Practice Essentials
Botulism is an acute neurologic disorder manifested by life-threatening paralysis due to a neurotoxin produced by Clostridium botulinum or related species (C baratii and C butyricum). Exposure may occur via 4 routes [1, 2] :
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Ingestion (foodborne botulism)
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Colonization of a wound (wound botulism) or intestines (infant botulism) by C botulinum
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Cosmetic or therapeutic injection (iatrogenic botulism)
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Bioterrorism (inhalational or ingestion-related botulism)
Signs and symptoms
Botulism generally progresses as follows:
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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
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Cranial nerve paralysis manifests as blurred vision, diplopia, ptosis, extraocular muscle weakness or paresis, fixed/dilated pupils, dysarthria, dysphagia, and/or suppressed gag reflex
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Additional neurologic manifestations include symmetrical descending paralysis or weakness of motor and autonomic nerves
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Respiratory muscle weakness may be subtle or progressive, advancing rapidly to respiratory failure
The autonomic nervous system is also involved in botulism (typically in cases caused by toxin type B), with manifestations that include the following [23] :
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Paralytic ileus advancing to severe constipation
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Gastric dilatation
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Bladder distention advancing to urinary retention
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Orthostatic hypotension
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Reduced salivation
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Reduced lacrimation
Other neurologic findings include the following [2, 4] :
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Changes in deep tendon reflexes, which may be either intact or diminished
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Incoordination due to muscle weakness
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Absence of pathologic reflexes and normal findings on sensory and gait examinations
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Normal results on mental status examination
Ophthalmic manifestations may reflect the anticholinergic effects of the neurotoxins.
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Accommodation paresis, with blurred vision
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Pupil dysfunction with mydriasis and poorly reactive pupils
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Dry eye symptoms with impairment of lacrimation
Ocular manifestations may be the manifesting features of botulism. However, their absence does not exclude this disease, since the 8 different toxins appear to involve the ocular system to various degrees.
As reported by physicians caring for 332 different botulism patients [5] :
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99% had NO fever
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93% experienced descending paralysis
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91% had NO mental status change
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84% had at least 1 ocular weakness finding
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82% had NO acute neuroimaging changes
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80% had blurry vision
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78% had difficulty speaking
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75% had diplopia
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69% had a change in their voice
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65% had shortness of breath
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63% had a dry mouth
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62% experienced sensation of a thick tongue
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58% had impaired gag reflex
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55% had dizziness
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54% had palatal weakness
Diagnosis
The diagnosis initially must be made clinically, as waiting for laboratory confirmation would harmfully delay therapy. [6]
The standard for laboratory diagnosis is a mouse neutralization bioassay confirming botulism by isolation of the toxin. Toxin may be identified in the following:
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Serum
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Stool
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Vomitus
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Gastric aspirate
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Suspected foods
Clostridium botulinum may be grown on selective media from samples of stool or foods. Note that the specimens for toxin analysis should be refrigerated, but culture samples of C botulinum should not be refrigerated. Wound cultures that grow C botulinum suggest the presence of wound botulism.
Characteristic electromyographic findings in patients with botulism include the following:
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Brief, low-voltage compound motor-units
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Small M-wave amplitudes
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Overly abundant action potentials
An incremental increase in M-wave amplitude with rapid repetitive nerve stimulation may help to localize the disorder to the neuromuscular junction.
See Workup for more detail.
Management
Rigorous supportive care, including use of the following, is essential in patients with botulism:
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Meticulous airway management: Of paramount importance, since respiratory failure is the most important threat to survival in patients with botulism
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Cathartics and enemas: Administered to patients with bowel sounds to remove unabsorbed botulinum toxin from the intestine
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Stress ulcer prophylaxis: A standard component of intensive care management
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Nasogastric suction and intravenous hyperalimentation: Helpful if an ileus is present; if no ileus is present, tube feeding can be used for nutritional supplementation
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Foley catheter: Often used to treat bladder incontinence; the catheter must be monitored conscientiously and changed regularly
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Antibiotic therapy: Useful in wound botulism, but has NO role in foodborne botulism
Magnesium salts, citrate, and sulfate should not be administered, because magnesium can potentiate the toxin-induced neuromuscular blockade.
Wound botulism requires the following:
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Incision and thorough debridement of the infected wound
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Antitoxin therapy
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Penicillin G IV (metronidazole if penicillin-allergic)
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Tetanus toxoid booster
Prevention of nosocomial infections
Measures to reduce the risk of nosocomial infections include the following:
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Close observation for hospital-acquired infections: Especially pneumonia (particularly aspiration pneumonia); precaution against aspiration also is necessary
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Close observation for urinary tract infection
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Meticulous skin care: To prevent decubital ulcers and skin breakdown
Careful attention to peripheral and central intravenous catheters with regular site rotation to reduce the risks of thrombophlebitis, cellulitis, and line infections should be part of the patient’s supportive care.
