Botulism …

B Jane Distad MD

Infectious Disorders

Updated 09.16.2025
Released 12.07.1993
Expires For CME 09.16.2028

Botulism

Author: B Jane Distad MD

See Contributor Disclosures

Editor: Christina M Marra MD

Cite this article

Botulism

In This Article

Quick Link

Introduction

Overview

In this article, the author reviews the clinical manifestations, diagnostic tests, and management of patients with botulism: foodborne, wound, adult intestinal toxemia, iatrogenic, and inhalational botulism. Recent information on wound and foodborne botulism is presented, along with diagnostic evaluations and treatments. Antitoxin treatment recommendations are included. An increasing number of iatrogenic cases are reported.

Key points

	• Botulinum toxin is the most potent neurotoxin in the world, with a lethal dose of approximately 1 ng/kg of body weight in humans.
	• Botulinum toxin acts at the neuromuscular junction. It interferes with proteins involved in acetylcholine vesicle fusion at the presynaptic nerve terminal, impeding acetylcholine release into synapses of the peripheral nervous system.
	• Most cases of foodborne botulism come from improperly home-canned foods whose preparation does not destroy C botulinum spores.
	• Wound botulism occurs through skin infections, with an increased incidence in people who inject drugs.
	• The definitive diagnosis of botulism is made by laboratory confirmation, along with supportive clinical and electrodiagnostic features.
	• Frequent monitoring of respiratory function is critical – either by forced vital capacity or negative inspiratory force; consider elective intubation for forced vital capacity less than 30% of predicted.
	• Laboratory confirmation is made by demonstrating the presence of botulinum toxin in serum, stool, or food, or by culturing Clostridium species from stool or a wound.
	•The Centers for Disease Control and Prevention (CDC) recommend administration of botulinum antitoxin as soon as the diagnosis is suspected.

Historical note and terminology

Following an increase in outbreaks of sausage intoxication in the early 1800s, Kerner (a German physician and poet) described 230 cases, characterizing the clinical syndrome of botulism (68). Further clarification of botulism as an entity was reported in 1897, when van Ermengem described the clinical, toxicological, and bacteriological features of an outbreak of foodborne botulism. He demonstrated that botulism was not due to an infection, but to an intoxication produced by a gram-positive, rod-shaped bacterium he named Bacillus botulinus, later called Clostridium botulinum. In the 1970s, Midura and Arnon identified infants who developed paralysis following C botulinum colonization of the gastrointestinal tract, with subsequent release of botulinum toxin into the gut (74). Wound botulism was historically described in connection with traumatic injury. Its association with drug injection use was first reported in 1982 in New York City.

Before 1950, mortality from botulism was approximately 60% (28). More recent data showed that of reported cases, 5% of patients died (Centers for Disease Control and Prevention 2019).

Although termed “botulinum neurotoxin” (BoNT), the toxin comes from six groups of bacteria: Clostridium botulinum I-IV, Clostridium baratii, and Clostridium butyricum (79). Botulinum toxin is a family of serologically related neurotoxins: types A, B, C1, D, E, F, G, and a variably classified H (31; 41).

Clinical manifestations

Presentation and course

Botulism classically presents with prominent cranial nerve palsies, followed by symmetric, descending, “flaccid paralysis” in an afebrile patient with normal mentation. The prominent cranial nerve palsies are loss of visual accommodation, causing blurred vision, external ophthalmoparesis, dysarthria, dysphagia, and facial weakness (65; 81). Limbs become weak over 1 to 3 days, potentially leading to quadriplegia. Deep tendon reflexes are normal or decreased. Patients often develop fixed pupils. Weakness of respiratory muscles may require intubation and mechanical ventilation in up to two-thirds of patients (84). At hospital admission, up to 40% of patients may have respiratory weakness, and these patients show a shorter median incubation time (22). Using defined criteria, Rao and colleagues collected data on 332 cases (2002-2015) from the CDC for which botulism antitoxin was provided (84). Chatham Stephens’s systematic review of the literature (1932-2015) included 402 cases. The most common signs and symptoms in these two large series were dysphagia (65% and 86%), weakness (50% and 85%), blurred (36% and 80%) or double (49% and 76%) vision, dysarthria (78%), and ptosis (37%) (22; 84).

Autonomic symptoms result from impaired acetylcholine release at peripheral cholinergic nerve terminals and include blurred vision, dry mouth, reduced sweating, constipation, and orthostatic hypotension (85). Topakian and colleagues found significant abnormal sudomotor function and heart rate variability or blood pressure response, or both, to standing in all five patients with foodborne botulism (108). Postprandial hypotension was seen in 40% of foodborne botulism (n=20) versus 3% of controls (n=34) (73) and conveyed a 733% increased likelihood of intubation by logistic regression analysis.

Aside from infant botulism (discussed elsewhere), foodborne and wound botulism are the most common forms. Other syndromes include adult intestinal toxemia botulism, iatrogenic botulism, and inhalation botulism.

Foodborne botulism. After ingestion of food containing botulinum toxin, the mean incubation period is 2 days, with a range from 0.5 to 6 days (65; 34). Gastrointestinal symptoms develop within 12 to 72 hours of ingestion: abdominal pain, nausea, and vomiting. In general, the longer the incubation period, the milder the symptoms.

In a review of cases of botulism types A and B in the United States (n=55), over 70% of patients complained of dysphagia, dry mouth, double vision, dysarthria, fatigue, and arm weakness, with a normal level of alertness and ptosis on examination (53).

In general, intoxication from type A is more severe than from types B, E, or F, although the frequency of clinical signs and symptoms varies from outbreak to outbreak (115; 39; 45).

Wound botulism. Patients with wound botulism develop neurologic signs and symptoms similar to those in foodborne botulism. The incubation period ranges from 4 to 51 days (48). Most wounds appear infected. Individuals with wound botulism usually lack the gastrointestinal prodrome seen in foodborne intoxication. A rise in wound botulism cases has been seen in people who inject drugs (76). Skin or muscle “popping,” whereby users inject contaminated heroin subcutaneously or into muscle, increases risk for botulism by creating an anaerobic environment of necrotic tissue in which BoNT can readily form and release. Two series reported 22 cases in California and Texas. Most were men (83%) and 83% had skin abscesses. The most common symptoms were dysphagia, generalized weakness, dysarthria and visual problems; 88% required mechanical ventilation (83; 78). Black tar heroin, which is an acetylated morphine, causes increased injection site vein loss and soft tissue infections, thereby increasing abscess formation and contamination of the wound by clostridial spores (105).

Adult intestinal toxemia botulism or adult intestinal colonization botulism. This entity is rarely reported and, therefore, not easily classified. It can present with nausea, vomiting, abdominal pain, constipation, and abdominal distension, lasting for weeks to months. Patients with bowel surgery or anomalies, or recent use of antimicrobials, are at risk, although adult intestinal toxemia botulism is rarely reported in healthy individuals (44). It has been proposed that an abnormal gastrointestinal tract and altered bacterial flora enable Clostridia organisms (C botulinum, C butyricum, C baratii) to colonize the gut (25). The in vivo toxin produced is then absorbed through the gut to produce botulism that may have a more protracted onset and duration than foodborne or wound botulism. Recovery typically occurs over months. However, of the 25 cases Harris and colleagues collected from the literature, eight ultimately died (44). Relapse of symptoms after antitoxin treatment are reported, presumably from continued gastrointestinal toxin production (103). Key observations from several cases can help confirm adult intestinal toxemia botulism. These include prolonged excretion (10 to 100+ days) of viable Clostridium spores or neurotoxin in the stool, a high level of botulinum neurotoxin in the feces compared to serum, and persistent recurrence of disease symptoms (44).

