad Medical Complex (HMC), Pakistan. The eight patients, including a nurse and 6 Afghan nationals, died between April and July 2014.<ref>{{cite web|last1=Khan|first1=Hidayat |title=Stemming outbreaks: Eighth patient dies of Congo hemorrhagic fever at HMC|url=http://tribune.com.pk/story/734275/stemming-outbreaks-eighth-patient-dies-of-congo-hemorrhagic-fever-at-hmc/|access-date=13 July 2014|url-status=live|archive-url=https://web.archive.org/web/20140713125529/http://tribune.com.pk/story/734275/stemming-outbreaks-eighth-patient-dies-of-congo-hemorrhagic-fever-at-hmc/|archive-date=13 July 2014|date=2014-07-11}}</ref>{{clarify}}',
131 => '* {{As of|2015}}, sporadic confirmed cases have been reported from [[Bhuj]], Amreli, Sanand, [[Idar]] and [[Vadnagar]] in Gujarat, India. In November 2014, a doctor and a labourer in north Gujarat tested positive for the disease. In the following weeks, three more people died from CCHF.<ref name="The Times of India Mobile Site 2015">{{cite web| title=Health officials confirm congo fever death of Jaisalmer man| website=The Times of India Mobile Site| date=26 January 2015| url=http://m.timesofindia.com/city/jaipur/Health-officials-confirm-congo-fever-death-of-Jaisalmer-man/articleshow/46017452.cms| access-date=30 March 2015| url-status=live| archive-url=https://web.archive.org/web/20150402102143/http://m.timesofindia.com/city/jaipur/Health-officials-confirm-congo-fever-death-of-Jaisalmer-man/articleshow/46017452.cms| archive-date=2 April 2015}}</ref> In March 2015, one more person died of CCHF in Gujarat.<ref name="Cities2015">{{cite web | title=Kutch resident dies of Confo fever | website=The Indian Express | date=March 29, 2015 | url=http://indianexpress.com/article/india/gujarat/kutch-resident-dies-of-confo-fever/ | access-date=March 29, 2015 | url-status=live | archive-url=https://web.archive.org/web/20150403090229/http://indianexpress.com/article/india/gujarat/kutch-resident-dies-of-confo-fever/ | archive-date=April 3, 2015 }}</ref>As of 2015, among livestock, CCHF was recognized as "widespread" in India, only 4 years after the first human case had been diagnosed.<ref>{{cite web|url=http://outbreaknewstoday.com/crimean-congo-hemorrhagic-fever-spreads-across-india-82283/|title=Crimean-Congo hemorrhagic fever spreads across India - Outbreak News Today|date=9 October 2015|url-status=live|archive-url=https://web.archive.org/web/20151220080259/http://outbreaknewstoday.com/crimean-congo-hemorrhagic-fever-spreads-across-india-82283/|archive-date=20 December 2015}}</ref>',
132 => '* In August 2016, the first local case of CCHF in Western Europe occurred in Western Spain. A 62-year-old man, who had been bitten by a tick in Spain died on August 25, having infected a nurse.<ref>{{Cite web|url=http://www.scientificamerican.com/article/first-local-case-of-tick-borne-disease-kills-man-in-spain/|title=First Local Case of Tick-Borne Disease Kills Man in Spain|access-date=2016-09-03|date=n.d.|publisher=Scientif American|url-status=live|archive-url=https://web.archive.org/web/20160902144044/http://www.scientificamerican.com/article/first-local-case-of-tick-borne-disease-kills-man-in-spain/|archive-date=2016-09-02}}</ref> The tick bite occurred in the [[province of Ávila]], 300 km away from the [[province of Cáceres]], where CCHF viral RNA from ticks was amplified in 2010.<ref name="nejmspain">{{cite journal | vauthors = Negredo A, de la Calle-Prieto F, Palencia-Herrejón E, Mora-Rillo M, Astray-Mochales J, Sánchez-Seco MP, Bermejo Lopez E, Menárguez J, Fernández-Cruz A, Sánchez-Artola B, Keough-Delgado E, Ramírez de Arellano E, Lasala F, Milla J, Fraile JL, Ordobás Gavín M, Martinez de la Gándara A, López Perez L, Diaz-Diaz D, López-García MA, Delgado-Jimenez P, Martín-Quirós A, Trigo E, Figueira JC, Manzanares J, Rodriguez-Baena E, Garcia-Comas L, Rodríguez-Fraga O, García-Arenzana N, Fernández-Díaz MV, Cornejo VM, Emmerich P, Schmidt-Chanasit J, Arribas JR | display-authors = 6 | title = Autochthonous Crimean-Congo Hemorrhagic Fever in Spain | journal = The New England Journal of Medicine | volume = 377 | issue = 2 | pages = 154–161 | date = July 2017 | pmid = 28700843 | doi = 10.1056/NEJMoa1615162 | doi-access = free }}</ref>{{As of|July 2017}} it was unclear what specific ecology led to the Spanish cases.<ref name=spain>{{cite journal | vauthors = Spengler JR, Bente DA | title = Crimean-Congo Hemorrhagic Fever in Spain - New Arrival or Silent Resident? | journal = The New England Journal of Medicine | volume = 377 | issue = 2 | pages = 106–108 | date = July 2017 | pmid = 28700846 | pmc = 5922251 | doi = 10.1056/NEJMp1707436 }}</ref>',
