National Agricultural Biosecurity Center

Synopsis of Botulism

Botulism, a serious but relatively rare disease, is caused by an extremely potent toxin produced by the bacterium Clostridium botulinum. C. botulinum is an anaerobic, gram-positive, spore-forming bacterium that most commonly affects wild fowl and poultry, cattle, horses, and some species of fish. The organism is widely distributed in nature throughout the world and produces spores that are able to survive in a dormant state until more favorable conditions allow them to grow. They can be found in cultivated and forest soils; bottom sediments of streams, lakes, and coastal waters; the intestinal tracts of fish and mammals; and in the gills and viscera of shellfish. Although the incidence of botulism is relatively low in humans (~ 9 outbreaks of foodborne botulism per year with and average of 2.4 cases per outbreak), the disease is of considerable concern because of its high infectivity and high mortality rate (untreated). Only a few nanograms of toxin can cause human illness. And, in the 962 recorded botulism outbreaks in humans (2,320 cases) in the U.S. from 1899 to 1990, there have been 1,036 deaths.

In animals, botulism is classified into two forms: foodborne and toxicoinfectious. The foodborne form occurs when animals ingest preformed toxins in food or C. botulinum spores germinate in anaerobic tissues and produce toxins as they grow. The main sources include decaying vegetable matter, such as grass, hay, grain, spoiled silage, etc. and contaminated meat. Birds can ingest the toxins in maggots that have fed on contaminated carcasses or in dead invertebrates from water with decaying vegetation. The toxicoinfectious form, which corresponds to the wound form in humans, occurs when the bacteria grow in necrotic areas in the liver and GI tract, abcesses in the navel and lungs, or anaerobic wounds in the skin and muscle and appears to be responsible for shaker foal syndrome in horses. In humans, botulism is classified into three forms: foodborne, wound, and infant botulism. Foodborne botulism is the most common form and occurs when humans ingest toxins in various foods. Foods associated with botulism are characteristically associated with inadequately processed, home-canned foods or inappropriate handling and cooking of meat products, canned vegetables, and seafood products.

• There are seven distinct toxins produced by C. botulinum (designated by the letters A through G). Toxin types B, C, and D cause most cases in animals and toxin types A, B, E, and F cause most cases in humans. Toxin types A and E are occasionally seen in mink and birds. Thus far, there have been few recognizable outbreaks associated with toxin type G; the few cases that have been reported occurred in Texas and Montana.
• The botulinum toxin causes flaccid paralysis by blocking motor nerve terminals at the myoneural junction. This paralysis progresses symmetrically downward, usually starting with the eyes and face, to the throat, chest, and extremities and death results when the diaphragm and chest muscles become fully involved, resulting in asphyxiation.
• Botulinum toxins have been found to be beneficial for certain human diseases, such as muscle problem (crossed eyes) and to eliminate facial wrinkles. For more information on the healing power of botulinum toxin, click here.²⁶

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Clinical Signs and Symptoms

Infections in Animals:

• Clinical disease is most often seen in wildfowl, poultry, mink, cattle, sheep, horses, and some species of fish. Botulism has occasionally been seen in dogs and pigs (both are relatively resistant) but has not been reported in cats.
• Incubation: 2 hours to 2 weeks (most cases appear after 12 to 24 hours).
• Post-mortem lesions: no pathognomonic lesions; lesions are usually the result of general muscle paralysis (respiratory paralysis may cause nonspecific signs in the lungs).
• Post-mortem lesions (shaker foal syndrome): excess pericardial fluid with strands of fibrin, pulmonary edema and congestion.