Iatrogenic botulism following medical or cosmetic administration. Both botulinum A and B toxins are widely used as therapeutic and cosmetic medicines. The 50% lethal dose for an adult is about 3000 U of botulinum toxin (depending on the type), and therapeutic botulinum doses rarely exceed 400 U (12). In 18 cases of iatrogenic botulism from botulinum neurotoxin type A (BoNT/A), age range from 16 to 74 years, all patients had been treated for underlying neurologic disorders (66). The most common symptoms were dysphagia (56%) and upper, greater than lower, limb weakness (39%). Twenty-eight percent of cases had diplopia; speaking difficulty; and face, tongue, or neck weakness, with two cases having spontaneous remission over months. Eighty-six botulism cases caused by cosmetic injection of BoNT were diagnosed (05), with symptoms of headache, dizziness, insomnia, fatigue, blurred vision, eye opening difficulty, slurred speech, and dysphagia occurring up to 36 days after BoNT injection, (mean 2nd to 6th day postinjection). The dose of BoNT was negatively related to latent period. All patients were treated with antitoxin and discharged within 20 days. Cases of severe botulism were reported following cosmetic procedures with unlicensed, highly concentrated botulinum preparations (24). In the case of off-label intragastric use for weight loss, clinical courses were long (30), 10 weeks to 6 months.

Inhalational botulism. Botulism may be acquired via inhalation on the battlefield, following inhalation of cocaine, in laboratory technicians performing postmortem exams on BoNT-exposed animals or in farmers or construction workers (63; 94). The signs and symptoms of inhalational botulism are like those from ingestion of the toxin, except for the absence of gastrointestinal symptoms. They include difficulty swallowing, extremity weakness, speech problems, abnormal extraocular movements, and moderately dilated pupils. The incubation period for inhalational botulism ranges from 24 hours to several days, rarely as early as 4 to 12 hours post-exposure (28). Unusual outbreaks, large numbers of victims affected in different locations, or lack of a common food source should lead the physician to consider bioterrorism or biological warfare and promptly notify local health authorities.

Prognosis and complications

Recovery is dependent on dose and toxin type. Rapidly progressing cases are more likely to require intubation. BoNT types A and E typically lead to a faster onset than type B (51). Patients who died had a shorter reported median incubation period and a shorter reported median time from illness onset to hospital admission (22).

Therapy with equine antitoxins became available in the early 1970s. Antitoxin cannot neutralize toxin once it is bound to the nerve receptors, and, therefore, does not reverse weakness. Antitoxin prevents the progression of the symptoms, but this may take up to 12 hours following administration. The clinical evidence for botulinum antitoxin efficacy in humans is based on retrospective analyses of small numbers of patients and animal studies. Despite limited evidence, it is believed that early treatment, especially within 24 hours of symptom onset, is most effective in preventing progression of weakness. Although antitoxin can reduce the duration of the hospital stay and mechanical ventilation by several weeks, recovery of strength occurs over weeks to months, requiring development of new neuromuscular junctions (37). Data from the Centers for Disease Control and Prevention suggest that roughly 5% of patients with botulism die (16). The 2021 National Botulism Surveillance Summary from the CDC included two deaths in 66 wound botulism cases, two deaths among 22 foodborne cases, and two deaths of uncertain cause. Death usually occurs from respiratory failure due to respiratory muscle weakness or from pneumonia.

Complications of all forms of botulism are a result of prolonged weakness, including aspiration pneumonia and decubitus ulcers. Persistent symptoms up to a year following recovery include exercise intolerance (60%), shortness of breath (60%), general weakness (55%), and dry mouth (51%) (70). Most patients do not return to full-time work for months.

Clinical vignette

Vignette 1. A 35-year-old male presented with 2 days of blurred and double vision, ptosis, and difficulty swallowing (111). Initial testing including brain MRI was normal, and he was sent home. Over days, his symptoms worsened, and he re-presented with slurred speech and facial weakness. Skin examination revealed no abscesses or open wounds. He was admitted to the hospital for possible stroke and treated for laryngitis.

Past medical history included methamphetamine use over many years. He had recently injected methamphetamine, mixed with water from a glass (sitting for an unknown time), intravenously, 36 hours before his symptoms began. The recent intravenous drug use raised suspicion for botulism.

Heptavalent botulinum antitoxin was provided by the Centers for Disease Control and Prevention and administered to the patient within 24 hours of admission to the hospital. He did not require ventilatory support, and his symptoms of double vision, ptosis, difficulty swallowing, and facial weakness gradually improved until hospital discharge 5 days after antitoxin administration. Serum obtained before antitoxin administration contained BoNT type B by the BoNT Endopep-MS assay.

Vignette 2. A 54-year-old woman with a history of Crohn disease on immunosuppressant medications presented with sudden-onset right ptosis, dysarthria, and shortness of breath, followed over days by diplopia, soft voice, proximal arm weakness, and difficulty swallowing. Symptoms were preceded by abdominal pain and distension. She was intubated 8 days after symptom onset.

On examination, she communicated by writing. Facial muscles, tongue, and neck were moderately weak, with complete ptosis and no diplopia. She had severe proximal, greater than distal, weakness in the upper, more than lower, extremities. Reflexes were mildly reduced. Although antibodies for myasthenia gravis were negative, she was treated presumptively for myasthenia gravis with a 5-day course of intravenous immunoglobulin. Nerve conduction study showed small-amplitude motor responses, and EMG showed small, short duration motor unit action potentials with early recruitment, consistent with a myopathic pattern. Given the constellation of symptoms, she was treated with botulinum antitoxin and penicillin G 2 weeks into her course. Botulinum neurotoxin type A, both in serum and stool, was detected by mouse bioassay. One month later, she was weaned from tracheostomy, and after 2 months she ambulated with a walker and her swallowing normalized. Because she was treated late in the course, this may have limited her response to botulinum antitoxin.

Biological basis

Etiology and pathogenesis

Botulism is caused by the release of botulinum neurotoxins, which are polypeptides that are naturally produced by the spore-forming, strictly anaerobic, gram-positive bacillus, Clostridium botulinum, as well as certain strains of Clostridium baratii (toxin type F) and butyricum (toxin type E). C botulinum is found ubiquitously in soil and aquatic sediments (103; 62).

Botulinum toxin is a family of serologically closely related neurotoxins: A, B, C, D, E, F, G, and a variably classified type H or FA (31; 41). On a milligram-per-kilogram basis, botulinum toxin is the most potent biological toxin known. The estimated human dose (assuming 70 kg weight) of BoNT/A lethal to 50% of a population that is exposed (LD50) based on animal studies is approximately 0.09 to 0.15 μg by intravenous administration, 0.7 to 0.9 μg by inhalation, and 70 μg by oral administration (28). Other reports include BoNT LD50 is between 0.1 and 500 ng/kg (107).

In foodborne botulism, the individual ingests the preformed toxin. In infant botulism and adult intestinal toxemia botulism, C botulinum spores germinate in and produce toxin directly in the gastrointestinal tract (113). In wound botulism, anaerobic wound infections that contain C botulinum produce the toxin that is then systemically absorbed.

Pathophysiology. Botulinum neurotoxins must travel via the circulation to reach their final target, the neuromuscular junction (102; 50). In foodborne botulism, this begins in the gastrointestinal tract. BoNT itself is rapidly inactivated by the acid and proteolytic activity of stomach fluids. However, it is released from bacteria as part of a noncovalent multimeric complex containing auxiliary proteins. This complex is formed by BoNTs and nontoxic neurotoxin-associated proteins. The nontoxic non-haemagglutinin component (NTNHA) plays an important role in protecting BoNTs from the gastrointestinal tract. Other subunits enable binding to the surface of intestinal cells for subsequent transcytosis of the neurotoxin complex from the apical membrane to the basolateral membrane of intestinal epithelium (107; 71). HA complex is believed to form a docking station on the intestinal lumen and allow efficient transport of the BoNT across the intestinal epithelium into the bloodstream. Additionally, the HA proteins are known to disrupt the intestinal epithelial barrier through binding of E-cadherin between epithelial cells, compromising the integrity of the epithelium and facilitating absorption of the toxin (91). The toxin then spreads via the lymphatic and vascular circulations. Although BoNT does not cross the blood-brain barrier (104), it does cross the blood-nerve barrier. In wound botulism, spores of C botulinum contaminate a wound, germinate, and produce botulinum neurotoxin in the wound, which then enters the circulation.

