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Botulinum toxin, which is produced by a bacterium known as Clostridium botulinum, is the most poisonous substance known to man. In animals, only 0.001 microgram per kilogram of body weight results in a fatality rate of 50%. Recent concern has focused on the possible use of botulinum toxin as a biological weapon, either by contamination of water supplies or aerosol dissemination. However, botulinum toxin is readily inactivated by sunlight, heat, and chlorine, which would limit though not eliminate its potential as a biological weapon.
Most cases of botulism are caused by ingestion of pre-formed toxin in contaminated foods. In newborns, botulism may develop from multiplication of Clostridium botulinum organisms in the immature gut. Rarely, botulinum toxin enters the body through an open wound. Though this does not happen in nature, the toxin can be aerosolized and absorbed from the respiratory tract. Regardless of how the toxin enters the body, the resulting clinical syndrome is essentially the same.
Botulinum toxin acts by blocking acetylcholine release at peripheral cholinergic synapses, chiefly at the neuromuscular junction. Clinically, botulism presents as a symmetric, descending flaccid paralysis that begins in the head and face and spreads downward. Initial findings may include drooping eyelids, blurred vision, double vision, dry mouth, slurred speech and difficulty swallowing, followed by loss of muscle tone, generalized weakness, and loss of the gag reflex, which may require intubation to protect the airway. Patients may appear lethargic, but mentation is otherwise normal. Sensory abnormalities do not occur. There is no fever. The cerebrospinal fluid is normal. Electromyography may be helpful in distinguishing botulism from other flaccid paralyses,
Diagnosis is usually made on the basis of symptoms and physical examination. The diagnosis should be confirmed by assaying blood, stool, gastric aspirate, and possibly other body fluids for botulinum toxin, which is performed at a small number of reference laboratories. Samples must be obtained before the patient has received antitoxin.
The treatment of botulism is to give antitoxin, which is available from the health department, and to support aggressively, preferably in an ICU. The licensed antitoxin contains antibodies against three of the seven types of botulinum toxin (A, B, and E), which cause most cases of human disease. An investigational antitoxin which is active against all seven types is held by the US Army. Because botulinum antitoxin is derived from horses, hypersensitivity reactions, including hives, serum sickness, and anaphylaxis, occur in a significant minority of patients.
Those who have been exposed to botulinum toxin but remain asymptomatic are generally observed closely and not given antitoxin, due to short supplies of antitoxin and the frequency of hypersensitivity reactions. An investigational vaccine containing botulinum toxoid (analogous to tetanus toxoid) has been used for more than thirty years to immunize laboratory workers, but is not routinely given to the general population due to the rarity of botulism and the scarcity of the vaccine. The vaccine is not effective when given after exposure.
From the Centers for Disease Control
From the Journal of the American Medical Association (JAMA)
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