Background
Botulism is an acute neurologic disorder that causes potentially life-threatening neuroparalysis due to a neurotoxin produced by Clostridium botulinum. The toxin binds irreversibly to the presynaptic membranes of peripheral neuromuscular and autonomic nerve junctions. Toxin binding blocks acetylcholine release, resulting in weakness, flaccid paralysis, and, often, respiratory arrest. Cure occurs following sprouting of new nerve terminals.
The 3 main clinical presentations of botulism include infant botulism (IB), foodborne botulism (FBB), and wound botulism (WB). Additionally, because of the potency of the toxin, the possibility of botulism as a bioterrorism agent or biological weapon is a great concern.[1] For more information, see CBRNE – Botulism.
Infant botulism is caused by ingested C botulinum spores that germinate in the intestine and produce toxin. These spores typically come from bee honey or the environment. Most infants fully recover with supportive treatment; the attributed infant mortality rate is less than 1%. Improperly canned or home-prepared foods are common sources of the toxin that can result in foodborne botulism. Wound botulism results from contamination of a wound with toxin-producing C botulinum. Foodborne botulism and wound botulism occur predominantly in adults and are the focus of this article.
C botulinum is an anaerobic gram-positive rod that survives in soil and marine sediment by forming spores. Under anaerobic conditions that permit germination, it synthesizes and releases a potent exotoxin. Microbiologically, the organism stains gram-positive in cultures less than 18 hours old. The organism may stain gram-negative after 18 hours of incubation, potentially complicating attempts at diagnosis. On a molecular weight basis, botulinum toxins are the most potent toxins known.
Eight antigenically distinct C botulinum toxins are known, including A, B, C (alpha), C (beta), D, E, F, and G. Each strain of C botulinum can produce only a single toxin type. Types A, B, E, and, rarely, F cause human disease. Toxins A and B are the most potent, and the consumption of small amounts of food contaminated with these types has resulted in full-blown disease. During the last 20 years, toxin A has been the most common cause of foodborne outbreaks; toxins B and E follow in frequency. In 15% of C botulinum infection outbreaks, the toxin type is not determined. Toxins C and D cause disease in various animals. Type G toxin has been associated with sudden death but not with neuroparalytic illness. It was isolated from autopsy material from 5 patients in Switzerland in 1977.
Pathophysiology
The mechanism of action involves toxin-mediated blockade of neuromuscular transmission in cholinergic nerve fibers. This is accomplished by either inhibiting acetylcholine release at the presynaptic clefts of the myoneural junctions or by binding acetylcholine itself. Toxins are absorbed from the stomach and small intestine, where they are not denatured by digestive enzymes. Subsequently, they are hematogenously disseminated and block neuromuscular transmission in cholinergic nerve fibers. The nervous, gastrointestinal, endocrine, and metabolic systems are predominantly affected.
Because the motor end plate responds to acetylcholine, botulinum toxin ingestion results in hypotonia that manifests as descending symmetric flaccid paralysis and is usually associated with gastrointestinal symptoms of nausea, vomiting, and diarrhea. Cranial nerves are affected early in the disease course. Later complications include paralytic ileus, severe constipation, and urinary retention.
Wound botulism results when wounds are contaminated with C botulinum spores. Wound botulism has developed following traumatic injury that involved soil contamination, among injection drug users (particularly those who use black-tar heroin[2] ), and after cesarean delivery. The wound may appear deceptively benign. Traumatized and devitalized tissue provides an anaerobic medium for the spores to germinate into vegetative organisms and to produce neurotoxin, which then disseminates hematogenously. The nervous, endocrine, and metabolic systems are predominantly affected. Symptoms develop after an incubation period of 4-14 days, with a mean of 10 days. The clinical symptoms of wound botulism are similar to those of foodborne botulism except that gastrointestinal symptoms (including nausea, vomiting, diarrhea) are uncommon.
Epidemiology
Frequency
United States
In the United States, approximately 154 cases of botulism are reported annually to the Centers for Disease Control and Prevention (CDC). Infant botulism accounts for nearly 75% of all botulism cases.
The incidence of foodborne botulism is approximately 24 cases per year. The incidence of wound botulism is 3 cases per year. The incidence of infant botulism is 71 cases per year, with a mean age of 3 months.
Toxin A is found predominantly west of the Mississippi River. Toxin B is found most commonly in the eastern United States. Toxin E is found in northern latitudes, such as the Pacific Northwest, the Great Lakes region, and Alaska. The frequency of botulism in native Alaskans is among the highest in the world.[3] Toxin E outbreaks are frequently associated with fish products.
International
Human botulism is found worldwide. Spores from C botulinum strains that produce type A or B toxins are distributed widely in the soil and have been found throughout the world. Toxin type B is commonly found in Europe. Toxin G was originally isolated in Switzerland.
Mortality/Morbidity
- Mortality rates vary based on the age of the patient and the type of botulism. Foodborne botulism carries an overall mortality rate of 5-10%. Wound botulism carries a mortality rate that ranges from 15-17%. The risk of death due to infant botulism is usually less than 1%.
- The recovery period from botulism is often prolonged (30-100 d). Some patients demonstrate residual weakness or autonomic dysfunction for 1 year after the onset of the illness. However, most patients achieve full neurologic recovery. Permanent deficits may occur in those who sustain significant hypoxic insults.
