Botulinum Toxin as a Biological Weapon

Abstract

An aerosolized or foodborne botulinum toxin weapon would cause acute symmetric, descending flaccid paralysis with prominent bulbar palsies such as diplopia, dysarthria, dysphonia, and dysphagia that would typically present 12 to 72 hours after exposure. Effective response to a deliberate release of botulinum toxin will depend on timely clinical diagnosis, case reporting, and epidemiological investigation. Persons potentially exposed to botulinum toxin should be closely observed, and those with signs of botulism require prompt treatment with antitoxin and supportive care that may include assisted ventilation for weeks or months. Treatment with antitoxin should not be delayed for microbiological testing.

Sensing the Deadliest Toxin: Technologies for Botulinum Neurotoxin Detection

“…Besides soil and spoiled food, C. botulinum can grow in wounds or the human intestine and can be also cultured in large scale in a laboratory. Due to the extreme potency, lethality and easy procurement, BoNTs have the potential to be very dangerous biological weapon and therefore represent significant warfare and terrorism threat [5]. Consequently, BoNTs are one of the six category A agents listed as the highest risk threat agents for bioterrorism by the US Centers for Disease Control and Prevention (CDC) [6].…”

“…Ingestion of food contaminated with BoNT-producing C. botulinum , wound infections and intestinal colonizing infections in infants (as well as adults with misbalanced intestinal flora) are three most common causes of botulism disease [5,20,21]. In the case of an infected wound or intestine, toxin is produced in vivo by C. botulinum .…”

Synthesis and structure–activity relationships of second-generation hydroxamate botulinum neurotoxin A protease inhibitors

“…An effective immunoprophylactic vaccine is available, but the development of protection is slow, with annual boosters required to produce adequate antibody titers. 5 In addition, equine antitoxins can be used for the treatment of adult botulism, but this therapy also can cause severe adverse reactions including serum sickness and anaphylaxis. 6 Finally, there are reports of the successful use of multiple monoclonal antibodies as BoNT/A antitoxins.…”

Botulinum Neurotoxin Serotype F: Identification of Substrate Recognition Requirements and Development of Inhibitors with Low Nanomolar Affinity

“…In the United States, there are ∼200 cases of human botulism each year, due to ingestion of toxin-contaminated food, wound infections, or colonization of the intestinal tract by C. botulinum (5-7). However, much of the current interest in BoNTs 1 stems from their use as tools in research on the mechanisms of neurotransmission (1,8,9), an ever-expanding number of applications in the treatment of human muscle dysfunctions (10-13), and their potential for use as bioterrorist weapons (14).Intoxication resulting in the flaccid paralysis of botulism or the spastic paralysis of tetanus has been described as a four-step process, consisting of (1) toxin binding to specific receptors on neurons, (2) receptor-mediated toxin endocytosis, (3) translocation through the endosomal membrane, and (4) proteolytic inactivation of neuronal proteins critical to the mechanism of neurotransmitter release. The first three steps are mediated by the heavy chain, while the fourth is effected by the zinc metalloprotease activity of the light chain (15,16).…”