133 => '* In August 2016, a number of Pakistani news sources raised concerns regarding the disease.<ref>{{cite web|url=http://tribune.com.pk/story/1164812/congo-virus-doctors-warn-outbreak-disease|title=Congo virus: Doctors warn against outbreak of disease|date=17 August 2016|publisher=The Express Tribune|url-status=live|archive-url=https://web.archive.org/web/20160906235102/http://tribune.com.pk/story/1164812/congo-virus-doctors-warn-outbreak-disease/|archive-date=6 September 2016}}</ref><ref>{{cite web|url=http://dunyanews.tv/en/Pakistan/351274-Karachi-Congo-virus-claims-another-life|title=Karachi: Congo virus claims another life - Pakistan - Dunya News|url-status=live|archive-url=https://web.archive.org/web/20160904100756/http://dunyanews.tv/en/Pakistan/351274-Karachi-Congo-virus-claims-another-life|archive-date=2016-09-04}}</ref> Between January and October 2016, CCHF outbreaks in Pakistan were reported with highest numbers of cases and deaths during August 2016, just before the festival of [[Eid-al-Adha]] (held on September 13–15 in 2016). It was hypothesized that the festival could play an important part as people could come into contact with domestic or imported animals potentially infected with CCHF virus.<ref name=statefair>{{cite journal | vauthors = Karim AM, Hussain I, Lee JH, Park KS, Lee SH | title = Surveillance of Crimean-Congo haemorrhagic fever in Pakistan | journal = The Lancet. Infectious Diseases | volume = 17 | issue = 4 | pages = 367–368 | date = April 2017 | pmid = 28346174 | doi = 10.1016/S1473-3099(17)30119-6 | url = http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(17)30119-6/abstract | doi-access = free }}</ref> The Pakistani NIH showed there was no correlation, and that CCHF cases have coincided with the peak tick proliferation during the preceding 8–10 years.<ref>{{cite journal | vauthors = Alam MM, Khurshid A, Rana MS, Aamir UB, Salman M, Ahmad M | title = Surveillance of Crimean-Congo haemorrhagic fever in Pakistan | journal = The Lancet. Infectious Diseases | volume = 17 | issue = 8 | pages = 806 | date = August 2017 | pmid = 28741546 | doi = 10.1016/S1473-3099(17)30403-6 | doi-access = free }}</ref>',
134 => '* On February 5, 2020, an outbreak occurred in the central region of Mali. The infected are from Douentza and Mopti region. <ref>{{cite web |title=7 dead in Congo fever outbreak in Mali |url=https://medicalxpress.com/news/2020-02-dead-congo-fever-outbreak-mali.html |website=medicalxpress.com |access-date=8 February 2020 |language=en-us |archive-date=29 July 2020 |archive-url=https://web.archive.org/web/20200729000001/https://medicalxpress.com/news/2020-02-dead-congo-fever-outbreak-mali.html |url-status=live }}</ref><ref>{{cite web |title=Crimean-Congo hemorrhagic fever: 7 deaths in Mali village |url=http://outbreaknewstoday.com/crimean-congo-hemorrhagic-fever-7-deaths-in-mali-village-63526/ |website=Outbreak news |accessdate=25 March 2022 |archive-date=31 January 2022 |archive-url=https://web.archive.org/web/20220131072319/http://outbreaknewstoday.com/crimean-congo-hemorrhagic-fever-7-deaths-in-mali-village-63526/ |url-status=live }}</ref>',
135 => '',
136 => '==History==',
137 => '[[File:JPWoodallatICEID1998.jpg|thumb|right|150px|Jack Woodall, Virologist]]',
