What is Botulism?

Key Facts:
  • Human botulism is a potentially fatal condition caused by a neurotoxin secreted by the Gram negative bacterium, Clostridium botulinum.
  • C.botulinum grows well in low-oxygen environments and is found naturally in soil. Create spores that can remain dormant for 30 years or more. Figure 1.
  • The botulinum toxin is one of the most lethal biological substances in the world and may cause complete respiratory and muscular paralysis by blocking nerve transmission.[1] Figure 2, Figure 3 Video
  • Botulism can be classified as both a disease (involving live bacterium) or as intoxication (poisoning by pre-formed or purified toxin protein). The three main categories of botulism transmission are described below (Figure 4.)
    • Foodborne botulism occurs when a person ingests pre-formed toxin that leads to illness within a few hours to days. Foodborne botulism is a public health emergency because the contaminated food may still be available to other persons besides the patient.I
    • Infant botulism occurs in a small number of susceptible infants each year who harbor live C. botulinum in their intestinal tract.
    • Wound botulism occurs when wounds are infected with C. botulinum that secretes the toxin.[2]
  • With foodborne botulism, symptoms begin within 6 hours to 10 days (most commonly between 12 and 36 hours) after eating food that contains the toxin. Symptoms of botulism include double vision, blurred vision, drooping eyelids, slurred speech, difficulty swallowing, dry mouth, and muscle weakness that moves down the body, usually affecting the shoulders first, then the upper arms, lower arms, thighs, calves, etc. Paralysis of breathing muscles can cause a person to stop breathing and die, unless assistance with breathing (mechanical ventilation) is provided.[3]

Figure 1: Image of C. botulinum showing the thick endospores that may survive intense heat treatments. (Image Source: http://www.cfs.gov.hk/english/multimedia/multimedia_pub/multimedia_pub_fsf_86_01.html)
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Scanning electron micrographs of C. botulinum. (Image Source: http://www.foodsafetycounsel.com/food-safety-law/common-food-borne-pathogens/clostridium-botulinum/)
Scanning electron micrographs of C. botulinum. (Image Source: http://www.foodsafetycounsel.com/food-safety-law/common-food-borne-pathogens/clostridium-botulinum/)

Figure 2: The illustration below depicts the mechanism of botulism neurotoxin. The toxin blocks release of the neurotransmitter, acetyl-choline, at the neuro-muscular junction. (Image Source: http://protoplasmix.files.wordpress.com/2012/05/picture-12.png)

Botulin mechanism
(Image Source: http://protoplasmix.files.wordpress.com/2012/05/picture-12.png)

Figure 3: Video clips of neurotoxin mechanism. The first version is the advanced version; The second version is simplified.

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Figure 4: The image to the left illustrates the incidence of each category of botulism cases worldwide. (Image source: http://www.thekitchn.com/how-not-to-die-from-botulism-193426

History of Botulism

  • 1735: The first recorded history of botulism began when the disease was first associated with the consumption of sausage.[4]
  • 1817: German physician and poet Justinus Kerner (1786—1862) developed the idea of a possible therapeutic use for the toxin in cases of "hypersalivation and hyperhidrosis (salivation). [5]
  • I870: John Muller, a German physician, derived the name botulism from the Latin word for sausage.[6]
  • 1895: the bacterium is first isolated in laboratory after a severe outbreak in Germany.
  • 1919: U.S. mounts campaign on proper canning procedures after outbreak in California from olive consumption. [7]
  • 1930: The head of the Japanese biological warfare group admitted to feeding cultures of C. botulinum to prisoners with lethal effect during that country’s occupation of Manchuria.
  • 1949: Arnold Burgen's group discovered, through an elegant experiment, that botulinum toxin blocks neuromuscular transmission through decreased acetylcholine release. [8]
  • 1980: Alan Scott, MD, officially used Botox-A serotoxin for the first time in humans to treat "crossed eyes" (strabismus) and blepharospasms, (Figure 5)
  • 1989: Dr. Richard Clark, with FDA approval, used Botulism Toxin A for cosmetic use for facial creases. (Figure 6)
  • 1991: Iraq admitted to the United Nations inspection team to having produced 19000 L of concentrated botulinum toxin, of which approximately 10000 L were loaded into military weapons.
  • 1995: Japanese cult leader Aum Shinrikyo tried to use botulinum toxin as a weapon on a Tokyo subway; most recent use of botox toxin outside of routine medical/cosmetic application. [9] Figure 7

external image what-is-botox-how-does-botox-work-blepharospasm.jpg?w=534&h=224

Figure 5: Woman treated for severe blepharo-paralysis. (Image Source: malaghadotcom.files.wordpress.com)

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Figure 6: Woman treated for facial wrinkles using Botulinum-toxin A. (Image source: http://www.themartincenter.com/wordpress/wp-content/uploads/2013/02/xeomin_before_after_1.png)

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Figure 7: Most current known attempted use of Botulinum toxin as weapon of terror, 1995 subway incident in Japan. (Image source: http://www.au.af.mil/au/awc/awcgate/cpc-conf2000/post/sld016.htm).

