Botulism


Clinical Overview

The clostridial neurotoxins are the most toxic substances known to science. The neurotoxins produced from Clostridium tetani (tetanus toxin) and Clostridium botulinum (ie, the botulinum toxins, of which there are seven in all), are the most likely to be contacted by humans. The primary means of contact with botulism is by food poisoning, although there are rare incidents of wound botulism and a colonizing infection of neonates known as infant botulism. Rates of exposure to tetanus toxin are controlled via routine vaccination, but since the incidence of botulinum poisoning by all routes is very rare, immunization of the general population is not warranted on the basis of cost and the expected rates of adverse reactions to even the best vaccines.

Thus, humans are not protected from botulinum toxins and, because of their relative ease of production and other characteristics, these toxins are likely biological warfare agents.

C. botulinum is a spore forming, anaerobic bacteria found worldwide in soil. Food poisoning due to botulinum toxin emerged as a problem when food preservation became a widespread practice. C. botulinum grows and produces neurotoxin in the anaerobic conditions frequently encountered in the canning or preservation of foods. The dose that is lethal to 50 percent of the population if exposed (ie, the LD50) has been estimated to be approximately 1 ng/kg. All of the botulinum toxins are slightly less toxic when exposure is by the pulmonary route; the human LD50 by inhalation is 3 ng/kg. The toxin acts presynaptically to prevent the release of acetylcholine.

Clinical Presentation

In food poisoning, the symptoms appear several hours to 1 or 2 days after contaminated food is consumed. Botulism presents with the classic “4 D’s” diplopia, dysarthria, dysphonia and dysphagia. This presents in combination with the classic triad of symmetric descending flaccid paralysis, prominent bulbar palsies, afebrile, with a clear sensorium. The symptoms of botulism are nearly pathognomonic. Additional symptoms can include: retarded ocular motions, pupils dilated with nystagmus, indistinct speech, uncertain gait, intermittent ptosis, severe weakness of postural muscles of the neck, mouth breathing, serous nasal discharge, salivation, rales, anorexia, lateral recumbency, extreme weakness and respiratory failure.

Inhalational botulism is rare. However, this is the most likely route in the event of a terrorist attack using botulinum toxin.

Diagnosis

Making a diagnosis of botulism might be very difficult during the early stages of a biological warfare attack. A history of simultaneous onset of bulbar and neuromuscular disease in a group of patients should alert medical personnel to botulism. The absence of convulsions would differentiate botulinum intoxication from chemical nerve agent poisoning.

Because of the small quantity of toxin protein needed to kill, botulinum toxin exposure does not typically induce an antibody response after exposure. The most likely means of laboratory diagnosis is through enzyme-linked immunosorbent assay identification of botulinum toxin from swabs taken from the nasal mucosa within 24 hours of inhalational exposure.

Medical Management

Supportive care is the mainstay for treatment of botulism; prolonged intensive care, mechanical ventilation and parenteral nutrition may be required. Botulinum antitoxin can also be administered and is most effective if given early in the clinical course. Although antitoxin will not reverse existing paralysis, it will prevent additional nerve damage if given before all circulating toxin is bound at the neuromuscular junction.

Antitoxin should be requested as soon as the diagnosis of botulism is suspected, since confirmation of botulism may take several days and antitoxin is most effective if given within 24 hours after symptom onset. Antitoxin for use in the United States is of equine origin and only available through the CDC via state and local health departments. The CDC traditionally has released trivalent ABE antitoxin for treatment of suspected or confirmed botulism cases in the United States. The FDA has temporarily suspended use of the trivalent ABE product until further safety testing can be accomplished.

Currently, two separate formulations are available for release by CDC: botulinum antitoxin bivalent (equine) for types A and B (licensed by the FDA), and botulinum antitoxin (equine) type E (an investigational product). The US army has developed an investigational heptavalent botulinum antitoxin (types A, B, C, D, E, F, G). This product could potentially be used during a bioterrorist attack involving aerosolized botulism; however, its efficacy in humans is not yet known.

If the type of botulinum toxin is not known, both types of antitoxin should be administered. If the toxin type is known (i.e., in an outbreak setting where the toxin type has been previously identified), then either bivalent AB antitoxin or type E antitoxin should be administered on the basis of the identified toxin type. According to the package inserts, each vial of bivalent AB antitoxin contains 7,500 IU of type A antitoxin and 5,500 IU of type B antitoxin. Each vial of type E antitoxin contains 5,000 IU of type E antitoxin. One IU neutralizes 1,000 mouse LD50 of toxin E or 10,000 mouse LD50 of toxins A and B. These amounts are more than adequate to neutralize the amount of toxin likely to be present in the circulation for naturally occurring botulism cases.

