II. Epidemiology
- Mean Incidence: 110 per year in U.S.
- Foodborne Botulism accounts for 25% of cases
- No gender predisposition
- Age
- Infant Botulism is most common (accounts for 70% of cases)
- Intestinal Botulism (spore ingestion and intestinal colonization)
- Child and Adult mean age: 46 years (range 3 to 78 years old)
- Primarily Foodborne Botulism from preformed Toxin Ingestion (esp. improper canning)
- Infant Botulism is most common (accounts for 70% of cases)
- U.S. Regional concentration of 50% of cases in western states
- California
- Washington
- Colorado
- Oregon
- Alaska (esp. native Alaskan)
- References
- Botulism: Epidemiological Overview for Clinicians (CDC, accessed 10/24/2024)
III. Pathophysiology: Toxin mediated disease
- Source: Clostridium botulinum
- Gram Positive Rod
- Anaerobic
- Spore forming Bacteria
- Botulinum Toxin is heat labile
- Toxin is inactivated at high Temperature (boiled water for 5 minutes at 85 C, or 185 F)
- Clostridium botulinum spores are, in contrast, heat resistant
- Spores are killed at high Temperatures (250 F or 121 C), as achieved in a pressure cooker or canner
- Without proper food preservation, spores germinate and produce Botulinum Toxins
- C. botulinum organisms mature and reproduce in anaerobic environments (mason jars, cans, freezer bags)
- Botulinum Toxin has 7 different serotypes
- Botulinum Toxins A, B and E are pathogenic in humans
- Botulinum Toxin is typically cleaved into active heavy chains and light chains
- Heavy chains irreversibly bind Acetylcholine containing Neurons
- Light chains interfere with Acetylcholine exocytosis
- Botulinum Toxin binds to presynaptic nerve terminal
- Neuromuscular terminal (motor endplates)
- Autonomic Nervous System presynaptic nerves (Cholinergic)
- Receptor binding is irreversible
- Receptors are replaced however over time
- Affects Neuromuscular Junction only
- Prevents presynaptic Acetylcholine release
- Results in bulbar palsy (CN 9-12), Autonomic Dysfunction and skeletal Muscle Weakness
- Does not cause sensory deficit or pain
- Botulinum Toxin medical uses (Botox)
- Treatment for oculomotor disorders
- Strabismus
- Blepharospasm
- Treatment for Dystonias
- Torticollis
- Hemifacial spasm
- Treatment for oculomotor disorders
IV. Transmission
- Not spread from person to person
- Aerosol spread as warfare Biological Toxin
- See Biological Weapon
- Incubation: 1 to 5 days
-
Wound Infection (Wound Botulism)
- Epidemiology
- Less common than Foodborne Illness
- More common in adults, esp. women (mean 41 years old, range 23 to 58 years old)
- More common in western United States (esp. California)
- Causes
- Trauma with a wound contaminated with soil has historically caused Wound Botulism
- Deep space infections
- Puncture Wounds
- Substance Abuse related Botulism has become more common
- IV Drug Abuse (e.g. Heroin use)
- Chronic Cocaine Abuse may result in nasal or sinus Wound Botulism
- Trauma with a wound contaminated with soil has historically caused Wound Botulism
- Clostridium botulinum spores germinate and colonize the wound
- Leads to local production of Botulinum Toxin that is absorbed systemically
- Incubation Period: 10 days
- Course differs from Foodborne Illness
- Longer Incubation Period: 4 to 14 days
- Minimal gastrointestinal symptoms
- Fever and elevated White Blood Cell Count is more common in Wound Botulism
- Epidemiology
-
Foodborne Illness (ingestion of Bacteria or preformed toxin)
- Incubation: 12-72 hours (median 24 hours, but may be up to 2 weeks)
- Toxin types A and B in the United States
- West of the Mississippi: Type A toxins
- East of the Mississippi: Type B toxins
