Botulism as a Potential Agent of Bioterrorism

  • Thomas P. Bleck
Part of the Emerging Infectious Diseases of the 21st Century book series (EIDC)

Abstract

The clostridial neurotoxins are among the most potently lethal substances in the world, with median lethal doses (LD50) for humans in the nanogram/kilogram range. The toxins are closely related proteins, produced as a single polypeptide chain and subsequently altered to produce a heavy chain and a light chain connected by disulfide bonds. The genetic information encoding the seven botulinum toxins is encoded on the bacterial chromosome; in contrast, tetanospasmin, the tetanus neurotoxin, is encoded on a plasmid. Both botulinum and tetanus toxins are relatively simple to produce. The botulinum toxins affect the neuromuscular junction and muscarinic peripheral autonomic synapses; their major manifestations are weakness and autonomic dysfunction. In stark relief, the predominant effect of tetanospasmin is in the central nervous system, where it produces failure of inhibition leading to hypertonia and spasms.

Keywords

Hydrolysis Magnesium Cocaine Neuropathy Diarrhea 

References

  1. Ahn-Yoon, S., DeCory, T.R., and Durst, R.A. (2004). Ganglioside-liposome immunoassay for the detection of botulinum toxin. Anal. Bioanal. Chem. 378:68–75.PubMedCrossRefGoogle Scholar
  2. Arnon, S.S., Schechter, R., Inglesby, T.V., Henderson, D.A., Bartlett, S.G., Ascher, M.S., Eitzen, E., Hauer, J., Layton, M., Lillibridge, S., Osterholm, M.T., O'Toole, T., Parker, G., Perl, T.M., Russell, P.K., Swerdlow, D.L., and Tonat, K, for the Working Group on Civilian Biodefence. (2001). Botulinum toxin as a biological weapon: medical and public health management. J.A.M.A. 285:1059–1070.PubMedCrossRefGoogle Scholar
  3. Barrett, D.H. (1991). Endemic food-borne botulism: clinical experience, 1973–1986. Alaska. Med. 33:101–108.PubMedGoogle Scholar
  4. Black, R.E., and Gunn, R.A. (1980). Hypersensitivity reactions associated with botulinal antitoxin. Am. J. Med. 69:567–70.PubMedCrossRefGoogle Scholar
  5. Buchman, A.S., Comella, C.L., Stebbins, G.T., Tanner, C.M., and Goetz, C.G. (1993). Quantitative electromyographic analysis of changes in muscle activity following botulinum toxin therapy for cervical dystonia. Clin. Neuropharmacol. 16:205–10.PubMedCrossRefGoogle Scholar
  6. Centers for Disease Control and Prevention. (1998). Botulism in the United States 1899–1996. In: Handbook for epidemiologists, clinicians, and laboratory workers. Centers for Disease Control and Prevention, Atlanta, Ga.Google Scholar
  7. Centers for Disease Control and Prevention. (1999). The history of bioterrorism. [Video]. Available at http://www.bt.cdc.gov/training/historyofbt/index.asp.
  8. Cherington, M. (1990). Botulism. Semin. Neurol. 10:27–31.PubMedCrossRefGoogle Scholar
  9. Cherington, M. (1982). Electrophysiologic methods as an aid in diagnosis of botulism. A review. Muscle. Nerve. 6:528–529.Google Scholar
  10. Chia, J.K., Clark, J.B., Ryan, C.A., and Pollack, M.(1986). Botulism in an adult associated with food-borne intestinal infection with Clostridium botulinum. N. Engl. J. Med. 315:239–241.PubMedCrossRefGoogle Scholar
  11. Cohen, F.L., Hardin, S.B., Nehring, W., Keough, M.A., Laurenti, S., McNabb, J., Platis, C., and Weber, C. (1998). Physical and psychosocial health status 3 years after catastrophic illness - botulism. Issues Mental Health Nurs. 9:387–398.CrossRefGoogle Scholar
  12. Colerbatch, J.G., Wolff, A.H., Gilbert, R.J., Mathias, C.J., Smith, S.E., Hirsch, N., and Wiles, C.M. (1989). Slow recovery from severe foodborne botulism. Lancet. 2:1216–1217.CrossRefGoogle Scholar
  13. Comella, C.L., Tanner, C.M., DeFoor-Hill, L., and Smith, C. (1992). Dysphagia after botulinum toxin injections for spasmodic torticollis: clinical and radiologic findings. Neurology 42(7):1307–1310.PubMedCrossRefGoogle Scholar
  14. Cornblath, D.R., Sladky, J.T., and Sumner A.J. (1983). Clinical electrophysiology of infantile botulism. Muscle. Nerve. 6:448–452.PubMedCrossRefGoogle Scholar
