{{short description|Degenerative brain disease caused by prions}} {{cs1 config|name-list-style=vanc}} {{distinguish|Creutzfeldt–Jakob disease}} {{for|the disease in cattle|Bovine spongiform encephalopathy}} {{Infobox medical condition |name = Variant Creutzfeldt–Jakob disease |synonyms = New variant Creutzfeldt–Jakob disease (nvCJD) (dated), human mad cow disease, human BSE (colloquial) |image = VCJD Tonsil.jpg |caption = Biopsy of the tonsil in variant CJD. PrP<sup>sc</sup> deposits are stained brown and are visible. |field = Infectious disease, Neurology |symptoms = '''Initial''': Psychiatric problems, behavioral changes, painful sensations<ref name="CDC2015Comp"/><br /> '''Later''': Poor coordination, dementia, hallucinations, involuntary movements<ref name="CDC2015Criteria"/> |complications = Aspiration pneumonia, akinetic mutism |onset = Years after initial exposure<ref name="CDC2015Diag"/> |duration = ~13-month life expectancy after onset of symptoms<ref name="CDC2015Comp"/> |types = |causes = Prions, specifically PrP<sup>BSE</sup> |risks = Eating beef from cows with bovine spongiform encephalopathy<ref name="CDC2015Diag"/><ref name="Iron2010"/> |diagnosis = Suspected based on symptoms, confirmed by brain biopsy, Protein misfolding cyclic amplification (PMCA), or Real-time quaking-induced conversion (RT-QuIC)<ref name="CDC2015Diag"/> |differential = Multiple sclerosis, classic Creutzfeldt–Jakob disease |prevention = Not eating contaminated beef |treatment = Supportive care<ref name="CDC2015Tx"/> |medication = Pentosan polysulfate (experimental), morphine, methadone (for pain relief), clonazepam, valproate (for involuntary movements), haloperidol (for agitation) |prognosis = Always fatal<ref>{{cite news | work = U.S. Centers for Disease Control and Prevention (CDC) |title=Variant Creutzfeldt-Jakob Disease (VCJD) &#124; Prion Diseases |date=25 January 2022 |url=https://www.cdc.gov/prions/vcjd/index.html}}</ref> |frequency = Fewer than 250 reported cases as of 2012<ref name="Iron2012"/> |deaths = 178 in the United Kingdom as of 2024<ref>{{Cite web | url=https://www.cjd.ed.ac.uk/sites/default/files/figs.pdf | title=Creutzfeldt-Jakob disease in the UK (by calendar year) | website=www.cjd.ed.ac.uk | access-date=2024-08-22 | archive-date=2024-12-14 | archive-url=https://web.archive.org/web/20241214193026/https://www.cjd.ed.ac.uk/sites/default/files/figs.pdf | url-status=dead }}</ref> |alt = }} <!-- Definition and symptoms -->

'''Variant Creutzfeldt–Jakob disease''' ('''vCJD'''), formerly known as '''new variant Creutzfeldt–Jakob disease''' ('''nvCJD''') and referred to colloquially as "'''Creutzfeldt–Jakob Disease'''", "'''mad cow disease'''" or "'''human mad cow disease'''" (to distinguish it from its BSE counterpart), is a fatal type of brain disease within the transmissible spongiform encephalopathy family.<ref name="Iron2012" /> Initial symptoms include psychiatric problems, behavioral changes, and painful sensations.<ref name="CDC2015Comp" /> In the later stages of the illness, patients may exhibit poor coordination, dementia and involuntary movements.<ref name="CDC2015Criteria" /> The length of time between exposure and the development of symptoms is unclear, but is believed to be years to decades.<ref name="CDC2015Diag">{{cite web|title=Classic CJD versus Variant CJD|url=https://www.cdc.gov/prions/vcjd/classic-variant.html|archive-url=https://web.archive.org/web/20150831053519/http://www.cdc.gov/prions/vcjd/classic-variant.html|url-status=dead|archive-date=August 31, 2015|website=CDC|access-date=23 January 2018|language=en-us|date=11 February 2015}} </ref> Average life expectancy following the onset of symptoms is 13 months.<ref name="CDC2015Comp">{{cite web|title=Clinical and Pathologic Characteristics {{!}} Variant Creutzfeldt-Jakob Disease, Classic (CJD)|url=https://www.cdc.gov/prions/vcjd/clinical-pathologic-characteristics.html|website=CDC|access-date=22 January 2018|language=en-us|date=10 February 2015}}</ref>

<!-- Cause and diagnosis --> It is caused by prions, which are misfolded proteins.<ref name="CDC2015About">{{cite web|title=About vCJD|url=https://www.cdc.gov/prions/vcjd/about.html|website=CDC|access-date=22 January 2018|language=en-us|date=10 February 2015}}</ref> Spread is believed to be primarily due to eating beef infected with BSE.<ref name="Iron2012"/><ref name="CDC2015About"/> Infection is also believed to require a specific genetic susceptibility.<ref name="Iron2010">{{cite journal | vauthors = Ironside JW | title = Variant Creutzfeldt-Jakob disease | journal = Haemophilia | volume = 16 | issue = Suppl 5 | pages = 175–180 | date = July 2010 | pmid = 20590878 | doi = 10.1111/j.1365-2516.2010.02317.x | s2cid = 24635924 | doi-access = free }}</ref><ref name="Iron2012">{{cite journal | vauthors = Ironside JW | title = Variant Creutzfeldt-Jakob disease: an update | journal = Folia Neuropathologica | volume = 50 | issue = 1 | pages = 50–56 | date = 2012 | pmid = 22505363 }}</ref> Spread may potentially also occur via blood products or contaminated surgical equipment.<ref name=":0">{{cite book| vauthors = Ferri FF |title=Ferri's Clinical Advisor 2018 E-Book: 5 Books in 1|date=2017|publisher=Elsevier Health Sciences|isbn=9780323529570|page=343|url=https://books.google.com/books?id=wGclDwAAQBAJ&pg=PA343-IA4|language=en}}</ref> Diagnosis is by brain biopsy but can be suspected based on certain other criteria.<ref name="CDC2015Diag"/> It is different from typical Creutzfeldt–Jakob disease, though both are due to prions.<ref name="CDC2015About"/>

