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'''Bovine spongiform encephalopathy''' ('''BSE'''), commonly known as '''[[Mad cow crisis|mad cow disease]]''', is an incurable and invariably fatal [[neurodegenerative disease]] of [[cattle]].<ref name=WHO2002/> Symptoms include abnormal behavior, trouble walking, and weight loss.<ref name=Cas2018/> Later in the course of the disease, the cow becomes unable to function normally.<ref name=Cas2018/> There is conflicting information about the [[incubation period|time between infection and onset of symptoms]]. In 2002, the [[World Health Organization]]
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BSE is thought to be due to an infection by a misfolded protein, known as a [[prion]].<ref name=CDC2018Ab/><ref name=FDA2018>{{cite web |title=Bovine Spongiform Encephalopathy (BSE) Questions and Answers |url=https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/bovine-spongiform-encephalopathy-bse-questions-and-answers |website=FDA |access-date=16 June 2019 |language=en |date=22 May 2019}}</ref> Cattle are believed to have been infected by being fed [[meat-and-bone meal]]
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Four cases were reported globally in 2017, and the condition is considered to be nearly eradicated.<ref name=Cas2018/> In the [[United Kingdom]]
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==Signs==
[[File:Bse-cattle-250.jpg|thumb|upright=1.3|This cow with BSE displays abnormal posturing and weight loss.]]
Signs are not seen immediately in cattle, due to the disease's extremely long incubation period.<ref>{{Cite web|url=http://www.afrivip.org/sites/default/files/bse_complete.pdf|title=Bovine Spongiform Encephalopathy (BSE)| vauthors = Thomson G |access-date=21 November 2016}}</ref> Some cattle have been observed to have an abnormal gait, changes in behavior, tremors and hyper-responsiveness to certain stimuli.<ref name=":0">{{Cite web|url=http://www.cfsph.iastate.edu/Factsheets/pdfs/bovine_spongiform_encephalopathy.pdf|title=Bovine Spongiform Encephalopathy | date=August 2016|website=The Center for Food Security & Public Health|access-date=30 October 2016}}</ref> Hindlimb [[ataxia]] affects the animal's gait and occurs when muscle control is lost. This results in poor balance and coordination.<ref>{{Cite web|url=http://www.ninds.nih.gov/disorders/ataxia/ataxia.htm|title=Ataxias and Cerebellar or Spinocerebellar Degeneration Information Page: National Institute of Neurological Disorders and Stroke (NINDS)|website=www.ninds.nih.gov|access-date=2016-12-01|archive-date=9 February 2015|archive-url=https://web.archive.org/web/20150209002034/http://www.ninds.nih.gov/disorders/ataxia/ataxia.htm|url-status=dead}}</ref> Behavioural changes may include aggression, anxiety relating to certain situations, nervousness, frenzy and an overall change in temperament. Some rare but previously observed signs also include persistent pacing, rubbing and licking. Additionally, nonspecific signs have also been observed which include weight loss, decreased milk production, lameness, ear infections and teeth grinding due to pain. Some animals may show a combination of these signs, while others may only be observed demonstrating one of the many reported. Once clinical signs arise, they typically get worse over the subsequent weeks and months, eventually leading to [[recumbency]], coma and death.<ref name=":0" />
== Cause ==
BSE is an infectious disease believed to be due to a misfolded protein, known as a [[prion]].<ref name=CDC2018Ab/><ref name=FDA2018/> Cattle are believed to have been infected from being fed [[meat and bone meal]]
BSE prions are misfolded forms of the particular brain protein called [[PRNP|prion protein]]. When this protein is misfolded, the normal [[Alpha helix|alpha-helical]] structure is converted into a [[beta sheet]]. The prion induces normally-folded proteins to take on the misfolded phenotype in an exponential cascade. These sheets form small chains which aggregate and cause cell death. Massive cell death forms lesions in the brain which lead to degeneration of physical and mental abilities and ultimately death.<ref>{{cite journal | vauthors = Orge L, Lima C, Machado C, Tavares P, Mendonça P, Carvalho P, Silva J, Pinto ML, Bastos E, Pereira JC, Gonçalves-Anjo N, Gama A, Esteves A, Alves A, Matos AC, Seixas F, Silva F, Pires I, Figueira L, Vieira-Pinto M, Sargo R, Pires MD | display-authors = 6 | title = Neuropathology of Animal Prion Diseases | journal = Biomolecules | volume = 11 | issue = 3 | pages = 466 | date = March 2021 | pmid = 33801117 | pmc = 8004141 | doi = 10.3390/biom11030466 | doi-access = free }}</ref> The prion is not destroyed even if the beef or material containing it is cooked or heat-treated under normal conditions and pressures.<ref name="TSE">{{cite web |title=Bovine Spongiform Encephalopaphy: An Overview |url=http://www.aphis.usda.gov/publications/animal_health/content/printable_version/BSEbrochure12-2006.pdf |access-date=8 April 2008 |date=December 2006 |publisher=[[Animal and Plant Health Inspection Service]], [[United States Department of Agriculture]] |url-status=dead |archive-url=https://web.archive.org/web/20080308030306/http://www.aphis.usda.gov/publications/animal_health/content/printable_version/BSEbrochure12-2006.pdf |archive-date=8 March 2008 |df=dmy }}</ref> Transmission can occur when healthy animals come in contact with tainted tissues from others with the disease, generally when their food source contains tainted meat.<ref name="WHO2002" />
