Issue: March 2020
Disclosures: Kaye reports no relevant financial disclosures
March 23, 2020
7 min read

Botulism: A rare, life-threatening illness

Issue: March 2020
Disclosures: Kaye reports no relevant financial disclosures
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Botulism is a rare, life-threatening toxemia caused by the toxin of Clostridium botulinum and rarely Clostridium butyricum and Clostridium baratii. Botulinum toxin is listed as a Class A biological weapon and is toxic when ingested or inhaled. The CDC lists five types of botulism: foodborne, wound, infant and iatrogenic botulism and the very rare disease called infant-type botulism in adults (adult intestinal botulism).

Donald Kaye
Donald Kaye

C. botulinum, the major cause of botulism, is a gram-positive, anaerobic, spore-forming, motile bacillus that can produce eight different toxins, labeled A through H. It requires an anaerobic, aciidic environment to multiply (pH 4–6). Spores are commonly found in the environment, including soil and bodies of water. Only toxins A, B, E, F and H produce disease in humans. Types F and H poisoning are much less common than poisoning from A, B or E toxins. Types A, B and E are associated with poisoning from food; type E is associated with poisoning from specifically fish and fish products. Botulinum toxin is a neurotoxin with activity in humans and animals and is the most potent toxin known, with a lethal dose of 1.3 to 2.1 ng/kg in humans. Toxin type H is the most potent of the botulinum toxins. Botulinum toxin acts by preventing the release of acetylcholine from the axon ending at neuromuscular junctions of striated muscle and autonomic synapses of smooth muscle. This results in flaccid paralysis and loss of tone in smooth muscle.

Types C and D toxin cause botulism in animals but not in humans. No disease is associated with type G botulinum toxin.

Although the spores are resistant to boiling and require cooking or canning under pressure for sterilization, the toxin is destroyed by heating to 80°C.


In a review of worldwide reported foodborne outbreaks from 1920 to 2014, toxin types A, B, E and F were identified as the causative agent in 34%, 16%, 17% and 1% of outbreaks, respectively. The type F outbreaks were caused by botulinum toxin produced by C. baratii. There have been a small number of poisonings due to type H toxin.

In the 5-year period from 2012 through 2016, there were 153 to 205 confirmed cases of botulism each year in the United States, with an additional eight to 16 probable cases. Most of the confirmed cases were infant botulism, 71% to 88% each year, with the rest divided between foodborne and wound botulism. Most of the foodborne cases were related to either home canned foods or pruno, an illicit alcoholic beverage brewed by inmates in prison. The great majority of the wound cases were in injection drug users. Although botulism from commercially processed food is rare, it does occur, and when it does, the number of cases may potentially be large.

bilateral pupillary dilation
A close view of a 14-year-old boy’s eyes, revealing the presence of bilateral pupillary dilation due to the subsequent onset of wound botulism after the boy had fractured his distal right ulna and radius just proximal to his wrist.

Source: CDC/Dr. Michael Merson


Botulism occurs when C. botulinum multiplies in an anaerobic environment and releases botulinum toxin, which is produced in the body or absorbed into the body from an external source. The spores of C. botulinum are heat resistant and require temperatures of 120°C for 5 minutes to be destroyed. On the other hand, the toxin is heat labile and is inactivated by exposure to 80°C. The toxin has no smell or taste.

Infant botulism

Infant botulism, the most common type in the U.S., occurs when the spores of C. botulinum enter the intestines of an infant, multiply and release toxin. Honey is known to contain spores of C. botulinum and should be avoided in infants. After the age of 1 year, there are apparently defense mechanisms, probably related to the bacterial flora developed in the gastrointestinal tract, that prevent the multiplication of the C. botulinum. The source of the organisms in most cases of infant botulism is unknown but is undoubtedly ingestion of spores from the environment.

Foodborne botulism

Most cases of foodborne botulism result from ingestion of toxin in improperly preserved canned or fermented foods (usually home processing). In these situations, Clostridium spores have contaminated the food somewhere in the process (washing, cleaning or sterilizing items). Pressure canners must be used for low-acid content foods like potatoes, most other vegetables and meats. If any steps have not been carried out properly, spores that are present can germinate and multiply in the anaerobic environment and produce toxin. Foods with low acid content (eg, potatoes and corn) are most commonly involved, especially when not using pressure canners, which are required to kill the spores in these foods. Fish and fish products (including fermented fish) have served as a cause of botulism, especially in Alaska among native Alaskans.