<!-- Epidemiology and history --> Treatment for vCJD involves supportive care.<ref name="CDC2015Tx">{{cite web|title=Treatment Variant Creutzfeldt-Jakob Disease|url=https://www.cdc.gov/prions/vcjd/treatment.html|website=CDC|access-date=23 January 2018|language=en-us|date=10 February 2015}}</ref> As of 2020, 178 cases of vCJD have been recorded in the United Kingdom,<ref name=":1">{{cite journal | vauthors = Gill ON, Spencer Y, Richard-Loendt A, Kelly C, Brown D, Sinka K, Andrews N, Dabaghian R, Simmons M, Edwards P, Bellerby P, Everest DJ, McCall M, McCardle LM, Linehan J, Mead S, Hilton DA, Ironside JW, Brandner S | display-authors = 6 | title = Prevalence in Britain of abnormal prion protein in human appendices before and after exposure to the cattle BSE epizootic | journal = Acta Neuropathologica | volume = 139 | issue = 6 | pages = 965–976 | date = June 2020 | pmid = 32232565 | pmc = 7244468 | doi = 10.1007/s00401-020-02153-7 }}</ref> due to a 1990s outbreak, and 50 cases in the rest of the world.<ref name="Iron2012"/> The disease has become less common since 2000.<ref name="Iron2012"/> The typical age of onset is less than 30 years old.<ref name="CDC2015Diag"/> It was first identified in 1996 by the National CJD Surveillance Unit in Edinburgh, Scotland.<ref name="Iron2012"/> Controversial research by Harash Narang, who worked as a virologist at the Public Health Laboratory Service (PHLS) suggested a link between BSE and CJD as early as 1989.<ref>{{Cite web |date=1999-08-10 |title=How a scientist obtained thousands for a BSE test he could not prove |url=https://www.independent.co.uk/news/how-a-scientist-obtained-thousands-for-a-bse-test-he-could-not-prove-1112025.html |access-date=2026-03-18 |website=The Independent |language=en}}</ref><ref>{{Cite web |date=1996-03-21 |title=Thousands may have caught CJD during three years before Government clamped down on meat Deadly legacy of infection |url=https://www.heraldscotland.com/news/12051687.thousands-may-have-caught-cjd-during-three-years-before-government-clamped-down-on-meat-deadly-legacy-of-infection/ |access-date=2026-03-18 |website=The Herald |language=en}}</ref>

==Signs and symptoms== Initial symptoms include psychiatric problems, behavioral changes, and painful sensations.<ref name="CDC2015Comp"/> In the later stages of the illness, patients may exhibit poor coordination, dementia and involuntary movements.<ref name="CDC2015Criteria"/> The length of time between exposure and the development of symptoms is unclear, but is believed to be years.<ref name="CDC2015Diag"/> Average life expectancy following the onset of symptoms is 13 months.<ref name="CDC2015Comp"/>

==Cause== ===Tainted beef === In Britain, the primary cause of vCJD has been eating beef tainted with bovine spongiform encephalopathy.<ref name="NIH2003"/> A 2012 study by the Health Protection Agency found that around 1 in 2000 had abnormal prions present in appendix cells.<ref name="Health Protect Report">{{cite web|last=HPA Press Office|title=Summary results of the second national survey of abnormal prion prevalence in archived appendix specimens |url=http://www.hpa.org.uk/hpr/archives/2012/news3212.htm#bnrmlprn|date=August 10, 2012 |url-status=live|archive-url=https://web.archive.org/web/20130325082156/http://www.hpa.org.uk/hpr/archives/2012/news3212.htm#bnrmlprn|archive-date=March 25, 2013}}</ref>

Jonathan Quick, instructor of medicine at the Department of Global Health and Social Medicine at Harvard Medical School, stated that bovine spongiform encephalopathy (BSE) is the first man-made epidemic, or "Frankenstein" disease, because a human decision to feed meat and bone meal to previously herbivorous cattle (as a source of protein) caused what was previously an animal pathogen to enter into the human food chain, and from there to begin causing humans to contract vCJD.<ref name=":2">{{cite book| vauthors = Quick HD, Fryer B |title=The End of Epidemics: The Looming Threat to Humanity and How to Stop it|publisher=St. Martin's Press|date=2018| pages=51–53|isbn=9781250117779|url=https://books.google.com/books?id=FzhCDwAAQBAJ&pg=PA51}}</ref>

The risk of contracting vCJD from ingestion of cattle products has led to many countries banning the import of beef from countries where BSE has been known to occur, such as the ban on beef from the United States imposed by Japan, South Korea, Mexico, Canada, and other countries in 2003 immediately following the first reported case of BSE in American cattle. Stringent preventative and surveillance practices implemented since then to prevent the disease from entering the human and cattle food chains have caused some to conclude that such bans are unnecessary.<ref>{{cite journal |last1=Kim |first1=Keun Soo |last2=Kim |first2=Taesu |last3=Choi |first3=Hanbyul |last4=Ahn |first4=Christine |last5=Lee |first5=Christopher C. |date=July 2016 |title=Beef from the United States: Is It Safe? |journal=Journal of Korean Medical Science |language=en |volume=31 |issue=7 |pages=1009–1010 |doi=10.3346/jkms.2016.31.7.1009 |issn=1011-8934 |pmc=4900988 |pmid=27365995 }}</ref>

===Blood products=== As of 2018, evidence suggests that there may be prions in the blood of individuals with vCJD, but this is not the case in individuals with sporadic CJD.<ref name="NIH2003">{{cite web|title=Creutzfeldt-Jakob Disease Fact Sheet {{!}} National Institute of Neurological Disorders and Stroke|url=https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Creutzfeldt-Jakob-Disease-Fact-Sheet|website=NINDS|access-date=16 July 2017|date=March 2003|url-status=dead|archive-url=https://web.archive.org/web/20170704234755/https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Creutzfeldt-Jakob-Disease-Fact-Sheet|archive-date=4 July 2017}}</ref>