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The tests used for detecting BSE vary considerably, as do the regulations in various jurisdictions for when, and which cattle, must be tested. For instance in the EU, the cattle tested are older (30 months or older), while many cattle are slaughtered younger than that. At the opposite end of the scale, Japan tests all cattle at the time of slaughter. Tests are also difficult, as the altered prion protein has very low levels in blood or urine, and no other signal has been found. Newer tests{{specify|date=July 2016}} are faster, more sensitive, and cheaper, so future figures possibly may be more comprehensive. Even so, currently the only reliable test is examination of tissues during a [[necropsy]].{{citation needed|date=December 2020}}
As for vCJD in humans, autopsy tests are not always done, so those figures, too, are likely to be too low, but probably by a lesser fraction. In the United Kingdom, anyone with possible vCJD symptoms must be reported to the Creutzfeldt–Jakob Disease Surveillance Unit. In the United States, the [[Centers for Disease Control and Prevention|CDC]] has refused to impose a national requirement that physicians and hospitals report cases of the disease. Instead, the agency relies on other methods, including death certificates and urging physicians to send suspicious cases to the National Prion Disease Pathology Surveillance Center
To control potential transmission of vCJD within the United States, the FDA had established strict restrictions on individuals' eligibility to donate blood. Individuals who had spent a cumulative time of three months or more in the United Kingdom between 1980 and 1996, or a cumulative time of five years or more from 1980 to 2020 in any combination of countries in Europe, were prohibited from [[Blood donation|donating blood]].<ref>[http://www.redcrossblood.org/donating-blood/eligibility-requirements/eligibility-criteria-alphabetical-listing#arc5 Eligibility Criteria for Blood Donation], American Red Cross</ref> Due to blood shortages associated with the [[COVID-19 pandemic|2020 COVID-19 outbreak]] these restrictions were temporarily rescinded in 2020.<ref>[https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-provides-updated-guidance-address-urgent-need-blood-during-pandemic FDA Provides Updated Guidance Addressing Urgent Need For Blood During The Pandemic], Food and Drug Administration</ref> This recommendation was removed in 2022.<ref>{{Cite web |last=Research |first=Center for Biologics Evaluation and |date=2022-05-24 |title=Recommendations to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease by Blood and Blood Components |url=https://www.fda.gov/regulatory-information/search-fda-guidance-documents/recommendations-reduce-possible-risk-transmission-creutzfeldt-jakob-disease-and-variant-creutzfeldt |access-date=2023-04-01 |website=U.S. Food and Drug Administration |language=en}}</ref>
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The use of animal by-product feeds was never common, as it was in Europe.{{verify source|date=July 2022}} Soybean meal is cheap and plentiful in the [[United States]], and cottonseed meal (1.5 million tons of which are produced in the US every year, none of which is suitable for humans or any other simple-stomach animals) is even cheaper than soybean meal. Historically, meat and bone meal, blood meal, and meat scraps have almost always commanded a higher price as a feed additive than oilseed meals in the US, so little incentive existed to use animal products to feed ruminants. However, US regulations only partially prohibited the use of animal by-products in feed. In 1997, regulations prohibited the feeding of mammalian by-products to [[ruminant]]s such as cattle and goats. However, the by-products of ruminants can still be legally fed to pets or other livestock, including pigs and [[poultry]]. In addition, it is legal for ruminants to be fed by-products from some of these animals.<ref>{{cite book| vauthors = Rampton S, Stauber J |title=Mad Cow USA|edition=1st|year=2004|publisher=Common Courage Press|location=Monroe, Maine|isbn=978-1-56751-110-9|url-access=registration|url=https://archive.org/details/madcowusa00shel}}</ref> Because of this, some authors have suggested that under certain conditions, it is still possible for BSE incidence to increase in U.S. cattle.<ref>{{cite journal | vauthors = Barnes R, Lehman C | title = Modeling of bovine spongiform encephalopathy in a two-species feedback loop | journal = Epidemics | volume = 5 | issue = 2 | pages = 85–91 | date = June 2013 | pmid = 23746801 | doi = 10.1016/j.epidem.2013.04.001 | arxiv = 1511.04470 | s2cid = 1185101 }}<!--|access-date=12 April 2014--></ref>
The US Department of Agriculture (USDA) announced on 19 May 2023 an atypical case of
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US meat producer [[Creekstone Farms Premium Beef|Creekstone Farms]] alleged in a lawsuit that the
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