- Ingested spores (esp. from honey) may also cause Botulism in high risk patients
- Primary cause of Infantile Botulism (Intestinal Botulism)
- May also occur with altered GI Tract (e.g. Gastric Bypass surgery, Proton Pump Inhibitors)
- Spores germinate in Stomach, colonize and produce toxin in colon (incubates over weeks)
- Improperly preserved pickled or canned foods (e.g. tomatoes)
- Most common cause of adult Botulism
- In-ground vegetables (potatoes, onions, Garlic)
- Potatoes baked in aluminum foil
- Meat products in Europe (Toxin Type B)
- Vegetable products in China (Toxin Type A)
- Preserved fish (Toxin type E)
- Found in Alaska, Japan, Russia, Scandinavia
V. Precautions
- Keep Botulism in the differential diagnosis of weakness and Anticholinergic Symptoms despite its rarity
- Missed diagnosis of Botulism or Infant Botulism is associated with high morbidity and mortality
VI. Symptoms
- Sudden onset symptoms
- Symptoms follow ingestion or exposure by 12-72 hours, or inhalation by 12-80 hours
- Dysphagia, Diplopia and Dry Mouth are among the most common presenting complaints
- Acute bilateral Cranial Nerve deficits (esp. CN 6) is a strong clinical clue on presentation
- No associated fever
- Descending symmetric paralysis
- Early changes: Cranial Nerve palsy occurs first
- Diplopia with Blurred Vision (90%)
- Dysphagia (76%)
- Dysarthria
- Dysphonia (55%)
- Later changes
- Progressive, bilateral descending Flaccid Paralysis
- Generalized Weakness (58%)
- Early changes: Cranial Nerve palsy occurs first
-
Anticholinergic Symptoms
- Dry Mouth
- Decreased tears
- Blurred Vision
- Dizziness (Postural Hypotension)
- Urinary Retention
- Constipation with Abdominal Pain or cramping (Paralytic Ileus)
- Other symptoms
VII. Signs
- Early signs
- Bilateral Cranial Nerve 6 (Abducens Nerve) paralysis
- Ptosis
- Mydriasis with sluggish pupil reaction
- Nystagmus
- Diminished Gag Reflex
- Swollen Tongue
- Later signs
- Symmetrical descending Flaccid Paralysis
- Hyporeflexia
- Incoordination
- Irregular respirations to Respiratory Failure
- Distinguishing features from other causes
- Mentation clear
- Patient is usually afebrile
- Neurologic changes are bilateral, descending and motor (not sensory)
VIII. Differential Diagnosis
- See Floppy Infant
- See Symmetric Peripheral Neuropathy
- See Acute Motor Weakness Causes
- Myasthenia Gravis
- Guillain Barre Syndrome
- Eaton-Lambert Syndrome
- Trichinosis
- Cerebrovascular Accident
- Electrolyte disturbance
- Tick Paralysis or Tick Toxicosis (ascending paralysis)
- Other toxin exposure
- Organophosphate Poisoning
- Atropine Poisoning
- Shellfish Poisoning or puffer fish Poisoning
IX. Labs
- Precautions
- Labs are sent, but typically delayed, and diagnosis and management is started empirically
- Patient sources
- Test suspected food source for toxin
- Classic testing (historical)
- Lab mice die after ingesting suspected food source
- Illness reversed by type specific antitoxin
- Other testing to consider
- Lumbar Puncture (evaluate differential diagnosis)
X. Diagnostics
- Negative Inspiratory Force
-
Electromyogram (EMG)
- Protocol
- Initial supramaximal single nerve stimulation
- Repetitive stimulation at 40 to 50 hz
- Differentiates from other neuromuscular conditions
- Single maximal stimulus: Diminished Action Potentials
- Repetitive stimuli: Facilitation of Action Potentials
- Hypermagnesemia may give similar EMG
- Protocol
- Other testing
XI. Management: General
- Contact Centers for Disease Control for suspected cases
- Supportive care
-
Ventilator support often required
- Admit to Intensive Care
- Follow Vital Capacity or Negative Inspiratory Flow on serial Pulmonary Function Testing