Wound botulism

Most cases of wound botulism occur when spores of C. botulinum are injected into tissue by drug users as a contaminant of street drugs. If the environment is anaerobic, which it apparently is on occasion, the spores can germinate, multiply and produce toxin. Injection of black tar heroin has been especially linked to botulism. Wound botulism can also occur following trauma, especially with foreign bodies introduced into the wound.


Iatrogenic botulism

Iatrogenic botulism results from the injection of toxin A as used medically (eg. toxin injections for cosmetic purposes or toxin injections for chronic pain), when the dose is sufficient to cause symptoms beyond the muscles that are meant to be paralyzed.

Adult intestinal botulism

This very rare disease occurs when spores are ingested and evolve to produce toxin in the intestines. Most patients who develop adult intestinal botulism have a history of gastrointestinal surgery or disease, such as inflammatory bowel disease.

Botulism from biowarfare

Botulinum toxin can be used as a biowarfare agent by either aerosolization of the toxin or introducing it into food or water. Aerosolization would be the most effective method if appropriate techniques were developed for aerosolization. Contamination of drinking water would be less effective because the toxin is rapidly inactivated in chlorinated water and inactivated over days in unchlorinated water. Botulinum toxin is known to have been weaponized by several countries. The potential use of toxin H as a bioweapon is particularly concerning because there is no known antitoxin available.

Clinical manifestations

The incubation period after ingestion of toxin is usually 12 to 72 hours. The incubation period for wound botulism is usually days and can be many days. Botulism produces weakness/paralysis in skeletal and visceral muscles. The onset usually involves cranial nerves with double vision, drooping eyelids, slurred speech and difficulty swallowing. Dryness of the mouth is a frequent complaint. Dilatation of the pupils is common. Cranial nerve involvement is followed by bilateral descending weakness and difficulty breathing. Respiratory failure may occur. The differential diagnosis includes myasthenia gravis, Lambert-Eaton syndrome, various viral causes of paralysis such as poliomyelitis and acute flaccid myelitis, tick paralysis, central nervous system disease such as stroke and various poisonings. Fever is absent except with wound botulism, when fever may be absent or present. There are no sensory abnormalities.

Any patient with evidence of cranial nerve palsies should be considered for the diagnosis of botulism. The addition of descending bilateral motor weakness with absence of any sensory deficit is highly suggestive, if not diagnostic, of botulism. Constipation is part of the syndrome.

The manifestations in infants are lethargy, weak cry, constipation and floppy appearance due to muscle weakness.

Laboratory diagnosis

Diagnostic work with botulinum toxin should be restricted to laboratories appropriately equipped to handle the toxins.

The initial diagnosis is clinical. Treatment should not await laboratory confirmation because progression may be rapid and life threatening. Confirmation of the presence of botulism has classically depended on demonstration of the toxin in a mouse model using serum or stool or the presumed source (eg, food) or isolating the causative Clostridium from stool, a wound or the presumed source. The toxin type has classically been determined by mouse bioassay. Currently, PCR testing for toxin genes is used, when available.



All patients with suspected botulism should be hospitalized. Supportive measures are critical, including respiratory support, if needed. Therapy consists of prompt administration of botulism antitoxin. For adults and children aged older than 1 year, heptavalent antitoxin is used, which is of equine derivation and has antibodies against toxins A through G. For infants and children up to the age of 1 year, Botulism Immune Globulin Intravenous (Human) is used; it contains antibodies against toxins A and B. The antitoxin will not reverse paralysis but will neutralize circulating toxin. Recovery requires regeneration of neuromuscular connections, which can take months.

For wound botulism, debridement is required, even if the wound is not impressive. Penicillin G is often given in addition; when penicillin cannot be used, metronidazole has been substituted.

There is no antitoxin available for type H toxin, the most potent of the toxins.

The mortality rates for foodborne botulism and infant botulism have been low in the U.S.: less than 4% and less than 1%, respectively.


The major approach to prevention of botulism relates to proper handling of food. Infants aged younger than 12 months should not be given honey; home canning should be performed as recommended by the U.S. Department of Agriculture in the USDA Complete Guide to Home Canning. Most importantly, a pressure canner should be used, as specified by the USDA and CDC.

The FDA considers uneviscerated fish that are salt cured, dried or smoked or other products derived from uneviscerated fish to be unsafe. They are considered hazardous, whether stored at ambient temperature, refrigerated or frozen, or whether packaged in air, vacuum or modified atmosphere.

In addition, wounds should be managed promptly and properly, and, obviously, injection of street drugs should be avoided.

Disclosure: Kaye reports no relevant financial disclosures.