Chapter 134. Botulism (Part 1)

Harrisons Internal Medicine Chapter 134. BotulismDefinition Botulism is a paralytic disease caused by potent protein neurotoxins elaborated by Clostridium botulinum. Illness begins with cranial nerveinvolvement and proceeds caudally to involve the extremities. Cases may be classified as (1) food-borne botulism, from ingestion of preformed toxin in food contaminated with C. botulinum; (2) wound botulism, from toxin produced in wounds contaminated with the organism; and (3) intestinal botulism, from ingestion of spores and production of toxin in the intestine of infants (infant botulism) or adults. Botulinum toxin, because of its extraordinary potency, has long been considered a threat as...
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Chapter 134. Botulism (Part 1) Chapter 134. Botulism (Part 1) Harrisons Internal Medicine > Chapter 134. Botulism Definition Botulism is a paralytic disease caused by potent protein neurotoxinselaborated by Clostridium botulinum. Illness begins with cranial nerveinvolvement and proceeds caudally to involve the extremities. Cases may beclassified as (1) food-borne botulism, from ingestion of preformed toxin in foodcontaminated with C. botulinum; (2) wound botulism, from toxin produced inwounds contaminated with the organism; and (3) intestinal botulism, fromingestion of spores and production of toxin in the intestine of infants (infantbotulism) or adults. Botulinum toxin, because of its extraordinary potency, haslong been considered a threat as an agent of bioterrorism or biologic warfare thatcould be acquired by inhalation or ingestion (Chap. 214). Iatrogenic botulism canfollow cosmetic or therapeutic use of toxin. †Deceased. A contributor to HPIM since the 12th edition, Dr. Abrutynpassed away on February 22, 2007. Etiologic Agent C. botulinum, a species encompassing a heterogeneous group of anaerobicgram-positive organisms that form subterminal spores, is found in soil and marineenvironments throughout the world and elaborates the most potent bacterial toxinknown. Organisms of types A through G have been distinguished by the antigenicspecificities of their toxins; a classification system based on physiologiccharacteristics has also been described. Rare strains of other clostridial species—C. butyricum and C. baratii—have been found to produce toxin. C. botulinumstrains with proteolytic activity can digest food and produce a spoiled appearance;nonproteolytic types leave the appearance of food unchanged. Of the eight distinct toxin types described (A, B, C 1, C2, D, E, F, and G), allexcept C2 are neurotoxins; C2 is a cytotoxin of unknown clinical significance.Botulinum neurotoxin, whether ingested, inhaled, or produced in the intestine or awound, enters the vascular system and is transported to peripheral cholinergicnerve terminals, including neuromuscular junctions, postganglionicparasympathetic nerve endings, and peripheral ganglia. The central nervoussystem is not involved. Steps in neurotoxin activity include binding,internalization in endocytic vesicles, translocation to the cytosol, and proteolysisresulting in a blockage of the release of the neurotransmitter acetylcholine (Fig.134-1). Cure follows sprouting of new nerve terminals. Figure 134-1 The synaptic vesicle release apparatus and the sites of action ofbotulinum toxins. Toxin acts to block neurotransmitter release from the synapticvesicle into the synaptic cleft. The site of action of tetanus toxin is also shown.[From TP Bleck et al: In WM Scheld et al (eds): Infections of the Central NervousSystem, 2d ed. New York, Raven Press, 1997; with permission.] Toxin types A, B, E, and (rarely) F cause disease in humans; type G (fromC. argentinense) has been associated with sudden death, but not withneuroparalytic illness, in a few patients in Switzerland; and types C and D causedisease in animals. Epidemiology Human botulism occurs worldwide. In the United States, the geographicdistribution of cases by toxin type parallels the distribution of organism typesfound in the environment. Type A predominates west of the Rocky Mountains;type B is generally distributed but is more common in the East; and type E isfound in the Pacific Northwest, Alaska, and the Great Lakes area. Food-borne botulism in the United States is associated primarily withhome-canned food (particularly vegetables, fruit, and condiments) and lesscommonly with meat and fish. Type E outbreaks are frequently associated withfish products. Commercial products occasionally cause outbreaks, some of whichare attributable to improper handling after purchase. Outbreaks in restaurants,schools, and private homes have been traced to uncommon sources (commercialpotpies, beef stew, turkey loaf, sautéed onions, baked potatoes, preserved greenolives, bamboo shoots, and chopped garlic in oil). Food-borne botulism can occurwhen (1) food to be preserved is contaminated with spores, (2) preservation doesnot inactivate the spores but kills other putrefactive bacteria that might inhibitgrowth of C. botulinum and provides anaerobic conditions at a pH and temperaturethat allow germination and toxin production, and (3) food is not heated to atemperature that destroys toxin before being eaten.