All BoNTs are protoxins that target and enter motor nerve terminals at neuromuscular junctions. The protoxin undergoes a post-translational cleavage losing 11 amino acids in a process termed “nicking.” The mature and active toxin (known as the di-chain holoenzyme) comprises a 50 kDa light chain (LC) and 100 kDa heavy chain (HC) linked by non-covalent interactions and a disulfide bond. The light chain incorporates the catalytic zinc-dependent protease activity within the core of the structure (29; 91). The heavy chain contains two functional 50 kDa domains: a C-terminal domain, which delivers the light chain into the cytosol, and an N-terminal domain (HN) that recognizes specific cell-surface receptors. Although all BoNT serotypes inhibit acetylcholine release, their mechanisms of action, specific toxicities, and durations of persistence within the nerve cell differ. Mechanisms of action vary among different intracellular protein targets (there are seven different cleavage sites within the three protein targets--specific soluble N-ethylmaleimide-sensitive factor attachment protein receptors; SNAREs). After BoNT binds to high-affinity presynaptic receptors, it is transported into the nerve cell through receptor-mediated endocytosis within approximately 30 minutes. Acidification of the endosome triggers conformational changes of the toxins that lead to the N-terminal HC domain enabling the catalytic domain (LC) to translocate across the endosomal membrane into the cytosol of the peripheral cholinergic nerve cell. Once inside the cytosol, the catalytic domain blocks neurotransmitter acetylcholine release by selectively targeting and cleaving a specific set of SNARE proteins, which mediate fusion of synaptic vesicles to the presynaptic membrane in neurons. The SNARE proteins and their sensitivities to BoNT are synaptosomal-associated protein of 25 kDa (SNAP-25; cleaved by BoNT/A, BoNT/C, BoNT/E); syntaxin 1 (cleaved by BoNT/C); and synaptobrevin (also known as vesicle-associated membrane protein [VAMP]) (cleaved by BoNT/B, BoNT/D, BoNT/F, BoNT/G) (102; 28; 29; 114).

Recovery from botulism occurs by new axon terminal sprouting and by the nerve cell body producing and transporting new SNARE proteins down to the synapse via axoplasmic flow, with the regenerating axon sprouting and forming contacts at the original synaptic sites. The recovery time is weeks to months and depends on the regeneration speed of nerve terminals and presynaptic membranes (68).

Epidemiology

BoNT toxin types A, B, E, and F are the main toxins that affect humans. C botulinum strains that produce toxins A, B, and F are usually found in soil of geographic areas having low rainfall and moderate temperatures.

In the 2019 national botulism surveillance summary, the Centers for Disease Control and Prevention found 201 laboratory-confirmed cases: 71% infant, 19% wound, 10% foodborne, and <1% other (probable adult intestinal colonization). These percentages are similar to those from 2018.

Foodborne botulism. In the United States in 2021, cases were of the following toxin types: 78% A, 22% E, and 5% F. The median age was 57 years, and 61% of cases were male. More information can be found at https://www.cdc.gov/botulism/php/national-botulism-surveillance/2021.html. Le Bouquin and colleagues described 100 foodborne outbreaks in France between 2008 and 2018, which have remained relatively stable at 0.02 cases per 100,000: 90% of cases were foodborne, 10% of cases were infant, and less than 1% of cases were wound botulism (64).

More than 40% of foodborne botulism cases come from improperly home-canned vegetables and meats that fail to destroy C botulinum spores (34). Anaerobic conditions, low acidity (pH> 4.6), low salt and sugar concentrations, and temperatures higher than 39°F (4°C) promote germination of C botulinum spores and botulinum toxin production (15).

Individual reports identify numerous sources: home-canned vegetables, meats and fish; carrot juice; stink heads; seal oil; commercially packaged vegetables and potatoes; salt cured or fermented seafood, tofu, or roach; potato salad; brewing of pruno (Centers for Disease Control and Prevention 2014; 17; Centers for Disease Control and Prevention 2019; 86). Home canned meats and fish caused two large outbreaks in Iran (252 cases) and Ukraine (8641 cases, mostly type B) (57; 97). Hendrickx and colleagues reported six cases involving salt cured dried roach in Germany and Spain, type E (47).

Wound botulism. Areas where skin popping is practiced, such as the southwest United States, experience higher numbers of botulism due to black tar heroin use (83).

In the 2021 National Botulism Surveillance Summary, 66 cases of wound botulism were reported to the CDC, with 40 confirmed cases (Centers for Disease for Control and Prevention 2025). All 24 with exposure information occurred in persons who injected drugs; 42% reported black tar heroin use. Seventy-three percent were toxin type A, and 15% were toxin type B. The median age was 45 years, and 68% were male. Two deaths were reported. More information can be accessed at https://www.cdc.gov/botulism/php/national-botulism-surveillance/2021.html.

From 2001 to 2016, 291 of 353 wound botulism cases in the United States reported to the Centers for Disease Control and Prevention were from California (17). Two series reported fifteen cases of wound botulism in Texas and nine cases in California in persons who inject drugs (83; 78).

Other, including adult intestinal toxemia and iatrogenic. Iatrogenic cases are on the rise. Eighty-seven cases of iatrogenic botulism were reported in 2023 across Europe with most confirmed by endopeptidase assays, as the longest case was 11 days out from treatment. This followed intragastric botulinum toxin injections for weight reduction, most of which were performed in Turkey (30). In the last 18 months, at least 10 additional cases of iatrogenic botulism have been reported, typically from either unlicensed or high-dose injections, or both (27; 32; 35; 42; 92).

Guru and colleagues identified 35 cases of intestinal toxemia botulism in the literature (40). Three species of clostridia (botulinum, baratii, and butyricum) were incriminated as the cause in 51%, 31%, and 9%, respectively. Four cases reported by the Centers for Disease Control and Prevention in 2021 were toxin A (75%) and toxin type F. One was suspected adult intestinal toxemia. There were two deaths. More information can be found at https://www.cdc.gov/botulism/php/national-botulism-surveillance/2021.html.

Carpentier and colleagues described 141 complications over 6 years from botulinum toxin treatment, a number of which could be consistent with botulism, but as a pharmacovigilance analysis, there were no confirmatory data (13).

Diagnostic workup

Although the following tests aid in the confirmatory diagnosis, strong clinical suspicion is key to providing prompt treatment.

Basic laboratory and CSF evaluations are usually normal. Testing for toxin or bacterium needs to be performed prior to any antitoxin treatment.

The definitive diagnosis of botulism is made by demonstrating the presence of botulinum toxin in serum, stool, or food, or by culturing C botulinum, C butyricum, or C baratii from stool or a wound. Although many DNA-based methods have been developed to identify the presence of C botulinum spores in food, clinical, or environmental samples, the sensitivity is too low to be reliable (90).

BoNT detection methods include the in vivo mouse bioassay and in vitro assays using immunological detection methods, endopeptidase assays, or a combination of the two, such as the endopeptidase-mass spectrometry assay and cell-based assays. The Centers for Disease Control and Prevention perform mouse bioassay, mass spectrometry, and polymerase chain reaction on samples.

The gold standard test for the presence of botulinum toxin is the mouse bioassay (MBA). It is the only method approved by the U.S. Food and Drug Administration (FDA) for laboratory confirmation of botulism. Although seldom performed at most hospitals, this test is usually available at state reference laboratories or the Centers for Disease Control and Prevention. Only a biological assay, such as the mouse bioassay, or an appropriate cell-based assay, can selectively detect biologically active BoNTs, as well as all subtypes and novel BoNTs (80). The mouse bioassay involves mouse intraperitoneal inoculation (with or without antitoxin) from the patient's serum, stool, or food extracts, to determine whether the mouse becomes weak and dies over 96 hours. Results might be available within 24 hours of receipt of the specimen if the botulinum neurotoxin level is high. However, low levels of toxin that are sufficient to produce human illness might not produce signs in mice. Injection of specimens intraperitoneally into the mice with antitoxin is performed to determine the BoNT serotype (49). Clostridial organisms may be cultured from stool, food samples, or wounds. These samples must be cultured in special anaerobic enrichment broth media for 4 or more days and then media are tested for the presence of botulinum toxin (46). If toxin is present, the bacteria can then be specifically isolated. Polymerase chain reaction (PCR) detects clostridial DNA, not the actual proteinaceous toxin. Although PCR can identify the Clostridium species, another method must be used to confirm that a strain produces toxin. Specimen types, quantities, storage and shipping are detailed by Rao and colleagues (85).

