American College of Physicians: Internal Medicine — Doctors for Adults ®



From the May ACP Observer, copyright © 2004 by the American College of Physicians.

The botulism neurotoxin, which is generated by Clostridium botulinum and related anaerobic bacteria, is the most poisonous substance known. The toxin's extreme potency, combined with its ease of production and transport, make it a significant bioterrorism threat. In addition, victims' need for prolonged intensive care, ventilators and antitoxin would all pose a major health care crisis if large numbers of people were affected.

Eight distinct C. botulinum toxin types have been described: A, B, C1, C2, D, E, F and G. Of these eight, types A, B, E, and rarely F and G cause human disease, while C and D cause disease in animals such as cattle, ducks and chickens. Food-borne, wound and infantile forms of botulism occur naturally. Food-borne botulism is the result of ingesting pre-formed toxin, while infantile botulism results from ingestion of bacterial spores that later colonize the intestinal tract, producing the botulinum toxin.

Clostridium botulinum bacteria, stained with Gentian violet. The bacterium produces a nerve toxin that causes botulism.

For unknown reasons, infantile botulism is the most common, naturally occurring form. A few cases of adult intestinal botulism analogous to infantile botulism have been reported, but are extremely rare. Wound botulism is the result of a wound becoming contaminated with C. botulinum bacteria that subsequently produce the toxin in vivo.

There have been no reports of water-borne botulism, presumably because the toxin is inactivated by chlorination and aeration. But the toxin could remain stable for several days in untreated water or beverages.

Any botulism infection caused by exposure to an aerosol form of the bacteria would indicate a bioterrorist attack.

Botulism is spread by absorption of the botulinum toxin into the circulation system from either a mucosal surface, such as the gut or the lungs, or an open wound. Botulinum toxin does not penetrate intact skin, nor does it naturally spread by person-to-person contact.

The United States, the former Soviet Union, Iran, Iraq, North Korea and Syria have developed or are believed to be developing botulinum toxin as a weapon. (The United States disbanded its bioweapons program in 1970.)

Terrorists have been able to isolate C. botulinum from the soil with relative ease. They could also access therapeutic botulinum toxin, which is used to treat dystonias, migraines and other conditions. However, terrorists are not likely to use medicinal preparations of the toxin because such extremely low concentrations limit their effectiveness as a weapon.

If inhaled, a single gram of crystalline botulism toxin could kill more than one million people. Fortunately, it is very hard to overcome the technical difficulties of dispersing the toxin in aerosol form. In the 1990s, a Japanese cult collected C. botulinum from the soil, but it was unable to use an aerosolized form of its toxin as a bioweapon.

In addition to spreading aerosolized botulism, terrorists could contaminate food with the toxin or bacteria, or disperse it via genetically engineered, contagious bacteria that produce botulinum toxin. Although Soviet scientists have testified that they tried to splice the botulinum toxin gene into other bacteria species, a contagious strain of botulism has not yet been detected.

A bioterrorist attack using botulinum toxin or organisms that produce it would be difficult to distinguish from naturally occurring, food-borne botulism. In the past 20 years, botulism outbreaks have gone from being primarily associated with home-preserved food to being caused by mass-produced, processed foods or foods served in restaurants. Common foods have been linked to botulism outbreaks, including fish, yogurt, cream cheese, jarred peanuts, cheese sauce, baked potatoes and potato salad, and oils infused with chopped garlic. In infants, honey has been identified as a source of botulism.

It may also be hard to track down the source of an outbreak in the event of an aerosol dissemination. The mobility of individuals exposed during the incubation period would make it hard to pinpoint a common exposure site.

Clinicians should suspect a bioterrorist botulism attack under the following circumstances:

  • Many simultaneous outbreaks of botulism occur without a common source.
  • Large numbers of people develop botulism.
  • Afflicted patients are linked by locale—co-workers, for instance, or travelers who use the same airport—but not dietary exposures. This would indicate an aerosol attack.
  • A botulism outbreak caused by an unusual botulinum toxin type, such as type C, D, F or G.

Clinical presentation and diagnosis

Botulism is an afebrile, neuroparalytic disease characterized by symmetric, descending flaccid paralysis of motor and autonomic nerves. The paralysis always begins with the cranial nerves.

Symptoms include diplopia, blurred vision, drooping eyelids, dysphagia, dysphonia, dysarthria, weakened jaw clench, dry mouth and muscle weakness. The prominent bulbar palsies that typify botulism can be summarized in part as the "4 Ds": diplopia, dysarthria, dysphonia and dysphagia.

When untreated, botulism can progress to descending paralysis of respiratory muscles, arms and legs. Death can ultimately result from respiratory failure. Patients have a clear sensorium and no sensory deficits, but they may have trouble communicating because of the bulbar palsies.

In patients with acquired food-borne disease, abdominal cramps, nausea, vomiting or diarrhea may precede the neurological signs of botulism. These gastrointestinal symptoms may be due to other bacterial metabolites in the contaminated food and may not occur if the botulinum toxin is intentionally placed in foods or aerosols.

