Skip to main content
    • Aa
    • Aa

Botulism: Cause, Effects, Diagnosis, Clinical and Laboratory Identification, and Treatment Modalities


Botulism is a neuroparalytic disease caused by neurotoxins produced by the bacteria Clostridium botulinum. Botulinum neurotoxins (BoNTs) are among the most potent naturally occurring toxins and are a category A biological threat agent. The 7 toxin serotypes of BoNTs (serotypes A–G) have different toxicities, act through 3 different intracellular protein targets, and exhibit different durations of effect. Botulism may follow ingestion of food contaminated with BoNT, from toxin production of C botulinum present in the intestine or wounds, or from inhalation of aerosolized toxin. Intoxication classically presents as an acute, symmetrical, descending flaccid paralysis. Early diagnosis is important because antitoxin therapy is most effective when administered early. Confirmatory testing of botulism with BoNT assays or C botulinum cultures is time-consuming, and may be insensitive in the diagnosis of inhalational botulism and in as many as 32% of food-borne botulism cases. Therefore, the decision to initiate botulinum antitoxin therapy is primarily based on symptoms and physical examination findings that are consistent with botulism, with support of epidemiological history and electrophysiological testing. Modern clinical practice and antitoxin treatment has reduced botulism mortality rates from ∼60% to ≤10%. The pentavalent botulinum toxoid is an investigational product and has been used for more than 45 years in at-risk laboratory workers to protect against toxin serotypes A to E. Due to declining immunogenicity and potency of the pentavalent botulinum toxoid, novel vaccine candidates are being developed. (Disaster Med Public Health Preparedness. 2007;1:122–134)

Corresponding author
Address correspondence and reprint requests to Dr Zygmunt Dembek, USAMRIID, 1425 Porter St, Ft Detrick, MD 21702(e-mail:
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

2. RL Shapiro , C Hatheway , DL. Swerdlow Botulism in the United States: a clinical and epidemiological review. Ann Intern Med. 1998;129:221228.

3. SM. White Chemical and biological weapons. Implications for anaesthesia and intensive care. Br J Anaesth. 2002;89:306324.

6. BJ. Bernstein The birth of the US biological-warfare program. Sci Am. 1987;256:116121.

18. J Sobel , N Tucker , A Sulka , J McLaughlin , S. Maslanka Foodborne botulism in the United States, 1900-2000. Emerg Infect Dis. 2004;10:16061611.

21. JB McLaughlin , J Sobel , T Lynn , E Funk , JP. Middaugh Botulism type E outbreak associated with eating a beached whale, Alaska. Emerg Infect Dis. 2004;10:16851687.

23. M. Leitenberg Aum Shinrikyo’s efforts to produce biological weapons: a case study in the serial propagation of misinformation. Terrorism Political Violence. 1999;11:149158.

25. TJ Torok , RV Tauxe , RP Wise , et alA large community outbreak of salmonellosis caused by intentional contamination of restaurant salad bars. JAMA. 1997;278:389395.

29. TW Hennessy , CW Hedberg , L Slutsker , et alA national outbreak of Salmonella enteritidis from ice cream. N Engl J Med. 1996;334:12811296.

30. CA Ryan , MK Nickels , NT Hargrett-Bean , et alMassive outbreak of antimicrobial-resistant salmonellosis traced to pasteurized milk. JAMA. 1987;258:32693274.

31. LM Wein , Y. Liu Analyzing a bioterrorist attack on the food supply: the case of botulinum toxin in milk. Proc Natl Acad Sci U S A. 2005;102:99849989.

32. B. Alberts Modeling attacks on the food supply. Proc Natl Acad Sci U S A. 2005;102:97379738.

38. SS Arnon , R Schechter , TV Inglesby , et alBotulinum toxin as a biological weapon. Medical and public health management. JAMA. 2001;285:10591070.

42. P Aureli , L Fenicia , B Pasolini , M Gianfranceschi , LM McCroskey , CL. Hatheway Two cases of type E infant botulism caused by neurotoxigenic Clostridium butyricum in Italy. J Infect Dis. 1986;154:207211.

43. JR Barash , TWH Tang , SS. Arnon First case of infant botulism caused by Clostridium baratii type F in California. J Clin Microbiol. 2005;43:42804282.

44. O Sonnabend , O Sonnabend , R Heinzle , T Sigrist , R Dirnhofer , U. Krech Isolation of Clostridium botulinum type G and identification of type G botulinal toxin in humans: report of five sudden unexpected deaths. J Infect Dis. 1981;143:2227.

