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What is Botulism (Clostridium botulinum toxin)?

Botulism is a disease caused by a bacterial toxin produced by Clostridium botulinum (Figure 5). There are 7 different types of botulinum toxin: A, B, C, D, E, F, and G. The bacterium is found all over the world and is commonly isolated from water and soil. Most cases of botulism are associated with food consumption. The most common types of toxin seen in foodborne disease are A, B, and E. The toxin inhibits proper functioning of the nerves and prevents muscle contraction.  As a result a person with severe botulism will have flaccid paralysis and may not be able to breathe (Figure 6). The death rate of botulism during the 1990’s was 6% (9, 47). 

This bacterium exists in two forms: vegetative cells and spores. The vegetative cells of Clostridium botulinum are killed by oxygen. The spores allow the organism to survive when nutrients are low and/or oxygen levels are too high. The vegetative cells produce the toxin. This toxin is very potent. Only minute amounts are needed to cause severe disease (LD50= 1 ng/kg). Usually the toxin is ingested which results in symptoms of botulism 24-36 hours later. 

Clostridium botulinum spores are highly resistant to killing by heat. Temperatures of 121o C (250o F) or higher are needed to kill the spore. If a canned food is improperly prepared the surviving spores germinate producing vegetative cells. The vegetative cells can grow in the low oxygen environment inside the can and produce toxin. Once toxin is made the food must be cooked for at least 5 minutes at 85o C (185o F; 60) to destroy it. 

The initial signs of botulism include blurred vision with fixed and dilated pupils, dry mouth, constipation and abdominal pain; fever is absent. Many patients will complain of difficulty seeing, speaking and swallowing. Other symptoms of botulism include double vision, drooping eyelids, slurred speech, difficulty swallowing, muscle weakness that descends starting at the head: the shoulders are then affected, followed by the upper arms, and then the lower arms, thighs, calves, and so forth. Paralysis of breathing muscles can cause a person to stop breathing and die, unless mechanical ventilation is provided. The most common cause of death is respiratory failure. If mechanical ventilation is not given the death rate can be as high as 70%. It can take several weeks before a person with severe botulism can breathe without mechanical ventilation. Complete recovery of all the nerves can take many months to years. Botulism, similar to, anthrax is not spread from person-to-person. 

There are three kinds of botulism: 

Foodborne botulism occurs when people ingest pre-formed toxin in improperly canned or fermented food. If the food is improperly processed then spores of Clostridium botulinum present on the food survive and will become vegetative cells. The vegetative cells produce the toxin. This toxin is the most poisonous substance known to man. The lethal dose of botulinum toxin for humans is not known but can be estimated from studies with primates. It is estimated that lethal amounts of crystalline type A toxin for a 155-lb (70-kg) human would be about 70 mg (47). Symptoms begin within 6 hours to 2 weeks (most commonly between 12 and 36 hours) after eating toxin-containing food. Foodborne botulism is a public health emergency because the contaminated food may still be available for ingestion by others. Around 23 cases of foodborne botulism have occurred per year from 1990 to 2000 (60). 

Infant botulism, the most common form of botulism, occurs in around 100 infants each year (9). Usually infants under 1 year of age consume the spores of the botulinum bacteria, which then germinate and become vegetative cells in the intestines and release toxin. Most cases of infant botulism result from ingestion of spores present in the soil and dust. In most cases the source of the spores is not known. The most common foodstuff associated with infant botulism is honey.

Once infants ingest Clostridium botulinum spores the spores escape being killed in the stomach due to the fact that they produce lower levels of acid in their stomach. The intestines of the infants also lack the proper number of normal bacterial flora to prevent the growth of the vegetative Clostridium botulinum cells. Symptoms include constipation, and a weakness in sucking, swallowing, or crying, general muscle weakness followed by progressive weakness of the muscles in the mouth and throat as well as weakness of the limbs (figure 6). These infants do not eat well or gain weight at a normal rate. Flaccid paralysis can can occur but is less common than in foodborne botulism only affecting 1-2% of infants. 

Wound botulism, the least common (around 4 cases/year) occurs when wounds are contaminated with Clostridium botulinum spores. The spores germinate in the wound and then produce the toxin. The incubation time is longer than with the other forms of this disease: 4 days or longer. Symptoms associated with the gastrointestinal tract are less common (dry mouth, abdominal pain). Injection drug users (IV drug abusers) are at higher risk for this form of botulism. 

Why is botulinum toxin an attractive BW?
The botulism toxin can be used in an aerosol attack and may result in many causalities. If the toxin is inhaled symptoms might not appear for several days (61). Fortunately, botulism cannot spread to others who have close contact with them. One gram of this toxin if dispersed and inhaled evenly could kill 1 million people. If released as an aerosol it could incapacitate or kill 10% of the people within 500 meters downwind of the BW release. There are seven different types of the toxin. Antibodies used to treat botulism are only useful in treating people that have toxins A, B and E in their systems. If botulinum toxin to any of the other 4 toxins were released antitoxin therapy would not be helpful. Treatment of this disease is labor intensive, may require expensive equipment and takes weeks to months before the persons completely recover. 

Laboratory Diagnosis

Physicians may consider the diagnosis if the patient's history and physical examination suggest botulism. However, a number of other diseases have similar symptoms. Diseases such as Guillain-Barré syndrome, stroke, and myasthenia gravis have to be excluded to confirm a diagnosis of botulism. Other tests that can help in diagnosis include brain scans, spinal fluid examination, nerve conduction tests (electromyography, or EMG), and a tensilon test (myasthenia gravis). 

The most direct way to confirm the diagnosis of botulism is to demonstrate the botulinum toxin in the patient's serum or stool by injecting serum or stool into mice and looking for signs of botulism. The bacteria can also be isolated from the stool of persons with foodborne and infant botulism. These tests can be performed at some state health department laboratories and at the Centers for Disease Control in Atlanta, Georgia. 

Treatment

The following treatments are required for someone with botulism.

  1. Ensure they are breathing properly. Mechanical ventilation may be required. This treatment is essential in reducing the death rate.
  2. In infants with infant botulism, elimination of the botulinum toxin by washing out the stomach (gastric lavage) and giving antibiotics that kill the bacteria is important.
  3. Give the patient antitoxin against botulism. This antitoxin is a mixture of antibodies that react with the three most common types of botulism toxin (A, B and E). The CDC maintains a supply of this antitoxin. Antitoxin is effective in reducing the severity of symptoms if administered early in the course of the disease.

Most patients eventually recover after weeks to months of supportive care.  

Prevention

Do not give infants under the age of one food known to contain Clostridium botulinum spores (honey). Certain conditions stop growth of Clostridium botulinum; temperatures below 4oC, acid pH (acidic foods like tomato sauces), heating the food before consumption (85oC or 185oF for 5 minutes). Home canning of food is more likely to result in botulism so the safest canned foods would be those purchased from commercial sources. If you still wish to can foods at home follow the manufacturers instructions exactly when canning foodstuffs. 

A vaccine is currently being developed and could in the near future be available. However, it is likely that at first it will only be available for military personnel.

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© 2005 Neal Chamberlain. All rights reserved. 
Site Last Revised 5/5/05
Neal Chamberlain, PhD. A. T. Still University of Health Sciences/Kirksville College of Osteopathic Medicine.

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