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Basic Information

AUTHOR: Russell J. McCulloh, MD

Definition

Botulism is an illness caused by a neurotoxin produced primarily by Clostridium botulinum. Five types of disease can occur: Foodborne botulism, wound botulism, infant intestinal botulism, adult enteric botulism (similar to infant botulism), and inhalational botulism.1 Of note, inhalational botulism is exceedingly rare, but could occur as a result of bioterrorism.2

Synonyms

Clostridium botulinum food poisoning

Botulinum toxin food poisoning

Wound botulism

Infantile botulism

ICD-10CM CODES
A05.1Botulism food poisoning
A48.51Infant botulism
A48.52Wound botulism
Epidemiology & Demographics
Incidence (In U.S.)

In 2018, 242 cases of botulism were reported in the U.S. Foodborne botulism accounts for 7% of cases; over 67% of cases are infant botulism.3 Systemic botulism toxicity resulting from cosmetic use of botulinum toxin is exceedingly rare and has only been reported with unlicensed use.

Physical Findings & Clinical Presentation2

  • Symptoms usually begin 12 to 36 h following ingestion of the toxin.
  • Severity of illness is related to the quantity of toxin ingested.
  • Significant findings:
    1. Acute, bilateral cranial nerve palsies, with ocular and bulbar manifestations being most frequent (diplopia, ophthalmoplegia, ptosis, dysphagia, dysarthria, fixed and dilated pupils, and dry mouth)
    2. Bilateral motor nerve involvement that may progress to a descending flaccid paralysis
    3. No sensory deficits aside from possible blurred vision
    4. GI symptoms (dry mouth, nausea, vomiting, diarrhea, or cramps)
    5. Normal heart rate, blood pressure, and temperature
    6. Normal mental status
  • Wound botulism:
    1. Occurs primarily in injection drug users (subcutaneous “black tar” heroin injection-“skin popping”) or with traumatic injury.2
    2. Presentation is similar to that of foodborne disease, except for a longer incubation period (4 to 14 days) and absence of GI symptoms.
    3. Fever is uncommon and if present may be due to wound infection, which is not always apparent.
Etiology

  • Botulism is caused by one of several neurotoxins (usually A, B, E, or F) produced by C. botulinum, an anaerobic, gram-positive bacillus.1,4 Spore production guarantees survival of the organism in extreme conditions; it is found worldwide. Botulinum toxin blocks acetylcholine-mediated neurotransmission and is the most powerful neurotoxin known.
  • Disease results from absorption of toxin into the circulation from a mucosal surface or wound. Botulinum toxin does not penetrate intact skin.
  • In foodborne botulism, disease is caused by ingestion of preformed toxin. Although rapidly inactivated by heat, the toxin can survive the proteolytic environment of the stomach.
  • In wound botulism, toxin is elaborated by organisms that contaminate a wound.
  • In infant botulism (and probably adult botulism of unknown etiology), toxin is produced by organisms in the GI tract. Antibiotic use and achlorhydria can predispose to colonization by C. botulinum and elaboration of toxin.
  • Inhalational botulism has been demonstrated experimentally in primates. Rare case reports of inhalational botulism from snorting contaminated cocaine have been reported, and there is concern for the potential use of manufactured aerosolized toxin as a bioterrorism agent.

Diagnosis

Differential Diagnosis

  • Myasthenia gravis, Lambert-Eaton myasthenic syndrome (Table E1)
  • Guillain-Barré syndrome or other acute inflammatory demyelinating polyneuropathy
  • Tick paralysis
  • Stroke
  • Polio
  • Acute flaccid myelitis
  • Heavy metal intoxication
  • Shellfish poisoning

TABLE E1 Differential Diagnoses (In Alphabetical Order)