See Treatment and Medication for more detail.
Background
Botulism is a critical neurologic syndrome characterized by acute neuroparalytic manifestations resulting from a neurotoxin secreted by Clostridium botulinum. [2, 9] 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 or intestinal botulism, [10] foodborne botulism, and wound botulism. Iatrogenic botulism also may ccur via cosmetic or therapeutic injection of any commercially made botulinum toxin (eg, Botox, Dysport, Xeomin, Myobloc). [2] Additionally, because of the potency of the toxin and ease of aerosolization, the possibility of inhalational botulism as a bioterrorism agent or biological weapon is of great concern. [2, 11] For more information, see CBRNE – Botulism.
Pathophysiology
Clostridium botulinum produces 8 distinct neurotoxins, including types A through G and the potent F/A Hybrid. [2] Among these, types A, B, E, and occasionally F and F/A Hybrid (previously known as H) can impact human health. These botulinum toxins are highly toxic proteins that can withstand degradation from stomach acid and proteolytic enzymes. Type F/A Hybrid is considered the most potent toxin among them. In the United States, around 50% of foodborne outbreaks are attributed to type A toxin, followed by types B and E. Geographically, type A toxin is more prevalent in areas west of the Mississippi River, type B is common in eastern states, and type E often is associated with regions such as Alaska and the Great Lakes area where ingestion of fish and fish products is frequent.
The mechanism of action involves toxin-mediated blockade of neuromuscular transmission in cholinergic nerve fibers. [12] This is accomplished by inhibiting acetylcholine release at the presynaptic clefts of the myoneural junctions. Toxins are absorbed from the stomach and small intestine, where they remain stable despite digestive enzymes. Subsequently, they are hematogenously disseminated to peripheral cholinergic nerve terminals (neuromuscular junctions, postganglionic parasympathetic nerve terminals, peripheral ganglia). The toxin is endocytosed by the neuron and then is allowed to cleave proteins essential for neurotransmitter release. The toxin does not cross the blood-brain barrier, likely secondary to its large size, however, it may be transported to the central nervous system axonally. [13]
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.
Humans commonly ingest C botulinum spores, but germination typically does not occur in the adult intestine since special conditions are required (ie, anaerobic environment, low acidity, specific amino acid, salt and sugar concentrations, and temperatures 37°F-99°F). [1, 14]
Wound botulism results when wounds are contaminated with C botulinum spores. [2] Wound botulism has developed rarely after cesarean delivery, following traumatic injury that involved soil contamination, and more commonly among injection drug users (particularly those who use black-tar heroin). [15, 16] 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. Symptoms develop after an incubation period of 4-13 days, with a median 6.5 days. [17] The clinical symptoms of wound botulism are similar to those of foodborne botulism except that gastrointestinal symptoms (including nausea, vomiting, diarrhea) are uncommon.
Frequency
In the United States over hundreds of cases of botulism are reported annually to the Centers for Disease Control and Prevention (CDC). [18] The latest available US surveillance summaries are from 2019. The European CDC has reported that although the annual botulism occurrence in Europe is fewer than 1 per 1,000,000 individuals, children younger than 12 months have the highest risk. [19]
Notably, based on open-source epidemic intelligence, the frequency of reported botulism cases in Ukraine has increased dramatically since the February 2022 invasion by Russia; within months of the invasion, case reporting increased by almost 400%, however, at this point the case-numbers likely are underestimated given the weakening / absence of formal reporting systems. [20] Prior to the analysis of the increase in Ukrainian cases, Romania had reported the highest number of cases in Eastern Europe in 2014 with 31 cases. [21]
The increasing instances of C botulinum in Vietnam have raised alarm among healthcare authorities and policymakers due to the inadequate availability of BAT antitoxin. [22]
Infant botulism
For 2019, the CDC reported 152 cases of infant botulism, all of which were laboratory-confirmed, with the highest case-counts coming from California and Pennsylvania. [18]
Infant botulism with mean age of 13 weeks accounts for 60-70% of all botulism cases. [23, 24]
Foodborne botulism
For 2019, the US CDC reported 21 cases of foodborne botulism. Outbreak-related cases are shown below:
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Alaska: Type E outbreak of 4 cases related to home-prepared fermented beluga flipper
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Colorado: Type A outbreak of 4 cases related to commercially prepared, prepackaged roasted potatoes
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Texas: Type A outbreak of 3 cases related to commercially prepared preserved peppers produced in Mexico
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China witnessed a total of 80 foodborne botulism outbreaks between 2004 and 2020, largely attributed to the excessive consumption of canned beans, tofu, and dried meat prepared with traditional techniques. [19]
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For 2019, the CDC reported 41 cases of wound botulism; the highest number of cases overwhelmingly were reported by California. All laboratory confirmed cases occurred in persons who injected drugs and 66% of those patients reported black tar heroin use. [18]
Wound botulism
For 2019, the US CDC reported 41 cases of wound botulism; the highest number of cases were overwhelmingly reported by California.