The mass spectrometry method for detecting botulinum neurotoxin (endopep-MS) is highly sensitive and specific and can differentiate among botulinum neurotoxin serotypes A, B, E, and F within several hours. This method is only available at the Centers for Disease Control and Prevention and a limited number of other public health laboratories in the United States. This method successfully identified nine of 12 cases in a 2023 iatrogenic series up to 2 weeks after exposure and was more sensitive than MBA.

Laboratory confirmation of botulism acquired by inhalation can be difficult. If only toxin is inhaled without spores, then bacterial cultures will be negative. Toxin may be detectable in the nares for up to 24 hours postexposure. An enzyme-linked immunosorbent assay or polymerase chain reaction of a nasal mucosal swab may be considered a diagnostic tool for inhalational exposure to botulinum toxin (detects contaminating bacterial DNA), but these tests have not been validated (28).

Electrodiagnostic studies provide support for the diagnosis of all forms of botulism and may be particularly useful in situations in which laboratory confirmation is lacking. Nerve conduction studies show small-amplitude compound muscle action potentials (CMAPs) with normal distal latencies, conduction velocities, and sensory nerve action potentials. As a presynaptic neuromuscular junction disorder, botulism shares electrodiagnostic features with Lambert-Eaton syndrome. Repetitive nerve stimulation at low rates (2 to 3 Hz) may show decrement in CMAP amplitude (82; 99). Facilitation (or increment) of CMAP amplitude is often seen after exercise or high-frequency (30 to 50 Hz) repetitive nerve stimulation. This occurs due to significant increase in calcium influx into the presynaptic terminal contributing to an increase in acetylcholine release. Compared to Lambert-Eaton syndrome, only about 60% of adult patients with botulism exhibit significant postexercise facilitation, and the amount of postexercise facilitation is typically less (30% to 100% vs. > 100%), but the duration of facilitation is longer, usually over 2 minutes (55) and may be absent in severely affected muscles. Nonspecific EMG changes include low-amplitude and short-duration motor unit action potentials (a myopathic pattern) (72). One explanation of this incongruent finding is that blocking of neuromuscular transmission causes a large percentage of individual muscle fibers of a motor unit to fail to generate action potentials. The resultant motor unit action potential is diminished in amplitude and duration. Later in the clinical course, the EMG often demonstrates fibrillation potentials, a sign of muscle membrane instability. Single fiber electromyography may be a useful adjunct as it has very high sensitivity for neuromuscular junction abnormalities, demonstrating increased jitter and blocking. However, it is not specific (82). Nerve conduction study/EMG usually distinguishes between other causes of weakness, such as Guillain-Barré syndrome (or the Miller Fisher variant), where there is slowed conduction; myasthenia gravis, which shows normal baseline CMAP amplitudes, CMAP amplitude following exercise; poliomyelitis where there is abundant active denervation; and tick paralysis, which may show reduced CMAP amplitudes and mildly prolonged motor and sensory latencies during the paralytic phase, and, if prolonged weakness, then fibrillation potentials (99; 60). Normal electrodiagnostic studies do not exclude the diagnosis of botulism, particularly early in the disease.

Following an outbreak of foodborne botulism, a single center evaluation of 18 males in acute, early post-acute, and late post-acute phases, found reduced CMAP amplitudes in 100%, 20%, and 17% of patients; abnormal postexercise CMAP facilitation in 100%, 40%, and 0% of patients; and pathological incremental responses to high-frequency RNS in 80%, 50%, and 8% of patients, respectively (09). On needle EMG, small MUAPs were found in 100% of patients in the acute and early post-acute phases and in 50% of patients in the late post-acute phase.

Management

Treatment comprises supportive care, botulinum antitoxin, and potentially antibiotics and should begin as soon as the diagnosis is suspected (26; 93; 23). Patients with all forms of botulism require medical attention in an intensive care unit. They should be monitored carefully, particularly in the early stages of the disease because weakness may progress rapidly. The patient should undergo frequent respiratory monitoring and neurologic examinations for adequacy of gag and cough reflexes, ability to swallow and handle oropharyngeal secretions, and limb strength.

Monitoring for impending neuromuscular respiratory failure includes serial measurements with handheld bedside spirometry for forced vital capacity or negative inspiratory force (NIF). A normal vital capacity is approximately 65 mL/kg. A poor cough occurs at around 30 mL/kg. Typically, a vital capacity of less than 20 mL/kg ideal body weight, NIF less than -25 cm H20, or a rapidly declining vital capacity on serial measures are indications for elective endotracheal intubation (Chang 2019). Oxygen desaturation or hypoxemia with absolute or relative hypercarbia on arterial blood gas measurements does not develop until just before frank respiratory failure.

In the United States, the Centers for Disease Control and Prevention recommends administration of heptavalent (types A to G) botulinum antitoxin (HBAT) as soon as possible. Trivalent and tetravalent antitoxin therapies are available in other countries (89). Symptoms may often progress for up to 12 hours after antitoxin administration before an effect is observed. HBAT is composed of equine polyclonal antibody fragments F(ab)2 against BoNT A through G. In circulation the polyclonal antibody fragments bind to free BoNT. This prevents the BoNT from interacting with anchorage sites and protein receptors on the cholinergic nerve endings. In turn, this prevents BoNT internalization into the target cells (U.S. Food & Drug Administration 2023). HBAT is available through the Centers for Disease Control and Prevention, the Alaska Division of Public Health, and the California Department of Public Health. Antitoxin for infants is available from the California Department of Public Health (19). Fagan and coworkers found that toxin was detected in serum for up to 12 days after ingestion (33). This finding supports administering an antitoxin up to 12 days after toxin ingestion.

Each vial of HBAT contains varying units of antitoxin against each botulinum type and sufficiently neutralizes circulating toxin found in all forms of botulism. The half-life of the circulating antitoxin is 5 to 7 days. The Centers for Disease Control and Prevention recommend administration of one vial (02; 85). The antitoxin vial should be diluted 1:10 in 0.9% saline solution and administered by slow intravenous infusion 0.5 mL/min and gradually increased to a maximum 2 mL/min in adults.

Administration of equine antitoxin may produce allergic reactions, and the antitoxin should not be given to individuals with known allergies to equine products. Diphenhydramine and epinephrine should be immediately available during the antitoxin administration for possible allergic reaction. Incidence of hypersensitivity, serum sickness, and anaphylaxis occurred in approximately 3.5%, 0.1%, and 1.0% of botulinum antitoxin product–exposed individuals, respectively, in a 15-year systematic review (77). A joint task force report by the major infectious disease public health departments concluded that skin testing prior to administration of HBAT is not indicated (96). The IgG-Fc (receptor-binding fragment) is mostly responsible for hypersensitivity reactions and is commonly removed from heterogenous preparations.

To obtain the antitoxin, one should contact local and state health departments. In the United States, if local health departments are unavailable, the Centers for Disease Control and Prevention can be telephoned at the emergency number (during or after hours): (770) 488-7100.

As the use of antibiotics in botulism has not been established (14), antibiotics have no current role in foodborne, iatrogenic, or inhalational botulism except to treat secondary bacterial infections. Patients with wound botulism should have the wound surgically debrided and appropriate anaerobic cultures obtained. If antibiotics are required for secondary infections, they should be ideally given after administration of botulinum antitoxin is administered, as lysing C botulinum with the antibiotic will release more toxin. Additionally, individuals with botulism may worsen clinically if they receive aminoglycoside antibiotics, which can potentially increase presynaptic neuromuscular blockade (59).

There are no guidelines for postexposure prophylaxis. Kodihalli and colleagues described the therapeutic efficacy of equine antitoxin in Rhesus monkeys as a postexposure prophylaxis treatment (61). The antitoxin delayed the progression of signs, reduced the severity of the disease, and decreased the number of deaths.