Differential DiagnosisDistinguishing Features
CNS infectionsAltered mental status; abnormal CSF; EEG changes
CNS space-occupying lesionAsymmetric weakness and upper motor neuron signs; abnormal brain imaging
Diabetic neuropathySensory features; limited cranial nerve involvement
DiphtheriaAntecedent pharyngitis; sensory features; associated cardiac complications
Eaton-Lambert syndromeSimilar EMG findings; often evidence of underlying lung cancer
Electrolyte disturbances (e.g., hypermagnesemia)Abnormal serum electrolytes
Guillain-Barré syndromeAscending paralysis with early areflexia; history of antecedent infection; raised CSF protein; abnormal nerve conduction studies
HyperthyroidismThyrotoxic features; abnormal thyroid function tests
Inflammatory myopathyElevated creatine kinase; EMG findings
Intoxication (e.g., alcohol, drugs, carbon monoxide)History of exposure; CNS features; elevated serum drug levels
Myasthenia gravisFatigable muscle weakness with positive response to edrophonium; acetylcholine receptor antibodies; decrease in muscle action potentials with repetitive stimulation
Organophosphate poisoningHistory of exposure; prominent cholinergic features (e.g., rhinorrhea, excess salivation, bronchospasm) before onset of paralysis
Paralytic shellfish poisoningHistory of shellfish ingestion; rapid disease onset; sensory findings
PoliomyelitisTravel to endemic region; antecedent febrile illness; asymmetric weakness; CSF pleocytosis and elevated protein
Psychiatric conversion disorderNormal EMG; atypical or inconsistent neurologic signs
StrokeAsymmetric weakness and upper motor neuron signs; abnormal brain imaging
Tick paralysisResident or traveler to endemic areas; ascending paralysis often with paresthesia; tick attached to skin; abnormal nerve conduction

CNS, Central nervous system; CSF, cerebrospinal fluid; EEG, electroencephalogram; EMG, electromyography.

From Ryan ET et al: Hunter’s tropical medicine and emerging infectious diseases, ed 10, Philadelphia, 2019, Elsevier.

Workup

Diagnosis of botulism depends on high clinical suspicion and a thorough neurologic examination.2,3

Laboratory Tests

  • Treatment should start before laboratory confirmation in suspected cases, as laboratory testing may take several days.1,3-5
  • Serum, food, and/or stool should be sent for anaerobic cultures and toxin assay.
    1. Public health laboratories may perform mouse bioassay testing, which confirms toxin type in 75% of cases. Immunoassays and PCRs are under investigation for rapid source tracking.
    2. Specimens for botulism laboratory confirmation and testing parameters are summarized in Table E2.

TABLE E2 Specimens for Botulism Laboratory Confirmation, By Specimen Type and Testing Parameters

Specimen TypeOptimal AmountTest for Botulinum ToxinTest for Botulinum Toxin-Producing Clostridium SpeciesTime From Receipt of Specimen by Laboratory to Test ResultAdditional Information
Serum5-15 ml (for children: 4 ml)YesNoPreliminary results for toxin in 24-48 h, final results in 96 h.
  • Collect before antitoxin treatment.
  • Blood sample must be collected without anticoagulant.
Stool10-20 gYesYesPreliminary results for toxin in 24-48 h, final results in 96 h; final results for Clostridium species might take 2-3 wk.
  • If an enema is needed, use sterile, nonbacteriostatic water (not tap water) and non-glycerin-containing suppositories.
  • Ideally, collect before antitoxin treatment; however, can obtain after antitoxin treatment.
Gastric aspirate5-10 mlYesYesPreliminary results for toxin in 24-48 h, final results in 96 h; final results for Clostridium species might take 2-3 wk.
  • Collect before antitoxin treatment.
Debrided tissue, wound swab sample, or anaerobic wound cultureNo specific requirementsNoYesFinal results for Clostridium species might take 2-3 wk.
  • Broth is preferable to agar slants or plates.
Food suspected as source10-20 g (or ml)YesYesPreliminary results for toxin in 24-48 h, final results in 96 h; final results for Clostridium species might take 2-3 wk.
  • Ideally, the entire food item should be submitted for testing.
  • Keep foods in original containers; if not available, place in sterile unbreakable containers.
  • Empty containers with remnants of suspected foods can be tested.

Times are estimates; testing might take longer during an outbreak.

Do not delay administration of antitoxin while attempting to obtain a specimen.

From Clinical Guidelines for Diagnosis and Treatment of Botulism: MMWR 70(2), 2021.