Cattle and Horses:

• Signs and symptoms:
  • Restlessness
  • Knuckling and incoordination
  • Paralysis of the tongue with drooling
  • Urine retention
  • Dysphagia
  • Sternal recumbency (lateral recumbent animals are usually very close to death)
  • Progressive muscular paralysis from hindquarters to frontquarters, head, and neck
• In cattle, death generally occurs within 6 to 72 hours after sternal recumbency.
• Click here for more information on botulism in cattle published on the University of California - Davis Website.⁸
• Shaker foal syndrome:
  • Seen in animals less than 4 weeks old
  • Stilted gait, muscle tremors, and an inability to stand for more than 4 to 5 minutes
  • Other symptoms: dysphagia, constipation, mydriasis, and frequent urination; tachycardia and dyspnea in the later stages
  • Death occurs within 24 to 72 hours following initial symptoms and results from respiratory paralysis
• Click here for more information on botulism in horses published by the Agricultural Extension Service at the University of Tennessee.²¹

Sheep:

• Signs and symptoms:
  • Serous nasal discharge and drooling
  • Abdominal respiration
  • Stiffness upon walking and incoordination
  • Switching of the tail on the side
  • Limb paralysis

Swine, Dogs, and Cats:

• Relatively resistant
• Signs and symptoms (dogs, pigs):
  • Anorexia
  • Refusal to drink
  • Vomiting
  • Papillary dilation
  • Muscular paralysis
• Most dogs with botulism recover within 2 weeks

Foxes and Mink:

• During an outbreak of botulism, many animals are typically found dead.
• Symptoms: various degrees of paralysis and dyspnea.

Birds:

• One of the three most important disease problems among wild migratory birds; botulism kills an estimated 10 to 50 thousand wild birds per year. Ducks appear to be more susceptible than other migratory birds.
• Signs and symptoms:
• Flaccid paralysis of the legs, wings, neck, and eyelids
• Death occurs due to drowning.
• Toxicoinfectious form: Flaccid paralysis of the legs, wings, neck, and eyelids, diarrhea with excess urates
• Mortality rate (chickens): varies from a few birds to 40% of the flock.
• Click here for more information on avian botulism published by the National Park Service and the Fish and Wildlife Service.²⁰

Humans:

• Primary clinical signs:
  • Intoxication
  • Marked lassitude
  • Weakness and vertigo
  • Double vision
  • Difficulty speaking and swallowing
  • Difficulty breathing
  • Weakness of muscles
  • Abdominal distention
  • Constipation
• Click here for more human-related information on botulism posted on the UAB Website for Bioterrorism and Emerging Infectious Education.⁵

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Diagnosis and Treatment

Diagnostic Samples:

• Samples for diagnostic purposes in animals include feed, stomach or intestinal contents, vomitus, or feces.
• Samples for diagnostic purposes in humans include blood (least reliable), feces (most reliable), vomitus, gastric aspirates, respiratory secretions, or food samples.

Differential Diagnosis:

• In animals, the differential diagnoses include parturient paresis, paralytic rabies, equine encephalomyelitis, ragwort poisoning in horses, miscellaneous plant poisons, louping ill in sheep, and hypocalcaemia in sheep.
• In humans, the differential diagnoses include Guillain-Barré Syndrome, stroke, paralytic shellfish poisoning or ingestion of puffer fish, and myasthenia gravis.

Clinical Diagnosis:

• In animals, botulism can be diagnosed by clinical symptoms although differentiation from other diseases may be difficult.
• In humans, botulism can be diagnosed by clinical symptoms although differentiation from other diseases may be difficult.

Laboratory Tests:

• Botulism in animals can be difficult to diagnose since the toxin is not always found in clinical samples or the feed.
• Diagnostic tests:
  • Mouse neutralization test
  • ELISA
  • Electrochemiluminescence
  • Serology is not useful since small amounts of toxin are involved and survivors rarely develop antibodies
• In humans, the most direct and effective way to confirm the clinical diagnosis of botulism is to demonstrate the presence of toxin in the serum or feces of the patient or in the food which the patient consumed. The most sensitive and widely used method for detecting toxin is the mouse neutralization test, which takes approximately 48 hours, followed by culturing of sample in an enrichment medium for the detection and isolation of the causative organism (takes ~ 5-7 days).
• For a more detailed description of assays that detect botulinum toxin, please refer to the Bacteriological Analytic Manual on the FDA Website by clicking here.²³