Outcomes

HBAT is safe and provides clinical benefit. Improvements in any botulism sign or symptom were detected a median of 2.4 days, and in muscle strength a median of 4.8 days, after treatment (117). Systematic reviews show that timely administration of antitoxin reduces mortality and improves survival (75; 22). Mortality rates vary according to mechanism and report. A French review noted 1% to 2% mortality between 1991 and 2016 in food-borne botulism (88).

The time to full recovery varies by the type of toxin and the intensity of the exposure. Botulinum type A is the most toxic, whereas type E is the least. Patients requiring ventilator assistance often report that they continue to have marked fatigue for up to a year or more after infection (70). A case control study involving 211 patients, with a median time since onset of illness of 4.3 years, found that patients were more likely than control subjects to report fatigue, weakness, dizziness, dry mouth, difficulty lifting objects, and difficulty breathing (36). In experimental animal studies and human volunteers who were given IM injections of the toxin to paralyze specific muscles, recovery of normal muscle function required 12 months (56). One major factor that could contribute to prolonged recovery is the long half-life of the catalytic light chain, which remains enzymatically active months after entry into cells and evades breakdown by means of a deubiquitinating enzyme.

Treatments on the horizon. Research studies for identification and use of non-antitoxin treatment strategies have led to other proposed treatments (not approved by the FDA), including guanidine hydrochloride, 3,4-diaminopyridine, and plasma exchange (20; 07). However, a systematic review and meta-analysis of case reports and treatments with antitoxins from 1923 to 2016 suggested that therapeutic agents other than antitoxin offered no clear benefit (75). Single-chain antibodies have been shown to be efficacious but are limited by their shorter lives in circulation. Huang and colleagues engineered mouse red cells to express these single-domain antibodies (VHHs) and described the protective properties to lethal doses of the toxin (52). Some relatively newer agents may offer therapeutic relevance, such as quinolinol inhibitors, which inhibit SNAP-25 cleavage, and picolinic acids, which inhibit the beta-exocite, a largely unexplored site on the LC that holds therapeutic relevance for botulism treatment (11; 10).

New-generation therapies are based on a combination of humanized monoclonal antibodies (mAbs), which exhibit improved safety and pharmacokinetics. In a mouse model, homologous Fc increased the potency of the antibotox 1 mAbs and increased efficacy, arguing for development of human monoclonal antibodies as treatment (109). To develop recombinant antibodies that neutralize botulinum neurotoxins, targeting heavy and light chains (HC and LC) of the BoNT serotypes A, B, and E macaques were immunized, followed by the generation of immune phage-display libraries. Antibodies were selected and challenged with toxins from Clostridium strains. Protective antibody combinations against BoNT/A and BoNT/B were evident, and for BoNT/E, the anti-LC antibody alone was found highly protective (87) and may be suitable for further development. Significant progress has been made using mAbs, but further progress is still required to address the BoNTs great variability (88). Two research teams have developed modified forms of botulinum toxin that join botulinum toxin endocytosis to motor nerve terminals and inactivate the toxin. One group made three genetic changes to botulinum toxin that prevented it from slicing SNARE proteins. The other team combined components of a disease-causing form with a related botulinum toxin that does not invade nerves. Both teams linked their engineered toxin to a nanobody, which can inactivate the toxin. Compared with full-size antibodies, nanobodies can be engineered to reach and keep their structure within specific targets in cells. This resulted in more rapid recovery, better recovery, and survival to 10 days in monkeys, whereas those untreated died in 3.5 days (98).

Several publications highlight future candidates for the treatment of botulism, most of which focus on monoclonal antibodies: chimeric neutralizing nanobodies binding to the HC domain of BoNT/B to inhibit toxin binding to the host receptor (54), human Mab specific to native BoNT/A and the proteolytic (LC) domain of BoNT to neutralize BoNT/A (101), humanized mAb (HZ45) HC against BoNT/A that prevents toxin from entering the nerve terminal in animal models up to 8 hours after exposure (116), neutralizing nanoantibodies to L-HN BoNT/F fused with a human Fc fragment (106), three specific murine mAbs to the catalytic and receptor-binding domains of BoNT/A (119), and a peptide derived from arg-arg-glyc-tryp (RRGW) against BoNT/A (69).

Investigations into the use of antibiotic therapy have shown some promise. C botulinum type A and B strains and neurotoxigenic C baratii strains from California were highly susceptible to penicillin, cephalosporins, moxifloxacin, and trimethoprim-sulfamethoxazole (06). Yutani and colleagues investigated the effects of antibiotics on the viability of and toxin production by C botulinum group I strains in the stationary phase by measuring the minimal growth inhibitory concentrations (MICs) of these antibiotics against C botulinum cultivated from spores in anaerobic culture. Metronidazole was shown to rapidly reduce the viability of C botulinum strains, without enhancing BoNT production and may serve as a future alternative treatment (118).

Vaccines can play a future role in treatment by preventing the disease and protecting workers connected to BoNT. Genetically engineered inactivated chimeric molecules using HC and L-HN domain antigens produced a highly effective immune response against BoNT/A and E in animal models, suggesting its effectiveness as a bivalent vaccine (112). To develop a trivalent vaccine against BoNT/A, BoNT/B, and BoNT/E, Liu and colleagues conjugated HC/E (fused with core-streptavidin) with an atoxic chimeric protein incorporating neutralizing epitopes from BoNT/A (binding domain) and BoNT/B (protease-inactive LC and translocation domains) (67).

Saini and colleagues emphasized the use of biosensors to detect BoNT in foods as potential mechanisms to prevent ingestion and disease, given that electrochemical biosensors often exhibit higher sensitivity and selectivity by utilizing specific recognition elements like immobilized enzymes and antibodies (95). This may prove beneficial in environmental monitoring, food safety, and biodefense. Initial studies demonstrated that Citrus limon leaf extract in fishery products suppressed the growth of C botulinum (43) and ultraviolet-C inactivated C botulinum spores in a suspending medium (03).

