Editing Botulism (section)

== Cause ==
[[File:Clostridium botulinum.jpg|thumb|A photomicrograph of ''[[Clostridium botulinum]]'' bacteria.]]

''[[Clostridium botulinum]]'' is an [[Anaerobic organism|anaerobic]], [[Gram-positive bacteria|Gram-positive]], spore-forming rod. [[Botulinum toxin]] is one of the most powerful known toxins: about one [[microgram]] is lethal to humans when inhaled.<ref name="Emmeluth2010">{{cite book | first = Donald | last = Emmeluth |title=Botulism|url=https://books.google.com/books?id=3fzYL6virMQC&pg=PA38|year=2010|publisher=Infobase Publishing|isbn=978-1-60413-235-9|page=38|url-status=live|archive-url=https://web.archive.org/web/20170101014327/https://books.google.com/books?id=3fzYL6virMQC&pg=PA38|archive-date=1 January 2017}}</ref> It acts by blocking [[nerve]] function ([[neuromuscular blockade]]) through inhibition of the excitatory [[neurotransmitter]] [[acetylcholine]]'s release from the [[presynaptic]] membrane of [[neuromuscular junction]]s in the [[somatic nervous system]]. This causes paralysis. Advanced botulism can cause [[respiratory failure]] by paralysing the muscles of the chest; this can progress to [[respiratory arrest]].<ref name="Arnon">{{cite journal | vauthors = Arnon SS, Schechter R, Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Fine AD, Hauer J, Layton M, Lillibridge S, Osterholm MT, O'Toole T, Parker G, Perl TM, Russell PK, Swerdlow DL, Tonat K | title = Botulinum toxin as a biological weapon: medical and public health management | journal = JAMA | volume = 285 | issue = 8 | pages = 1059–70 | date = February 2001 | pmid = 11209178 | doi = 10.1001/jama.285.8.1059 }}</ref> Furthermore, acetylcholine release from the presynaptic membranes of [[muscarinic acetylcholine receptor|muscarinic]] nerve synapses is blocked. This can lead to a variety of autonomic signs and symptoms described above.{{citation needed|date=December 2022}}

In all cases, illness is caused by the botulinum toxin which the bacterium ''C. botulinum'' produces in anaerobic conditions and not by the bacterium itself. The pattern of damage occurs because the toxin affects nerves that fire (depolarize) at a higher frequency first.<ref>''Oxford Textbook of Medicine'', 4th Ed., Section 7.55</ref>

Mechanisms of entry into the human body for botulinum toxin are described below.{{citation needed|date=December 2022}}

=== Colonization of the gut ===
The most common form in Western countries is infant botulism. This occurs in infants who are [[Colonization (biology)|colonized]] with the bacterium in the small intestine during the early stages of their lives. The bacterium then produces the toxin, which is absorbed into the bloodstream. The consumption of [[honey]] during the first year of life has been identified as a risk factor for infant botulism; it is a factor in a fifth of all cases.<ref name=Sobel2005/> The adult form of infant botulism is termed ''adult intestinal toxemia'', and is exceedingly rare.<ref name=Sobel2005/>

=== Food ===
Toxin that is produced by the bacterium in containers of food that have been improperly preserved is the most common cause of food-borne botulism. Fish that has been pickled without the salinity or acidity of brine that contains [[acetic acid]] and high [[sodium]] levels, as well as smoked fish stored at too high a temperature, presents a risk, as does improperly canned food.<ref>{{cite journal |last1=Dolman |first1=Claude E. |title=Type E (fish-borne) botulism: a review |journal=Japanese Journal of Medical Science and Biology |date=1957 |volume=10 |issue=6 |page=383-395 |doi=10.7883/yoken1952.10.383}}</ref>

Food-borne botulism results from contaminated food in which ''[[Clostridium botulinum|C. botulinum]]'' spores have been allowed to germinate in low-oxygen conditions. This typically occurs in improperly prepared home-canned food substances and fermented dishes without adequate salt or acidity.<ref>{{cite web |title=About Botulism |url=https://www.cdc.gov/botulism/about/index.html |website=CDC |access-date=5 January 2025 |language=en-us |date=16 May 2024}}</ref> Given that multiple people often consume food from the same source, it is common for more than a single person to be affected simultaneously. Symptoms usually appear 12–36 hours after eating, but can also appear within 6 hours to 10 days.<ref>{{cite web | title = Facts About Botulism | url = http://www.bt.cdc.gov/agent/botulism/factsheet.asp | work = Emergency Preparedness and Response | publisher = [[Centers for Disease Control and Prevention]] | date = 14 October 2001 | access-date = 2 July 2011 | url-status = dead | archive-url = https://web.archive.org/web/20110705125238/http://www.bt.cdc.gov/agent/botulism/factsheet.asp | archive-date = 5 July 2011 }}</ref>