In 2004, a report showed that vCJD can be transmitted by blood transfusions.<ref name="pmid15302196">{{cite journal | vauthors = Peden AH, Head MW, Ritchie DL, Bell JE, Ironside JW | title = Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient | journal = Lancet | volume = 364 | issue = 9433 | pages = 527–529 | year = 2004 | pmid = 15302196 | doi = 10.1016/S0140-6736(04)16811-6 | s2cid = 18617259 }}</ref> The finding alarmed healthcare officials because a large epidemic of the disease could result in the near future. A blood test for vCJD infection is possible<ref name=":3">{{cite journal | vauthors = Edgeworth JA, Farmer M, Sicilia A, Tavares P, Beck J, Campbell T, Lowe J, Mead S, Rudge P, Collinge J, Jackson GS | display-authors = 6 | title = Detection of prion infection in variant Creutzfeldt-Jakob disease: a blood-based assay | journal = Lancet | volume = 377 | issue = 9764 | pages = 487–493 | date = February 2011 | pmid = 21295339 | doi = 10.1016/S0140-6736(10)62308-2 | s2cid = 39891588 }}</ref> but is not yet available for screening blood donations. Significant restrictions exist to protect the blood supply. The UK government banned anyone who had received a blood transfusion since January 1980 from donating blood.<ref name=":4">{{cite web |title=Variant CJD and blood donation |url=http://www.blood.co.uk/pdfdocs/vcjd.pdf |publisher=National Blood Service |date=August 2004 |access-date=2009-06-20 |url-status=dead |archive-url=https://web.archive.org/web/20071011080433/http://www.blood.co.uk/pdfdocs/vcjd.pdf |archive-date=October 11, 2007 }} </ref> Since 1999 there has been a ban in the UK for using UK blood to manufacture fractional products such as albumin.<ref name=":5">{{cite journal | vauthors = Regan F, Taylor C | title = Blood transfusion medicine | journal = BMJ | volume = 325 | issue = 7356 | pages = 143–147 | date = July 2002 | pmid = 12130612 | pmc = 1123672 | doi = 10.1136/bmj.325.7356.143 }}</ref> Whilst these restrictions may go some way to preventing a self-sustaining epidemic of secondary infections, the number of infected blood donations is unknown and could be considerable. In June 2013 the government was warned that deaths, then at 176, could rise five-fold through blood transfusions.<ref name="rowena">{{cite news |url=https://www.telegraph.co.uk/health/healthnews/10024078/Mad-cow-infected-blood-to-kill-1000.html |title=Mad cow infected blood 'to kill 1,000'|author=Rowena Mason |work=Daily Telegraph|date=April 28, 2013 |access-date=July 2, 2013 |location=London|url-status=dead|archive-url=https://web.archive.org/web/20130703025447/http://www.telegraph.co.uk/health/healthnews/10024078/Mad-cow-infected-blood-to-kill-1000.html|archive-date=July 3, 2013}}</ref>

On 28 May 2002, the United States Food and Drug Administration instituted a policy that excludes from blood donation anyone having spent at least six months in certain European countries (or three months in the United Kingdom) from 1980 to 1996. Given the large number of U.S. military personnel and their dependents residing in Europe, it was expected that over 7% of donors would be deferred due to the policy. Later changes to this policy first relaxed the restriction to a cumulative total of five years or more of civilian travel in European countries (six months or more if military) then, in 2022, removed it entirely.<ref>{{cite web | url=https://americasblood.org/news/abc-supports-fdas-updated-guidance-on-vcjd/ | title=Learn More About FDA's Updated Guidance on VCJD | date=23 May 2022 }}</ref>

In New Zealand, the New Zealand Blood Service (NZBS) in 2000 introduced measures to preclude permanently donors having resided in the United Kingdom (including the Isle of Man and the Channel Islands) for a total of six months or more between January 1980 and December 1996. The measure resulted in ten percent of New Zealand's active blood donors at the time becoming ineligible to donate blood. In 2003, the NZBS further extended restrictions to permanently preclude donors having received a blood transfusion in the United Kingdom since January 1980, and in April 2006, restrictions were further extended to include the Republic of Ireland and France.<ref>{{cite web |url= https://www.nzblood.co.nz/assets/Give-Blood/PDFs/CJD-Creutzfeldt-Jakob-Disease-Information-for-blood-donors-111I077.pdf |title= CJD (Creutzfeldt–Jakob Disease) - Information for blood donors |publisher= New Zealand Blood Service |access-date= 31 May 2017 |url-status= live |archive-url= https://web.archive.org/web/20170410052943/http://www.nzblood.co.nz/assets/Give-Blood/PDFs/CJD-Creutzfeldt-Jakob-Disease-Information-for-blood-donors-111I077.pdf |archive-date= 10 April 2017}}</ref> The restriction was rescinded in late February 2024.<ref>{{cite web |url= https://www.nzblood.co.nz/madcow/ |publisher= New Zealand Blood Service |title= Variant Creutzfeldt-Jakob Disease (vCJD) | access-date= 28 December 2023 }}</ref>

In Canada, individuals were formerly ineligible to donate blood or plasma if they had spent a cumulative total of three months or more in the mainland UK or its Crown Dependencies or six months or more in Saudi Arabia from January 1, 1980, through December 31, 1996. They were also ineligible if they had spent a cumulative total of five years or more in France or the Republic of Ireland from January 1, 1980, through 31 December 2001. These restrictions were removed by December 2023.<ref>{{cite web |title=Eligibility for mad cow-affected countries |url=https://at.blood.ca/eligibility-for-mad-cow-affected-countries/ |access-date=2023-12-06 |website=at.blood.ca}}</ref>

In Poland, anyone having spent cumulatively six months or longer between 1 January 1980 and 31 December 1996 in the UK, Ireland, or France is permanently barred from donating.<ref>{{cite web|title=Permanent exclusion criteria / Dyskwalifikacja stała |url=http://www.rckik-warszawa.com.pl/dlakrwio_ds.html |publisher=RCKiK Warszawa |language=pl |access-date=2010-03-03 |url-status=dead |archive-url=https://web.archive.org/web/20090830053230/http://www.rckik-warszawa.com.pl/dlakrwio_ds.html |archive-date=August 30, 2009 }} </ref>

In France, anyone having lived or stayed in the United Kingdom a total of over one year between 1 January 1980 and 31 December 1996 is permanently barred from donating.<ref>{{Cite web|url=https://www.santepubliquefrance.fr/don-de-sang/articles/quelles-sont-les-contre-indications-au-don-de-sang|title=Quelles sont les contre-indications au don de sang ?|website=www.santepubliquefrance.fr}}</ref>

