(See also Overview of Anaerobic Bacteria Overview of Anaerobic Bacteria Bacteria can be classified by their need and tolerance for oxygen: Facultative: Grow aerobically or anaerobically in the presence or absence of oxygen Microaerophilic: Require a low oxygen concentration... read more and Overview of Clostridial Infections Overview of Clostridial Infections Clostridia are spore-forming, gram-positive, anaerobic bacilli present widely in dust, soil, and vegetation and as normal flora in mammalian gastrointestinal tracts. Pathogenic species produce... read more .)
C. botulinum is one of several species of clostridia that cause human disease. Botulism is a rare, life-threatening disorder that occurs when botulinum toxin spreads hematogenously and interferes irreversibly with release of acetylcholine at peripheral nerve endings manifesting as weakness. Botulism is a medical emergency and sometimes a public health emergency.
C. botulinum elaborates 8 types of antigenically distinct neurotoxins (types A through G and F/A Hybrid). Five of the toxins, types A, B, E, and rarely F and F/A Hybrid (formerly labeled H) affect humans. Botulinum toxins are highly poisonous proteins resistant to degradation by gastric acidity and proteolytic enzymes. Type F/A Hybrid is the most potent toxin known. About 50% of food-borne outbreaks in the US are caused by type A toxin, followed by types B and E.
Type A toxin occurs predominantly west of the Mississippi River, type B in the eastern states, and type E in Alaska and the Great Lakes area (type E is frequently associated with ingestion of fish and fish products).
Botulism can occur when neurotoxin is elaborated in vivo by C. botulinum or when preformed neurotoxin is acquired in an external source.
In vivo elaboration causes the following forms:
Adult enteric botulism (rare)
In wound botulism, neurotoxin is elaborated in infected tissue.
In infant botulism and in adult enteric botulism, spores are ingested, and neurotoxin is elaborated in the gastrointestinal tract. Adult enteric botulism usually occurs only in adults with impaired resistance.
Acquisition of preformed neurotoxin causes the following forms:
In food-borne botulism, neurotoxin produced in contaminated food is eaten.
In iatrogenic botulism, type A or B toxin is injected therapeutically to relieve excess muscle activity; rarely, botulism has occurred after cosmetic injections (with botulinum toxin).
In inhalation botulism, toxins becomes aerosolized either accidentally or when intentionally used as a bioweapon; aerosolized toxins do not occur in nature.
C. botulinum spores are highly heat-resistant and may survive boiling for several hours at 100° C. However, exposure to moist heat at 120° C for 30 minutes kills the spores. Toxins, on the other hand, are readily destroyed by heat, and cooking food at 80° C for 30 minutes safeguards against botulism. C. botulinum can produce type E toxin at temperatures as low as 3° C (ie, inside a refrigerator—for example, in vacuum-packed smoked fish).
Pearls & Pitfalls
Sources of toxin
Home-canned foods, particularly low-acid foods (ie, pH > 4.5), are the most common sources of ingested toxin, but commercially prepared foods have been implicated in about 10% of outbreaks. Vegetables (but usually not tomatoes), fish, fruits, and condiments are the most common vehicles, but beef, milk products, pork, poultry, and other foods have been involved. Of outbreaks caused by seafood, type E causes about 50%; types A and B cause the rest. In recent years, foods that are not canned (eg, foil-wrapped baked potatoes, chopped garlic in oil, patty melt sandwiches) have caused restaurant-associated outbreaks.
Sometimes the toxin is absorbed through the eyes or a break in the skin and, in such cases, may cause serious disease.
C. botulinum spores are common in the environment; most cases of infant botulism are caused by ingestion of spores, typically when honey is ingested.
Spores can also enter the body when drugs are injected with unsterilized needles; wound botulism may result. Injecting contaminated black tar heroin into a muscle or under the skin (skin popping) is riskiest; it can cause gas gangrene as well as botulism.
If botulinum toxins enter the bloodstream, botulism results, regardless of how the toxins are acquired.
Symptoms and Signs of Botulism
Common botulism symptoms and signs include
Blurred or double vision
Pupillary light reflex is diminished or totally lost. Dysphagia can lead to aspiration pneumonia. These neurologic symptoms are characteristically bilateral and symmetric, beginning with the cranial nerves and followed by descending weakness or paralysis.
There are no sensory disturbances, and the sensorium usually remains clear.
Muscles of respiration and of the extremities and trunk progressively weaken in a descending pattern. Fever is absent, and the pulse remains normal or slow unless intercurrent infection develops. Constipation is common after neurologic impairment appears.
Major complications of botulism include
Respiratory failure caused by diaphragmatic paralysis
Pulmonary and other nosocomial infections
Symptoms begin abruptly, usually 18 to 36 hours after toxin ingestion, although the incubation period may vary from 4 hours to 8 days. Nausea, vomiting, abdominal cramps, and diarrhea frequently precede neurologic symptoms.
Neurologic symptoms appear, as in food-borne botulism, but there are no gastrointestinal symptoms or evidence implicating food as a cause. A history of a traumatic injury or a deep puncture wound (particularly if due to injection of illicit drugs) in the preceding 2 weeks may suggest the diagnosis.
A thorough search should be made for breaks in the skin and for skin abscesses caused by self-injection of illegal drugs.
Diagnosis of Botulism
Botulism may be confused with Guillain-Barré syndrome (Miller-Fisher variant), poliomyelitis, stroke, myasthenia gravis, tick paralysis, and poisoning caused by heavy metals, curare, or belladonna alkaloids. Electromyography shows characteristic augmented response to rapid repetitive stimulation in most cases.
