ABSTRACT

I. Introduction.......................................................................................................................... 390 A. Characteristics of BoNT Intoxication......................................................................... 391 B. Symptomology............................................................................................................ 392 C. Functional Domains of BoNT .................................................................................... 392

II. Manifestations of Botulism.................................................................................................. 393 A. Foodborne Botulism ................................................................................................... 394 B. Wound Botulism......................................................................................................... 395 C. Intestinal Botulism ...................................................................................................... 395

1. Infant Botulism .................................................................................................... 395 2. Adult Intestinal Botulism..................................................................................... 396

D. Inhalation Botulism .................................................................................................... 396 III. Prophylaxis and Treatment Options .................................................................................... 397

A. Antitoxin ..................................................................................................................... 398 1. Equine Botulinum Antitoxin................................................................................ 398 2. Recombinant Monoclonal Antibodies ................................................................. 398

B. Prophylaxis ................................................................................................................. 399 C. Pharmacological Intervention ..................................................................................... 399

1. Potassium Channel Blockers................................................................................ 400 2. Inhibitors for Specific Stages of Intoxication ...................................................... 401

IV. Conclusions and Future Research ....................................................................................... 411 Acknowledgments......................................................................................................................... 413 References ..................................................................................................................................... 413

The botulinum neurotoxins (BoNTs)* comprise a family of seven distinct neurotoxic proteins (A-G) produced by immunologically discrete strains of the anaerobic bacterium Clostridium botulinum and in rare cases by Clostridium baratii and Clostridium butyricum (Habermann and Dreyer, 1986; Harvey et al., 2002; Simpson, 2004). These toxins act on peripheral cholinergic synapses to inhibit spontaneous and impulse-dependent release of acetylcholine (ACh) (Brooks, 1956; Kao et al., 1976). Intoxication by BoNT results in muscle weakness, which can be fatal when the diaphragm and intercostal muscles become sufficiently compromised to impair ventilation (Dickson and Shevky, 1923). The BoNTs are the most potent substances in nature, and exposure to as little as 1-3 ng=kgmay be sufficient to cause human lethality (Gill, 1982; Middlebrook and Franz, 1997; Arnon et al., 2001).