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   MORPHOLOGY
   PATHOGENESIS
   TOXINS
   CLINICAL FINDINGS
   LABORATORY TESTS
   TREATMENT
   PREVENTION & CONTROL
   Clostridium botulinum, which causes botulism, is worldwide
    in distribution; it is found in soil and occasionally in animal
    feces.
   Clostridium botulinum is a rod-shaped microorganism.
   It is an obligate anaerobe, meaning that oxygen is poisonous
    to the cells.
   However,C. botunlinum tolerates traces of oxygen due to the
    enzyme called superoxide dismutase (SOD) which is an
    important antioxidant defense in nearly all cells exposed to
    oxygen. 
   C. botulinum does not form endospores as a way to protect
    the viability of the organism, but rather as a mechanism to
    produce the neurotoxin. 
   C. botulinum is only able to produce the neurotoxin during
    sporulation, which can only happen in an anaerobic
    environment.
   Other bacterial species produce spores in an
    unfavorable growth environment to preserve the
    organism's viability and permit survival in a dormant
    state until the spores are exposed to favorable
    conditions.
   In the laboratory Clostridium botulinum is usually
    isolated in tryptose sulfite cycloserine (TSC) growth
    media in an anaerobic environment with less than 2%
    of oxygen.
   C. botulinum is a lipase negative microorganism that
    grows between pH of 4.8 and 7 and it can't
    use lactose as a primary carbon source
   Spores of the organism are highly resistant to heat,
    withstanding 100 °C for several hours.
   Although C.botulinum types A and B have been implicated in
    cases of wound infection and botulism, most often the illness is
    not an infection.
   Rather, it is an intoxication resulting from the ingestion of food
    in which C botulinum has grown and produced toxin.
   The most common offenders are spiced, smoked, vacuum-
    packed, or canned alkaline foods that are eaten without
    cooking.
    In such foods, spores of C botulinum germinate; under
    anaerobic conditions, vegetative forms grow and produce toxin.
   The toxin acts by blocking release of acetylcholine at synapses
    and neuromuscular junctions.
    Flaccid paralysis results. [reduced muscle tone]
   The electromyogram strength tests are typical.
   During the growth of C botulinum and during autolysis
    of the bacteria, toxin is liberated into the environment.
   Seven antigenic varieties of toxin (A–G) are known.
   Types A, B, and E (and occasionally F) are the principal
    causes of human illness.
   Types A and B have been associated with a variety of
    foods
   Type E predominantly with fish products.
    Type C produces limberneck in birds;
    Type D causes botulism in mammals.
    The toxin is a 150,000-MW protein that is cleaved into
    100,000-MW and 50,000-MW proteins linked by a
    disulfide bond.
   Botulinum toxin is absorbed from the gut and binds to
    receptors of presynaptic membranes of motor neurons of
    the peripheral nervous system and cranial nerves.
   Proteolysis—by the light chain of botulinum toxin—of the
    target proteins in the neurons inhibits the release of
    acetylcholine at the synapse, resulting in lack of muscle
    contraction and paralysis.
   The proteins are synaptobrevin, SNAP 25, and syntaxin.
   The toxins of C botulinum types A and E cleave the 25,000-
    MW SNAP-25.
   Type B toxin cleaves synaptobrevin.
   C botulinum toxins are among the most toxic substances
    known: The lethal dose for a human is probably about 1–2
    g.
   The toxins are destroyed by heating for 20 minutes at 100
    °C.
   Symptoms begin 18–24 hours after ingestion of the toxic
    food, with visual disturbances (incoordination of eye
    muscles, double vision), inability to swallow, and speech
    difficulty;
    signs of paralysis are progressive, and death occurs from
    respiratory paralysis or cardiac arrest.
   Gastrointestinal symptoms are not regularly prominent.
   There is no fever.
    The patient remains fully conscious until shortly before
    death.
   In the United States, infant botulism is as common as or
    more common than the classic form of paralytic botulism
    associated with the ingestion of toxin-contaminated food.
   The infants in the first months of life develop poor
    feeding, weakness, and signs of paralysis ("floppy
    baby").
    Infant botulism may be one of the causes of
    sudden infant death syndrome.
    C botulinum and botulinum toxin are found in
    feces but not in serum.
   It is assumed that C botulinum spores are in the
    babies' food, yielding toxin production in the gut.
   Honey has been implicated as a possible vehicle
    for the spores.
   Mice injected with toxin intraperitoneally die
    rapidly.
   The antigenic type of toxin is identified by
    neutralization with specific antitoxin in mice.
    C botulinum may be grown from food remains
    and tested for toxin production.
    In infant botulism, C botulinum and toxin can
    be demonstrated in bowel contents but not in
    serum.
   Toxin may be demonstrated by passive
    hemagglutination or radioimmunoassay.
   Potent antitoxins to three types of botulinum toxins
    have been prepared in horses.
    Since the type responsible for an individual case is
    usually not known, trivalent (A, B, E) antitoxin must be
    promptly administered intravenously with customary
    precautions.
