Lecture 30

Question 1

1. What is botulism?
2. What is the causative agent?
3. What do the spores allow the bacteria to do?

Answer 1

1. A food-borne disease.
2. Clostridium botulinum, an obligately anaerobic, Gram-positive spore-forming rod-shaped soil bacterium.
3. The spores allow the bacteria to survive in a dormant state until exposed to conditions that can support vegetative reproduction, i.e., anaerobic, low-salt, low-acid environment. When the cells reproduce vegetatively, they produce and release a toxin neurotoxin.

Question 2

1. Where did botulism originate?
2. What does it cause?
3. Under what conditions does the bacterium produce the toxin?

Answer 2

1. In Europe in the 18th century, the disease was often acquired from eating sausages; now, it is most commonly acquired from canned foods and poorly heated foods.
2. A flaccid paralysis caused by neurotoxin (an exotoxin, released from the bacterium as it grows).
3. Produced by the bacterium under anaerobic conditions; the toxin blocks nerve impulses at neuromuscular junctions, stopping muscle contraction.

Question 3

1. What are the symptoms of botulism?
2. What happens if the disease is not treated?

Answer 3

1. Double vision, blurred vision, drooping eyelids, slurred speech, difficulty swallowing, dry mouth, and muscle weakness. Symptoms of muscle paralysis.
2. If the disease is not treated, the paralysis can progress to the arms, legs, trunk and to the respiratory muscles and the heart, leading to suffocation and cardiac arrest.

Question 4

1. What is Botulinum Nerurotoxin?

Answer 4

1. The most toxic substance known. 30 grams would be enough to kill the entire U.S. population. The toxin is a zinc metalloprotease; it cleaves and inactivates specific cellular proteins essential for the release of the neurotransmitter, acetylcholine; the toxin is genetically encoded by a lysogenic bacteriophage.

Question 5

1. How many cases of botulism are reported each year?
2. What is foodborne botulism?
   
   1. How is the toxin absobed?
   2. Is binding irreversible?
   3. What is done with the toxin?

Answer 5

1. Typically 100 to 150 cases of botulism are reported each year; about 25% are fatal, with death due to respiratory paralysis or cardiac failure.
2. This is an intoxication, not an infection. It results from eating foods containing the toxin, which is colorless and tasteless. Spores of C. botulinum are everywhere in the environment, and if they get into food, they can germinate then, the reproducing bacteria produce toxin and release it into the food.
   
   1. Absorbed by the intestine into the circulation and is carried by the bloodstream to peripheral nerve synapses at neuromuscular junctions.
   2. Binds irreversibly
   3. The toxin is then internalized by the nerve cells and enzymatically blocks acetylcholine release, so muscles cannot contract. In foodborne botulism, symptoms generally begin 18 to 36 hours after eating a contaminated food, by they can occur as early as 6 hours or as late as 10 days after ingesting contaminated food; the neurological symptoms may be preceded by abdominal cramps, nausea, vomiting, or diarrhea, due to other bacterial metabolites present in the food.

Question 6

1. What are foodborne botulism outbreaks often due to?
2. What is an example of canned foods that caused botulism?

Answer 6

1. Home canned foods, particularly low acids foods; restaurants; traditional Alaska Native foods, especially fermented foods like fish and fish eggs, seal, beaver, and whale. Home canned foods can be dangerous; if live anaerobic bacteria, such as Clostridium, or their viable spores, remain after the heating and sealing of the can, their growth may result in substantial amounts of gas.
2. 14 people contracted botulism from eating Castleberry’s canned hot dog chili sauce. All were hospitalized and required mechanical ventilation.
   
   1. Cause - poor handling of food at the chili sauce canning plant. The plant was closed by the FDA and USDA due to health violations. After briefly being allowed to re-open under a “temporary emergency operating permit”, the canning plant was permanently close.

Question 7

1. What is infant botulism?
2. Where do the spores come from?

Answer 7

1. Occurs in babies under 6 months of age, before the normal bacterial community of the intestine is well established. If spores are ingested, they can germinate, and reproduction of C. botulinum leads to toxin production. Infants with botulism appear lethargic, feed poorly, are constipated, and have weak cry and poor muscle tone.
2. Honey often contains botulism spores, which can germinate in the infant intestine. Do not feed babies under 12 months of age any honey.

Question 8

1. What is wound botulism (and intestinal botulism)?

Answer 8

1. An infection that leads to intoxication; an infection that occurs when spores of C. botulinum germinate in deep wounds, where tissue damage can create anaerobic conditions, or in the intestine, which is anaerobic. The spores germinate, and the bacteria then reproduce and produce botulinum toxin.