In the Czech Republic, anyone having spent more than twelve months in the UK or France between 1980 and 1996 or received transfusion in the UK after the year 1980 is not allowed to donate blood.<ref>{{Cite web |date=2024-07-29 |title=INFORMATION FOR BLOOD DONORS |url=https://www.ftn.cz/upload/ftn/Kliniky/tra/Dokumenty/FTN_TRA_Information_for_blood_donors.pdf |access-date=2025-07-05 |website=Thomayer University Hospital (Fakultní Thomayerovy nemocnice)}}</ref>

In Finland, anyone having lived or stayed in the mainland United Kingdom or its Crown Dependencies for a total of over six months between 1 January 1980 and 31 December 1996 was formerly barred from donating; the restriction was removed in March 2026.<ref>{{cite web |title=FAQ |url=https://www.veripalvelu.fi/en/faq/?category=eligibility |access-date=2026-04-09 |website=Finnish Red Cross Blood Service |language=en-US}}</ref><ref>{{Cite web |date=2026-03-30 |title=More people will be able to donate blood – restriction on people who lived in the UK removed |url=https://www.veripalvelu.fi/en/more-people-will-be-able-to-donate-blood-restriction-on-people-who-lived-in-the-uk-removed/ |access-date=2026-04-09 |website=Finnish Red Cross Blood Service |language=en-US}}</ref>

===Sperm donation=== In the U.S., the FDA has banned import of any donor sperm, motivated by a risk of variant Creutzfeldt–Jakob disease, inhibiting the once popular<ref name="Stein">{{cite news | vauthors = Stein R |title=Mad Cow Rules Hit Sperm Banks' Patrons |newspaper=Washington Post |date=13 August 2008 |url=https://www.washingtonpost.com/wp-dyn/content/article/2008/08/12/AR2008081203131.html |access-date=2008-10-04 |url-status=live | archive-url = https://web.archive.org/web/20120426014840/http://www.washingtonpost.com/wp-dyn/content/article/2008/08/12/AR2008081203131.html |archive-date=26 April 2012 |df=dmy-all}}</ref> import of Scandinavian sperm. Despite this, the scientific consensus is that the risk is negligible, as there is no evidence Creutzfeldt–Jakob is sexually transmitted.<ref name="kotler">{{cite news |date=2007-09-27 |title=The God of Sperm |publisher=LA Weekly |url=http://www.laweekly.com/2007-09-27/news/the-god-of-sperm/ |url-status=dead |access-date=2009-06-20 |archive-url=https://web.archive.org/web/20090706135047/http://www.laweekly.com/2007-09-27/news/the-god-of-sperm/ |archive-date=2009-07-06 |vauthors=Kotler S |df=dmy-all}}</ref><ref name="Mortimer">{{cite journal | vauthors = Mortimer D, Barratt CL | title = Is there a real risk of transmitting variant Creutzfeldt-Jakob disease by donor sperm insemination? | journal = Reproductive Biomedicine Online | volume = 13 | issue = 6 | pages = 778–790 | date = December 2006 | pmid = 17169195 | doi = 10.1016/S1472-6483(10)61024-3 | doi-access = }}</ref><ref name="Lapidos">{{cite news |title=Is Mad Cow an STD? | vauthors = Lapidos J |url= http://www.slate.com/articles/life/the_sex_issue/2007/09/is_mad_cow_an_std.html |publisher=Slate |date=2007-09-26 |access-date=2017-01-07 |url-status= live |archive-url= https://web.archive.org/web/20170108101512/http://www.slate.com/articles/life/the_sex_issue/2007/09/is_mad_cow_an_std.html |archive-date=2017-01-08 |df=dmy-all}}</ref>