- Ventilator support is often needed for weeks until Botulinum Toxin affects subside
-
Gastric Decontamination if recent ingestion in Foodborne Botulism
- Consider even in delayed presentation
- If no ileus, may give Laxatives and enemas
- Surgical Wound Debridement (source control) in Wound Botulism
- Excise devitalized tissue
- Indicated even in benign appearing wounds
-
Antibiotic precautions
- Indications
- Antibiotics are only recommended in Wound Botulism
- However, even in isolated Wound Botulism, Antibiotic use is not typically recommended
- No evidence that Antibiotics speed paralysis recovery
- First-Line Antibiotics
- Penicillin G 3 million units IV q4 hours
- Alternative (if Penicillin allergic)
- Metronidazole (Flagyl) 500 mg IV every 8 hours
- Avoid Aminoglycosides and Clindamycin
- Indications
- Antitoxin
- Indicated in both food-borne and Wound Botulism in adults and children over age 1 year
- See below
- Other measures
- Tetanus Toxoid booster
XII. Management: Antitoxin (from CDC)
- May shorten disease course if used early
- Does not reverse paralysis, but stops progression
- Indicated in both food-borne and Wound Botulism in adults and children over age 1 year
- Depreciated Heptavalent equine antitoxin (preferred)
- Available from CDC and from state department
- Covers types A, B, C, D, E, F, G
- Reduced risk of Serum Sickness
- Effective if given prior to or early in symptoms
- Trivalent equine antitoxin (replaced by heptavalent Vaccine)
- Risk of Serum Sickness and Anaphylaxis
- Skin Test for Horse Serum Sensitivity first
- Do not use in Infant Botulism
XIII. Prevention
- Avoid honey in infants under 1 year of age
- See Infant Botulism
- DOD Pentavalent toxoid Vaccine
- Covers types A, B, C, D, E
- Dose: 0.5 SC at 0, 2, and 12 weeks, then annually
- Protective Antibody >90% after 1 year
XIV. Prognosis
- Untreated: Mortality 60% from Respiratory Failure
- Treated with intensive support: Mortality <7%
XV. References
- (2019) Sanford Guide, acccessed 6/5/2019
- Bartlett in Goldman (2000) Cecil Medicine, p. 1673-4
- Della-Giustina (2024) Crit Dec Emerg Med 38(10): 27-34
- Schechter in Behrman (2000) Nelson Pediatrics, p. 875-8
- Seeyave (2015) Crit Dec Emerg Med 29(5): 13-21
- Shearer in Marx (2002) Rosen's Emergency Med, p. 1525
- Sun and Tomaszewski (2017) Crit Dec Emerg Med 31(6): 24
- Arnon (2001) JAMA 285:1059-70 [PubMed]
- Rathjen (2021) Am Fam Physician 104(4): 376-85 [PubMed]
- Rao (2021) MMWR Recomm Rep 70(2):1-30 +PMID: 33956777 [PubMed]
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Related Studies
Definition (MSH) | Toxic proteins produced from the species CLOSTRIDIUM BOTULINUM. The toxins are synthesized as a single peptide chain which is processed into a mature protein consisting of a heavy chain and light chain joined via a disulfide bond. The botulinum toxin light chain is a zinc-dependent protease which is released from the heavy chain upon ENDOCYTOSIS into PRESYNAPTIC NERVE ENDINGS. Once inside the cell the botulinum toxin light chain cleaves specific SNARE proteins which are essential for secretion of ACETYLCHOLINE by SYNAPTIC VESICLES. This inhibition of acetylcholine release results in muscular PARALYSIS. |
Definition (CSP) | toxins produced by Clostridium botulinum; there are at least seven different substances, most being proteins; they have neuro-, entero-, and hemotoxic properties, are immunogenic, and are among the most potent poisons known; used medically to block release of acetylcholine at cholinergic synapses. |
Concepts | Hazardous or Poisonous Substance (T131) , Amino Acid, Peptide, or Protein (T116) , Pharmacologic Substance (T121) |