References

01: Anonymous. Botulism antitoxin. In: Drugs and Lactation Database (LactMed®) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development, 2006. PMID 39836859
02: Arnon SS, Schechter R, Inglesby TV, et al. Botulinum toxin as a biological weapon: medical and public health management. JAMA 2001;285(8):1059-70. PMID 11209178
03: Assal N, Boone R, Harris RA, Gabriel M, Sasges M, Petri B, Ramaswamy H, Austin JW. Inactivation of group I and group II clostridium botulinum spores by ultraviolet irradiation in water. Int J Food Microbiol 2023;395:110191. PMID 37019040
04: Badell ML, Rimawi BH, Rao AK, Jamieson DJ, Rasmussen S, Meaney-Delman D. Botulism during pregnancy and the postpartum period: a systematic review. Clin Infect Dis 2017;66(suppl 1):S30-7. PMID 29293925
05: Bai L, Peng X, Liu Y, et al. Clinical analysis of 86 botulism cases caused by cosmetic injection of botulinum toxin (BoNT). Medicine (Baltimore) 2018;97(34):e10659. PMID 30142749
06: Barash JR, Castles JB 3rd, Arnon SS. Antimicrobial susceptibility of 260 clostridium botulinum type A, B, Ba, and Bf strains and a neurotoxigenic Clostridium baratii type F strain isolated from California infant botulism patients. Antimicrob Agents Chemother 2018;62(12):e01594-18. PMID 30275093
07: Beske PH, Hoffman KM, Machamer JB, Eisen MR, McNutt PM. Use-dependent potentiation of voltage-gated calcium channels rescues neurotransmission in nerve terminals intoxicated by botulinum neurotoxin serotype A. Sci Rep 2017;15862. PMID 29158500
08: Bleck TP. Clostridium botulinum (Botulism). In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. 5th ed. Philadelphia: Churchill Livingstone, 2000:2543-8.
09: Boccagni C, Prestandrea C, D’Agostino T, et al. Neurophysiological patterns of acute and post-acute foodborne botulism. Muscle Nerve 2021;64(4):435-44. PMID 34255868
10: Bremer PT, Adler M, Phung CH, Singh AK, Janda KD. Newly designed quinolinol inhibitors mitigate the effects of botulinum neurotoxin A in enzymatic, cell-based, and ex vivo assays. J Med Chem 2017;60(1):338-48. PMID 27966961
11: Bremer PT, Xue S, Janda KD. Picolinic acids as β-exosite inhibitors of botulinum neurotoxin A light chain. Chem Commun (Camb) 2016;52(84):12521-4. PMID 27722252
12: Brin MF. Botulinum toxin: chemistry, pharmacology, toxicity, and immunology. Muscle Nerve 1997;(Suppl 6):S146-68. PMID 9826987
13: Carpentier VT, Weiss N, Salem JE, et al. Real-life prognosis of neurological complications of botulinum toxin: a nationwide pharmacovigilance study of adverse drug reactions reported in France between 1994 and 2020. Ann Phys Rehabil Med 2025;68(3):101924. PMID 40081132
14: Carrillo-Marquez MA. Botulism. Pediatr Rev 2016;37(5):183-92. PMID 27139326
15: Centers for Disease Control and Prevention. Botulism associated with commercial carrot juice–Georgia and Florida, September 2006. MMWR 2006;55:1098-9. PMID 17035929
16: Centers for Disease Control and Prevention. Clinical overview of botulism. Available at: https://www.cdc.gov/botulism/hcp/clinical-overview/. Accessed 2025.
17: Centers for Disease Control and Prevention. National botulism surveillance. Atlanta, GA: US Department of Health and Human Services, CDC, 2018.
18: Centers for Disease Control and Prevention. Botulism Annual Summary, 2019. Atlanta, Georgia: US Department of Health and Human Services, CDC, 2023.
19: Centers for Disease Control and Prevention. National botulism surveillance system overview. Atlanta, Georgia: US Department of Health and Human Services, CDC, 2012.
20: Chalk CH, Benstead TJ, Keezer M. Medical treatment for botulism. Cochrane Database Syst Rev 2014;2:CD008123. PMID 24558013
21: Chang CWJ. Myasthenia gravis and Guillain Barre syndrome. In: Parrillo J, Dellinger R, editors. Critical care medicine: principles of diagnosis and management in the adult. 5th ed. Amsterdam: Elsevier, 2019:61, 1020-9.
22: Chatham-Stephens K, Fleck-Derderian S, Johnson S, Sobel J, Rao A, Meaney-Delman D. Clinical features of foodborne and wound botulism: a systematic review of the literature, 1932–2015. Clin Infect Dis 2017;66(suppl_1):S11-16. PMID 29293923
23: Cherington M. Botulism: update and review. Semin Neurol 2004;24:155-63. PMID 15257512
24: Chertow DS, Tan ET, Maslanka SE, et al. Botulism in 4 adults following cosmetic injections with an unlicensed, highly concentrated botulinum preparation. JAMA 2006;296:2476-9. PMID 17119144
25: Chia JK, Clark JB, Ryan AC, Pollack M. Botulism in an adult associated with food-borne intestinal infection with Clostridium botulinum. N Engl J Med 1986;315:239-41. PMID 3523248
26: Davis LE. Botulism. Curr Treat Option Neurol 2003;5(1):23-31. PMID 12521561
27: Dawson EF, Pateriya S, Blashinsky Z, Landa-Galindez A. From botox party to botulism: a case report and public health warning on adulterated botulinum toxin injection. Cureus 2024;16(8):e68016. PMID 39211826
28: Dembek ZF, Smith LA, Rusnak JM. Botulism: cause, effects, diagnosis, clinical and laboratory identification, and treatment modalities. Disaster Med Public Health Prep 2007;1(2):122-34. PMID 18388640
29: Dong M, Masuyer G, Stenmark P. Botulinum and tetanus neurotoxins. Annu Rev Biochem 2019;88:811-37.** PMID 30388027
30: Dorner M, Bernhard, Wilking H, et al. A large travel-associated outbreak of iatrogenic botulism in four European countries following intragastric botulinum neurotoxin injections for weight reduction, Türkiye, February to March 2023. Euro Surveill 2023;28(23):2300203. PMID 37289431
31: Dover N, Barash JR, Hill KK, Xie G, Arnon SS. Molecular characterization of a novel botulinum neurotoxin type H gene. J Infect Dis 2014;209(2):192-202. PMID 24106295
32: Eser F, Hasanoğlu I, Kayaaslan B, et al. Iatrogenic botulism cases after gastric and axillary application of botulinum toxin and review of literature. J Infect Dev Ctries 2024;18(3):480-7. PMID 38635607
33: Fagan RP, McLaughlin JB, Middaugh JP. Persistence of botulinum toxin in patients' serum: Alaska, 1959-2007. J Infect Dis 2009;199 (7):1029-31. PMID 19203262
34: Fleck-Derderian S, Shankar M, Rao AK, et al. The epidemiology of foodborne botulism outbreaks: a systematic review. Clin Infect Dis 2017;66(suppl 1):S73-81. PMID 29293934
35: Frazao J, Pera R, De Sousa X, Fragoso M, Mira P. Iatrogenic botulism following botulinum toxin injection as an adjunct to abdominal wall reconstruction for incisional hernia. Cureus 2024;16(11):e73773. PMID 39677231
36: Gottlieb SL, Kretsinger K, Tarkhashvili N, et al. Long-term outcomes of 217 botulism cases in the Republic of Georgia. Clin Infect Dis 2007;45(2):174-80. PMID 17578775
37: Guidon AC. Lambert-Eaton myasthenic syndrome, botulism, and immune checkpoint inhibitor-related myasthenia gravis. Continuum (MinneapMinn) 2019;25(6):1785-806. PMID 31794471
38: Gupta S, Pellett S. Recent developments in vaccine design: from live vaccines to recombinant toxin vaccines. Toxins (Basel) 2023;15(9):563. PMID 37755989
39: Gupta A, Sumner CJ, Castor M, Maslanka S, Sobel J. Adult botulism type F in the United States, 1981-2002. Neurology 2005;65(11):1694-700. PMID 16344510
40: Guru PK, Becker TL, Stephens A, et al. Adult intestinal botulism: a rare presentation in an immunocompromised patient with short bowel syndrome. Mayo Clin Proc Innov Qual Outcomes 2018;2(3):291-6. PMID 30225463
41: Hackett G, Moore K, Burgin D, et al. Purification and characterization of recombinant botulinum neurotoxin serotype FA, also known as serotype H. Toxins (Basel) 2018;10(5):195. PMID 29751611
42: Hagberg G, Skytøen E, Nakstad I, et al. Iatrogenic botulism. Tidsskr Nor Laegeforen 2024;144(2). PMID 38349108
43: Hamad G, Hafez EE, Sobhy SE, et al. Detection of clostridium botulinum in some egyptian fish products, its control in vitro using citrus leaves extracts, and applicability of citrus limon leaf extract in tuna. Foods 2023;12(7):1466. PMID 37048287
44: Harris RA, Anniballi F, Austin JW. Adult intestinal toxemia botulism. Toxins (Basel) 2020;12(2):81. PMID 31991691
45: Harris RA, Tchao C, Prystajecky N, et al. Foodborne botulism, Canada, 2006-2021. Emerg Infect Dis 2023;29(9):1730-7. PMID 37610295
46: Hatheway CL. Botulism: the present status of the disease. Curr Top Microbiol Immunol 1995;195:55-75. PMID 8542759
47: Hendrickx D, Varela Martínez C, Contzen M, et al. First cross-border outbreak of foodborne botulism in the European Union associated with the consumption of commercial dried roach (Rutilus rutilus). Front Public Health 2023;10:1039770. PMID 36684858
48: Hikes DC, Manoli A. Wound botulism. J Trauma 1981;21:68-71. PMID 7463544
49: Hobbs RJ, Thomas CA, Halliwell J, Gwenin CD. Rapid detection of botulinum neurotoxins-a review. Toxins (Basel) 2019;11(7):418. PMID 31319550
50: Horowitz BZ. Botulinum toxin. Crit Care Clin 2005;21(4):825-39, viii. PMID 16168317
51: Horowitz BZ. Type E botulism. Clin Toxicol (Phila) 2010;48(9):880-95. PMID 21171846
52: Huang NJ, Pishesha N, Mukherjee J, et al. Genetically engineered red cells expressing single domain camelid antibodies confer long-term protection against botulinum neurotoxin. Nat Commun 2017;8(1):423. PMID 28871080
53: Hughes JM, Blumenthal JR, Merson MH, Lombard GL, Dowell VR Jr, Gangarosa EJ. Clinical features of types A and B food-borne botulism. Ann Intern Med 1981;95:442-5. PMID 7283294
54: Jiang Y, Wang R, Guo J, et al. Front Immunol 2024;15:1380694. PMID 38779676
55: Juel VC. Evaluation of neuromuscular junction disorders in the electromyography laboratory. Neurol Clin 2012;30(2):621-39. PMID 22361377
56: Keller JE. Recovery from botulinum neurotoxin poisoning in vivo. Neuroscience 2006;139:629-37. PMID 16490322
57: Khorasan MRM, Rahbar M, Bialvaei AZ, Gouya MM, Shahcheraghi F, Eshrati B. Prevalence, risk factors, and epidemiology of food-borne Botulism in Iran. J Epidemiol Glob Health 2020;10(4):288-92. PMID 32959610
58: Khouri JM, Motter RN, Arnon SS. Safety and immunogenicity of investigational recombinant botulinum vaccine, rBV A/B, in volunteers with pre-existing botulinum toxoid immunity. Vaccine 2018;36(15):2041-8. PMID 29475762
59: Kimberlin DW, Brady MT, Jackson MA, Long SS; Committee on Infectious Diseases; American Academy of Pediatrics. Botulism. In: Red book: 2015 report of the Committee on Infectious Diseases. Itasca, IL: American Academy of Pediatrics, 2015.**
60: Kimura J. Electrodiagnosis in diseases of nerve and muscle: principles and practice. Fourth edition. Philadelphia: FA Davis, 2013.
61: Kodihalli S, Emanuel A, Takla T, et al. Therapeutic efficacy of equine botulism antitoxin in Rhesus macaques. PLoS One 2017;12(11):e0186892. PMID 29166654