The circulating equine antitoxins have a half-life of 5 to 8 days. In the setting of a bioterrorist attack, where cases may have been exposed to unusually large amounts of toxin, additional doses of antitoxin may be necessary. According to the package inserts, additional doses may be given (at least 2 to 4 hours after an initial dose or between doses) if the patient’s condition continues to deteriorate. Alternatively, the patient’s serum could be retested for the ongoing presence of circulating toxin.

Transmissibility and Infection Control

In the hospital setting, standard precautions are adequate for patients with botulism, since person-to-person transmission does not occur. Sodium hypochlorite (0.1%) or sodium hydroxide (0.1 N) inactivate the toxin and are recommended by CDC for decontaminating work surfaces and spills of cultures or toxin.

As with any bioterrorism agent, a case or suspected case of botulism poisoning in someone living or working in the County should be immediately reported by phone call to the Anne Arundel County Department of Health at 410-222-7256. To report communicable diseases, click here for instructions.


Patient Handouts

What is botulism?
Botulism is a muscle-paralyzing disease caused by a toxin made by a bacterium known as Clostridium botulinum.

How does a person get botulism?
There are three natural ways botulism occurs, as well as exposure through deliberate criminal release.

  • Foodborne botulism occurs when a person ingests pre-formed toxin that leads to illness within a few hours to days. Foodborne botulism is a public health emergency because the contaminated food may still be available to other persons besides the patient.
  • Infant botulism occurs in a small number of susceptible infants each year who harbor C. botulinum in their intestinal tract.
  • Wound botulism occurs when wounds are infected with C. botulinum.
  • Inhalation botulism results from breathing in aerosolized toxin.

What are the natural sources of botulism?
Foodborne botulism is due to eating food containing the toxin. It often involves improperly processed home canned foods. Since Clostridium boutlinum is an anaerobic bacterium, it can grow in cooked foods that are not properly stored. Infant botulism has been associated with eating honey that contains the bacterial spores. Light and dark corn syrups have also been reported to contain the spores, although cases of infant botulism have not been linked to corn syrup. Wound botulism occurs when toxin is produced in a wound infected with Clostridium botulinum organisms. Inhalation botulism would most likely occur as a result of an act of bioterrorism.

What are the symptoms of botulism?
Foodborne and infant botulism produce symptoms that affect the nervous system’s control over muscles. The symptoms of foodborne botulism include blurred or double vision, dry mouth, and muscle paralysis that may affect breathing. About 5-10% of persons with foodborne botulism die. Infant botulism has a wide range of symptoms including constipation, weakness, difficulty breathing, poor feeding and poor reflexes. About 1% of the cases of infant botulism die. Wound and inhalation botulism produce symptoms similar to foodborne botulism.

How long after exposure do symptoms appear?
Symptoms of foodborne botulism usually occur 12 – 36 hours after eating the food, but may take several days.

What is the treatment for botulism?
Supportive care in a hospital is almost always necessary. If antitoxin is given early in the course of foodborne botulism, it can be life-saving. Antitoxin is not used to treat infant botulism; however, the use of intravenous antibodies against the botulinum toxin may be effective in treating infants.

Can botulism be prevented?
Recognized sources of infant botulism, such as honey, should not be fed to infants. All canned and preserved foods should be properly processed and prepared. Bulging containers should not be opened and foods with off-odors should not be eaten or even tasted. Commercial cans with bulging lids should be returned unopened to the vendor.

Could botulinum toxin be used for bioterrorism?
Yes. Botulinum toxin is one of the agents that could be used for bioterrorism because it is easy to obtain and transport, and people who get sick from botulinum toxin would require long-term care.

Additional information may be obtained from the Centers for Disease Control and Prevention at www.cdc.gov.


Trainings and Powerpoint Presentations

BW Agents: Botulinum Toxin (2003) is available as a PowerPoint Presentation or as a PDF.


Additional Resources

Essential Reading

Dennis DT, Henderson DA, Inglesby TV, et al. Botulinum Toxin as a Biological Weapon: Medical and Public Health Management. JAMA 2001;285:1059-1070.

Additional Readings

Recognition of Illness Associated with the Intentional Release of a Biologic Agent. Morbidity and Mortality Weekly Report. 2001;50(41);893-7.

Notice to Readers: New Telephone Number to Report Botulism Cases and Request Antitoxin. Morbidity and Mortality Weekly Report. 2003;52(32);774-774

Internet Resources

Centers for Disease Control and Prevention, Information for Health Professionals

Center for Infectious Disease Research and Policy of University of Minnesota

Infectious Disease Reporting, MDH