MSH | D001905 |
SnomedCT | 419254007, 129470006, 372915002, 11894001, 418236003 |
LNC | LP18030-4, MTHU002713 |
English | Botulin, Botulinum Toxin, Clostridium botulinum Toxins, Toxins, Botulinum, Toxins, Clostridium botulinum, Toxin, Botulinum, botulin, botulinum toxin (medication), neuromuscular blockers botulinum toxin, Botulinum Toxins [Chemical/Ingredient], botulinum toxins, clostridium botulinum toxin, botulinum toxin (BTX), botulinum toxin, BTX - Botulinum toxin, Botulinum toxin (substance), Botulinum toxin (product), Botulinum toxin, Clostridium botulinum toxin, Botulism toxin, Botulin toxin, Clostridium botulinum toxin (substance), Botulinum Toxins, Clostridium botulinum toxin agent (substance), Clostridium botulinum toxin agent, Clostridium botulinum toxin product (product), Clostridium botulinum toxin product |
Spanish | agente con toxina de Clostridium botulinum (sustancia), agente con toxina de Clostridium botulinum, producto con toxina botulínica, producto con toxina de Clostridium botulinum (producto), producto con toxina de Clostridium botulinum, Toxinas de Clostridium botulinum, toxina botulínica, toxina botulínica (sustancia), toxina botulínica (producto), toxina de Clostridium botulinum (sustancia), toxina de Clostridium botulinum, Botulina, Toxinas Botulínicas |
Swedish | Botulinumgifter |
Czech | botulotoxiny |
Finnish | Botuliinit |
Russian | BOTULINICHESKIE TOKSINY, TOKSINY BAKTERII CLOSTRIDIUM BOTULINUM, BOTULIN, BOTULOTOKSINY, БОТУЛИН, БОТУЛИНИЧЕСКИЕ ТОКСИНЫ, БОТУЛОТОКСИНЫ, ТОКСИНЫ БАКТЕРИИ CLOSTRIDIUM BOTULINUM |
French | Toxines de clostridium botulinum, Toxines botuliniques, Botuline, Bontoxilysine, Toxine botulinique, Toxines botuliques |
Italian | Botulino, Tossina botulinica, Tossine del Clostridium botulinum, Tossine botuliniche |
Portuguese | Toxinas de Clostridium botulinum, Botulina, Toxinas Botulínicas |
Croatian | Not Translated[Botulinum Toxins] |
Polish | Toksyny botulinowe |
Japanese | ボツリヌス菌毒素, ボツリヌス毒素, ボツリン, ボツリヌストキシン |
Norwegian | Not Translated[Botulinum Toxins] |
German | Botulinus-Toxine, Botulin, Clostridium-botulinum-Toxine |
Ontology: Botulism (C0006057)
Definition (CHV) | a neurologic disease caused by the toxin of the bacteria called Clostridium botulinum |
Definition (CHV) | a neurologic disease caused by the toxin of the bacteria called Clostridium botulinum |
Definition (MEDLINEPLUS) |
Botulism is a rare but serious illness. The cause is a toxin (poison) made by a bacterium called Clostridium botulinum. It occurs naturally in soil. There are several kinds of botulism. Foodborne botulism comes from eating foods contaminated with the toxin. Wound botulism happens when a wound infected with the bacteria makes the toxin. It is more common in heroin users. Infant botulism happens when a baby consumes the spores of the bacteria from soil or honey. All forms can be deadly and are medical emergencies. Symptoms include double or blurred vision, drooping eyelids, slurred speech, difficulty swallowing, dry mouth, and muscle weakness. Treatment may include antitoxins, intensive medical care, or surgery of infected wounds. To prevent botulism:
Centers for Disease Control and Prevention |
Definition (MSHCZE) | Otrava způsobená botulotoxinem. Jed působí v nervovém systému a na nervosvalové ploténce (inhibičně). Po požití (cca za 6–72 hodin) se objeví suchost v ústech, polykací a zrakové obtíže, obrna svalů s nebezpečím ochrnutí dýchacího svalstva a zadušení. Vědomí přitom zůstává zachováno. Je nutné podat antisérum obsahující protilátky proti toxinu. Existuje rovněž b. ranný a b. kojenců. (cit. Velký lékařský slovník online, 2013 http://lekarske.slovniky.cz/ ) |
