II. Etiology

  1. Clostridium botulinum
    1. Gram Positive rod
    2. Anaerobic
    3. Spore forming Bacteria

III. Pathophysiology: Toxin mediated disease

  1. Botulinum Toxin is heat labile (inactivated at high Temperature)
  2. Botulinum Toxin has 7 different serotypes
    1. Botulinum Toxins A, B and E are pathogenic in humans
  3. Botulinum Toxin is typically cleaved into active heavy chains and light chains
    1. Heavy chains irreversibly bind acetylcholine containing Neurons
    2. Light chains interfere with acetylcholine exocytosis
  4. Botulinum Toxin binds to presynaptic nerve terminal
    1. Neuromuscular terminal
    2. Cholinergic autonomic site
  5. Receptor binding is irreversible
    1. Receptors are replaced however over time
  6. Affects Neuromuscular Junction only
    1. Prevents presynaptic acetylcholine release
    2. Results in bulbar palsy (CN 9-12), Autonomic Dysfunction and skeletal Muscle Weakness
    3. Does not cause sensory deficit or pain
  7. Botulinum Toxin medical uses (Botox)
    1. Treatment for oculomotor disorders
      1. Strabismus
      2. Blepharospasm
    2. Treatment for Dystonias
      1. Torticollis
      2. Hemifacial spasm

IV. Transmission

  1. Not spread from person to person
  2. Aerosol spread as warfare Biological Toxin
    1. Incubation: 1 to 5 days
  3. Wound Infection
    1. Associated with Trauma and IV Drug Abuse (e.g. Heroin use)
    2. Course differs from Foodborne Illness
      1. Longer Incubation Period: 4 to 14 days
      2. Minimal gastrointestinal symptoms
  4. Foodborne Illness (ingestion of Bacteria or preformed toxin)
    1. Incubation: 12-72 hours (median 24 hours)
    2. Toxin types A and B in the United States
      1. West of the Mississippi: Type A toxins
      2. East of the Mississippi: Type B toxins
    3. Ingested spores (esp. from honey) may also cause Botulism in high risk patients
      1. Spores germinate in Stomach, grow and produce toxin (incubates over weeks)
      2. Infants (See Infant Botulism)
      3. Altered Gastrointestinal Tract (e.g. Gastric Bypass surgery, Proton Pump Inhibitors)
    4. Improperly preserved pickled or canned foods (e.g. tomatoes)
    5. In-ground vegetables (potatoes, onions, Garlic)
      1. Potatoes baked in aluminum foil
    6. Meat products in Europe (Toxin Type B)
    7. Vegetable products in China (Toxin Type A)
    8. Preserved fish (Toxin type E)
      1. Found in Alaska, Japan, Russia, Scandinavia

V. Symptoms

  1. Sudden onset symptoms
    1. Symptoms follow ingestion or exposure by 12-72 hours, or inhalation by 12-80 hours
    2. No associated fever
  2. Descending symmetric paralysis
    1. Early changes: Cranial Nerve palsy occurs first
      1. Diplopia with Blurred Vision (90%)
      2. Dysphagia (76%)
      3. Dysarthria
      4. Dysphonia (55%)
    2. Later changes
      1. Progressive, bilateral descending Flaccid Paralysis
      2. Generalized Weakness (58%)
  3. Anticholinergic Symptoms
    1. Dry Mouth
    2. Decreased tears
    3. Blurred Vision
    4. Dizziness
    5. Urinary Retention
    6. Abdominal Pain or cramping (ileus)
    7. Constipation
  4. Other symptoms
    1. Nausea or Vomiting (56%)
    2. Headache
    3. Fever (Wound Botulism)

VI. Signs

  1. Early signs
    1. Bilateral Cranial Nerve 6 (Abducens Nerve) paralysis
    2. Ptosis
    3. Mydriasis with sluggish pupil reaction
    4. Nystagmus
    5. Diminished Gag Reflex
    6. Swollen Tongue
  2. Later signs
    1. Symmetrical descending Flaccid Paralysis
    2. Hyporeflexia
    3. Incoordination
    4. Irregular respirations to Respiratory Failure
  3. Distinguishing features from other causes
    1. Mentation clear
    2. Patient is usually afebrile
    3. Neurologic changes are bilateral, descending and motor (not sensory)

VII. Differential Diagnosis

  1. See Floppy Infant
  2. Myasthenia Gravis
  3. Guillain Barre Syndrome
  4. Eaton-Lambert Syndrome
  5. Trichinosis
  6. Cerebrovascular Accident
  7. Electrolyte disturbance
    1. Hypocalcemia
    2. Hypermagnesemia
  8. Tick Paralysis or Tick Toxicosis (ascending paralysis)
  9. Other toxin exposure
    1. Organophosphate Poisoning
    2. Atropine Poisoning
    3. Shellfish Poisoning or puffer fish Poisoning