No withdrawal periods have been established for cows affected by Botulism. Lactating cows injected with various doses of Botulinum toxin C have not resulted in detectable Botulinum [[neurotoxin]] in milk produced.<ref>{{Cite journal |last1=Moeller |first1=Robert B. |last2=Puschner |first2=Birgit |last3=Walker |first3=Richard L. |last4=Rocke |first4=Tonie |last5=Galey |first5=Frank D. |last6=Cullor |first6=James S. |last7=Ardans |first7=Alex A. |date=November 2003 |title=Determination of the Median Toxic Dose of Type C Botulinum Toxin in Lactating Dairy Cows |journal=Journal of Veterinary Diagnostic Investigation |volume=15 |issue=6 |pages=523–526 |doi=10.1177/104063870301500603 |pmid=14667014 |doi-access=free }}</ref> Using [[mouse bioassay]]s and [[immunostick ELISA test]]s, botulinum toxin was detected in whole blood and serum but not in milk samples, suggesting that botulinum type C toxin does not enter milk in detectable concentrations.<ref>{{Cite journal |last1=Moeller |first1=R.B. |last2=Puschner |first2=B. |last3=Walker |first3=R.L. |last4=Rocke |first4=T.E. |last5=Smith |first5=S.R. |last6=Cullor |first6=J.S. |last7=Ardans |first7=A.A. |date=June 2009 |title=Short communication: Attempts to identify Clostridium botulinum toxin in milk from three experimentally intoxicated Holstein cows |journal=Journal of Dairy Science |language=en |volume=92 |issue=6 |pages=2529–2533 |doi=10.3168/jds.2008-1919|pmid=19447984 |doi-access=free }}</ref> Cooking and pasteurization denatures botulinum toxin but does not necessarily eliminate spores. Botulinum spores or toxins can find their way into the dairy production chain from the environment.<ref>{{cite journal |last1=Lindström |first1=Miia |last2=Myllykoski |first2=Jan |last3=Sivelä |first3=Seppo |last4=Korkeala |first4=Hannu |title=Clostridium botulinum in Cattle and Dairy Products |journal=Critical Reviews in Food Science and Nutrition |date=19 March 2010 |volume=50 |issue=4 |pages=281–304 |doi=10.1080/10408390802544405 |pmid=20301016 }}</ref> Despite the low risk of milk and meat contamination, the protocol for fatal bovine botulism cases appears to be incineration of carcasses and withholding any potentially contaminated milk from human consumption. It is also advised that raw milk from affected cows should not be consumed by humans or fed to calves.<ref>{{Cite journal |last1=Frye |first1=Elisha A. |last2=Egan |first2=Christina |last3=Perry |first3=Michael J. |last4=Crouch |first4=Esther E. |last5=Burbank |first5=Kyle E. |last6=Kelly |first6=Kathleen M. |date=September 2020 |title=Outbreak of botulism type A in dairy cows detected by MALDI-TOF mass spectrometry |journal=Journal of Veterinary Diagnostic Investigation |volume=32 |issue=5 |pages=722–726 |doi=10.1177/1040638720943127 |pmid=32715936 |pmc=7488966 }}</ref>