Definition (NCI) | A serious bacterial infection caused by botulinum toxin which is produced by Clostridium botulinum. Patients are infected usually by ingestion of contaminated food or wound contamination. It leads to muscle paralysis which may result in respiratory failure. |
Definition (MSH) | A disease caused by potent protein NEUROTOXINS produced by CLOSTRIDIUM BOTULINUM which interfere with the presynaptic release of ACETYLCHOLINE at the NEUROMUSCULAR JUNCTION. Clinical features include abdominal pain, vomiting, acute PARALYSIS (including respiratory paralysis), blurred vision, and DIPLOPIA. Botulism may be classified into several subtypes (e.g., food-borne, infant, wound, and others). (From Adams et al., Principles of Neurology, 6th ed, p1208) |
Definition (CSP) | disease caused by potent protein neurotoxins produced by Clostridium botulinum, which interfere with the presynaptic release of acetylcholine at the neuromuscular junction; clinical features include abdominal pain, vomiting, acute paralysis, blurred vision and diplopia; botulism may be classified into several subtypes such as food borne, infant, wound, and others. |
Concepts | Injury or Poisoning (T037) |
MSH | D001906 |
ICD10 | A05.1 |
SnomedCT | 398565003, 154276003, 186110004, 49248004, 266177004, 414531002, 398523009, 398530003 |
English | Botulism, BOTULISM, BOTULISM TOXICO INFECT, TOXICO INFECT BOTULISM, botulism (diagnosis), botulism, Clostridium botulinum poisoning, Botulism, Toxico Infectious, Botulism, Toxico-Infectious, Toxico Infectious Botulism, Toxico-Infectious Botulism, Infection due to Clostridium botulinum (disorder), Infection due to clostridium botulinum, Infection due to Clostridium botulinum, Infection due to clostridium botulinum (disorder), Botulism NOS, Botulism [Disease/Finding], botulisms, Botulism (disorder), Botulism due to infection with Clostridium botulinum, Clostridium botulinum intoxication, poisoning; Clostridium botulinum, Clostridium; botulinum, poisoning, Clostridium; botulinum, Intoxication with Clostridium botulinum toxin (disorder), Intoxication with Clostridium botulinum toxin |
French | BOTULISME, Intoxication à Clostridium botulinum, Botulisme, Infection à Clostridium botulinium, Toxi-infection botulinique |
Portuguese | BOTULISMO, Intoxicação por Clostridium botulinum, Botulismo |
German | BOTULISMUS, Clostridium botulinum-Vergiftung, Botulismus |
Dutch | Clostridium botulinum vergiftiging, Clostridium; botulinum, vergiftiging, Clostridium; botulinum, vergiftiging; Clostridium botulinum, botulisme, Botulisme |
Italian | Avvelenamento da Clostridium botulinum, Botulismo |
Spanish | Intoxicación por Clostridium botulinum, botulismo (trastorno), infección por Clostridium botulinum (trastorno), infección por Clostridium botulinum, botulismo, intoxicación con toxina de Clostridium botulinum (trastorno), intoxicación con toxina de Clostridium botulinum, Botulismo |
Swedish | Botulism |
Japanese | ボツリヌスチュウドク, ボツリヌスキンチュウドク, ボツリヌス中毒, ボツリスム, ボツリヌス菌食中毒, ボツリヌス中毒症, 腸詰め中毒, ボツリヌス菌中毒, 中毒-ボツリヌス, ソーセージ中毒, 食中毒-ボツリヌス菌, ボツリヌス症 |
Czech | botulismus, Otrava vyvolaná Clostridium botulinum, Botulismus |
Finnish | Botulismi |
Russian | BOTULIZM, БОТУЛИЗМ |
Korean | 보툴리누스 중독 |
Polish | Botulizm, Zakażenie Clostridium botulinum, Zatrucia jadem kiełbasianym, Zatrucie jadem kiełbasianym |
Hungarian | botulismus, Clostridium botulinum mérgezés |
Norwegian | Botulisme |
Ontology: Clostridium botulinum (C0009055)
Definition (NCI) | A species of anaerobic, Gram positive, rod shaped bacteria assigned to the phylum Firmicutes. This species is indole negative, ferments glucose but not mannose and does not reduce nitrate. C. putrificum is considered pathogenic and may cause post-operative tetanus. |