Treatment

• In animals:
  • Supportive care, including gastric lavage to remove some of the toxin
  • Botulinum antitoxin may be useful, the success rate depends on the type of toxin causing the illness
  • Some success with guanidine hydrochloride
  • Antibiotics useful in the treatment of the toxicoinfectious form
• In humans:
  • Intensive supportive care, including mechanical breathing assistance
  • Early administration of botulinum antitoxin (available from the CDC)
  • The death rate has been decreasing with improvements in supportive care. Prior to 1950, the mortality rate was 60%; currently, it is less than 5%
  • Recovery may be slow and can take several months or longer and survivors report fatigue and shortness of breath for years

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Economic Consequences and Disease Eradication

Economic Consequences:

• Loss of livestock.
• Costs associated with eradication efforts.

Disease Containment and Eradication:

• Immediate notification
  • Click here for information on who to notify in the event of an outbreak published by the CDC in the MMWR.¹⁸
• Prevention:
  • Proper food preparation
  • Proper food handling
  • Food preservatives
• Since botulism is a life-threatening disease, the FDA always initiates a Class I recall (For products that are considered to be dangerous or defective and that could cause serious health problems or death). For more information on FDA recall policies, please click here.¹⁶
• Good agricultural and industrial hygiene.
• Viability:
  • Optimal temperature for growth and toxin production of proteolytic strains is close to 35°C; for nonproteolytic
  • Botulinum toxins are large, easily denatured proteins:
    • Exposure to sunlight for 1 to 3 hours
    • Inactivated by 0.1% sodium hypochlorite, 0.1 N NaOH, chlorine and other disinfectants, heating at 80°C for 30 minutes, or 100°C for 10 minutes, acidification, and reduction of moisture
    • Refrigeration does not prevent growth and toxin formation by nonproteolytic strains unless the temperature is precisely controlled and kept below 3°C
  • Vegetative cells of C. botulinum:
    • Susceptible to many disinfectants, such as 1% sodium hypochlorite and 70% ethanol
  • The bacteria can only grow under anaerobic conditions and prefers low acidic conditions (pH above 4.6)

Botulinum and Bioterrorism:

• According to the Centers for Disease Control and prevention, botulinum toxin, along with anthrax, hemorrhagic fever viruses, smallpox, and tularemia, pose the greatest hazard to public health, based on their death rates, ease of dissemination and transmission, and potential to inspire public panic.
• Botulinum toxins are known to have been weaponized by several countries and terrorist groups and can be delivered by aerosols as well as food or water.
• Bioweapon potential:
  • Extremely potent and lethal; one gram of crystalline toxin can kill more than one million people if dispersed and inhaled evenly
  • Ease of production; recipes for botulinum toxin can be found on the internet and the bacteria can be grown on basic media
  • Ease of transport; C. botulinum is very stable under certain conditions and is not contagious
  • Need for prolonged intensive care; mechanical ventilation may be necessary and some may require up to seven months for muscular function to return
• Past efforts to weaponize botulinum toxin:
  • The U.S. produced botulinum toxin as a potential weapon during World War II
  • The former Soviet Union conducted research on use of botulinum toxin as a biological weapon as late as the early 1990s
  • Aum Shinrikyo, a Japanese cult, attempted to use aerosolized botulinum toxin in Japanese cites on at least three occasions between 1990 and 1995; these efforts were unsuccessful
• For more information on botulism and bioterrorism, click on one of the following links:
  • Analyzing a bioterror attack on the food supply: The case of botulinum toxin in milk from Proc Natl Acad Sci, published online June 28, 2005²⁵
  • Botulinum toxin as a biological weapon: Medical and public health management form JAMA, published on February 28, 2001¹⁹

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Outbreaks

Animal outbreaks

Outbreaks in Birds:

• 1910: Millions of wild migratory birds in Utah and California
• 1925: 100,000 in Oregon
• 1929: ~300,000 in Utah
• 1941: 250,000 in California
• 1952: ~4.5 Million in the Western United States
• 1978: 50,000 in Montana
• 1979: 100,000 in Montana
• 1980: 110,000 in Utah