46. K Aktories , H. Barth Clostridium botulinum C2 toxin—new insights into the cellular up-take of the actin-ADP-ribosylating toxin. Int J Med Microbiol. 2004;293:557–64.

47. H Barth , K Aktories , MR Popoff , BG. Stiles Binary bacterial toxins: biochemistry, biology, and applications of common Clostridium and Bacillus proteins. Microbiol Mol Biol Rev. 2004;68:373402.

49. AB Scott , D. Suzuki Systemic toxicity of botulinum toxin by intramuscular injection in the monkey. Mov Disord. 1988;3:333335.

51. BA Woodruff , AM Griffin , LM McCroskey , et alClinical and laboratory comparison of botulism from toxin types A, B, and E in the United States, 1975-1988. J Infect Dis. 1992;166:12811286.

52. S Swaminathan , S. Eswaramoorthy Structural analysis of the catalytic and biding sites of Clostridium botulinum neurotoxin B. Nat Struct Biol. 2000;7:696699.

53. C. Lamanna The most poisonous poison. Science. 1959;130:763772.

54. FN Fu , RB Lomneth , SS Cai , et alRole of zinc in the structure and toxic activity of botulinum neurotoxin. Biochemistry. 1998;37:52675278.

56. A De Paiva , FA Meunier , J Molgo , KR Aoki , JO. Dolly Functional repair of motor endplates after botulinum neurotoxin type A poisoning: biphasic switch of synaptic activity between nerve sprouts and their parent terminals. Proc Natl Acad Sci U S A. 1999;96:32003205.

57. P Foran , N Mohammed , G Lisk , et alEvaluation of the therapeutic usefulness of botulinum neurotoxin B, C1, E, and F compared to the long-lasting type A: basis for distinct durations of inhibition of exocytosis in central neurons. J Biol Chem. 2003;278:13631371.

58. KR Aoki , B. Guyer Botulinum toxin type A and other botulinum toxin serotypes: a comparative review of biochemical and pharmacological actions. Eur J Neurol. 2001;8 (Suppl 5):2129.

59. LL. Simpson Identification of the major steps in botulinum toxin action. Ann Rev Pharmacol Toxicol. 2004;44:167193.

62. O Rossetto , M deBernard , R Pellizzari , et alBacterial toxins with intracellular protease activity. Clin Chim Acta. 2000;291:189199.

63. CO Tacket , WX Shandera , JM Mann , et alEquine antitoxin use and other factors that predict outcome in type A foodborne botulism. Am J Med. 1984;76:794798.

64. JM Hughes , JR Blumenthal , MH Merson , GL Lombard , Jr VR Dowell , EJ. Gangarosa Clinical features of types A and B food-borne botulism. Ann Intern Med. 1981;95:442445.

65. JC. Maroon Late effects of botulinum intoxication. JAMA. 1977;238:129.

66. JM Mann , S Martin , R Hoffman , S. Marrazzo Patient recovery from type A botulism: morbidity assessment following a large outbreak. Am J Public Health. 1981;71:266269.

67. JK Varma , G Katstadze , M Moiscrafishvili , et alSigns and symptoms predictive of death in patients with foodborne botulism–Republic of Georgia, 1989–2002. Clin Infect Dis. 2004;39:357–62.

69. SB Werner , D Passaro , J McGee , R Schechter , DJ. Vugia Wound botulism in California, 1951–1998: recent epidemic in heroin injectors. Clin Infect Dis. 2000;31:10181024.

70. RA Maselli , N. Bakshi American Association of Electrodiagnostic Medicine case report 16: botulism. Muscle Nerve. 2000;23:11371144.

71. M. Cherington Clinical spectrum of botulism. Muscle Nerve. 1998;21:701710.

72. L Padua , I Aprile , ML Monaco , et alNeurophysiological assessment in the diagnosis of botulism: usefulness of single-fiber EMG. Muscle Nerve. 1999;22:13881392.

73. DR Franz , PB Jahrling , AM Friedlander , et alClinical recognition and management of patients exposed to biological warfare agents. JAMA. 1997;278:399411.

75. HY Chao , YC Wang , SS Tang , HW. Liu A highly sensitive immuno-polymerase chain reaction assay for Clostridium botulinum neurotoxin type A. Toxicon. 2004;43:2734.