Treatment

Nonpharmacologic Therapy

  • Supportive care with intubation if respiratory failure occurs; ventilation may need to continue for some time, as pharmacologic therapy halts only short-term disease progression
  • Débridement of the wound in wound botulism
Acute General Rx

The only specific therapy for botulism is botulinum antitoxin. The standard adult dose is one vial administered by intravenous infusion. The pediatric dose is based on weight.4-6

  • For noninfants: Give equine heptavalent botulinum antitoxin (HBAT), which contains antibodies for seven known botulism types (A through G), as early as possible. Antitoxin should be administered before laboratory confirmation if botulism is suspected.
    1. The antitoxin (BAT, Cangene Corporation) is available from the Centers for Disease Control and Prevention (24 h/day, 7 days/wk at 770-488-7100); it is derived from horse serum, so there is a significant incidence of serum sickness.
    2. Skin testing (conjunctival instillation and observation for 15 min), and possible desensitization, is recommended before treatment. Reported hypersensitivity rates range from 9% to 20%.
  • Give wound botulism patients penicillin 3 million U intravenous (IV) q4h after antitoxin has been administered. Use metronidazole 500 mg IV q8h as an alternative for penicillin-allergic patients. Avoid aminoglycosides and tetracyclines, as they are ineffective and can worsen neuromuscular blockade.3
  • For infants: Give human botulinum immunoglobulin (BabyBIG) IV as a single dose as early as possible. Immunoglobin should be administered before laboratory confirmation if botulism is suspected. Call 510-231-7600 to begin the process of drug acquisition and for administration instructions.4 Do not use equine antitoxin. Babies with infantile intestinal botulism may benefit from a cathartic to mechanically clear the number of C. botulinum vegetative forms and spores residing in the gastrointestinal tract. Avoid antibiotics in infant botulism because antimicrobials may lyse C. botulinum in the gut and increase toxin load.
Disposition

  • Highest mortality in the first cases in an outbreak, with subsequent cases receiving rapid treatment.
  • Complete recovery for most individuals (may take up to 1 yr).

Pearls & Considerations

Comments

  • Routine cooking inactivates the toxin, but spores are resistant to environmental factors. At room temperature, spores can germinate and produce toxin. Pressure cooking can kill spores.
  • Most outbreaks are associated with home-canned foods, including fruits, vegetables, and fish. Botulinum spores can be found in honey and corn syrup, and thus children under 12 mo of age should not eat honey or foods with honey in them.
  • Patients must be closely monitored for progression to respiratory failure.
  • Notify public health authorities immedia-tely to alert other health care services of possible additional cases and to initiate investigation into cause and scope of outbreak.
  • Immunity to botulism does not occur after toxin exposure/infection, and repeated botulism can occur.
  • Treat patients with suspected, symptomatic botulism with botulinum antitoxin on the basis of clinical findings; do not await laboratory confirmation because results might take several days, and they can be negative in patients who have botulism.7
Related Content

Botulism (Patient Information)

Related Content

  1. Carrillo-Marquez M.A. : Botulism, Pediatr Rev. ;37:183-192, 2016.
  2. Rao A.K. : Clinical characteristics and ancillary test results among patients with botulism-United States, 2002-2015Clin Infec Dis. ;66(Suppl 1):S4-S10, 2017.
  3. Centers for Disease Control and Prevention. Botulism for Healthcare Providers. Available at https://www.cdc.gov/botulism/health-professional.html. Accessed August 23, 2022.
  4. Infant botulism treatment and prevention program Available at, 2018.https://www.infantbotulism.org
  5. Sobel J., Rao A.K. : Making the best of the evidence: toward national clinical guidelines for botulismClin Infec Dis. ;66(Suppl 1):S1-S3, 2017.
  6. Rosow L.K., Strober J.B. : Infant botulism: review and clinical updatePediatr Neurol. ;52:487-492, 2015.
  7. Rao A.K. : Clinical guidelines for diagnosis and treatment of botulism, 2021MMWR Recomm Rep. ;70(2):1-30, 2021.
  8. Datta Gupta A. : A systematic review and meta-analysis of efficacy of botulinum toxin A for neuropathic pain PMID: 35051013; PMCID: PMC8780616 Toxins (Basel). ;14(1), 2022.doi:10.3390/toxins14010036
  9. Pifko E. : Infant botulism and indications for administration of botulism immune globulinPediatr Emerg Care. ;30:120-124, 2014.