138 => 'The virus may have evolved around 1500–1100 BC. It is thought that changing climate and agricultural practices around this time could be behind its evolution.<ref name=Carroll2010>{{cite journal | vauthors = Carroll SA, Bird BH, Rollin PE, Nichol ST | title = Ancient common ancestry of Crimean-Congo hemorrhagic fever virus | journal = Molecular Phylogenetics and Evolution | volume = 55 | issue = 3 | pages = 1103–10 | date = June 2010 | pmid = 20074652 | doi = 10.1016/j.ympev.2010.01.006 }}</ref>In the 12th century a case of a hemorrhagic disease reported from what is now [[Tajikistan]] may have been the first known case of Crimean–Congo hemorrhagic fever.<ref>{{cite web |title=Crimean-Congo Hemorrhagic Fever Virus: Biology and Pathogenesis |url=https://www.medscape.com/viewarticle/729785#:~:text=In%20the%2012th%20century%20a%20hemorrhagic%20disease%2C%20today,in%20a%20region%20that%20now%20corresponds%20to%20Tadzhikistan. |website=Medscape |accessdate=29 March 2022 |language=en |archive-date=11 June 2017 |archive-url=https://web.archive.org/web/20170611202947/http://www.medscape.com/viewarticle/729785#:~:text=In%20the%2012th%20century%20a%20hemorrhagic%20disease%2C%20today,in%20a%20region%20that%20now%20corresponds%20to%20Tadzhikistan. |url-status=live }}</ref>',
139 => 'During the [[Crimean War]], the disease was known as "Crimean fever" and contracted by many, including [[Florence Nightingale]].<ref>Cromwell, Judith Lissauer, Florence Nightingale, Feminist, McFarland, 2013, p.149</ref>',
140 => '',
141 => 'In 1944, Soviet scientists first identified the disease they called Crimean hemorrhagic fever in [[Crimea]].<ref>{{cite web|title=Природная очаговость зоонозных инфекций в Крыму|url=http://zooeco.com/nauc-st17-2.html|website=Мир Животных|url-status=live|archive-url=https://web.archive.org/web/20160923044225/http://zooeco.com/nauc-st17-2.html|archive-date=2016-09-23}}</ref> In February 1967, virologists [[John "Jack" P. Woodall|Jack Woodall]], David Simpson, Ghislaine Courtois and others published initial reports on a virus they called the Congo virus.<ref>{{cite journal | vauthors = Simpson DI, Knight EM, Courtois G, Williams MC, Weinbren MP, Kibukamusoke JW | title = Congo virus: a hitherto undescribed virus occurring in Africa. I. Human isolations--clinical notes | journal = East African Medical Journal | volume = 44 | issue = 2 | pages = 86–92 | date = February 1967 | pmid = 6040759 }}</ref><ref>{{cite journal | vauthors = Woodall JP, Williams MC, Simpson DI | title = Congo virus: a hitherto undescribed virus occurring in Africa. II. Identification studies | journal = East African Medical Journal | volume = 44 | issue = 2 | pages = 93–8 | date = February 1967 | pmid = 6068614 }}</ref> In 1956, the Congo virus had first been isolated by physician Ghislaine Courtois, head of the Provincial Medical Laboratory, [[Kisangani|Stanleyville]], in the [[Belgian Congo]]. Strain V3010, isolated by Courtois, was sent to the [[Rockefeller Foundation]] Virus Laboratory (RFVL) in New York City and found to be identical to another strain from [[Uganda]], but to no other named virus at that time.<ref>{{cite journal |last1=Uyar |first1=Yavuz |last2=Christova |first2=Iva |last3=Papa |first3=Anna |title=Current situation of Crimean Congo hemorrhagic fever (CCHF) in Anatolia and Balkan Peninsula |journal=Turkish Bulletin of Hygiene and Experimental Biology |date=2011 |volume=68 |issue=3 |pages=139–151 |doi=10.5505/TurkHijyen.2011.60352 |url=https://jag.journalagent.com/turkhijyen/pdfs/THDBD_68_3_139_151.pdf |accessdate=29 March 2022 |archive-date=21 January 2022 |archive-url=https://web.archive.org/web/20220121001526/https://jag.journalagent.com/turkhijyen/pdfs/THDBD_68_3_139_151.pdf |url-status=live }}</ref><ref>{{cite journal |last1=Ergönül |first1=Önder |title=Crimean-Congo haemorrhagic fever |journal=The Lancet. Infectious Diseases |date=2006 |volume=6 |issue=4 |pages=203–214 |doi=10.1016/S1473-3099(06)70435-2 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185836/ |accessdate=30 March 2022 |issn=1473-3099}}</ref>{{clarify}}',
142 => '',
143 => 'In June 1967, Soviet virologist [[Mikhail Chumakov]] registered an isolate from a fatal case that occurred in [[Samarkand]] in the Catalogue of Arthropod-borne Viruses.<ref>{{cite journal | vauthors = Chumakov MP, Butenko AM, Shalunova NV, Mart'ianova LI, Smirnova SE, ((Bashkirtsev Iu)), Zavodova TI, Rubin SG, Tkachenko EA, Karmysheva VI, Reĭngol'd VN, Popov GV, Savinov AP | display-authors = 6 | title = [New data on the viral agent of Crimean hemorrhagic fever] | language = Russian | journal = Voprosy Virusologii | volume = 13 | issue = 3 | pages = 377 | date = May–June 1968 | pmid = 4235803 }}</ref>',