=== Occupational contamination === In France, the last two victims of variant Creutzfeldt–Jakob disease, who died in 2019 and 2021, were research technicians at the National Research Institute for Agriculture, Food and the Environment (INRAE). Emilie Jaumain, who died in 2019, at the age of 33, had been the victim of a work accident in 2010, during which she had pricked herself with a tool contaminated with infected brain.<ref>{{cite journal | vauthors = Brandel JP, Vlaicu MB, Culeux A, Belondrade M, Bougard D, Grznarova K, Denouel A, Plu I, Bouaziz-Amar E, Seilhean D, Levasseur M, Haïk S | display-authors = 6 | title = Variant Creutzfeldt-Jakob Disease Diagnosed 7.5 Years after Occupational Exposure | journal = The New England Journal of Medicine | volume = 383 | issue = 1 | pages = 83–85 | date = July 2020 | pmid = 32609989 | doi = 10.1056/NEJMc2000687 | s2cid = 220309455 | doi-access = free | url = https://hal.science/hal-03758486/file/nejmc2000687.pdf }}</ref> The efficacy of this route of contamination was subsequently demonstrated in primates.<ref>{{cite journal | vauthors = Mikol J, Delmotte J, Jouy D, Vaysset E, Bastian C, Deslys JP, Comoy E | title = Direct neural transmission of vCJD/BSE in macaque after finger incision | journal = Acta Neuropathologica | volume = 141 | issue = 1 | pages = 119–122 | date = January 2021 | pmid = 33025140 | pmc = 7785535 | doi = 10.1007/s00401-020-02231-w }}</ref> Pierrette C., who died in 2021, had been victim of the same type of work accident;<ref>{{cite web |last=La-Croix.com |date=2021-12-06 |title=Recherche sur les prions, la sécurité des laboratoires français mise en cause |url=https://www.la-croix.com/Sciences-et-ethique/Recherche-prions-securite-laboratoires-francais-mise-cause-2021-12-06-1201188804 |access-date=2022-08-29 |website=La Croix |language=fr}}</ref><ref>{{cite web |title=Toulouse : la technicienne de l'Inrae morte de Creutzfeldt-Jakob avait déclaré deux accidents du travail |url=https://www.ladepeche.fr/2021/12/04/toulouse-la-technicienne-morte-de-creutzfeldt-jakob-avait-declare-deux-accidents-du-travail-9971354.php |access-date=2022-08-29 |website=ladepeche.fr |language=fr}}</ref> after her diagnosis, a moratorium was initiated in all French laboratories on research activities on infectious prions.<ref>{{cite journal | vauthors = Casassus B | title = France halts prion research amid safety concerns | journal = Science | volume = 373 | issue = 6554 | pages = 475–476 | date = July 2021 | pmid = 34326214 | doi = 10.1126/science.373.6554.475 | bibcode = 2021Sci...373..475C | s2cid = 236515731 }}</ref> In March 2022, INRAE recognized the occupational cause of these two deaths,<ref>{{cite web |title=L'Inrae reconnaît que la technicienne toulousaine morte de Creutzfeldt-Jakob a été victime d'un accident de laboratoire |url=https://www.ladepeche.fr/2022/03/17/linrae-reconnait-que-la-technicienne-toulousaine-morte-de-creutzfeldt-jakob-a-ete-victime-dun-accident-de-laboratoire-10176126.php |access-date=2022-08-29 |website=ladepeche.fr |language=fr}}</ref><ref>{{cite web |title=Creutzfeldt-Jakob : la contamination de deux anciennes salariées relevait bien de l'accident du travail, confirme l'INRAE de Toulouse |url=https://france3-regions.francetvinfo.fr/occitanie/haute-garonne/toulouse/creutzfeld-jakob-la-contamination-de-deux-anciennes-salariees-relevait-bien-de-l-accident-du-travail-confirme-l-inrae-de-toulouse-2500399.html |access-date=2022-08-29 |website=France 3 Occitanie |date=16 March 2022 |language=fr-FR}}</ref> raising serious questions about the safety of personnel in these laboratories. Inspections noted failures in the protection of agents in the face of this deadly risk,<ref>{{cite web |title=Deuxième mission d'expertise de la sécurité dans les laboratoires de recherche sur les prions infectieux - conditions de sortie du moratoire |url=https://www.enseignementsup-recherche.gouv.fr/fr/deuxieme-mission-d-expertise-de-la-securite-dans-les-laboratoires-de-recherche-sur-les-prions-83396 |access-date=2022-08-29 |website=enseignementsup-recherche.gouv.fr |date=26 January 2022 |language=fr}}</ref><ref>{{cite news |date=2022-01-31 |title=Recherche sur les prions : un rapport d'inspection dénonce des conditions de sécurité insuffisantes |language=fr-FR |work=La Croix |url=https://www.la-croix.com/Sciences-et-ethique/Recherche-prions-rapport-dinspection-denonce-conditions-securite-insuffisantes-2022-01-31-1201197804 |access-date=2022-08-29 |issn=0242-6056}}</ref> and the long incubation period of this disease led to fears of new cases in the future.<ref>{{cite web |title=ENTRETIEN. Maladie de Creutzfeldt Jakob : " On demande un recensement des personnels qui ont travaillé sur le prion " |url=https://www.ladepeche.fr/2021/12/01/maladie-de-creutzfeldt-jakob-on-demande-un-recensement-des-personnels-qui-ont-travaille-sur-le-prion-ces-25-dernieres-annees-9964400.php |access-date=2022-08-29 |website=ladepeche.fr |language=fr}}</ref>

===False link to consumption of squirrel brains=== A 1997 article in The Lancet<ref>{{cite journal |last1=Berger |first1=Joseph |title=Creutzfeldt-Jakob Disease and eating squirrel brains |journal=The Lancet |date=August 30, 1997 |url=https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(05)63333-8/abstract}}</ref> postulated that a connection existed between the consumption of squirrel brains and CJD. Media reporting on this myth was reignited in 2018 when an article by Live Science<ref>{{cite web |last1=Rettner |first1=Rachael |title=Man Dies from Extremely Rare Disease After Eating Squirrel Brains |url=https://www.livescience.com/63831-squirrel-brains-rare-disorder-creutzfeldt-jakob-disease.html}}</ref> reported on a Rochester man who was alleged to have contracted vCJD from his consumption of squirrel brains.

''Creutzfeldt-Jakob Disease and eating squirrel brains'', the 1997 article by the Lancet has been almost entirely discredited due its lack of scientific evidence and false statistical assumptions. An article published by the New Yorker in the year 2000, shortly following the release of the 1997 Lancet article was one of the first to report on the lack of scientific footing for the Lancet's study. It reported that many issues revolved around the researchers conflating statistical correlation with epidemiological causation. This is especially important with a slow moving, and hard to trace disease like vCJD, a point emphasized in their statement that "the Lancet study blundered blithely into such statistical pitfalls".<ref>{{cite news |last1=Bilger |first1=Burkhard |title=Squirrel and Man |url=https://www.newyorker.com/magazine/2000/07/17/squirrel-and-man |agency=The New Yorker}}</ref>

One of the most direct and robust dismissals of the connection between consumption of squirrel brains and vCJD was a statement made in 2018 by the Creutzfeldt–Jakob Disease Foundation, addressing both the 1997 Lancet article and Live Science article. This statement was part of a press release, reading that “The previous ProMed commentary mentioned a 1997 Lancet report that hypothesized about a potential link between consumption of squirrel brains and CJD; there was no mention of vCJD in that report. Since that brief report, there has been no convincing evidence found suggesting that the consumption of squirrel meat, brain or otherwise, is a risk factor for any prion disease. While prion diseases have been identified in several other types of mammals, they have never been identified in squirrels. Without additional experimental or epidemiological evidence, a link between consumption of squirrel brain and human prion disease is unjustifiably speculative.”<ref>{{cite web |title=10/19/18 Response submitted to ProMed by the National Prion Disease Pathology Surveillance Center regarding ProMed's recent article suggesting that there is a connection between human prion disease and squirrel brain |url=https://cjdfoundation.org/news/ |website=The CJD Foundation Inc.}}</ref>

An article by Democrat and Chronicle provided another primary source debunking this myth. This report included interviews with the epidemiologist overseeing the 2018 case reported on by Live Science. In a statement, Dr. Emil Lesho stated that “We never thought squirrel brains”.<ref>{{cite news |last1=Singer |first1=Patti |title=The story behind the viral story about a man who ate squirrel brain |url=https://www.democratandchronicle.com/story/news/2018/10/19/squirrel-brains-infectious-disease-cruetzfeldt-jakob-wasting-hunting-game-meat/1684817002/ |date=October 19, 2018}}</ref>

Despite the fact that there is no scientific basis for this connection, much reporting surrounds both the 1997 Lancet article, and the 2018 Live Science article, most echoing their statements. Although eating the nervous tissue of any mammal is not recommended due to the risk of disease transmission, fundamentally, there is no robust scientific evidence that the consumption of squirrel brains presents a risk factor for vCJD at any level, or has ever caused a case of vCJD in humans.