There have been several reports of botulism from [[pruno]] wine made of food scraps in prison.<ref>{{cite journal |last1=Adams |first1=Laura E. |last2=Yasmin |first2=Seema |last3=Briggs |first3=Graham |last4=Redden |first4=Kore |last5=Silvas |first5=Suzanne |last6=Anderson |first6=Shoana |last7=Weiss |first7=Joli |last8=Tsang |first8=Clarisse A. |last9=Henke |first9=Evan |last10=Francies |first10=Jessica |last11=Herrick |first11=Kristen |last12=Lira |first12=Rosa |last13=Livar |first13=Eugene |last14=Thompson |first14=Gerald |last15=Sunenshine |first15=Rebecca |last16=Robinson |first16=Byron F. |last17=Bisgard |first17=Kristine M. |last18=Komatsu |first18=Kenneth K. |title=Alcohol Production, Prevention Strategies, and Inmate Knowledge About the Risk for Botulism From Pruno Consumption in a Correctional Facility—Arizona, 2013 |journal=Journal of Correctional Health Care |date=October 2015 |volume=21 |issue=4 |pages=335–342 |doi=10.1177/1078345815599763 |pmid=26285594 |pmc=5549268 }}</ref><ref>{{cite journal |last1=Williams |first1=Benjamin T. |last2=Schlein |first2=Sarah M. |last3=Caravati |first3=E. Martin |last4=Ledyard |first4=Holly |last5=Fix |first5=Megan L. |title=Emergency Department Identification and Critical Care Management of a Utah Prison Botulism Outbreak |journal=Annals of Emergency Medicine |date=July 2014 |volume=64 |issue=1 |pages=26–31 |doi=10.1016/j.annemergmed.2013.10.027 |pmid=24331717 }}</ref><ref>{{cite journal |last1=Rao |first1=Agam K. |last2=Walters |first2=Maroya |last3=Hall |first3=Julia |last4=Guymon |first4=Colleen |last5=Garden |first5=Richard |last6=Sturdy |first6=Pauline |last7=Thurston |first7=Diana |last8=Smith |first8=Lori |last9=Dimond |first9=Melissa |last10=Vitek |first10=Dagmar |last11=Bogdanow |first11=Linda |last12=Hill |first12=Mary |last13=Lin |first13=Neal H. |last14=Luquez |first14=Carolina |last15=Griffin |first15=Patricia M. |title=Outbreak of Botulism Due to Illicit Prison-Brewed Alcohol: Public Health Response to a Serious and Recurrent Problem |journal=Clinical Infectious Diseases |date=2018 |volume=66 |issue=suppl_1 |pages=S85–S91 |doi=10.1093/cid/cix936 |jstor=26524925 |pmid=29293937 |doi-access=free }}</ref> In a Mississippi prison in 2016, prisoners illegally brewed alcohol that led to 31 cases of botulism. The research study done on these cases found the symptoms of mild botulism matched the symptoms severe botulism though the outcomes and progression of the disease were different.<ref>{{cite journal |last1=Marlow |first1=Mariel |last2=Edwards |first2=Leslie |last3=McCrickard |first3=Lindsey |last4=Francois Watkins |first4=Louise K. |last5=Anderson |first5=Jannifer |last6=Hand |first6=Sheryl |last7=Taylor |first7=Kathryn |last8=Dykes |first8=Janet |last9=Byers |first9=Paul |last10=Chatham-Stephens |first10=Kevin |title=Mild Botulism From Illicitly Brewed Alcohol in a Large Prison Outbreak in Mississippi |journal=Frontiers in Public Health |date=24 August 2021 |volume=9 |doi=10.3389/fpubh.2021.716615 |doi-access=free |pmid=34504830 |pmc=8421542 }}</ref>

=== Wound ===
Wound botulism results from the contamination of a wound with the bacteria, which then secrete the toxin into the bloodstream. This has become more common in [[Intravenous drug use (recreational)|intravenous drug users]] since the 1990s, especially people using [[black tar heroin]] and those [[skin popping|injecting heroin into the skin]] rather than the veins.<ref name=Sobel2005/> Wound botulism can also come from a minor wound that is not properly cleaned out; the skin grows over the wound thus trapping the spore in an anaerobic environment and creating botulism. One example was a person who cut their ankle while using a weed eater; as the wound healed over, it trapped a blade of grass and spec of soil under the skin that led to severe botulism requiring hospitalization and rehabilitation for months. Wound botulism accounts for 29% of cases.{{citation needed|date=December 2022}}

=== Inhalation ===
Isolated cases of botulism have been described after [[inhalation]] by laboratory workers.<ref>{{cite web | url= https://www.lecturio.com/concepts/botulism/ | title= Botulism | website= The Lecturio Medical Concept Library | access-date= 5 July 2021 | archive-date= 9 July 2021 | archive-url= https://web.archive.org/web/20210709190757/https://www.lecturio.com/concepts/botulism/ | url-status= live }}</ref>

