Topic Editor: Grant E. Fraser, M.D., FRACGP, FACRRM, ASTEM
Review Date: 12/13/2012
Definition
Botulism is a potentially life-threatening condition in which a neurotoxin from the anaerobic bacterium Clostridium botulinum results in an acute paralytic condition. This condition may occur due to ingestion of contaminated food or wound infection.
Description
- Botulism results in acute onset of neuropathy with symmetric descending weakness
- C. botulinum neurotoxin irreversibly binds at the neuromuscular junction of neurons and prevents exocytosis (release) of acetylcholine from presynaptic nerve membranes. This has the effect of blocking neuromuscular transmission in cholinergic nerve fibers, causing a flaccid paralysis
- This toxin does not cross into the central nervous system
- Botulism occurs in six forms depending on the route of toxin exposure:
- Foodborne botulism: Due to oral ingestion of food or fluids which contain botulinum toxin
- Wound botulism: Caused by contamination of wounds with C. botulinum which secretes botulinum toxin
- Infant botulism: Due to eating food contaminated with C. botulinum which produces thetoxin in the gastrointestinal (GI) tract
- Adult intestinal infectious botulism: Rare form of botulism attributable to GI colonization of C. botulinum, and associated with functional or structural GI abnormalities in children or adults
- Inhalation botulism: Unlikely to occur through natural mechanisms, aerosolized C. botulinum could be used as a biological weapon in terrorism
- Iatrogenic botulism: Overdose of injected botulinum toxin using commercially prepared Botox or similar (generally accidental)
- Diagnosis of botulism is primarily based on clinical signs and symptoms
- Management includes supportive care which may include ventilation, nutrition supplement via feeding tube, and treatment of secondary infections
Epidemiology
Incidence/Prevalence
- Very rare condition with 0.5 cases/million population
- 2010 data from the Centers for Disease Control and Prevention (CDC) cite the incidence of botulism in the U.S.as ~112 cases annually, 85 (76%) of which were infant botulism cases, 17 (15%) were wound botulism cases, and 9 (8%) were food-borne botulism cases
- Since 1950, nearly half of all reported food-borne outbreaks have occurred in the 5 western states: Alaska, Oregon, Colorado, California, and Washington
- The incidence of wound botulism is increasing, with many cases being due to injection drug use
Age
- Wound botulism and food botulism occur more commonly in adults
- In food-borne botulism,the mean age of infected individuals is 46 years(range 3-78 years)
- In infantile botulism,the mean age of onset is 13 weeks(range 1-63 weeks)
- In wound botulism,the mean patient age is 41 years (range 23-58 years)
Gender
- Food-borne botulism affects both genders equally
- Wound botulism predominantly affects females
Race
- Native Alaskans have the highest incidence of botulism in the world, possibly attributable to food consumption habits
Risk factors
- Infants
- Ingestion of contaminated food
- Ingestion of soil and honey by infants
- Intravenous (IV) or subcutaneous (SC) drug abuse
- Wound contamination with C. botulinum spores
- Anatomical abnormalities or functional disorders of the GI tract
Etiology
- The primary causative organism of botulism is C.botulinum, an anaerobic, gram-positive rod (bacilli) which mainly exists as a subterminal spore and germinates insuitable conditions
- There are seven recognized types of C. botulinum (A–G) differentiated by the antigenic properties of the neurotoxins they produce. Four types (A, B, E, and rarely F) affect humans. Types A and B are of highest concern and toxicity in humans
- C. botulinum neurotoxin irreversibly binds at the neuromuscular junction of neurons and prevents exocytosis (release) of acetylcholine from presynaptic nerve membranes. This has the effect of blocking neuromuscular transmission in cholinergic nerve fibers, causing a flaccid paralysis
- This toxin does not cross into the central nervous system
- Common sources of C. botulinum include
- Home-canned vegetables and fruits, prepared foods, or foods preserved in anaerobic conditions
- Fermented sea food
- Ingestion of spores present in the environment and honey consumption by infants
- Wounds contaminated by soil or dirt containing C. botulinum
- Aerosolized botulinum toxin as bioterrorism weapon
History
- Food-borne botulism:
- A food ingestion history should be obtained for the last 4-5 days prior to onset of symptoms