==Mechanism== Despite the consumption of contaminated beef in the UK being high, vCJD has infected a small number of people. One explanation for this can be found in the genetics of people with the disease. The human PRNP protein which is subverted in prion disease can occur with either methionine or valine at amino acid 129, without any apparent physiological difference. Of the overall white population, about 40% have two methionine-containing alleles, 10% have two valine-containing alleles, and the other 50% are heterozygous at this position. Only a single person with vCJD tested was found to be heterozygous; most of those affected had two copies of the methionine-containing form. It is not yet known whether those unaffected are actually immune or only have a longer incubation period until symptoms appear.<ref>{{cite journal | vauthors = Saba R, Booth SA | title = The genetics of susceptibility to variant Creutzfeldt-Jakob disease | journal = Public Health Genomics | volume = 16 | issue = 1–2 | pages = 17–24 | year = 2013 | pmid = 23548713 | doi = 10.1159/000345203 | doi-access = free }}</ref><ref>{{cite book|author1=Sikorska, B|author2=Liberski, PP|title=Protein Aggregation and Fibrillogenesis in Cerebral and Systemic Amyloid Disease |chapter=Human Prion Diseases: From Kuru to Variant Creutzfeldt-Jakob Disease |year=2012|volume=65|pages=457–96|pmid=23225013|doi=10.1007/978-94-007-5416-4_17|series = Subcellular Biochemistry|isbn = 978-94-007-5415-7}}</ref> Studies in transgenetic mice indicate that all of these genotypes can be affected.<ref name=Diack2014>{{cite journal|doi=10.4161/pri.29237 |title=Variant CJD |date=2014 |journal=Prion |volume=8 |issue=4 |pages=286–295 |pmid=25495404 |pmc=4601215 | vauthors = Diack AB, Head MW, McCutcheon S, Boyle A, Knight R, Ironside JW, Manson JC, Will RG }}</ref>

==Diagnosis== [[File:Eeg CJD.jpg|thumb|upright=1.3|Electroencephalogram of a person with suspected CJD showing typical periodic bursts of triphasic sharp waves]]

===Definitive=== Examination of brain tissue is required to confirm a diagnosis of variant CJD.<ref name="CDC2015Criteria"/> The following confirmatory features should be present:<ref name="CDC2015Criteria">{{cite web|title=Clinical Overview of Variant Creutzfeldt-Jakob Disease|url=https://www.cdc.gov/variant-creutzfeldt-jakob/hcp/clinical-overview/?CDC_AAref_Val=https://www.cdc.gov/prions/vcjd/diagnostic-criteria.html|website=CDC|access-date=February 24, 2026|language=en-us|date=November 2012}}</ref> * Numerous widespread kuru-type amyloid plaques surrounded by vacuoles in both the cerebellum and cerebrum – florid plaques.<ref name="CDC2015Criteria"/> * Spongiform change and extensive prion protein deposition shown by immunohistochemistry throughout the cerebellum and cerebrum.<ref name="CDC2015Criteria"/>

===Suspected=== * Current age or age at death less than 55 years (a brain autopsy is recommended, however, for all physician-diagnosed CJD cases).<ref name="CDC2015Criteria"/> * Psychiatric symptoms at illness onset and/or persistent painful sensory symptoms (frank pain and/or dysesthesia).<ref name="CDC2015Criteria"/> * Dementia, and development ≥4 months after illness onset of at least two of the following five neurologic signs: poor coordination, myoclonus, chorea, hyperreflexia, or visual signs. (If persistent painful sensory symptoms exist, ≥4 months' delay in the development of the neurologic signs is not required).<ref name="CDC2015Criteria"/> * A normal or an abnormal EEG, but not the diagnostic EEG changes often seen in classic CJD.<ref name="CDC2015Criteria"/> * Duration of illness of over 6 months.<ref name="CDC2015Criteria"/> * Routine investigations do not suggest an alternative, non-CJD diagnosis.<ref name="CDC2015Criteria"/> * No history of getting human pituitary growth hormone or a dura mater graft from a cadaver.<ref name="CDC2015Criteria"/> * No history of CJD in a first degree relative or prion protein gene mutation in the person.<ref name="CDC2015Criteria"/>

===Classification=== vCJD is a separate condition from classic Creutzfeldt–Jakob disease (though both are caused by PrP prions).<ref name="CDC2015About"/> Both classic and variant CJD are subtypes of Creutzfeldt–Jakob disease. There are three main categories of CJD disease: sporadic CJD, hereditary CJD, and acquired CJD, with variant CJD being in the acquired group along with iatrogenic CJD.<ref name="NINDS">{{cite web |url=https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Creutzfeldt-Jakob-Disease-Fact-Sheet |archive-url=https://web.archive.org/web/20161223103538/https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Creutzfeldt-Jakob-Disease-Fact-Sheet |url-status=dead |archive-date=December 23, 2016 |title=Creutzfeldt-Jakob Disease Fact Sheet |author=<!--Not stated--> |publisher=National Institute of Neurological Disorders and Stroke |access-date=21 November 2018 }}</ref><ref name="auto">{{cite journal | vauthors = Geschwind MD | title = Prion Diseases | journal = Continuum | volume = 21 | issue = 6 Neuroinfectious Disease | pages = 1612–1638 | date = December 2015 | pmid = 26633779 | pmc = 4879966 | doi = 10.1212/CON.0000000000000251 }}</ref> The classic form includes sporadic and hereditary forms.<ref>{{cite web |title=About CJD {{!}} Creutzfeldt-Jakob Disease, Classic (CJD) |url=https://www.cdc.gov/prions/cjd/about.html |website=CDC |access-date=21 November 2018 |language=en-us |date=2 October 2018}}</ref> Sporadic CJD is the most common type.<ref name="auto"/>