Sex
Wound botulism is more common in males. Foodborne botulism has no sexual predilection.
Age
Foodborne botulism and wound botulism predominately occur in adults. The mean age of infant botulism is 3 months.
[Guideline] Bossi P, Tegnell A, Baka A, et al. Bichat guidelines for the clinical management of botulism and bioterrorism-related botulism. Euro Surveill. Dec 15 2004;9(12):E13-4. [Medline].
Passaro DJ, Werner SB, McGee J, et al. Wound botulism associated with black tar heroin among injecting drug users. JAMA. Mar 18 1998;279(11):859-63. [Medline].
Shaffer N, Wainwright RB, Middaugh JP, et al. Botulism among Alaska Natives. The role of changing food preparation and consumption practices. West J Med. Oct 1990;153(4):390-3. [Medline].
Yuan J, Inami G, Mohle-Boetani J, Vugia DJ. Recurrent wound botulism among injection drug users in California. Clin Infect Dis. Apr 1 2011;52(7):862-6. [Medline].
Angulo FJ, Getz J, Taylor JP, et al. A large outbreak of botulism: the hazardous baked potato. J Infect Dis. Jul 1998;178(1):172-7. [Medline].
St Louis ME, Peck SH, Bowering D, et al. Botulism from chopped garlic: delayed recognition of a major outbreak. Ann Intern Med. Mar 1988;108(3):363-8. [Medline].
Arnon SS. Creation and development of the public service orphan drug Human Botulism Immune Globulin. Pediatrics. Apr 2007;119(4):785-9. [Medline].
Cai S, Singh BR, Sharma S. Botulism diagnostics: from clinical symptoms to in vitro assays. Crit Rev Microbiol. Apr-Jun 2007;33(2):109-25. [Medline].
Cardoso F, Jankovic J. Clinical use of botulinum neurotoxins. Curr Top Microbiol Immunol. 1995;195:123-41. [Medline].
Cherington M. Botulism: update and review. Semin Neurol. Jun 2004;24(2):155-63. [Medline].
Clemmens MR, Bell L. Infant botulism presenting with poor feeding and lethargy: a review of 4 cases. Pediatr Emerg Care. Jul 2007;23(7):492-4. [Medline].
Critchley EM, Mitchell JD. Human botulism. Br J Hosp Med. Apr 1990;43(4):290-2. [Medline].
Fox CK, Keet CA, Strober JB. Recent advances in infant botulism. Pediatr Neurol. Mar 2005;32(3):149-54. [Medline].
Glik D, Harrison K, Davoudi M, et al. Public perceptions and risk communications for botulism. Biosecur Bioterror. 2004;2(3):216-23. [Medline].
Hallett M. One man's poison--clinical applications of botulinum toxin. N Engl J Med. Jul 8 1999;341(2):118-20. [Medline].
Hatheway CL. Botulism: the present status of the disease. Curr Top Microbiol Immunol. 1995;195:55-75. [Medline].
Jahn R, Niemann H. Molecular mechanisms of clostridial neurotoxins. Ann N Y Acad Sci. Sep 15 1994;733:245-55. [Medline].
Lawrence DT, Dobmeier SG, Bechtel LK, et al. Food poisoning. Emerg Med Clin North Am. May 2007;25(2):357-73; abstract ix. [Medline].
Lecour H, Ramos H, Almeida B, et al. Food-borne botulism. A review of 13 outbreaks. Arch Intern Med. Mar 1988;148(3):578-80. [Medline].
Long SS. Infant botulism and treatment with BIG-IV (BabyBIG). Pediatr Infect Dis J. Mar 2007;26(3):261-2. [Medline].
Oguma K, Fujinaga Y, Inoue K. Structure and function of Clostridium botulinum toxins. Microbiol Immunol. 1995;39(3):161-8. [Medline].
Roblot P, Roblot F, Fauchere JL, et al. Retrospective study of 108 cases of botulism in Poitiers, France. J Med Microbiol. Jun 1994;40(6):379-84. [Medline].
Schiavo G, Rossetto O, Tonello F, et al. Intracellular targets and metalloprotease activity of tetanus and botulism neurotoxins. Curr Top Microbiol Immunol. 1995;195:257-74. [Medline].
Shapiro RL, Hatheway C, Swerdlow DL. Botulism in the United States: a clinical and epidemiologic review. Ann Intern Med. Aug 1 1998;129(3):221-8. [Medline].
Slater PE, Addiss DG, Cohen A, et al. Foodborne botulism: an international outbreak. Int J Epidemiol. Sep 1989;18(3):693-6. [Medline].
Sobel J, Tucker N, Sulka A, et al. Foodborne botulism in the United States, 1990-2000. Emerg Infect Dis. Sep 2004;10(9):1606-11. [Medline].
Varma JK, Katsitadze G, Moiscrafishvili M, et al. Signs and symptoms predictive of death in patients with foodborne botulism--Republic of Georgia, 1980-2002. Clin Infect Dis. Aug 1 2004;39(3):357-62. [Medline].
Weber JT, Goodpasture HC, Alexander H, et al. Wound botulism in a patient with a tooth abscess: case report and review. Clin Infect Dis. May 1993;16(5):635-9. [Medline].
Wilcox PG, Morrison NJ, Pardy RL. Recovery of the ventilatory and upper airway muscles and exercise performance after type A botulism. Chest. Sep 1990;98(3):620-6. [Medline].
Print