In food-borne botulism, the pattern of neuromuscular disturbances and ingestion of a likely food source are important diagnostic clues. The simultaneous presentation of at least 2 patients who ate the same food simplifies diagnosis, which is confirmed by finding C. botulinum toxin in serum or stool. Finding C. botulinum toxin in suspect food identifies the source.
In wound botulism, finding toxin in serum or isolating C. botulinum organisms on anaerobic culture of the wound confirms the diagnosis of botulism.
Toxin assays are done only by certain laboratories, which may be located through local health authorities or the Centers for Disease Control and Prevention (CDC).
Treatment of Botulism
Equine heptavalent antitoxin
Anyone known or thought to have been exposed to contaminated food must be carefully observed. Administration of activated charcoal may be helpful. Patients with significant symptoms often have impaired airway reflexes, so if charcoal is used, it should be given via gastric tube, and the airway should be protected by a cuffed endotracheal tube Tracheal Intubation Most patients requiring an artificial airway can be managed with tracheal intubation, which can be Orotracheal (tube inserted through the mouth) Nasotracheal (tube inserted through the nose)... read more .
The greatest threat to life is
Respiratory impairment and its complications
Patients with botulism should be hospitalized and closely monitored with serial measurements of vital capacity. Progressive paralysis prevents patients from showing signs of respiratory distress as their vital capacity decreases. Respiratory impairment requires management in an intensive care unit, where intubation and mechanical ventilation are readily available. Improvements in such supportive care have reduced the mortality rate to < 10%.
Nasogastric intubation Enteral Tube Nutrition Enteral tube nutrition is indicated for patients who have a functioning gastrointestinal (GI) tract but cannot ingest enough nutrients orally because they are unable or unwilling to take oral... read more is the preferred method of alimentation because it
Simplifies management of calories and fluids
Stimulates intestinal peristalsis (which eliminates C. botulinum from the gut)
Allows the use of breast milk in infants
Avoids the potential infectious and vascular complications inherent in IV alimentation
Patients with wound botulism require wound debridement and parenteral antibiotics such as penicillin or metronidazole.
A heptavalent equine botulinum antitoxin (HBAT [A to G]) is available in the US; it replaces the older trivalent antitoxin. Antitoxin does not inactivate toxin that is already bound at the neuromuscular junction; therefore, preexisting neurologic impairment cannot be reversed rapidly. (Ultimate recovery depends on regeneration of nerve endings, which may take weeks or months.) However, antitoxin may slow or halt further progression. In patients with wound botulism, antitoxin can reduce complications and mortality rate.
Antitoxin should be given as soon as possible after clinical diagnosis and not delayed to await culture or toxicology results. Antitoxin is less likely to be of benefit if given > 72 hours after symptom onset.
One 20- or 50-mL vial of the heptavalent antitoxin, diluted 1:10, is given to adults as a slow infusion; dose and infusion rate are adjusted for children. HBAT is not recommended for infants < 1 year of age. All patients who require the antitoxin must be reported to state health authorities, who then request the antitoxin from the CDC, which is the only source; practitioners cannot obtain antitoxin directly from the CDC.
Because antitoxin is derived from horse serum, there is a risk of anaphylaxis or serum sickness. (For precautions, see Drug Hypersensitivity Drug Hypersensitivity Drug hypersensitivity is an immune-mediated reaction to a drug. Symptoms range from mild to severe and include rash, anaphylaxis, and serum sickness. Diagnosis is clinical; skin testing is occasionally... read more ; for treatment, see Treatment Treatment Anaphylaxis is an acute, potentially life-threatening, IgE-mediated allergic reaction that occurs in previously sensitized people when they are reexposed to the sensitizing antigen. Symptoms... read more .)
Pearls & Pitfalls
Human botulinum immune globulin is available for the treatment of infant botulism Treatment Infant botulism results from ingestion of Clostridium botulinum spores, their colonization of the large intestine, and toxin production in vivo. Symptoms are initial constipation followed... read more types A and B; it is available from the Infant Botulism Treatment and Prevention Program (IBTPP— call 510-231-7600 or see the IBTPP web site). The dose is 50 mg/kg IV, given slowly.
Prevention of Botulism
Because even minute amounts of C. botulinum toxin can cause serious illness, all materials suspected of containing toxin require special handling. Toxoids are available for active immunization of people working with C. botulinum or its toxins. Details regarding specimen collection and handling can be obtained from state health departments or the CDC.
Correct canning and adequate heating of home-canned food before serving are essential. Canned foods showing evidence of spoilage and swollen or leaking cans should be discarded.
Botulism may develop from ingestion of food-borne toxin, from elaboration of toxin from a clostridial wound infection, or, in infants, from ingestion and enteric colonization by C. botulinum spores.
Botulism may result from man-made botulism toxin that is injected therapeutically or for cosmetic reasons or is inhaled (in an aerosolized form).
Botulinum toxins block release of acetylcholine at peripheral nerve endings and cause bilateral, symmetric, descending weakness, beginning with the cranial nerves.
Sensation and mental status are unaffected.
Cooking destroys botulinum toxin but not the spores.
For diagnosis, use toxin assays.
Give heptavalent equine botulinum antitoxin (HBAT) obtained from the Centers for Disease Control and Prevention (CDC) via the state department of health to adults and children; HBAT is not recommended for infants < 1 year of age.
The following are English-language resources that may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
Infant Botulism Treatment and Prevention Program: Web site or call 510-231-7600
Centers for Disease Control and Prevention: Clinical Guidelines for Diagnosis and Treatment of Botulism, 2021
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