76. D Akbulut , KA Grant , J. McLauchlin Improvement in laboratory diagnosis of wound botulism and tetanus among injecting illicit-drug users by use of real-time PCR assays for neurotoxin gene fragments. J Clin Microbiol. 2005;43:43424348.

77. S Kongsaengdao , K Samintarapanya , S Rusmeechan , et alAn outbreak of botulism in Thailand: clinical manifestations and management of severe respiratory failure. Clin Infect Dis. 2006;43:12471256.

78. JD. Marks Medical aspects of biologic toxins. Anesthesiol Clin N Am. 2004;22:509532.

80. SL Gottlieb , K Kretsinger , N Tarkhashvili , et alLong-term outcomes of 217 botulism cases in the Republic of Georgia. Clin Infect Dis. 2007;45:174180.

83. CK Fox , CA Keet , JB. Strober Recent advances in infant botulism. Pediatr Neurol. 2005;32:149154.

89. DS Chertow , ET Tan , SE Maslanka , et alBotulism in 4 adults following cosmetic injections with an unlicensed, highly concentrated botulinum preparation. JAMA. 2006;296:24762479.

90. N Souyah , H Karim , SS Kamin , J McArdle , S. Marcus Severe botulism after focal injection of botulinum toxin. Neurology. 2006;67:18551856.

96. JM Rusnak , MG Kortepeter , RJ Hawley , AO Anderson , E Boudreau , E. Eitzen Risk of occupationally-acquired illnesses from biological threat agents in unvaccinated laboratory workers. Biosecurity Bioterrorism. 2004;2:281293.

106. TR Gelzleichter , MA Myers , RG Menton , NA Niemuth , MC Matthews , MJ. Langford Protection against botulinum toxins provided by passive immunization with botulinum human immune globulin: evaluation using an inhalation model. J Appl Toxicol. 1999;19:S35S38.

107. R Edelman , SS Wasserman , SA Bodison , JG Perry , M O’Donnoghue , LJ. DeTolla Phase II safety and immunogenicity study of type F botulinum toxoid in adult volunteers. Vaccine. 2003;21:4335–47.

108. Y Torii , Y Tokumaru , S Kawaguchi , et alProduction and immunogenic efficacy of botulinum tetravalent (A, B, E, F) toxoid. Vaccine. 2002;20:25562561.

109. JL Holley , M Elmore , M Mauchline , N Minton , RW. Titball Cloning expression and evaluation of a recombinant sub-unit vaccine against Clostridium botulinum type F toxin. Vaccine. 2000;19:288292.

111. J Clayton , FL. Middlebrook Vaccination of mice with DNA encoding a large fragment of botulinum neurotoxin serotype A. Vaccine. 2000;18:18551862.

112. RH Shyu , MF Shaio , SS Tang , et alDNA vaccination using the fragment C of botulinum neurotoxin type A provided protective immunity in mice. J Biomed Sci. 2000;7:5157.

113. KJ Potter , MA Bevins , EV Vassilieva , et alProduction and purification of the heavy-chain fragment C of botulinum neurotoxin, serotype B, expressed in the methylotrophic yeast, Picia pastoris. Protein Exp Purif. 1998;13:357365.

115. S Foynes , JL Holley , HS Garmory , RW Titball , NF. Fairweather Vaccination against type F botulinum toxin using attenuated Salmonella enterica var typhimurium strains expressing the BoNT/F hc fragment. Vaccine. 2003;21:10521059.

116. LA Smith , JM Jensen , VA Montgomery , DR Brown , SA Ahmed , TJ. Smith Roads from vaccines to therapies. Mov Disord. 2004;19:S48S52.

117. JL. Middlebrook Protection strategies against botulinum toxin. Adv Exp Med Biol. 1995;383:9398.

118. JB Park , LL. Simpson Progress toward development of an inhalation vaccine against botulinum toxin. Expert Rev Vaccines. 2004;3:477487.

119. JB Park , LL. Simpson Inhalational poisoning by botulinum toxin and inhalation vaccination with its heavy-chain component. Infect Immun. 2003;71:11471154.

120. MP Byrne , LA. Smith Development of vaccines for prevention of botulism. Biochimie. 2000;82:955–66.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Disaster Medicine and Public Health Preparedness
  • ISSN: 1935-7893
  • EISSN: 1938-744X
  • URL: /core/journals/disaster-medicine-and-public-health-preparedness
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 16
Total number of PDF views: 70 *
Loading metrics...

Abstract views

Total abstract views: 599 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 22nd September 2017. This data will be updated every 24 hours.