Definition (NCI_CDISC) | Any bacterial organism that can be assigned to the species Clostridium putrificum. |
Definition (CSP) | etiologic agent of botulism in humans and waterfowl; produces a powerful exotoxin. |
Definition (MSH) | A species of anaerobic, gram-positive, rod-shaped bacteria in the family Clostridiaceae that produces proteins with characteristic neurotoxicity. It is the etiologic agent of BOTULISM in humans, wild fowl, HORSES; and CATTLE. Seven subtypes (sometimes called antigenic types, or strains) exist, each producing a different botulinum toxin (BOTULINUM TOXINS). The organism and its spores are widely distributed in nature. |
Concepts | Bacterium (T007) |
MSH | D003014 |
SnomedCT | 41531009, 13080008 |
LNC | LP20795-8, MTHU015550 |
Swedish | Clostridium botulinum |
Czech | Clostridium botulinum |
Finnish | Clostridium botulinum |
Russian | BOTULIZMA VOZBUDITEL', KLOSTRIDII BOTULIZMA, CLOSTRIDIUM BOTULINUM, BACILLUS BOTULINUS, ERMENGEMILLUS BOTULINUS, БОТУЛИЗМА ВОЗБУДИТЕЛЬ, КЛОСТРИДИИ БОТУЛИЗМА |
English | C. botulinum, Clostridium lentoputrescens, Clostridium putrificum, Clostridium botulinum, c. botulinum, botulinum clostridium, clostridium botulinum, Bacillus botulinus, Bacillus putrificus, Botulobacillus botulinus, Clostridium botulinum (van Ermengem 1896) Bergey et al. 1923, Clostridium putrificum (Trevisan 1889) Reddish and Rettger 1922 (Approved Lists 1980), Ermengemillus botulinus, Pacinia putrifica, Clostridium putrificum (organism), CLOSTRIDIUM PUTRIFICUM, CLOSTRIDIUM LENTOPUTRESCENS, Clostridium botulinum (organism) |
Polish | Laseczki jadu kiełbasianego, Clostridium botulinum |
Spanish | Clostridium putrificum (organismo), Clostridium putrificum, Clostridium botulinum (organismo), Clostridium botulinum |
Norwegian | Clostridium botulinum |
French | Clostridium botulinum |
German | Clostridium botulinum |
Italian | Clostridium botulinum |
Dutch | Botulismebacterie, Clostridium botulinum |
Portuguese | Clostridium botulinum |
Ontology: Wound Botulism (C1306794)
Concepts | Disease or Syndrome (T047) |
MSH | D001906 |
ICD9 | 040.42 |
ICD10 | A48.52 |
SnomedCT | 398530003 |
English | wound botulism, botulism wound, botulism wound (diagnosis), Botulism, Wound, Wound Botulism, Wound Botulisms, Botulisms, Wound, Wound botulism (disorder), Wound botulism, botulism; wound, wound; botulism |
Italian | Botulismo da ferita |
Czech | botulismus po zranění, traumatický botulismus |
Norwegian | Sårbotulisme |
Dutch | botulisme; wond, wond; botulisme |
Spanish | botulismo por herida (trastorno), botulismo por herida |
Ontology: Foodborne botulism (C1739094)
Concepts | Injury or Poisoning (T037) |
MSH | D001906 |
ICD9 | 005.1 |
ICD10 | A05.1 |
SnomedCT | 49248004, 398523009 |
English | foodborne botulism, botulism due to food poisoning, foodborne botulism (diagnosis), Botulism food poisoning, Foodborne botulism, Botulism, Foodborne, Botulisms, Foodborne, Foodborne Botulism, Foodborne Botulisms, Food poisoning due to Clostridium botulinum toxin, Foodborne botulism (disorder), food; poisoning, due to Clostridium botulinum, poisoning; food, due to Clostridium botulinum, Food poisoning due to Clostridium botulinum |
Italian | Botulismo alimentare |
Czech | alimentární botulismus, potravinový botulismus |
Spanish | intoxicación alimentaria por toxina de Clostridium botulinum, botulismo alimentario (trastorno), botulismo alimentario |
Norwegian | Matbåren botulisme |
Dutch | vergiftiging; voedsel, door Clostridium botulinum, voedsel; vergiftiging, door Clostridium botulinum |