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Image Source: http://www.nytimes.com/1982/04/28/garden/the-history-of-botulism.html>

Botulinum Toxin as a Biological Weapon

  • What is botulism toxin?
    • It is a purified protein neurotoxin derived from C. botulinum derived naturally from the soil.
    • The American Medical Association states the lethal inhalation dose is approximately 0.7-0.9 μg (that's billionths of a gram!!)
  • Why is botulinum toxin considered a bioterrorism threat?
    • Botulinum toxin is extremely potent, easy to isolate from soil, easy to manufacture and transport, as well as being colorless, odorless, and tasteless when in solution.
    • Botulinum intoxication requires prolonged care, which is unfeasible in a surprise attack.
  • What is its immediate mode of action?
    • Blocking neurotransmission; paralysis of muscles; most death attributed to suffocation due to paralysis of diaphragm.
  • How could botulinum toxin be used as a bioweapon?
    • Botulinum toxin could be released as an aerosol or as a food-borne contaminent via a "bomb." Inhalation is most effective route.
    • Man-made purified protein (does not occur naturally), utilizes aerosolized Botulinum toxin
      May involve freeze-drying and milling the toxin into an extremely fine powder. [9, 11]
    • Absorption of toxin through mucosal surface in the lung.
    • Gene splicing experiments in Russia involved creation of BoNT (botox neurotoxin) "superbug" that has potential of rapid reproduction in human tissue.
    • It’s unlikely botulinum toxin would be used to contaminate municipal water supplies because it
      would require large amounts of toxin, and standard water treatments inactivate the toxin anyway [9]
  • How would we know if botulinum toxin has been deliberately released?
    • According to the American Medical Association, the following features would indicate a
      deliberate release of botulinum toxin:
      • Outbreak of cases of paralysis characteristic of botulinum toxin (i.e., flaccid paralysis
        with bulbar palsies) See Figure 8.
      • Outbreak of an unusual or rare botulinum toxin type (for example toxin type G has never
        caused a foodborne botulism)
      • Outbreak within a common geographic area, but without a common dietary exposure
      • Multiple simultaneous outbreaks with no common source
  • Can the botulinum toxin be transmitted person-to-person?
    • No, the toxin does not penetrate intact skin. Rather, it enters via the gut, lungs, or a wound.
  • Does the botulinum toxin remain active once sprayed into the environment?
    • Yes and its decay depends on the atmospheric conditions and the particle size of the aerosol. Substantial inactivation could take as long as 2 days.
  • What are the symptoms of botulinum toxin?
    • Patients with botulism typically present with difficulty seeing, speaking, and or swallowing, dry mouth, muscle weakness.
    • Onset of paralysis depends on dosage. Food-borne develops with 18-36 hours. Purified toxin greater than 0.7 nanograms can kill within minutes.
  • When has botulinum toxin been used as a biological weapon?
    • The Japanese fed prisoners tainted food in the 1930's in an attempt to reduce prison population and test the effectiveness of C. botulinum as a lethal weapon. (See CDC video clip below).
    • In the late 1980's, Iraq and Russia together generated aerosols for inhalation and produced both missiles and bombs filled with botulinum toxin. They reported over 20,000 Liters of purified protein solution.
    • The 20000 L of Botulinum Toxin is around 3 times the amount needed to kill the entire human population by inhalation
    • In 1995, Japanese cult Aum Shinrikyo used aerosol-generating equipment during its attack on a subway in Tokyo; botulinum toxin was one of the agents used in this attempted terrorist attack.
  • How is a person treated if exposed to botulinum toxin in a terrorist attack or by natural exposure?
    • Immediate treatment with an antitoxin produced by the passive immunization of antitoxin produce in equine populations.
    • In 2007, the FDA announced stockpiles of the heptavalent antitoxin upon receiving 427 million dollars of federal monies for the project [10]
    • The paralysis of botulism can persist for weeks to months with concurrent requirements for fluid and nutritional support,
      assisted ventilation, and treatment of complications.[11]
    • Recovery follows the growth of new axon to reinnervate the paralyzed muscles. [12]

