Botulism

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 heroin²), 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.

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.

Clinical

History

Following the onset of symptoms, botulism quickly progresses over several days. The magnitude of the neuromuscular impairment can advance hourly. Persons who survive this phase eventually stabilize and then recover over a period of days to months. The mechanism of recovery is not fully understood but requires the generation of new presynaptic axons and the formation of new synapses, as the original synapses are permanently affected. As with tetanus, recovery from botulism does not confer long-term immunity. Rare reports have described a second episode in the same patient.

• Foodborne botulism
  • Foodborne botulism should be suspected in patients who present with an acute gastrointestinal illness associated with neurologic symptoms. Symptoms usually appear within 12-36 hours following consumption of contaminated food products. The severity of the illness varies from mild to severe, but death can occur within 24 hours.
  • The incubation period is usually 18-36 hours. Depending on toxin dose, the incubation period ranges from 2 hours to 8 days. The onset of symptoms can be abrupt or can evolve over several days.
• Wound botulism
  • Patients with wound botulism typically have a history of traumatic injury with wounds that are contaminated with soil.
  • Since 1994, the number of patients with wound botulism who have a history of chronic intravenous drug abuse has increased dramatically. In most cases, black-tar heroin has been the implicated vehicle.
  • Rare cases of wound botulism after cesarean delivery have been documented.
  • Aside from a longer incubation period, wound botulism is similar to foodborne botulism. The incubation period of wound botulism ranges from 4-14 days, with a mean of 10 days. Unlike foodborne botulism, wound botulism causes no gastrointestinal symptoms. Patients may be febrile, but this is more likely due to the wound infection rather than the wound botulism. In many cases, the wound appears benign.

Physical

More than 90% of patients with botulism have 3-5 of the following signs or symptoms: nausea, vomiting, dysphagia, diplopia, dilated/fixed pupils, and an extremely dry mouth unrelieved by drinking fluids.

• Generally, botulism progresses as follows:
• Preceding or following the onset of paralysis are nonspecific findings such as nausea, vomiting, abdominal pain, malaise, dizziness, dry mouth, dry throat, and, occasionally, sore throat. Except for nerves I and II, the cranial nerves are affected first.
• Cranial nerve paralysis manifests as blurred vision, diplopia, ptosis, extraocular muscle weakness or paresis, fixed/dilated pupils, dysarthria, dysphagia, and/or suppressed gag reflex. Additional neurologic manifestations include symmetric descending paralysis or weakness of motor and autonomic nerves.
• Respiratory muscle weakness may be subtle or progressive, advancing rapidly to respiratory failure. Progressive muscle weakness occurs and often involves the muscles of the head and neck, as well as intercostal diaphragmatic muscles and those of the extremities.
• The autonomic nervous system is also involved. Manifestations of this include the following:
• Paralytic ileus advancing to severe constipation
• Gastric dilatation
• Bladder distention advancing to urinary retention
• Orthostatic hypotension
• Reduced salivation
• Reduced lacrimation
• Other neurologic findings include the following:
• Changes in deep tendon reflexes, which may be either intact or diminished
• Incoordination due to muscle weakness
• Absence of pathologic reflexes and normal findings on sensory and gait examinations
• Normal results on mental status examination
• Many patients with foodborne botulism and wound botulism are afebrile.

Causes

• Causes of wound botulism have been associated with traumatic injury involving contamination with soil, chronic abuse of intravenous drugs (eg, black-tar heroin), and cesarean delivery. Wound botulism illness can occur even after antibiotics are administered to prevent wound infection.
• Foodborne botulism results from the ingestion of preformed neurotoxins; A, B, and E are the most common. On average, 24 cases of foodborne botulism are reported annually.
  • High-risk foods include home-canned or home-processed low-acid fruits and vegetables; fish and fish products; and condiments, such as relish and chili peppers.
  • Commercially processed foods and improperly handled fresh foods are occasionally associated with botulism outbreaks.
  • Outbreaks of foodborne botulism in restaurants, schools, and private homes have been traced to uncommon sources, such as commercial pot-pies, baked potatoes,⁴ beef stew, turkey loaf, sautéed onions, chopped garlic in oil,⁵ and cheese sauce.

References

Contents
Overview:	Botulism
Differential Diagnoses & Workup:	Botulism
Treatment & Medication:	Botulism
Follow-up:	Botulism
Multimedia:	Botulism