Pathogenesis

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Like other clostridia, C. botulinum produces endospores that are generally highly resistant to heat and therefore can persist in foods such as vegetables, fruit, meat, seafood, and cheese despite cooking and canning processes. These spores germinate if the environment is favorable—such as having a suitable nutrient, anaerobic conditions, a pH above 4.5, and a temperature above 39°F (4°C)—and growth of the bacteria results in the release of exotoxin into the food. When a person eats the food, the exotoxin resists digestion by stomach enzymes and acid, is absorbed by the small intestine, and can circulate in the bloodstream for 3 weeks or more. This exotoxin is a neurotoxin, meaning that it acts against the nervous system, and is one of the most powerful poisons known. A few milligrams of the toxin would be sufficient to kill the entire population of a large city. Indeed, cases of botulism have resulted from a person eating a single contaminated string bean, and from licking a finger contaminated with toxin.

The circulating neurotoxin attaches to motor nerves, blocking transmission of nerve signals to the muscles, and thereby producing paralysis. Normally, nerve signals are transmitted by a type of chemical known as a neurotransmitter, present in the nerve in tiny vesicles. The neurotoxin probably acts by preventing the vesicles from attaching to the cytoplasmic membrane of the nerve cell, thereby preventing discharge of the neurotransmitter by exocytosis. Like a number of other bacterial exotoxins, botulinal toxin is composed of two portions, A and B. The B portion attaches to specific receptors on motor nerve endings, and the A portion enters the nerve cell. The A portion then becomes an active peptidase enzyme that degrades the protein on the vesicle surface responsible for attachment to the cytoplasmic membrane. ■ A-B toxins, p. 472

Intestinal botulism occurs occasionally when C. botulinum colonizes the intestine, especially of infants 6 months of age or less, and produces a mild form of the disease characterized by constipation followed by generalized paralysis that can range from mild lethargy to respiratory insufficiency. In infants, C. botulinum organisms and toxin are often demonstrable in their feces, but the toxin levels are too low to be detectable in their blood. Most recover without receiving antitoxin treatment, although respirator support and tube feeding may be needed until the organisms are replaced by normal intestinal flora. These infections arise from C. botulinum spores, which are commonly present in dust and contaminate foods such as honey. Indeed, ingestion of honey has been implicated in 10% to 30% of infant botulism cases. Intestinal botulism also occurs in adults, particularly in immunodeficient patients whose normal intestinal flora have been suppressed by antibiotic treatment.

Clostridium botulinum can also colonize dirty wounds, especially those containing dead tissue. The bacteria do not invade, but they multiply in dead tissue and their neurotoxin diffuses into the bloodstream. Many cases have been due to wounds caused by abuse of injected drugs.

674 Chapter 26 Nervous System Infections

Clostridium botulinum neurotoxin can be used to treat people with certain chronic spastic conditions. Minute amounts of the toxin injected into the area of spasm give prolonged relief of symptoms. ■ Botox, p. 814

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