Botulinum Neurotoxin And Botulism

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Botulism is a rare but life-threatening disease caused by spore-forming bacteria of the Clostridia genus, including Clostridium Botulinum, C. baratii, and C. butyricum1. The disease results from bacterial secretion of botulinum neurotoxin, the most poisonous substance known.2 Approximately 7pg of pure neurotoxin is the LD50 for a mouse, and it has been estimated that the human LD 50 is approximately 0.09-0.15 |mg intravenously, 0.7-0.9 |mg inhalationally, and 70 |mg orally.3-6

Botulism is characterized by prolonged paralysis, which if not immediately fatal requires prolonged hospitalization in an intensive care unit (ICU) and mechanical ventilation. The potent paralytic abilities of the neurotoxin have also resulted in its development as a biowarfare and biothreat agent,7 as well as a medicine to treat a range of overactive muscle conditions including cervical dystonias, cerebral palsy, post-traumatic brain injury, and post-stroke spasticity.8

Clostridial neurotoxins differ significantly from each other in their amino acid sequence, resulting in the elicitation of different antibody responses. The different antibody responses allow the classification of the neurotoxins into different serotypes; antibodies that recognize one serotype do not recognize other serotypes. There are seven neurotoxin serotypes (A, B, C, D, E, F, and G),9,10 four of which (A, B, E, and F) cause naturally occurring human botulism.7

Naturally occurring botulism can result from ingestion of preformed toxin (food botulism) or from toxin produced in situ due to wound infection (wound botulism) or colonization of the gastrointestinal tract (infant or intestinal botulism). Botulism can also occur in exposed laboratory workers or from an overdose of therapeutic neurotoxin. In addition, the botulinum neurotoxins are classified by the Centers for Disease Control (CDC) as one of the six highest-risk threat agents for bioterrorism, due to their extreme potency and lethality, ease of production and transport, and victims' need for prolonged intensive care.7 Intoxication can occur via oral ingestion of toxin or inhalation of aerosolized toxin.11,12 While only four of the neurotoxin serotypes cause natural human disease, aerosolized neurotoxin serotypes C, D, and G produce botulism in primates by the inhalation route,11 and would most likely also affect humans. Thus it is likely that any one of the seven neurotoxin serotypes can be used as a biothreat agent. Due to the severity of illness and the potential for outbreaks, both foodborne and biothreat botulism are public health emergencies.

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