  15. Davis, J.B., Mattman, L.H., and Wiley, M. (1951). Clostridium botulinum in a fatal wound infection. J.A.M.A. 146:646–648.CrossRefGoogle Scholar
  16. Dowell, V.R. Jr., McCroskey, L.M., Hatheway, C.L., Lombard, G.L., Hughes, J.M., and Merson, M.H. (1977). Coproexamination for botulinal toxin and Clostridium botulinum. A new procedure for laboratory diagnosis of botulism. J.A.M.A. 238:1829–1832.PubMedCrossRefGoogle Scholar
  17. Dunbar, E.M. (1990). Botulism. J. Infect. 20:1–3.PubMedCrossRefGoogle Scholar
  18. Edell, T.A., Sullivan, C.P., Jr., Osborn, K.M., Gambin, J.P., and Brenman, R.D. (1983). Wound botulism associated with a positive tensilon test. West. J. Med. 139:218–219.PubMedGoogle Scholar
  19. Elston, H.R., Wang, M., and Loo, L.K. (1991). Arm abscesses caused by Clostridium botulinum. J. Clin. Microbiol. 29:2678–2379.PubMedGoogle Scholar
  20. Frankovich, T.L., and Arnon, S.S. (1991). Clinical trial of botulism immune globulin for infant botulism. West. J. Med. 154:103.PubMedGoogle Scholar
  21. Franz, D.R., Pitt, L.M., Clayton, M.A., Hanes, M.A., and Rose, K.J. (1993). Efficacy of prophylactic and therapeutic administration of antitoxin for inhalation botulism. In: Das Gupta, B.R. (ed.), Bot-ulinum and Tetanus Neurotoxins: Neurotransmission and Biomedical Aspects. Plenum, New York, pp. 473–476.Google Scholar
  22. Friedman, D.I., Fortanasce, V.N., and Sadun, A.A. (1990). Tonic pupils as a result of botulism. Am. J. Ophthalmol. 109:236–237.PubMedGoogle Scholar
  23. Glauser, T.A., Maquire, H.C., and Sladky, J.T. (1990). Relapse of infant botulism. Ann. Neurol. 28:187–189.PubMedCrossRefGoogle Scholar
  24. Gutmann, L., and Pratt, L. (1976). Pathophysiologic aspects of human botulism. Arch. Neurol. 33:175–179.PubMedCrossRefGoogle Scholar
  25. Hatheway, C.L. (1989). Bacterial sources of clostridial neurotoxins. In: Simpson, L.L. (ed.), Botu-linum Neurotoxin and Tetanus Toxin. Academic Press, San Diego, pp. 4–25.Google Scholar
  26. Holzer, V.E. (1962). Botulismus durch inhalation. Med. Klin. 57:1735–1738.PubMedGoogle Scholar
  27. Hughes, J.M., Blumenthal, J.R., Merson, M.H., Lombard, G.L., Dowell, V.R. Jr., and Gangarosa, E.J. (1981). Clinical features of types A and B foodborne botulism. Ann. Intern. Med. 95:442– 445.PubMedGoogle Scholar
  28. Kaplan, J.E., Davis, L.E., Narayan, V., Koster, J., and Katzenstein, D. (1979). Botulism, type A, and treatment with guanidine. Ann. Neurol. 6:69–71.PubMedCrossRefGoogle Scholar
  29. Kerner, J. (1928). Neue Beobachtungen über die in Würtemburg so haüfig vorfallen Vergiftung durch den Genuss gerauchter Würst. Tubingen, 1820. Quoted in: Damon, S.R. (ed.), Food Infections and Food Intoxications. Williams & Wilkins, Baltimore, p. 67.Google Scholar
  30. Kortepeter, M.G., Cieslak, T.J., and Eitzen, E.M. (2001). Bioterrorism. J. Environ. Health 63:21–24.PubMedGoogle Scholar
  31. Kudrow, D.B., Henry, D.A., Haake, D.A., Marshall, G., and Mathiesen, G.E. (1988). Botulism associated with Clostridium botulinum sinusitis after intranasal cocaine abuse. Ann. Intern. Med. 109:984–985.PubMedGoogle Scholar
  32. Landman, G. (1984). Ueber die Ursache der Darmstadter Bohnen Vergiftung. Hyg. Rundsch. 14:449–452.Google Scholar
  33. Lifton, R.J. (2000). Destroying the World to Save It. Henry Holt and Company, New York, pp. 39, 186–188.Google Scholar
  34. Liu, W., Montana, V., Chapman, E.R., Mohideen, U., and Parpura, V. (2003). Botulinum toxin type B micromechanosensor. Proc. Natl. Acad. Sci. U.S.A. 100:13621–13625.PubMedCrossRefGoogle Scholar
  35. Middlebrook, J.L., and Franz, D.R. (1997). Botulinum toxins. In: Sidell, F.R., Takafuji, E.T., and Franz, D.R. (eds), Medical Aspects of Chemical and Biological Warfare. Office of the Surgeon General, Washington, D.C. Available online at: https://ccc.apgea.army.mil.