144 => 'In 1969, the Russian strain, which Chumakov had sent to the RFVL, was published to be identical to the Congo virus.<ref>{{cite journal | vauthors = Casals J | title = Antigenic similarity between the virus causing Crimean hemorrhagic fever and Congo virus | journal = Proceedings of the Society for Experimental Biology and Medicine | volume = 131 | issue = 1 | pages = 233–6 | date = May 1969 | pmid = 5770109 | doi = 10.3181/00379727-131-33847 }}',
145 => '</ref>',
146 => '',
147 => 'The [[International Committee on Taxonomy of Viruses]] proposed the name ''Congo–Crimean hemorrhagic fever virus'', but the Soviets insisted on ''Crimean–Congo hemorrhagic fever virus''. In 1973, against all principles of scientific nomenclature based on priority of publication, it was adopted as the official name, in possibly the first instance of a virus losing its name to politics and the [[Cold War]].<ref>{{cite book | last1 = Ergönül | first1 = Onder | last2 = Whitehouse | first2 = Charles A. | title = Congo Hemorrhagic Fever: A Global Perspective | url = https://archive.org/details/crimeancongohemo00ergo | url-access = limited | place = Netherlands | publisher = Springer | year = 2007 | chapter = Personal Reflections, Jack Woodall | page = [https://archive.org/details/crimeancongohemo00ergo/page/n41 23] | isbn = 978-1-4020-6105-9 }}</ref> ',
148 => '',
149 => 'These reports include records of the occurrence of the virus or antibodies to the virus from Greece, Portugal, South Africa, [[Madagascar]] (the first isolation from there), the [[Maghreb]], [[Dubai]], [[Saudi Arabia]], [[Kuwait]] and [[Iraq]].<ref>{{cite journal | vauthors = Crowcroft NS, Morgan D, Brown D | title = Viral haemorrhagic fevers in Europe--effective control requires a co-ordinated response | journal = Euro Surveillance | volume = 7 | issue = 3 | pages = 31–2 | date = March 2002 | pmid = 12631941 | doi = 10.2807/esm.07.03.00343-en | doi-access = free }}</ref><ref name=BullWHO>{{cite journal | vauthors = Al-Tikriti SK, Al-Ani F, Jurji FJ, Tantawi H, Al-Moslih M, Al-Janabi N, Mahmud MI, Al-Bana A, Habib H, Al-Munthri H, Al-Janabi S, AL-Jawahry K, Yonan M, Hassan F, Simpson DI | display-authors = 6 | title = Congo/Crimean haemorrhagic fever in Iraq | journal = Bulletin of the World Health Organization | volume = 59 | issue = 1 | pages = 85–90 | year = 1981 | pmid = 6790183 | pmc = 2396030 }}</ref><ref name=vector>{{cite journal | vauthors = Okorie TG | title = Comparative studies on the vector capacity of the different stages of Amblyomma variegatum Fabricius and Hyalomma rufipes Koch for Congo virus, after intracoelomic inoculation | journal = Veterinary Parasitology | volume = 38 | issue = 2–3 | pages = 215–23 | date = March 1991 | pmid = 1907050 | doi = 10.1016/0304-4017(91)90131-e }}</ref>',
150 => '',
151 => '== References ==',
152 => '',
153 => '{{Reflist}}',
154 => '',
155 => '== External links ==',
156 => '{{Medical resources',
157 => '| ICD10 = {{ICD10|A|98|0|a|90}}',
158 => '| ICD9 = {{ICD9|065.0}}',
159 => '| ICDO =',
160 => '| OMIM =',
161 => '| DiseasesDB = 31969',
162 => '| MedlinePlus = article',
163 => '| eMedicineSubj = 830594',
164 => '| eMedicineTopic =',
165 => '}}',
166 => '* [http://www.who.int/mediacentre/factsheets/fs208/en/ World Health Organization Fact Sheet] {{Webarchive|url=https://web.archive.org/web/20170713160035/http://www.who.int/mediacentre/factsheets/fs208/en/ |date=2017-07-13 }}',
167 => '',
168 => '{{Zoonotic viral diseases}}',
169 => '{{Tick-borne diseases}}',
170 => '{{Taxonbar|from=Q29002571|from2=Q1788951|from3=Q24757193}}',
171 => '',
172 => '{{DEFAULTSORT:Crimean-Congo Hemorrhagic Fever}}',
173 => '[[Category:Arthropod-borne viral fevers and viral haemorrhagic fevers]]',
174 => '[[Category:Hemorrhagic fevers]]',
175 => '[[Category:Nairoviridae]]',
176 => '[[Category:Tick-borne diseases]]',
177 => '[[Category:RTT]]',
178 => '[[Category:RTTID]]'
] |
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Unix timestamp of change (timestamp ) | 1648691022 |