62: Koussoulakos S. Botulinum neurotoxin: the ugly duckling. Eur Neurol 2009;61(6):331-42. PMID 19365125
63: Kudrow DB, Henry DA, Haake DA, Marshal G, Mathisen GE. Botulism associated with Clostridium botulinum sinusitis after intranasal cocaine abuse. Ann Intern Med 1988;109:984-5. PMID 3057986
64: Le Bouquin S, Lucas C, Souillard R, et al. Human and animal botulism surveillance in France from 2008 to 2019. Front Public Health 2022;10:1003917. PMID 36504929
65: Lecour H, Ramos MH, Almeida B, Barbosa R. Food-borne botulism: a review of 13 outbreaks. Arch Intern Med 1988;148:578-80. PMID 3341859
66: Leonardi L, Haggiag S, Petrucci A, Lispi L. Electrophysiological abnormalities in iatrogenic botulism: two case reports and review of the literature. J Clin Neurosci 2019;60:138-41. PMID 30348587
67: Liu Y, Liu X, Chen W, Yu Y, Meng J, Wang J. Novel platform for engineering stable and effective vaccines against botulinum neurotoxins A, B and E. Front Immunol 2024;15:1469919. PMID 39315101
68: Lonati D, Schicchi A, Crevani M, et al. Foodborne Botulism: clinical diagnosis and medical treatment. Toxins (Basel) 2020;12(8):509. PMID 32784744
69: Ma W, Wang L, Tan X, et al. A novel RRGW derived peptide is a promising inhibitor of BoNT/A. J Enzyme Inhib Med Chem 2023;38(1):2203878. PMID 37106479
70: Mann JM, Martin S, Hoffman R, Marrazzo S. Patient recovery from type A botulism: morbidity assessment following a large outbreak. Am J Public Health 1981;71:266-9. PMID 7468858
71: Maselli RA, Bakshi N. AAEM case report 16. Botulism. American Association of Electrodiagnostic Medicine. Muscle Nerve 2000;23(7):1137-44. PMID 10883013
72: Maselli RA, Ellis W, Mandler RN, et al. Cluster of wound botulism in California: clinical, electrophysiologic, and pathologic study. Muscle Nerve 1997;20:1284-95. PMID 9324085
73: Miceli G, Cassataro G, Volpe V, et al. Postprandial hypotension as a predictor of respiratory failure in patients with foodborne botulinum intoxication - a case-control study in outbreak investigation. Int J Infect Dis 2023;136:111-4. PMID 37741312
74: Midura TF, Arnon SS. Infant botulism: identification of Clostridium botulinum and its toxins in faeces. Lancet 1976;2(7992):934-6. PMID 62164
75: O'Horo JC, Harper EP, El Rafei A, et al. Efficacy of antitoxin therapy in treating patients with foodborne botulism: a systematic review and meta-analysis of cases, 1923-2016. Clin Infect Dis 2017;66(suppl_1):S43-56. PMID 29293927
76: Palmateer NE, Hope VD, Roy K, et al. Infections with spore-forming bacteria in persons who inject drugs, 2000-2009. Emerg Infect Dis 2013;19(1):29-34. PMID 23260795
77: Parrera GS, Astacio H, Tunga P, Anderson DM, Hall CL, Richardson JS. Use of botulism antitoxin heptavalent (A, B, C, D, E, F, G)-(Equine) (BAT®) in clinical study subjects and patients: a 15-year systematic safety review. Toxins (Basel) 2021;14(1):19. PMID 35050996
78: Peak CM, Rosen H, Kamali A, et al. Wound botulism outbreak among persons who use black tar heroin - San Diego County, California, 2017-2018. MMWR Morb Mortal Wkly Rep 2019;67(5152):1415-8. PMID 30605447
79: Peck MW. Biology and genomic analysis of Clostridium botulinum. Adv Microb Physiol 2009;55:183-265. PMID 19573697
80: Pellett S, Tepp WH, Johnson EA. Critical analysis of neuronal cell and the mouse bioassay for detection of botulinum neurotoxins. Toxins (Basel) 2019;11(12):713. PMID 31817843
81: Penas SC, Faria OM, Serrao R, Capao-Filipe JA, Mota-Miranda A, Falcao-Reis F. Ophthalmic manifestations in 18 patients with botulism diagnosed in Porto, Portugal between 1998 and 2003. J Neuroophthalmol 2005;25(4):262-7. PMID 16340490
82: Pickett JB 3rd. AAEE case report #16: botulism. Muscle Nerve 1988;11:1201-5. PMID 3070381
83: Qureshi IA, Qureshi MA, Rauf Afzal M, et al. Black tar heroin skin popping as a cause of wound botulism. Neurocritical Care 2017;27(3):415-9. PMID 28569348
84: Rao AK, Lin NH, Jackson KA, Mody RK, Griffin PM. Clinical characteristics and ancillary test results among patients with botulism-United States, 2002-2015. Clin Infect Dis 2017a;66(suppl_1):S4-10. PMID 29293936
85: Rao AK, Sobel J, Chatham-Stephens K, Luquez C. Clinical guidelines for diagnosis and treatment of Botulism, 2021. MMWR Recomm Rep 2021;70(2):1-30. PMID 33956777
86: Rao AK, Walters M, Hall J, et al. Outbreak of botulism due to illicit prison-brewed alcohol: public health response to a serious and recurrent problem. Clin Infect Dis 2017b;66(suppl 1):S85-91. PMID 29293937
87: Rasetti-Escargueil C, Avril A, Miethe S, et al. The European AntibotABE framework program and its update: development of innovative botulinum antibodies. Toxins (Basel) 2017;9(10). PMID 28974033
88: Rasetti-Escargueil C, Lemichez E, Popoff MR. Human botulism in France, 1875-2016. Toxins (Basel) 2020;12(5):338. PMID 32455538
89: Rasetti-Escargueil C, Popoff MR. Antibodies and vaccines against botulinum toxins: available measures and novel approaches. Toxins (Basel) 2019;11(9):528.** PMID 31547338
90: Rasetti-Escargueil C, Popoff MR. Recent developments in botulinum neurotoxins detection. Microorganisms 2022;10(5):1001. PMID 35630444
91: Rawson AM, Dempster AW, Humphreys CM, Minton NP. Pathogenicity and virulence of clostridium botulinum. Virulence 2023;14(1):2205251. PMID 37157163
92: Richardson J, Viviano S. From beauty to botulism: a case report highlighting the rare risk of botox administration. Cureus 2024;16(2):e54090. PMID 38487143
93: Robinson RF, Nahata MC. Management of botulism. Ann Pharmacother 2003;37:127-31. PMID 12503947
94: Roblot F, Popoff M, Carlier JP, et al. Botulism in patients who inhale cocaine: the first cases in France. Clin Infect Dis 2006;43:e51-2. PMID 16886143
95: Saini A, Yadav N, Singh B, Rana JS. An overview of biosensor advancements for detecting botulinum neurotoxins: addressing food safety and biowarfare risks. Anal Biochem 2025;701:115801. PMID 39921138
96: Schussler E, Sobel J, Hsu J, et al. Workgroup report by the Joint Task Force Involving American Academy of Allergy, Asthma & Immunology (AAAAI); Food Allergy, Anaphylaxis, Dermatology and Drug Allergy (FADDA) (Adverse Reactions to Foods Committee and Adverse Reactions to Drugs, Biologicals, and Latex Committee); and the Centers for Disease Control and Prevention Botulism Clinical Treatment Guidelines Workgroup-Allergic Reactions to Botulinum Antitoxin: a systematic review. Clin Infect Dis 2017;66(suppl 1):S65-72. PMID 29293931
97: Semenko N, Mokhort H, Sokolovska O, Kolesnikova I, Kuzin I, Saylors K. Foodborne Botulism in Ukraine from 1955 to 2018. Foodborne Pathog Dis 2021;18(4):260-6. PMID 33332209
98: Servick K. Decoy toxin harnessed to fight Botulism. Science 2021;371(6525):113-4. PMID 33414201
99: Shapiro BE, Soto O, Shafqat S, Blumenfeld H. Adult botulism. Muscle Nerve 1997;20:100-2. PMID 8995590
100: Shi DY, Lu JS, Mao YY, et al. Characterization of a novel tetravalent botulism antitoxin based on receptor-binding domain of BoNTs. Appl Microbiol Biotechnol 2023;107(10):3205-16. PMID 37058230
101: Silkina MV, Kartseva AS, Riabko AK, et al. New approach to generating of human monoclonal antibodies specific to the proteolytic domain of botulinum neurotoxin A. Bioimpacts 2024;14(4):27680. PMID 39104622
102: Simpson LL. Identification of the major steps in botulinum toxin action. Annu Rev Pharmacol Toxicol 2004;44:167-93. PMID 14744243
103: Sobel J. Botulism. Clin Infect Dis 2005;41(8):1167-73. PMID 16163636
104: Sugiyama H. Clostridium botulinum neurotoxin. Microbiol Rev 1980;44:419-48. PMID 6252433
105: Summers PJ, Struve IA, Wilkes MS, Rees VW. Injection-site vein loss and soft tissue abscesses associated with black tar heroin injection: A cross-sectional study of two distinct populations in USA. Int J Drug Policy 2017;39:21-7. PMID 27768990
106: Sun K, Luo S, Jiang Y, et al. Neutralizing chimeric heavy-chain antibody targeting the L-HN domain of Clostridium botulinum neurotoxin type F. Arch Toxicol 2024;98(12):4187-95. PMID 39311906
107: Surana S, Tosolini AP, Meyer IFG, Fellows AD, Novoselov SS, Schiavo G. The travel diaries of tetanus and botulinum neurotoxins. Toxicon 2018;147:58-67. PMID 29031941
108: Topakian R, Heibl C, Stieglbauer K, et al. Quantitative autonomic testing in the management of botulism. J Neurol 2009;256(5):803-9. PMID 19240955
109: Torgeman A, Ozeri E, Ben David A, et al. Role of homologous Fc fragment in the potency and efficacy of anti-botulinum antibody preparations. Toxins (Basel) 2017;9(6). PMID 28555060
110: U.S. Food & Drug Administration. BAT (Botulism antitoxin heptavalent (A, B, C, D, E, F, G) – (Equine). Available at: https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/bat-botulism-antitoxin-heptavalent-b-c-d-e-f-g-equine. Accessed November 2023.
111: Waltenburg MA, Larson VA, Naor EH, et al. Notes from the field: botulism type B after intravenous methamphetamine use — New Jersey, 2020. MMWR Morb Mortal Wkly Rep 2020;69(39):1425-6. PMID 33001870
112: Wang J, Lu J, Li B, et al. New engineered-chimeric botulinum neurotoxin mutant acts as an effective bivalent vaccine against botulinum neurotoxin serotype A and E. Immunology 2025;174(1):113-27. PMID 39354747
113: Wilcke BW Jr, Midura TF, Arnon SS. Quantitative evidence of intestinal colonization by Clostridium botulinum in four cases of infant botulism. J Infect Dis 1980;141:419-23. PMID 6989924
114: Winner BM, Bodt SML, McNutt PM. Special delivery: potential mechanisms of botulinum neurotoxin uptake and trafficking within motor nerve terminals. Int J Mol Sci 2020;21(22):8715. PMID 33218099
115: Woodruff BA, Griffin PM, McCroskey LM, et al. Clinical and laboratory comparison of botulism from toxin types A, B, and E in the United States, 1975-1988. J Infect Dis 1992;166:1281-6. PMID 1431246
116: Yu CH, Song YJ, Song DH, et al. An effective prophylactic and therapeutic protection against botulinum type A intoxication in mice and rabbits using a humanized monoclonal antibody. Toxins (Basel) 2025;17(3):138. PMID 40137911
117: Yu PA, Lin NH, Mahon BE, et al. Safety and improved clinical outcomes in patients treated with new equine-derived heptavalent botulinum antitoxin. Clin Infect Dis 2017;66(suppl 1):S57-64. PMID 29293928
118: Yutani M, Matsumura T, Fujinaga Y. Effects of antibiotics on the viability of and toxin production by Clostridium botulinum. Microbiol Immunol 2021;65(10):432-7. PMID 34219270
119: Zeninskaya NA, Ryabko AK, Marin MA, et al. Selection of candidate monoclonal antibodies for therapy of botulinum toxin type A intoxications. Toxins (Basel) 2024;16(7):284. PMID 39057924