- Exposure to home-preserved or home-prepared food and similar symptoms in others whoingested the food,increasethe probability of a botulism diagnosis
- Botulism should be suspected in patients presenting with acute onset of GI symptoms along with neurological symptoms
- Wound botulism:
- History of traumatic injuries such as open fractures or punctures with soil contamination
- History of injectable drug abuse
- Adults with botulism may present with slurred speech, trouble swallowing, dry mouth, impaired vision, and ptosis (drooping eyelids)
- Infants with botulism may present with lethargy, constipation, feeding trouble, decreased muscle tone, drooling, anorexia, irritability, and a weak cry
Physical findings on examination
- Findings typical for botulinum toxin:
- Blurred vision
- Diplopia
- Dysarthria
- Dysphagia
- Flaccid paralysis (starts with facial muscles and progresses downward)
- Muscle weakness
- No change in mental alertness and cognitive function
- Ptosis
- Respiratory distress
- Xerostomia (dry mouth)
Additionally, based upon specific etiology of botulism, the following may be present:
- Food-borne botulism:
- GI symptoms (constipation, diarrhea, vomiting)
- Wound botulism:
- Patient may be febrile due to soft tissue infection
- Infant botulism
- Constipation
- Diminished sucking and crying ability
- Neck and peripheral muscle weakness
- Poor feeding
- Respiratory distress
- Inhalation botulism:
- Findings are typical for the botulinum toxin without additional findings
Botulism is typically diagnosed based on clinical symptoms as routine laboratory investigations are usually not helpful. Treatment should not be delayed pending laboratory confirmation. The most critical point is that this condition is a clinical diagnosis that requires empiric treatment early, with laboratory confirmation occurring thereafter.
Blood test findings
- Mouse bioassay:
- This test isolates the toxin and helps confirm botulism. This test should be performed on all patients suspected to have botulism. It however takes 4 days for completion of this test
- This test being negative in no way rules out botulism. One recent study of IV drug abusers with wound botulism found only 68% had a positive mouse bioassay. This lack of sensitivity reinforces that diagnosis should be made on clinical grounds
- Blood gas:
- Venous or arterial blood gases may be of value to evaluate for respiratory failure via tracking of serial PCO2 levels (which elevate with increasingly ineffective ventilation)
Other laboratory tests
- Cerebrospinal fluid(CSF) analysis
- CSF findings are usually normal. There may be a borderline elevation in protein levels
- Toxin testing and cultures
- Botulism is confirmed by identifying neurotoxin in serum, stool, vomitus, gastric aspirate or contaminated foods
- Culture of suspected food, stool and/or wound for C. botulinum
Radiographic findings
- Computed tomography (CT) or magnetic resonance imaging (MRI) of the brain may help evaluate for stroke and other conditions that may be confused with botulism
Other diagnostic tests findings
- Electromyography
- This test may be useful for differentiation of botulism from Guillain-Barré syndrome and myasthenia gravis
- Tensilon test may help differentiate botulism from myasthenia gravis. Some reports of "borderline positive" results may occur in botulism
General treatment items
- Patients in whom botulism is suspected should be admitted to an intensive care unit (ICU)
- Supportive care along with early administration of antitoxin is critical
- Careful monitoring of the patient's respiratory status and detection of respiratory failure is essential
- The decision to intubate depends on the assessment of patient's upper airway competency and vital capacity. Increasing PCO2 on venous or arterial blood gases can be an indicator of respiratory failure
- Tracheostomy may be helpful in the management of secretions. Some patients may need prolonged intubation and ventilatory support (days to months)
- In cases of food botulism, cathartics, whole bowel irrigation, and enemas may be administered in an attempt to remove unabsorbed botulinum toxin from the GI tract. Nasogastric lavage is recommended in cases of profound ileus
- Antibiotics are of no value in eradicating the organism from the intestine. With food botulism, antibiotics should not be administered as this may increase the risk of bacterial cell lysiswith increased release of toxin
- Antibiotics may be useful for treatment of certain secondary infectious complications occurring during treatment
