Botulism

Botulism is an acute neurologic disorder with potentially life-threatening neuroparalysis that is caused by a neurotoxin produced by Clostridium botulinum (CB). 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, food-borne, and wound. Additionally, because of the potency of the toxin, the possibility of botulism as a bioterrorism agent or biological weapon is a great concern.

Infant botulism (IB) arises from ingested botulism 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 infant mortality rate is less than 1%. Improperly canned or home-prepared foods are common sources of the toxin that can result in food-borne botulism (FBB). Wound botulism (WB) results from contamination of the wound with toxin-producing CB. FBB and WB occur predominantly in adults and are the focus of this article.

CB 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 CB toxins are known, including A, B, C (alpha), C (beta), D, E, F, and G. Each strain of CB is limited to producing 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 them has resulted in full-blown disease. During the last 20 years, toxin A has been the most frequent cause of food-borne outbreaks; toxins B and E follow in frequency. In 15% of CB outbreaks, the toxin type is not determined. Toxins C and D cause disease in a variety of 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 course of disease. Later complications include paralytic ileus, severe constipation, and urinary retention.

WB results when wounds are contaminated with CB spores. It has occurred (1) after traumatic injury that involved soil contamination, (2) among injection drug users, particularly those who use black-tar heroin, and (3) 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 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 WB are similar to those of FBB except that gastrointestinal symptoms (including nausea, vomiting, diarrhea) are uncommon.

Frequency
United States
The frequency is 0.034 cases out of 100,000 population, of which nearly 75% are associated with IB.

FBB incidences total 24 cases per year. WB incidences total 3 cases per year and 3 cases per year from the young adult cohort (aged 18-25 y). IB incidences total 71 cases per year, with a mean age of 3 months. FBB incidence totals 24 cases per year drawn from all age cohorts.

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 native peoples have some of the highest rates of botulism in the world. Toxin E outbreaks frequently are associated with fish products.

International
Human botulism is found worldwide. Spores from organisms producing type A or B toxins are distributed widely in the soil and have been found throughout the world. Toxin type B commonly is found in Europe. Toxin G originally was isolated in Switzerland.

Mortality/Morbidity

Mortality rates vary according to age of the patient and the type of botulism observed. In FBB, a 25% mortality rate exists overall; however, the rate is 10% in patients younger than 20 years. In WB, the mortality rate varies (15-17%); in IB, the mortality rate usually is less than 1%.
The recovery period from botulism often is quite long (30-100 d). Some patients demonstrate residual weakness or autonomic dysfunction for 1 year after the onset of the illness. However, full neurologic recovery is usual. Permanent deficits may occur in those who sustain significant hypoxic insults.

Sex
Males present more frequently with WB than females. Males and females present with FBB in equal numbers.

Age
FBB and WB predominately occur in adults.


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