The signs and symptoms of botulism, and the speed with which they develop, vary considerably, according to the amount of toxin absorbed into the circulation.

The clinical presentation of inhalation botulism is not well defined, as there have been only three cases in humans who were exposed to small amounts of the botulinum toxin. These patients developed increased oral secretions, dysphagia, dizziness, difficulty moving their eyes, dysarthria, unsteady gait and extreme weakness. More severe and extensive symptoms may accompany a higher-dose exposure to aerosol botulinum toxin.

To confirm a botulism diagnosis, laboratory tests use mouse neutralization assays of stool, vomitus or serum samples. These tests are conducted only at the CDC and some state health department laboratories. Results take days to complete.

Clinical diagnosis is therefore key to recognizing a bioterrorist attack with botulism early on and responding appropriately. Clinicians caring for patients with suspected botulism should notify their local public health department and hospital epidemiologist or infection control practitioner immediately to coordinate shipment of therapeutic antitoxin, laboratory diagnostic testing and epidemiological investigation.

Differential diagnosis

Botulism is frequently misdiagnosed as Guillain-Barré syndrome and its variants, or as myasthenia gravis, stroke, intoxication, poliomyelitis, a central nervous system infection or tumor, Lambert-Eaton syndrome or tick paralysis. The descending and symmetric nature of botulism paralysis, as well as its early and prominent cranial nerve involvement, distinguishes botulism from its mimics.

The disease can also be differentially diagnosed from similar conditions by its lack of the following symptoms:

  • sensory nerve damage;
  • fever;
  • history of preceding infection;
  • mental status changes; and
  • electromyogram, cerebral spinal fluid or electroencephalogram abnormalities.

The clustering of cases that would occur with an attack would also help distinguish botulism from other conditions.


For patients with food-borne botulism, physicians may try to remove contaminated food still in the gut by inducing vomiting or using enemas.

Wounds should be debrided to remove devitalized tissue and the toxin-producing bacteria.

Treat botulism patients as soon as possible with equine serum trivalent botulism antitoxin, which can be obtained from the CDC through state and local health departments. The antitoxin contains antibodies that neutralize the most common types of botulinum toxins (A, B and E).

The CDC has a 24-hour network for physicians who need antitoxin or assistance with clinical management that can be accessed by calling: 404-639-2206, Monday through Friday, 8 a.m. to 4:30 p.m., or 404-639-2888 at any other time.

The U.S. Army has an investigational antitoxin that works for all types of botulinum toxins and would be considered in the event of an attack. However, the amount of time required for correct toxin typing would limit the effectiveness of this investigational antitoxin.

Timely administration of antitoxin minimizes subsequent nerve damage and disease severity. It will not, however, reverse existing paralysis, which typically takes months to subside.

Give botulinum antitoxin to patients with the tell-tale neurologic signs of botulism as soon as possible. Do not wait for diagnostic test results to begin treatment.

For patients exposed to unusually large amounts of toxin from a biological weapon, retest their serum for toxin after treatment with antitoxin to confirm that they've received an adequate amount.

Hypersensitivity reactions to the equine antitoxin can occur. To avoid reactions, give patients small challenge does of antitoxin. If no wheal occurs at the injection site, administer the full dose. Patients responding to the challenge with a substantial wheal may be desensitized over three to four hours before giving them the full dose.

There is no evidence that children, pregnant women or immunocompromised persons should not receive a standard dose of antitoxin. (This recommendation, however, is not universally held.) Infants have a much higher rate of anaphylaxis (2%) and hypersensitivity reactions (20%).

Botulism patients often need extensive supportive care, including feeding by enteral tube or parenteral nutrition, mechanical ventilation and treatment of secondary infections. Patients must be closely monitored for airway obstruction and impending respiratory failure, and they must often be placed in intensive care units.

Post-exposure containment

Medical personnel treating botulism patients need to take standard precautions. The incubation period lasts between two hours and eight days for food-borne botulism, with most cases developing within 12 to 72 hours after ingesting contaminated food. The incubation period for inhalation botulism is unknown.

Any suspicion of even a single case of botulism should immediately raise concerns of an outbreak potentially associated with shared, contaminated food. Work with the CDC and local or state health departments to try to locate the contaminated food source, which should be promptly removed from potential consumers and submitted to public health authorities for testing. Physicians should also identify other persons who may have been exposed to contaminated food, and should monitor them for symptoms.

There is evidence that treating exposed individuals with antitoxin can prevent both food-borne and inhalation botulism. But the antitoxin's scarcity and reactogenicity will limit its use in post-exposure prophylaxis.

The current standard practice for food-borne botulism is to closely monitor people who may have been exposed to botulinum toxin. These patients should be treated promptly with antitoxin if they develop signs of botulism.

An investigational botulinum toxoid that protects against types A, B, C, D and E toxins is distributed by the CDC to laboratory workers at high risk of exposure to botulinum toxin, and by the military to protect troops against attack. The toxoid induces immunity over several months and thus is ineffective as post-exposure prophylaxis. Mass immunization with the toxoid is currently not recommended, nor is the toxoid routinely given to health care workers.


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