Question 9

1. What are some treatments for foodborne and wound botulism?
2. What can occur without treatment?
3. What does recovery result from?
4. How is the disease transmitted?

Answer 9

1. Includes prompt administration of polyvalent botulinum equine antitoxin (horse IgG preparation), which blocks the action of toxin circulating in the blood and which may arrest the progression of paralysis and decrease the duration of illness. Supportive care that may include assisted ventilation is also necessary.
2. Death can occur due to blockage of the airway and respiratory failure. The extent of the paralysis and how fast it sets in can vary with the person and the amount of toxin ingested.
3. From the growth of new motor axon branches that re-innervate paralyzed muscle fibers. Full recovery can take weeks to months requiring intensive care unit support, including mechanical ventilation, if needed.
4. Botulism and botulinum toxin are not contagious and are not transmitted from person to person. The toxin does not cross the intact skin.

Question 10

Prevention:

1. How can we prevent botulism?
2. How is the toxin destroyed?
3. How is botulism encountered the most?
4. Is there an immunization?

Answer 10

1. Cooking foods well, and heating previously cooked foods well, will prevent foodborne botulism.
2. Toxin is easily destroyed by heat at a temp. of 85°C for 5 minutes, or 80° for 10 minutes.
3. Almost any kind of food can carry botulism, but it is most commonly encountered with ‘low-acid’ vegetables such as carrots, asparagus, green beans, beets, peppers, and corn.
4. Immunization with botulinum toxid (inactivated toxin) can be used to induce endogenous immunity, but mass immunization is not carried out because of scarcity of the toxoid, rarity of the natural disease, and the potential for problems of any mass immunization program. Also, immunization would prevent use of botulinum toxin for medicinal use as therapy for certain eye problems and other dystonias.

Question 11

1. What is the potential for botulism as a biological weapon?

Answer 11

1. Extreme potency and lethality of botulinum toxin, ease of production and transport, need for prolonged intensive care for affected persons, potential for use as aerosolized botulinum toxin and toxin contamination of food.

Question 12

1. What is the causative agent of Tetanus?
2. How does the disease occur?
3. Is the bacterium invasive?
4. Where does the toxin move to?
5. How was the causative agent isolated?
6. Where does it occur?

Answer 12

1. Clostridium tetnani, an anaerobic Gram-positive, spore-forming, rod-shaped soil bacterium.
2. Occurs through infection of a skin injury (cut, scarpe, stab wound) with spores of C. tetani, often coming from dirt. The spores germinate into vegetative (reproductive) bacilli in damaged, necrotic tissue in which the level of oxygen is low.
3. Bacterium is non-invasive, and the infection remains localized, but the bacilli produce a toxin.
4. The toxin migrates along nerves to the central nervous system, where it causes a tetanic paralysis in which the muscles cannot relax.
5. In 1989, the causative agent of tetanus, Clostridium tetani, was isolated from a human victim by Kitasato Shibasaburo. He later demostrated that the isolate could cause disease when injected into animals, adn that the toxin could be neutralized by specific antibodies.
6. Worldwide

Question 13

1. What is the tetanus toxin?
2. What is a lethal dose to humans?
3. What are the characteristic appearances of a patient?
4. What are some typical infections?

Answer 13

1. A neurotoxin, called tetanospasmin. Binds to nerve endings, blocking the release of inhibitory neurotransmitter (glycine) - muscles cannot relax - rigid paralysis.
2. Highly potent - 2.5 ng per kg body weight.
3. Risus sardonicus - a rigid smile, Trismus - lockjaw, Opisthotonus - a rigid, arched back.
4. A cut on the thumb, stepped on a nail, amputation of a broken arm or an injured foot, nicked by a razor, battle wound.

Question 14

1. What is the most common symptom?
   
   1. What is the treatment?
2. How is it transmitted?
3. How is prevented?

Answer 14

1. Lockjaw, spasms of the muscles of the jaw.
   
   1. Immediate use of human tetanus immunoglobulin (TIG) or equine immunoglobulin antitoxin.
2. Results from contamination of a wound with spores of C. tetani. The anaerobic environment facilitates C. tetani germination, replication and secretion of the toxin.
3. Vaccination with tetanus toxoid (formaldehyde inactivated toxin) induces formation of specific antitoxins (IgG antibodies specific to the toxin).
   
   1. Immunity is induced only by immunization with the toxoid. The degree and duration of immunity increases with the number of doses of toxoid given.