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All laboratory confirmed cases occurred in persons who injected drugsand 66% of those patients reported black tar heroin use. [18]
Mortality/Morbidity
Mortality rates vary based on the age of the patient and the type of botulism and have significantly declined since the early 1900s due to improvements in supportive care.
Infant (Intestinal) botulism
The risk for death due to infant botulism usually is less than 1%. [23]
Foodborne botulism
The modern mortality for foodborne botulism is 5% or less. [1, 27]
Wound botulism
Wound botulism carries a mortality rate of roughly 10%. [28]
Epidemiology
Sources of Botulism
Clostridium botulinum is an anaerobic, gram-positive bacterium that survives adverse conditions by forming spores and is commonly found in soil and marine sediments. [1, 2] Under anaerobic conditions, these spores can germinate, leading to the production of a highly potent botulinum toxin, which is the most potent toxin known on a molecular weight basis. [2]
Infant botulism
Infant botulism is by ingested C botulinum spores that germinate in the infant's intestine. [2] Sources include environmental spores from soil, dust, or contaminated food products such as honey and corn syrup. [23] Despite the association with honey, most cases occur without known exposure to it.
Clinical management primarily involves supportive care, with an infant mortality rate of less than 1%. [14]
Foodborne botulism
Foodborne botulism typically results from ingestion of toxin in improperly canned or home-prepared food. [2] Sources include environmental spores from soil, dust, or contaminated food products like honey and corn syrup. [23]
Despite the association with honey, most cases occur without known exposure to it. Honey, due to its low water activity (0.5 - 0.65), does not support the germination of C. botulinum spores, which require a water activity over 0.94. [29]
Wound botulism
Occurs predominantly in adults and can be associated with intravenous drug use, as demonstrated by a case involving a 40-year-old patient who injected black tar heroin and developed botulism, requiring intensive care and antitoxin administration. [30]
Geographic and demographic distribution
C botulinum spores are detected in approximately 20% of soil samples worldwide, with specific toxins associated with different regions. [29, 31]
Toxin A is found predominantly west of the Mississippi River in cases of wound botulism.
Toxin B is most common in the eastern United States, associated with infant botulism.
Toxin E is linked to northern latitudes and frequently associated with fish products [32, 33] .
Impact on wildlife
Toxins C and D are frequent causes of botulism in animals, particularly affecting birds and carnivores. Vultures exhibit high resistance to these toxins, whereas waterfowl are vulnerable due to their feeding habits. [31]
Global incidence and public health implications
A comprehensive analysis of 6,932 botulism cases from 59 nations revealed a global case fatality rate of 1.37%, with significant underreporting estimated at 88.71% in 2016. [34]
The study emphasized the need for improved awareness among healthcare professionals, better global reporting mechanisms, and enhanced surveillance to reduce the incidence and improve outcomes of botulism cases worldwide.
Sex
Wound botulism is more common in females. [24] 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. [23] The vulnerability of infants at the 3-5 month age is thought to be secondary to the change in bacterial taxa while transitioning to foods other than breast milk. [29] From 1976 to 1983, California found a greater percentage of botulism patients who were breastfed versus age-matched controls; however, this discrepancy is attributed to the theory that breastfeeding delays the colonization of the infant microbiome with C botulinum and slows the development of life-threatening toxemia enough so that cases may be diagnosed in the hospital, rather than an infant death occurring at home and being attributed to sudden infant death syndrome (which is twice as likely to occur with formula-fed infants). [29, 35]
Prognosis
Prompt and vigorous supportive care, especially respiratory care, greatly improves the prognosis.
The recovery period from botulism flaccid paralysis takes weeks to months. [2] Death that occurs early in the course of disease is usually secondary to acute respiratory failure, whereas death later in the course of illness is typically secondary to complications associated with prolonged intensive care (ie, venous thromboembolism or hospital-acquired infection). 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.