VIII. Labs

  1. Precautions
    1. Labs are sent, but typically delayed, and diagnosis and management is started empirically
  2. Patient sources
    1. Serum for Botulinum Toxin (positive in 1/3 of cases)
    2. Gastric contents for Botulinum Toxin
    3. Stool for Botulinum Toxin (positive in 1/3 of cases)
    4. Stool for culture (positive in 60% of cases)
    5. Wound culture (if present) for organisms
  3. Test suspected food source for toxin
  4. Classic testing (historical)
    1. Lab mice die after ingesting suspected food source
    2. Illness reversed by type specific antitoxin
  5. Other testing to consider
    1. Lumbar Puncture (evaluate differential diagnosis)

IX. Diagnostics

  1. Negative Inspiratory Force
  2. Electromyogram (EMG)
    1. Protocol
      1. Initial supramaximal single nerve stimulation
      2. Repetitive stimulation at 40 to 50 hz
    2. Differentiates from other neuromuscular conditions
      1. Single maximal stimulus: Diminished Action Potentials
      2. Repetitive stimuli: Facilitation of Action Potentials
      3. Hypermagnesemia may give similar EMG
  3. Other testing
    1. Edrophonium Testing

X. Management: General

  1. Contact Centers for Disease Control for suspected cases
  2. Supportive care
  3. Ventilator support often required
    1. Follow Vital Capacity on serial Pulmonary Function Testing
  4. Gastric Decontamination if recent ingestion in foodborne Botulism
    1. Consider even in delayed presentation
    2. If no ileus, may give Laxatives and enemas
  5. Surgical Wound Debridement in Wound Botulism
    1. Indicated even in benign appearing wounds
  6. Antibiotic precautions
    1. Antibiotics are only recommended in Wound Botulism
    2. First-Line
      1. Penicillin G 3 million units IV q4 hours
    3. Alternative (if Penicillin allergic)
      1. Metronidazole (Flagyl) 500 mg IV every 8 hours
    4. Avoid Aminoglycosides and Clindamycin
  7. Antitoxin
    1. Indicated in both food-borne and Wound Botulism in adults and children over age 1 year
    2. See below
  8. Other measures
    1. Tetanus Toxoid booster

XI. Management: Antitoxin (from CDC)

  1. May shorten disease course if used early
  2. Does not reverse paralysis, but stops progression
  3. Indicated in both food-borne and Wound Botulism in adults and children over age 1 year
  4. Depreciated Heptavalent equine antitoxin (preferred)
    1. Available from CDC and from state department
    2. Covers types A, B, C, D, E, F, G
    3. Reduced risk of Serum Sickness
    4. Effective if given prior to or early in symptoms
  5. Trivalent equine antitoxin (replaced by heptavalent Vaccine)
    1. Risk of Serum Sickness and Anaphylaxis
    2. Skin Test for Horse Serum Sensitivity first
    3. Do not use in Infant Botulism

XII. Prevention

  1. Avoid honey in infants under 1 year of age
    1. See Infant Botulism
  2. DOD Pentavalent toxoid Vaccine
    1. Covers types A, B, C, D, E
    2. Dose: 0.5 SC at 0, 2, and 12 weeks, then annually
    3. Protective Antibody >90% after 1 year

XIII. Prognosis

  1. Untreated: Mortality 60% from Respiratory Failure
  2. Treated with intensive support: Mortality <7%

XIV. Resources

XV. References

  1. (2019) Sanford Guide, acccessed 6/5/2019
  2. Bartlett in Goldman (2000) Cecil Medicine, p. 1673-4
  3. Schechter in Behrman (2000) Nelson Pediatrics, p. 875-8
  4. Seeyave (2015) Crit Dec Emerg Med 29(5): 13-21
  5. Shearer in Marx (2002) Rosen's Emergency Med, p. 1525
  6. Sun and Tomaszewski (2017) Crit Dec Emerg Med 31(6): 24
  7. Arnon (2001) JAMA 285:1059-70 [PubMed]
  8. Rathjen (2021) Am Fam Physician 104(4): 376-85 [PubMed]

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Related Studies

Ontology: Botulinum Toxins (C0006055)

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
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:

  • Be very careful when canning foods at home
  • Do not let babies eat honey
  • Get prompt medical care for infected wounds

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
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
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