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BOTULISM

Botulism is a disease caused by exposure to a protein neurotoxin made by various subtypes of the bacterium Clostridium botulinum. This organism is gram-positive, anaerobic, forms spores (sub terminal) and exists naturally in soil and some marine environments. Exposure to the bacterial toxin, most potent of all bacterial toxins, occurs through ingestion of contaminated food, contaminated wounds, by bacterial production in the intestines of infants, and possibly through aerosolization in a bioterrorist attack. Note that this toxin does not penetrate skin, but requires a wound, ingestion or inhalation.

Botulinum toxin, of which there are multiple antigenic varieties, is carried through the blood vascular system to peripheral cholinergic nerve terminals, including neuromuscular junctions, and to postganglionic parasympathetic junctions, where it is taken into the cell cytoplasm. The toxin, a zinc endopeptidase, destroys the intracellular organelles that normally release acetylcholine, in an irreversible fashion. This produces a clinically characteristic flaccid paralysis.

The time of onset, severity of symptoms, and time course of the illness all depend upon the amount of toxin in the exposure and/or the amount of bacteria present. In food-borne botulism, the time of onset averages 18-36 hours, though symptoms may appear within a few hours or as late as several days later. Wound botulism typically takes a week or so to appear. Symptoms in infant botulism are variable in timing, again depending upon the length of time the bacteria are in the intestine. Little is published regarding the bioterrorist use of botulinum toxin, but it is thought that in such an attack (food-borne or aerosolized), symptoms would present within 12-72 hours after exposure1. The Japanese sect Aum Shinrikyo tried unsuccessfully to use botulinum toxin as a biological weapon in the early 1990s.

Patients with botulinum toxin poisoning typically present with difficulty speaking and swallowing, dizziness, blurred or double vision, dry mouth, dry or sore throat, and possibly, nausea, vomiting and abdominal pain, depending on the site of exposure. They are not typically febrile, tend to be mentally oriented, and may be drowsy, agitated and anxious. On examination, they classically present a symmetrical descending flaccid paralysis, beginning with the cranial nerves (bulbar paralysis), presenting diplopia, ptosis, dysarthria, possibly dysphagia, with papillary reflexes depressed, fixed or dilated. The flaccid paralysis/weakness then extends to the neck, chest, arms and legs, usually with normal to decreased deep tendon reflexes. Weakness may be asymmetrical and sensation is typically normal. Paralytic ileus, constipation and urinary retention are common and may be severe.

A diagnosis of botulinum toxin poisoning must be considered in an afebrile, mentally intact patient with symmetric descending flaccid paralysis without sensory findings. Though current development is underway for more rapid laboratory testing for the toxin (polymerase chain reaction and ELISA), the current testing available is a mouse bioassay, used for confirmation. If the source of the toxin is food or a wound, culture of the organism may be helpful. Other syndromes that may be confused with botulinum toxin poisoning include myasthenia gravis, Guillain-Barre’ syndrome, Lambert-Eaton syndrome, poliomyelitis, other intoxications (mushrooms, medications, etc.), tick-bite paralysis, and hypermagnesemia.

Patients with botulinum toxin poisoning should be hospitalized, supported and monitored closely for respiratory failure. Persons potentially exposed to botulinum toxin should be closely observed and quickly treated if signs and symptoms develop. In severe cases, intubation and sometimes prolonged (months) mechanical ventilation are necessary. A multivalent equine antitoxin, available from the state health department and CDC, has been used successfully in the food-borne variant and has been recommended for those exposed who show signs of botulism1. Treatment must proceed before microbiological or other testing is completed. Treatment with antitoxin is effective in rendering circulating toxin ineffective, but toxin that has already bound to neural synapses will destroy the synapse and a clinical return to normal functioning must await the regrowth of new synaptic cells (weeks to months).

Beyond bioterrorism concerns, it should be remembered that botulism is always a concern with improperly prepared or canned food. The botulinum toxin is destroyed by heating at 100 degrees C for 10 minutes, but C. botulinum spores, being very heat resistant, require heating at 120 degrees C (steam sterilizer or pressure cooker).

1 Arnon, et.al., Botulinum toxin as a biological weapon: medical and public health management. JAMA 2001 Feb 28;285(8):1059-70

Kenneth C. Cummings, MD
Chief, Clinical Pathology
December, 2001