Humans Cases

• 2002: Eight cases of type E botulism in Alaska associated with the consumption of muktuk (whale fluke). Five patients were hospitalized, two of which required mechanical ventilation. For more information, click here to review the report published by the CDC in the MMWR.¹⁷
• 2001: Three cases of type E botulism in Alaska associated with the consumption of fermented beaver tail and paw. Two of the three cases required mechanical ventilation. For more information, click here to review the report published by the CDC in the MMWR.¹⁵
• 2001: 15 cases of type A botulism in Texas associated with consumption of Chili.
• 1997: One case of type B botulism in Illinois due to consumption of improperly home-pickled eggs. For more information, click here to review the report published by the CDC in the MMWR.¹⁴
• 1994: One case of type A botulism in Oklahoma due to improperly reheated stew containing roast beef and potatoes. For more information, click here to review the report published by the CDC in the MMWR.¹³
• 1994: 30 cases of type A botulism in Texas due to consumption of a potato-based dip.⁷
• 1990: Three cases of type B botulism associated with the consumption of palani (surgeon fish) intestines. For more information, click here to review the report published by the CDC in the MMWR.¹²
• 1987: Eight cases of type E botulism - 2 in NY City and 6 in Israel; all 8 patients had consumed Kapchunka (uneviscerated, dry-salted, air-dried, whole whitefish) at a NY deli. One female died, 2 required breathing assistance, 3 were treated therapeutically with antitoxin, and 3 recovered spontaneously. As a result of this outbreak, regulations were published to prohibit the processing, distribution, and sale of Kapchunka and Kapchunka-type products in the U.S. For more information, click here to review the report published by the CDC in the MMWR.¹¹
• 1984: Three cases of botulism in California due to consumption of improperly handled food made from fresh ingredients. For more information, click here to review the report published by the CDC in the MMWR.¹⁰
• 1982: One case of type A botulism in California due to consumption of improperly reheated commercial pot pie. For more information, click herehere to review the report published by the CDC in the MMWR.⁹

• Click here to access more information on the causes and control procedures for avian botulism from the National Wildlife Health Center in Madison Wisconsin. The NWHC is a biomedical laboratory dedicated to the assessment and impact of diseases on wildlife. They also provide information, technical assistance, and research on national and international wildlife health issues.²⁰

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Sources and Related Articles

Sources:

1. FAO Agriculture Department, Animal Production and Health Division. Animal Health Disease Cards: Botulism. Available at http://www.fao.org/ag/againfo/subjects/en/health/diseases-cards/cards/botulism.html.
2. FDA Center for Food Safety and Applied Nutrition. December 2004. Clostridium botulinum in the Bad Bug Book: Foodborne Pathogenic Microorganisms and Natural Toxins Handbook. Available at http://www.cfsan.fda.gov/~mow/chap2.html.
3. National Institute of Allergy and Infectious Diseases. Botulism. Available at http://www.naiaid.nih.gov/publications/botulism.htm.
4. Center for Food Security and Public Health at Iowa State University College of Veterinary Medicine. Botulism. Available at http://www.cfsph.iastate.edu/Factsheets/pdfs/botulism.pdf.
5. UAB: Bioterrorism and Emerging Infections Education. Botulism Summary. Available at http://bioterrorism.uab.edu/CategoryA/Botulism/summary.asp.←
6. CIDRAP. July 2005. Botulism: Current, comprehensive information on pathogenesis, microbiology, epidemiology, diagnosis, and treatment. Available at http://www.cidrap.umn.edu/cidrap/content/bt/botulism/biofacts/botulismfactsheet.html.