=== Injection (iatrogenic botulism) ===

Symptoms of botulism may occur away from the injection site of [[botulinum toxin]].<ref name=Product2019/> This may include loss of strength, blurred vision, change of voice, or trouble breathing which can result in death.<ref name=Product2019/> Onset can be hours to weeks after an injection.<ref name=Product2019>{{cite web |title=Botox |url=https://media.allergan.com/actavis/actavis/media/allergan-pdf-documents/product-prescribing/20190620-BOTOX-100-and-200-Units-v3-0USPI1145-v2-0MG1145.pdf |access-date=6 December 2019 |archive-date=5 December 2019 |archive-url=https://web.archive.org/web/20191205180954/https://media.allergan.com/actavis/actavis/media/allergan-pdf-documents/product-prescribing/20190620-BOTOX-100-and-200-Units-v3-0USPI1145-v2-0MG1145.pdf |url-status=live }}</ref> This generally only occurs with inappropriate strengths of botulinum toxin for cosmetic use or due to the larger doses used to treat movement disorders.<ref name=Sobel2005/> However, there are cases where an off-label use of botulinum toxin resulted in severe botulism and death.<ref>{{cite journal |last1=You |first1=Geoffrey |last2=Khan |first2=Ahmed |last3=Shor |first3=Julia |last4=Forester |first4=Gary P. |title=Rapidly Progressive Muscle Paralysis and Acute Respiratory Failure Following Endoscopic Botulinum Toxin Injection |journal=ACG Case Reports Journal |date=2016 |volume=3 |issue=1 |pages=e166 |doi=10.14309/crj.2016.139 |pmid=27921065 |pmc=5126502 }}</ref> Following a 2008 review the FDA added these concerns as a [[boxed warning]].<ref>{{cite web |title=Update of Safety Review of OnabotulinumtoxinA (marketed as Botox/Botox Cosmetic), AbobotulinumtoxinA (marketed as Dysport) and RimabotulinumtoxinB (marketed as Myobloc) |website=[[Food and Drug Administration]] |url=https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm174959.htm |access-date=29 December 2019 |date=15 November 2017|archive-url=https://web.archive.org/web/20171115034159/https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm174959.htm |archive-date=15 November 2017 }}</ref> An international grassroots effort led by NeverTox to assemble the people experiencing Iatrogenic Botulism Poisoning (IBP) and provide education and emotional support serves 39,000 people through a Facebook group who are suffering from adverse events from botulinum toxin injections.<ref>{{cite web | url=https://www.toxsafety.com/resources | title=Resources }}</ref>
=== Lawsuits about botulism against pharmaceuticals ===
Prior to the boxed warning labels that included a disclaimer that botulinum toxin injections could cause botulism, there were a series of lawsuits against the pharmaceutical firms that manufactured injectable botulinum toxin. A Hollywood producer's wife brought a lawsuit after experiencing debilitating adverse events from migraine treatment.<ref>{{cite web | url=https://www.vanityfair.com/style/2003/05/celebrity-dermatologist-200305 | title=The Botoxed and the Boldfaced | website=[[Vanity Fair (magazine)|Vanity Fair]] | date=May 2003 }}</ref> A lawsuit on behalf of a 3-year-old boy who was permanently disabled by a botulinum toxin injection was settled in court during the trial.<ref>{{cite web | url=https://www.biospace.com/allergan-inc-settles-oklahoma-botox-case-during-trial | title=Allergan Inc. Settles Oklahoma Botox Case During Trial | date=27 February 2013 }}</ref> The family of a 7-year-old boy treated with botulinum toxin injections for leg spasms sued after the boy almost died.<ref>{{cite web | url=http://www.burlingtonfreepress.com/story/news/local/2014/11/22/couple-says-botox-almost-killed-boy/19365363/ | title=NY couple: Son almost died from Botox treatment }}</ref> Several families of people who died after treatments with botulinum toxin injections brought lawsuits.<ref>{{Cite web|url=https://www.findlaw.com/legalblogs/personal-injury/botox-death-suit-reaches-settlement/|title=Botox Death Suit Reaches Settlement|first=Aleksandr|last=Mashnitski|date=20 September 2010|website=FindLaw}}</ref><ref>{{cite web|url=https://www.reuters.com/article/us-allergan-botox-trial/allergan-wins-new-trial-in-big-botox-damages%20case-idUSBRE85019Y20120601/|title=Allergan wins new trial in big Botox damages case}}</ref><ref>{{cite web | url=https://www.burlingtonfreepress.com/story/news/local/2015/04/14/second-vermont-botox-lawsuit/25737279/ | title=Second Botox lawsuit filed in Vermont }}</ref><ref>{{cite web | url=https://abcnews.go.com/Health/Wellness/botox-led-daughters-death-mother-claims/story?id=9680014 | title=Could Alleged Botox Death Scare Patients? | website=[[ABC News (United States)|ABC News]] }}</ref> One lawsuit prevailed for the plaintiff who was awarded compensation of $18 million; the plaintiff was a physician who was diagnosed with botulism by thirteen neurologists at the NIH.<ref>{{cite web | url=https://kfor.com/news/health/investigation-allergan-botox/ | title=INVESTIGATION: What many don't know about popular wrinkle drug | date=4 May 2013 }}</ref> Deposition video from that lawsuit quotes a pharmaceutical executive stating that "Botox doesn't cause botulism."<ref>{{cite web | url=https://www.youtube.com/watch?v=e8wfajAovto&t=212s | title=16x9 - Worry Lines: Botox investigation | website=[[YouTube]] | date=25 August 2012 }}</ref>