- Wound botulism should be treated with thorough debridement of the wound and administration of IV penicillin G potassium
- Antitoxin therapy:
- Antitoxin therapy is important in the treatment of foodborne botulism and wound botulism
- Prompt IV administration of botulinum antitoxin is essential, with diagnosis based on clinical grounds and prior to laboratory verification
- Antitoxin is unable to inactivate toxin already bound at the neuromuscular junction;thusexisting neurologic impairment cannot be reversed and requires a lengthy period of normal regeneration of neuromuscular junctions which can take months
- Prior to administration of antitoxin, skin testing should be carried out to check for sensitivity to serum or antitoxin
- Less than 1% of patients have a serious reaction with use antitoxin
- Two botulism antitoxins are available and FDA approved:
- Botulism antitoxin bivalent (Equine) types A and B:For food-borne and wound botulism in adults (also appropriate for iatrogenic cases)
- Botulism immune globulin (human) known as BabyBIG: For infant botulism
Medication indicated with specific doses
- Penicillin G potassium [Injectable]
- Botulism antitoxin bivalent (Equine) types A and B
- Adult Dosing
- Treatment of botulism types A & B: 7,500 IU of Type A and 5,500 IU of Type B (one vial) diluted in 0.9% saline (1:10 dilution) by slow IV infusion. An additional 7,500 IU of Type A and 5,500 IU of Type B (one vial) is recommended using IM route in order to provide a reservoir of antitoxin which can be absorbed
- Prevention of botulism types A & B: In cases where a person has eaten food suspected of containing C. botulinum toxin, 1,500-7,500 IU of Type A and 1,100-5,500 IU of Type B antitoxin given IM is appropriate, depending on the amount of food eaten (1/5th to 1 vial). Additional doses IV or IM may be appropriate if symptoms develop
- Botulism immune globulin (human) [IV]
Dietary or Activity restrictions
- Nutrition should be administered to inpatients through a nasogastric tube
Disposition
Admission Criteria
- Patients with suspected botulism or who are suspected to have consumed food with botulinum toxin should be admitted
- Patients with respiratory impairment or significant muscular weakness generally require intensive care
Discharge Criteria
- Discharge criteria is difficult to establish due to the variable clinical course of botulism
- Patients with a lengthy period of active recovery may be discharged
- Patients with some generalized weakness, which is not progressing, who have no symptoms of respiratory failure may be discharged (after at least several days of observation) with close followup
Prevention
- Home canning, preservation and fermentation of food require rigorous hygienic procedures to minimize the risk of contamination. Use of pressure cookers/canners are recommended
- Food-borne botulism can be prevented to a large extent through careful food preparation. Heating food at high temperature for at least 10 minutes before eating can inactivate the toxic organisms. Botulism spores are extremely resistant to heat and often survive
- Wound botulism is commonly due to injection drug abuse of black tar heroin. This can effectively be prevented by avoiding such activities, and in other cases, seeking immediate medical care for infected wounds
- Honey should not be fed to infants less than 12 months of age
- Currently there is no vaccine available for prevention of botulism
Prognosis
- In the absence of serious complications, complete recovery occurs in infant botulism
- In adults, recovery may require weeks or months; complications may require long-term therapy
- Botulism has the potential to be a severe disease with mortality rates ranging from 5% to 10% for food-borne botulism
- Mortality for infant botulism is 1%
- Wound botulism has a good prognosis given timely and appropriate treatment
Pregnancy/Pediatric effects on condition
- Botulism does not appear to have direct adverse effects on pregnancy or the fetus since the neurotoxin is unable to cross the placental barrier due to its high molecular weight
- The equine antitoxin can be safely administered during pregnancy without adverse fetal effects
- Adverse effects on the mother, such as respiratory failure and hypoxia could influence fetal outcome
ICD-9-CM
- 005.1 Botulism food poisoning
- 040.41 Infant botulism
- 040.42 Wound botulism
ICD-10-CM
- A05.1 Botulism (food-borne intoxication)
- A48.51 Infant botulism
- A48.52 Wound botulism