  36. Midura, T.F., and Arnon, S.S. (1976). Infant botulism: identification of Clostridium botulinum and its toxin in faeces. Lancet. 2:934–936.PubMedCrossRefGoogle Scholar
  37. M'ikantha, N.M., Southwell, B., and Lautenbach, E. (2003). Automated laboratory reporting of infectious diseases in a climate of bioterrorism. Emerg. Infect. Dis. 9:1053–1057.PubMedCrossRefGoogle Scholar
  38. Notermans, S., and Nagel, J. (1989). Assays for botulinum and tetanus toxins. In: Simpson, L.L. (ed.), Botulinum Neurotoxin and Tetanus Toxin. Academic Press, San Diego, pp. 319–331.CrossRefGoogle Scholar
  39. Notermans, S.H.W., Wokke, J.H.J., and van. den. Berg., L.H. (1982). Botulism and Guillain-Barré syndrome. Lancet. 340:303.CrossRefGoogle Scholar
  40. Oguma, K., Yokota, K., Hayashi, S., Takeshi, K., Kumagai, M., Itosh, N., and Chiba S. (1990). Infant botulism due to Clostridium botulinum type C toxin. Lancet. 336:1449–1450.PubMedCrossRefGoogle Scholar
  41. Oken,A, Barnes, S., Rock, P., and Maxwell, L. (1992). Upper airway obstruction and infant botulism. Anesth. Analg. 75:136–138.PubMedCrossRefGoogle Scholar
  42. Peruski, A.H., Johnson, L.H. 3rd, and Peruski, L.F. Jr. (2002). Rapid and sensitive detection of biological warfare agents using time-resolved fluorescence assays. J. Immunol. Methods. 263:35–41.PubMedCrossRefGoogle Scholar
  43. Schreiner, M.S., Field, E., and Ruddy, R. (1991). Infant botulism: a review of 12 years experience at the Children's Hospital of Philadelphia. Pediatrics. 87:159–165.PubMedGoogle Scholar
  44. Smith, L.D.S. (1977). Botulism: The Organism, Its Toxins, The Disease. CC Thomas, Springfield, 236 pp.Google Scholar
  45. Tacket, C.O., and Rogawski, M.A. (1989). Botulism. In: Simpson, L.L. (ed.), Botulism Neurotoxin and Tetanus Toxin, Academic Press, San Diego, pp. 351–378.CrossRefGoogle Scholar
  46. Terranova, W., Breman, J.G., Locey, R.P., and Speck, S. (1978). Botulism type B: epidemiologic aspects of an extensive outbreak. Am. J. Epidemiol. 108:150–156.PubMedGoogle Scholar
  47. Terranova, W., Palumbo, J.N., and Berman, J.G. (1979). Ocular findings in botulism type B. J.A.M.A. 241:475–477.PubMedCrossRefGoogle Scholar
  48. Todd, E.C.D. (1989). Costs of acute bacterial foodborne disease in Canada and the United States. Int. J. Food Microbiol. 9:313–326.PubMedCrossRefGoogle Scholar
  49. van Ermengen, E. (1897). Ueber einen neuen anaëroben Bacillus und seine Beziehungen zum Botu-lismus. Zeitschrift für Hygiene und Infektionskrankheiten 26:1–256.Google Scholar
  50. Vita, G., Girlanda. P., Puglisi, R.M., Marbello, L., and Messina, C. (1987). Cardiovascular-reflex testing and single-fiber electromyography in botulism. A longitudinal study. Arch. Neurol. 44:202–206.PubMedCrossRefGoogle Scholar
  51. Wackers, G.L. (1994). Modern anaesthesiological principles for bulbar polio: manual IPPR in the 1952 polio-epidemic in Copenhagen. Acta. Anaesthesiol. Scand. 38:420–431.PubMedCrossRefGoogle Scholar
  52. Wilcox, P.G., Morrison, N.J., and Pardy, R.L. (1990), Recovery of the ventilatory and upper airway muscles and exercise performance after type A botulism. Chest. 98:620–626.PubMedCrossRefGoogle Scholar
  53. Williams, P., and Wallace, D. (1989). Unit 731: Japan's Secret Biological Warfare in World War II. The Free Press, New York, pp. 27–28.Google Scholar
  54. Woodruff, B.A., Griffin, P.M., McCroskey, L.M., Smart, J.F., Wainwright, R.B., Bryant, R.G., Hutwagner, L.C., and Hatheway, C.L. (1992). Clinical and laboratory comparison of botulism from toxin type A, B, and E in the United States, 1975–1988. J. Infect. Dis. 166:1281–1286.PubMedCrossRefGoogle Scholar
  55. Young, J.H. (1976). Botulism and the ripe olive scare of 1891–1920. Bull. History Med. 50:372–391.Google Scholar
  56. Zilinskas, R.A. (1997). Iraq's biological weapons. The past as future?. J.A.M.A. 278:418–424.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Thomas P. Bleck
    • 1
  1. 1.Neurological Surgery and Internal MedicineNeuroscience Intensive Care UnitCharlottesvilleVA

Personalised recommendations