Related Articles:

7. Angulo, F. J., J. Getz, J. P. Taylor, K. A. Hendricks, C. L. Hatheway, S. S. Barth, H. M. Solomon, A. E. Larson, E. A. Johnson, L. N. Nickey, and A. A. Ries. 1998. A Large Outbreak of Botulism: The Hazardous Baked Potato. J Infect Dis 178(1):172-177.←
8. Anonymous. Botulism in Cattle. Available at http://www.vmtrc.ucdavis.edu/dfs/botu/botulism.pdf.←
9. Anonymous, January 28, 1983. Botulism and Commercial Pot Pie - California. MMWR. 32(3):39-40,45. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/00001230.htm.←
10. Anonymous, March 22, 1985. Epidemiologic Notes and Reports Botulism from Fresh Foods - California. MMWR. 34(11):156-157. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/00000507.htm.←
11. Anonymous, December 18, 1987. International Outbreak of Type E Botulism Associated with Ungutted Salted Whitefish. MMWR. 36(49):812-813. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/00001014.htm.←
12. Anonymous. June 21, 1991. Epidemiologic Notes and Reports Fish Botulism - Hawaii, 1990. MMWR. 40(24):412-414. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/00014498.htm.←
13. Anonymous, March 24, 1995. Foodborne Botulism - Oklahoma, 1994. MMWR. 44(11):200-202. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/00036573.htm.←
14. Anonymous, September 1, 2000. Foodborne Botulism from Eating Home - Pickled Eggs - Illinois, 1997. MMWR. 49(34):778-780. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm4934a2.htm.←
15. Anonymous, August 17, 2001. Botulism Outbreak Associated with Eating Fermented Food - Alaska, 2001. MMWR. 50(32):680-682. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5032a2.htm.←
16. Anonymous, June 2002. FDA Recall Policies. Published in the Industry Affairs Staff Brochure by the FDA Center of Food Safety and Applied Nutrition. Available at http://www.cfsan.fda.gov/~lrd/recall2.html.←
17. Anonymous, January 17, 2003. Outbreak of Botulism Type E Associated with Eating a Beached Whale - Western Alaska, July 2002. MMWR. 52(02):24-26. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/005202a2.htm.
18. Anonymous, August 2003. Notice to Readers: New Telephone Number to Report Botulism Cases and Request Antitoxin. MMWR. 52(32):774. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5232a8.htm.←
19. Arnon, S. S., R. Schechter, T. V. Inglesby, D. A. Henderson, J. G. Bartlett, et. al., February 28, 2001. Botulinum Toxin as a Biological Weapon: Medical and Public Health Management. JAMA 285(8):1059-1070. Available at http://jama.ama-assn.org/cgi/reprint/285/8/1059.←
20. Friend, M, L. N. Locke, J. J. Kennelly, D. H. Cross, and R. Kampen. October 17, 2002. Avian Botulism. Located at the USGS National Wildlife Heath Center Website. Available at http://www.nwhc.usgs.gov/research/avian_botulism/avian_botulism.html.←
21. Harper, F., January 2003. Botulism May Become a Problem in Horses This Winter. Published by the Agricultural Extension Service at the University of Tennessee in the Animal Science Horse Information Series. Available at http://animalscience.ag.utk.edu/horses/pdf/Botulism_1-21-03.pdf.←
22. Sobel, J., N. Tucker, A. Sulka, J. McLaughlin, and S. Maslanka. 2004. Foodborne Botulism in the United States, 1990-2000. Emerg Infect Dis. 10(9):1606-1611. Available at http://www.cdc.gov/foodborneoutbreaks/publication/2004/....
23. Solomon, H. M. and T. Lilly, Jr., 1998. Bacteriological Analytical Manual, 8th Edition, Revision A, Chapter 17. Available at http://www.cfsan.fda.gov/~ebam/bam-17.html.←
24. Vangelova, L., December 1995. Botulinum Toxin: A Poison That Can Heal. FDA Consumer Magazine. Available at http://www.fda.gov/fdac/features/095_bot.html.
25. Wein, L. M. and Y. Liu. July 12, 2005. Analyzing a Bioterror Attack on the Food Supply: The Case of Botulinum Toxin in Milk. PNAS. 102(28):9984-9989. Available at http://iis-db.stanford.edu/pubs/20920/0408526102v1.pdf.←

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