ICD-10 has no separate code for vCJD and such cases are reported under the Creutzfeldt–Jakob disease code (A81.0).<ref>{{cite web |url=http://apps.who.int/classifications/icd10/browse/2016/en#/A81.0 |title=International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10)-WHO Version for 2016 — A81.0 |author=<!--Not stated--> |date=2016 |publisher=World Health Organization |access-date=21 November 2018 }}</ref>

==Epidemiology== thumb|upright=1.5|Dark green areas are countries that have confirmed human cases of variant Creutzfeldt–Jakob disease and light green are countries that have bovine spongiform encephalopathy cases ''The Lancet'' in 2006 suggested that it may take more than 50 years for vCJD to develop, from their studies of kuru, a similar disease in Papua New Guinea.<ref name="titleForbes.com"/> The reasoning behind the claim is that kuru was possibly transmitted through cannibalism in Papua New Guinea when family members would eat the body of a dead relative as a sign of mourning. In the 1950s, cannibalism was banned in Papua New Guinea.<ref name="Diamond">{{cite journal | vauthors = Diamond JM | title = Talk of cannibalism | journal = Nature | volume = 407 | issue = 6800 | pages = 25–26 | date = September 2000 | pmid = 10993054 | doi = 10.1038/35024175 | s2cid = 36954017 }} </ref> In the late 20th century, however, kuru reached epidemic proportions in certain Papua New Guinean communities, therefore suggesting that vCJD may also have a similar incubation period of 20 to 50 years. A critique to this theory is that while mortuary cannibalism was banned in Papua New Guinea in the 1950s, that does not necessarily mean that the practice ended. Fifteen years later Jared Diamond was informed by Papuans that the practice continued.<ref name="Diamond"/>

These researchers noticed a genetic variation<ref>{{cite web |url=https://www.livescience.com/51191-cannibalism-prions-brain-disease.html |title=Eating Brains: Cannibal Tribe Evolved Resistance to Fatal Disease |date=June 12, 2015| vauthors = Rettner R |publisher=LiveScience |access-date=April 9, 2022}}</ref> in some people with kuru that has been known to promote long incubation periods. They have also proposed that individuals having contracted CJD in the early 1990s represent a distinct genetic subpopulation, with unusually short incubation periods for bovine spongiform encephalopathy (BSE). This means that there may be many more people with vCJD with longer incubation periods, which may surface many years later.<ref name="titleForbes.com">{{cite journal | vauthors = Collinge J, Whitfield J, McKintosh E, Beck J, Mead S, Thomas DJ, Alpers MP | title = Kuru in the 21st century--an acquired human prion disease with very long incubation periods | journal = Lancet | volume = 367 | issue = 9528 | pages = 2068–2074 | date = June 2006 | pmid = 16798390 | doi = 10.1016/S0140-6736(06)68930-7 | s2cid = 11506094 }}</ref>

Prion protein is detectable in lymphoid and appendix tissue up to two years before the onset of neurological symptoms in vCJD. Large scale studies in the UK have yielded an estimated prevalence of 493 per million, higher than the actual number of reported cases. This finding indicates a large number of asymptomatic cases and the need to monitor.<ref>{{cite journal | vauthors = Diack AB, Head MW, McCutcheon S, Boyle A, Knight R, Ironside JW, Manson JC, Will RG | display-authors = 6 | title = Variant CJD. 18 years of research and surveillance | journal = Prion | volume = 8 | issue = 4 | pages = 286–295 | date = 1 November 2014 | pmid = 25495404 | pmc = 4601215 | doi = 10.4161/pri.29237 }}</ref>

==Society and culture== ===United Kingdom=== thumb|upright=1.3|Deaths in the UK from Creutzfeldt–Jakob disease 1990–2014: while cases of vCJD have declined (green), reported cases of sporadic CJD continue to increase (blue) The first human death from vCJD occurred in the United Kingdom; Wiltshire teenager Stephen Churchill died on 23 May 1995, aged 19.<ref name="ChurchillIndependant">{{cite news |last=Arthur |first=Charles |date=19 March 1997 |title=Agonising decline that led to first diagnosis of new illness |url=https://www.independent.co.uk/news/agonising-decline-that-led-to-first-diagnosis-of-new-illness-1273689.html |work=The Independent |location= |access-date=16 June 2023}}</ref><ref name="ChurchillMedium">{{cite news |last=Wells |first=Chloe |date=Jan 16, 2022 |title=The 'Mad Cow Disease' Scandal |url=https://chloewells.medium.com/the-mad-cow-disease-scandal-8d1665af2dc9 |work=Medium |location= |access-date=Jun 16, 2023}}</ref> Researchers believe one in 2,000 people in the UK is a carrier of the disease, linked to eating contaminated beef.<ref>{{cite news | url=https://www.bbc.co.uk/news/health-24525584 | work=BBC News | title=Estimate doubled for vCJD carriers in UK | date=2013-10-15 | url-status=live | archive-url=https://web.archive.org/web/20140210114617/http://www.bbc.co.uk/news/health-24525584 | archive-date=2014-02-10 }}</ref> The survey provides the most robust prevalence measure to date—and identifies abnormal prion protein across a wider age group than found previously and in all genotypes, indicating "infection" may be relatively common. This new study examined over 32,000 anonymous appendix samples. Of these, 16 samples were positive for abnormal prion protein, indicating an overall prevalence of 493 per million population, or one in 2,000 people are likely to be carriers. No difference was seen in different birth cohorts (1941–1960 and 1961–1985), in both sexes, and there was no apparent difference in abnormal prion prevalence in three broad geographical areas. Genetic testing of the 16 positive samples revealed a higher proportion of valine homozygous (VV) genotype on the codon 129 of the gene encoding the prion protein (PRNP) compared with the general UK population. This also differs from the 176 people with vCJD, all of whom to date have been methionine homozygous (MM) genotype. The concern is that individuals with this VV genotype may be susceptible to developing the condition over longer incubation periods.<ref>{{cite journal | vauthors = Gill ON, Spencer Y, Richard-Loendt A, Kelly C, Dabaghian R, Boyes L, Linehan J, Simmons M, Webb P, Bellerby P, Andrews N, Hilton DA, Ironside JW, Beck J, Poulter M, Mead S, Brandner S | display-authors = 6 | title = Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey | journal = BMJ | volume = 347 | article-number = f5675 | date = October 2013 | pmid = 24129059 | pmc = 3805509 | doi = 10.1136/bmj.f5675 }}</ref>

