Botulism- Etiology, Pathogenesis, Treatment and Prevention

Introduction of botulism

  • Botulism is an intoxication caused by neurotoxins produced by Clostridium botulinum, which adversely affects the synapses of the peripheral nervous system.
  • Botulinum is considered as most potent poison in the world.
  • Clinically, three types of manifestation of botulism are recognized – food-borne botulism, infant botulism, and wound botulism.

Etiology Agent

  • The etiology agent of botulism is Clostridium botulinum, a fastidious, anaerobic, and spore-forming rod.
Clostridium
Microscopic image of Clostridium
  • It is divided into four groups based on genetic and phenotypic properties.
  • Seven antigenic distinct botulinum toxins [A to G] have been recognized, basically, types A, B, E and F are associated with human diseases.
  • Other species of clostridia produce botulinum toxins, including C. butyricum [E- type], C. baratii [type F toxin], rarely associated with human disease, and C. argentinense [G- type toxin].

Pathogenicity and Virulence factors

  • Clostridium botulinum toxin is made up of 150,000 Da progenitor protein (A-B toxins).
  • Consists of a small subunit (light or A chain) with zinc- endopeptidase activity and large subunit B is nontoxic.
  • The toxin forms a complex with nontoxic proteins that protect neurotoxins during the passage through the digestive tract.
  • The carboxyl-terminal portion of the toxin, heavy chain interacts with specific sialic acid receptors along with glycoproteins present on the outer surface of motor neurons and triggers endocytosis of the toxin.
  • The neurotoxin remains at the neuromuscular junction, acidification of the endosome triggers the N- terminal, and heavy chain-mediated release of the light chain.
  • The botulinum endopeptidase inactivates the proteins that regulate the release of acetylcholine, by blocking the neurotransmission at peripheral cholinergic synapses.
  • In the normal function of nerve cells, a nerve impulse in the CNS causes vesicles filled with acetylcholine (ACh) to fuse with the neuron’s cytoplasmic membrane release of ACh into the synaptic cleft
  • Binding of ACh receptor of cell’s cytoplasmic membrane triggers the series of events that result in contraction of the muscle.
  • The botulinum toxin prevents the fusion of ACh to the neural cytoplasmic membrane which results in the clinical presentation of botulinum i.e., flaccid paralysis.
Mechanism of botulism toxin: [A] Normal Function at the neuromuscular junction [B] Botulinum toxin inhibits the fusion of ACh to the cell cytoplasmic membrane results in flaccid paralysis.

Epidemiology

  • C. botulinum is predominant in soil and water samples, A strains are found in the neutral and alkaline soil of the United States, B strains are found in the eastern part of organic soil, type E- strain is found in wet soil.

Three common forms of botulinum have been identified:

    1. Food- bourne Botulinum  
      • Annual cases reported is less than 30
      • Mostly consumption of home-canned food [include type A and B] cause symptoms
      • In rare cases, consumption of preserved fish [ include type E- toxin] may cause the botulinum
      • A small portion of intoxicated food can cause disease.
      • It usually starts 12- 36 hrs after consuming the toxin.
      • Later nerve dysfunction symptoms of botulinum like blurred vision, pupillary dilatation, and nystagmus, occur.
      • Paralysis begins with ocular, laryngeal, and respiratory muscles, later spread to the hand and legs.
      • The most serious symptom is respiratory paralysis.
      • The morality rate is 10- 20 %
    2. Infant Botulism
      • Occur in infants between ages 3 weeks to 8 months.
      • Cases are less than 100 – annually
      • Food contaminated with botulinum spores-e.g., honey, milk powder.
      • When spores are consumed, multiples in the colon
      • Symptoms- constipation, poor muscle tone, and paralysis
    3. Wound Botulism
      • Its rare, wound infection may cause C. botulinum to grow
      • C. botulinum produces toxins in a contaminated wound
      • Symptoms are identical to food- bourne botulinum
      • The incubation period is longer than 4 days.

Diagnosis

  • Diagnosed from blood samples, intestinal contents, or remaining food samples.
  • The test requires inoculation of mice also known as mouse bioassay,
  • In mouse bioassay, two aliquots are prepared, one mixed with antitoxin, inoculated intraperitoneal into the mice, if antitoxin protects the mice, toxin activity is confirmed.
  • Pre-heating treatment is done to remove all non- clostridia from the sample.
  • Enriched anaerobic media is used for culture; allow heat- resistance spores to germinate.

Treatment, Prevention, and Control

  • Patients with botulism require the following treatment measures:
    1. Adequate ventilatory support to reduce mortality
    2. Removal of the organisms from the gastrointestinal tract – via metronidazole or penicillin therapy.
    3. Use of trivalent botulinum antitoxin vs A, B, and C to inactivate the toxins
  • Prevention is carried out by:
    1. By destroying spores in food that is practically difficult
    2. By maintaining the food in acidic pH or storage at 4˚C or colder.
    3. By inactivating the preformed toxin by heating at 60˚ to 100˚ C for 10 mins.
    4. For infant botulism, avoiding the consumption of honey by infants.

Reference and Sources

  • https://quizlet.com/71591664/clostridium-flash-cards/
  • https://anaerobicinfections.blogspot.com/p/anaerobes-have-been-involved-in.html
  • https://www.sciencedirect.com/topics/neuroscience/botulinum-toxin
  • https://www.slideshare.net/ahbhuiyan/sporeforming-gram-positive-bacteria
  • https://link.springer.com/chapter/10.1007/82_2016_48
  • https://www.webmd.com/food-recipes/food-poisoning/what-is-botulism

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