Video of Botulism as a Bioweapon (CDC). 2008

Prevention of Botulism

  • Proper food preparation is one of the most effective ways to limit the risk of exposure to botulism toxin.
  • Boiling food or water for ten minutes can eliminate some strains of Clostridium botulinum as well as neutralize the toxin as well. However, this will not assure 100% elimination due to the presence of endospores that resist U.V. radiation and high heat.
  • Growth of most strains of Clostridium botulinum will not occur below 10 or above 50 degrees Celsius.
  • Clostridium botulinum will not grow in media with pH values lower than about 5.
  • Food preservatives such as nitrite, sorbic acid, parabens, phenolic antioxidants, polyphosphates, and ascorbates inhibit the growth of the microorganism.
  • Avoid home-processed foods (home-canned) if at all possible, especially those with a low salt and acid content.
  • Do not consume canned goods with dents or appear black when opened. [13]

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Figure 9: Image source: "NWedible.com."How not to Die from Botulism."


[1]"Facts about Botulism." CDC. N.p., n.d. Web. 26 Mar. 2014. <http://www.bt.cdc.gov/agent/botulism/factsheet.asp>.
[2]"Botulism." WHO. N.p., n.d. Web. 27 Feb. 2014. <http://www.who.int/mediacentre/factsheets/fs270/en/>.
[3]Erica. "How Not To Die From Botulism: What Home Canners Need To Know About The World’s Most Deadly Toxin." Northwest Edible Life. N.p., 22 July 2013. Web. 26 Feb. 2014. <http://www.nwedible.com/2013/07/how-not-to-die-from-botulism-what-home-canners-need-to-know-about-the-worlds-most-deadly-toxin.html>.
[4]Devriese P. On the discovery of Clostridium botulinum. Journal of the History of the Neuroscience 1999; 8: 43-50.
[5]Scott AB. Botulinum toxin injection of eye muscles to correct strabismus. Trans Am Ophthalmol Soc 1981; 79: 734-770.
[6] Smith Louis DS. Botulism. The organism, its toxins, the disease. Springfield IL: Charles C. Thomas Publishers; 1977
[7] Geissler E, Moon JE, eds. Biological and ToxinWeapons: Research, Development and Use From the Middle Ages to 1945. New York
[8] Sterba, James P. "THE HISTORY OF BOTULISM." The New York Times. The New York Times, 27 Apr. 1982. Web. 27 Feb. 2014. <http://www.nytimes.com/1982/04/28/garden/the-history-of-botulism.html>.
[9]"Botulinum Toxin." Wikipedia. Wikimedia Foundation, 27 Feb. 2014. Web. 24 Feb. 2014. <http://en.wikipedia.org/wiki/Botulinum_toxin>.
United Nations Security Council. Tenth Report of the Executive Chairman of the Special Commission Established by the Secretary-General Pursuant to Paragraph9(b)(I) of Security Council Resolution 687 (1991),and Paragraph 3 of Resolution 699 (1991) on the Activities of the Special Commission.NewYork, NY: United Nations Security Council; 1995. S/1995/1038.
Aron SS et al. 2001. Botulinum toxin as a biological weapon. JAMA 285 (8):1059-2081.www.bt.cdc.gAron SS et al. 2001. Botulinum toxin as a biological weapon. JAMA 285 (8):1059-2081.www.bt.cdc.gov
[10]"Medscape Log In." Medscape Log In. N.p., n.d. Web. 01 Mar. 2014. <http://www.medscape.com/viewarticle/781389>.
Aron SS et al. 2001. Botulinum toxin as a biological weapon. JAMA 285 (8):1059-2081.www.bt.cdc.gov
[11]Aron, SS. Botulism toxin as a biological weapon. JAMA 285 (8): 1059-2081.
[12] "Botulism - Causes, Symptoms, Diagnosis and Treatment." TabletsManual.com. N.p., n.d. Web. 27 Feb. 2014. <http://www.tabletsmanual.com/wiki/read/botulism>
[13]Centers for Disease Control and Prevention. Botulism in the United States 1899-1996: Handbook for Epidemiologists, Clinicians, and Laboratory Workers. Atlanta, Ga: Centers for Disease Control and Prevention; 1998.