===Human BSE Foundation=== thumb|Commemorative plaque in London paying tribute to people who died from vCJD In 2000 a voluntary support group was formed by families of people who had died from vCJD. The goal was to support other families going through a similar experience. This support was provided through a National Helpline, a Carer's Guide, a website and a network of family befriending. The support groups had an internet presence at the turn of the 21st century. The driving force behind the foundation was Lester Firkins, whose young son had died from the disease.<ref name="Oliver2009Lester">{{cite web|title= Pioneer profile: Lester Firkin |url= https://discovery.ucl.ac.uk/id/eprint/10005145/1/Oliver2009Lester1.pdf |website= The Patient - Patient-Centered Outcomes Research| access-date= 27 May 2020|language= en-uk|date= 2009-03-01}}</ref><ref name="AffiliatesNewsletter">{{cite web |title= James Lind Alliance Affiliates Newsletter |url= http://www.jla.nihr.ac.uk/news-and-publications/downloads/Newsletters/JLA-Newsletter-2012-January.pdf |website= James Lind Alliance |access-date= 27 May 2020 |language= en-uk |date= 2012-01-01 |archive-date= 2020-03-31 |archive-url= https://web.archive.org/web/20200331133605/http://www.jla.nihr.ac.uk/news-and-publications/downloads/Newsletters/JLA-Newsletter-2012-January.pdf |url-status= dead }}</ref>

In October 2000 the report of the government inquiry into BSE chaired by Lord Phillips was published.<ref name="chairedbyPhillips">{{cite news |author=<!--Staff writer(s); no by-line.--> |title= BSE crisis: Timeline |url= https://www.theguardian.com/uk/2000/oct/26/bse3#maincontent |work= The Guardian|location= London |date= 2019-10-26|access-date= 2020-05-27}}</ref> The BSE report criticised former Conservative Party Agriculture Ministers John Gummer, John MacGregor and Douglas Hogg.<ref>{{cite journal | vauthors = | title = From nannyism to public disclosure: the BSE inquiry report | journal = CMAJ | volume = 164 | issue = 2 | pages = 165, 167 | date = January 2001 | pmid = 11332300 | pmc = 80663 }}</ref> The report concluded that the escalation of BSE into a crisis was the result of intensive farming, particularly with cows being fed with cow and sheep remains. Furthermore, the report was critical of the way the crisis had been handled.<ref name="ReportConclusions">{{cite web|title= BSE outbreak: inquiry report|url= https://navigator.health.org.uk/theme/bse-outbreak-inquiry-report|website= The Health Foundation|access-date=4 February 2025|language= en-uk|date=1 October 2000}}</ref> There was a reluctance to consider the possibility that BSE could cross the species barrier. The government assured the public that British beef was safe to eat, with agriculture minister John Gummer famously feeding his daughter a burger. The British government were reactive more than proactive in response; the worldwide ban on all British beef exports in March 1996 was a serious economic blow.<ref name="tardyGovact">{{cite news | vauthors = Ainsworth C, Carrington D |title= BSE disaster: the history |url= https://www.newscientist.com/article/dn91-bse-disaster-the-history/ |work= New Scientist|location= London |date= 2019-10-25|access-date= 2020-05-27}}</ref>

The foundation had been calling for compensation to include a care package to help relatives look after those with vCJD. There have been widespread complaints of inadequate health and social services support.<ref name="BSEInquiry">{{cite news|title=BSE victims to get millions|url= https://www.theguardian.com/uk/2000/oct/22/bse.foodanddrink |newspaper=The Guardian |access-date=27 May 2020|date=22 October 2000}}</ref> Following the Phillips Report in October 2001, the government announced a compensation scheme for British people affected with vCJD. The multi-million-pound financial package was overseen by the vCJD Trust.

A memorial plaque for those who have died due to vCJD was installed in central London in approximately 2000.<ref>{{cite news |date=October 2016 |title=CREUTZFELDT-JAKOB DISEASE SUPPORT NETWORK NEWSLETTER |page=3 |work=CJD Support Network |url=https://www.cjdsupport.net/images/CJDSN_News_October_2016_online.pdf}}</ref> It is located on the boundary wall of St Thomas' Hospital in Lambeth facing the Riverside Walk of Albert Embankment.<ref name="location">{{cite web|title= memorial should be moved from listed wall, say Lambeth planners |url= https://www.london-se1.co.uk/news/view/8615 | website= London SE1 community website| access-date= 27 May 2020| language= en-uk| date= 23 January 2016}}</ref> {{-}}

== See also == * Jonathan Simms (1984–2011), a Northern Irish young man with vCJD who survived for 10 years after symptom onset and received experimental treatment with pentosan polysulfate, one of the longest survivals reported for the disease.<ref>{{Cite news|url=https://www.bbc.co.uk/news/uk-northern-ireland-12667709|title=Belfast man with VCJD dies after long battle|work=BBC News|date=7 March 2011}}</ref><ref>{{cite journal |last=Newman |first=PK |last2=Todd |first2=NV |last3=Scoones |first3=D |last4=Mead |first4=S |last5=Knight |first5=RSG |last6=Will |first6=RG |last7=Ironside |first7=JW |title=Postmortem findings in a case of variant Creutzfeldt–Jakob disease treated with intraventricular pentosan polysulfate |journal=Journal of Neurology, Neurosurgery, and Psychiatry |year=2014 |volume=85 |issue=8 |pages=921–924 |doi=10.1136/jnnp-2013-305590 |pmid=24554103 |pmc=4112497 }}</ref> * Mepacrine, a medication shown ''in vitro'' to bind to the prion protein (PrP) and to prevent the formation of protein aggregates, but which failed to demonstrate efficacy in clinical trials for CJD conducted in the 2000s and 2010s.

== References == {{Reflist}}

== External links == {{Commons}} {{Medical resources|Orphanet=576370|ICD10={{ICD10|A81.0}}|ICD11={{ICD11|8E01.2}}}}{{Prion diseases}} {{DEFAULTSORT:Variant Creutzfeldt-Jakob disease}} Category:Diseases named after discoverers Category:Foodborne illnesses Category:Rare diseases Category:Transmissible spongiform encephalopathies Category:Wikipedia medicine articles ready to translate Category:Zoonoses