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

B Jane Distad MD

Dr. Distad of the University of Washington has no relevant financial relationships to disclose.
See Profile

Editor

Christina M Marra MD

Dr. Marra of the University of Washington School of Medicine has no relevant financial relationships to disclose.
See Profile

Former Authors

Larry E Davis MD
Aarti U Jerath BA
Chandan Reddy MD
Nivedita U Jerath MD
Tyler R West DO
Kelly J Baldwin MD

Patient Profile

Age range of presentation: 0 month to 65+ years
Sex preponderance: Foodborne: male=female

Wound: male>female
Heredity: none
Population groups selectively affected: infants

people who inject drugs

consumers of home canned foods

groups that consume fish or marine mammal products preserved or stored by traditional native methods
Occupation groups selectively affected: construction workers

farmers

laboratory workers in direct contact with botulinum toxin

This is an article preview.
Start a Free Account
to access the full version.

Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.
Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660

Support: service@medlink.com

Editor: editor@medlink.com

ISSN: 2831-9125

Botulism

Associated Disorders

Infant botulism

Differential Diagnosis

Guillain-Barré syndrome and its variants, especially Miller Fisher
Myasthenia gravis
Lambert-Eaton syndrome
Brainstem stroke
diphtheric polyneuropathy
- tick paralysis
- curare poisoning
- poliomyelitis
- organophosphate intoxication
- nerve agent poisoning

Botulism

Cite this article

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Associated or underlying disorders

Diagnostic workup

Management

Outcomes

Special considerations

Pregnancy

Anesthesia

References

Contributors

Author

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Toxic peripheral neuropathies

Organophosphate neuropathy

Genital herpes: neurologic complications

Cryptococcal meningitis

Tuberculosis of the CNS

Headache associated with HIV and AIDS

Whipple disease

Post-polio syndrome

This is an article preview.
Start a Free Account
to access the full version.