   Adequate ventilation must be maintained by
    mechanical respirator, if necessary.
   These measures have reduced the mortality rate from
    65% to below 25%.
   Although most infants with botulism recover with
    supportive care alone, antitoxin therapy is
    recommended.
   Botulinum toxin is considered to be a major agent for
    bioterrorism and biologic warfare.
   Since spores of C botulinum are widely distributed in
    soil, they often contaminate vegetables, fruits, and other
    materials.
   A chief risk factor for botulism lies in home-canned
    foods, particularly string beans, corn, peppers, olives,
    peas, and smoked fish or vacuum-packed fresh fish in
    plastic bags.
   Toxic foods may be spoiled and rancid, and cans may
    "swell," or the appearance may be innocuous.
   When such foods are canned or otherwise preserved,
    they either must be sufficiently heated to ensure
    destruction of spores or must be boiled for 20 minutes
    before consumption.

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Cl.botulinum

  • 1.
  • 2. MORPHOLOGY  PATHOGENESIS  TOXINS  CLINICAL FINDINGS  LABORATORY TESTS  TREATMENT  PREVENTION & CONTROL
  • 3. Clostridium botulinum, which causes botulism, is worldwide in distribution; it is found in soil and occasionally in animal feces.  Clostridium botulinum is a rod-shaped microorganism.  It is an obligate anaerobe, meaning that oxygen is poisonous to the cells.  However,C. botunlinum tolerates traces of oxygen due to the enzyme called superoxide dismutase (SOD) which is an important antioxidant defense in nearly all cells exposed to oxygen.   C. botulinum does not form endospores as a way to protect the viability of the organism, but rather as a mechanism to produce the neurotoxin.   C. botulinum is only able to produce the neurotoxin during sporulation, which can only happen in an anaerobic environment.
  • 4. Other bacterial species produce spores in an unfavorable growth environment to preserve the organism's viability and permit survival in a dormant state until the spores are exposed to favorable conditions.  In the laboratory Clostridium botulinum is usually isolated in tryptose sulfite cycloserine (TSC) growth media in an anaerobic environment with less than 2% of oxygen.  C. botulinum is a lipase negative microorganism that grows between pH of 4.8 and 7 and it can't use lactose as a primary carbon source  Spores of the organism are highly resistant to heat, withstanding 100 °C for several hours.
  • 5. Although C.botulinum types A and B have been implicated in cases of wound infection and botulism, most often the illness is not an infection.  Rather, it is an intoxication resulting from the ingestion of food in which C botulinum has grown and produced toxin.  The most common offenders are spiced, smoked, vacuum- packed, or canned alkaline foods that are eaten without cooking.  In such foods, spores of C botulinum germinate; under anaerobic conditions, vegetative forms grow and produce toxin.  The toxin acts by blocking release of acetylcholine at synapses and neuromuscular junctions.  Flaccid paralysis results. [reduced muscle tone]  The electromyogram strength tests are typical.
  • 6. During the growth of C botulinum and during autolysis of the bacteria, toxin is liberated into the environment.  Seven antigenic varieties of toxin (A–G) are known.  Types A, B, and E (and occasionally F) are the principal causes of human illness.  Types A and B have been associated with a variety of foods  Type E predominantly with fish products.  Type C produces limberneck in birds;  Type D causes botulism in mammals.  The toxin is a 150,000-MW protein that is cleaved into 100,000-MW and 50,000-MW proteins linked by a disulfide bond.
  • 7. Botulinum toxin is absorbed from the gut and binds to receptors of presynaptic membranes of motor neurons of the peripheral nervous system and cranial nerves.  Proteolysis—by the light chain of botulinum toxin—of the target proteins in the neurons inhibits the release of acetylcholine at the synapse, resulting in lack of muscle contraction and paralysis.  The proteins are synaptobrevin, SNAP 25, and syntaxin.  The toxins of C botulinum types A and E cleave the 25,000- MW SNAP-25.  Type B toxin cleaves synaptobrevin.  C botulinum toxins are among the most toxic substances known: The lethal dose for a human is probably about 1–2 g.  The toxins are destroyed by heating for 20 minutes at 100 °C.
  • 8. Symptoms begin 18–24 hours after ingestion of the toxic food, with visual disturbances (incoordination of eye muscles, double vision), inability to swallow, and speech difficulty;  signs of paralysis are progressive, and death occurs from respiratory paralysis or cardiac arrest.  Gastrointestinal symptoms are not regularly prominent.  There is no fever.  The patient remains fully conscious until shortly before death.  In the United States, infant botulism is as common as or more common than the classic form of paralytic botulism associated with the ingestion of toxin-contaminated food.
  • 9. The infants in the first months of life develop poor feeding, weakness, and signs of paralysis ("floppy baby").  Infant botulism may be one of the causes of sudden infant death syndrome.  C botulinum and botulinum toxin are found in feces but not in serum.  It is assumed that C botulinum spores are in the babies' food, yielding toxin production in the gut.  Honey has been implicated as a possible vehicle for the spores.
  • 10. Mice injected with toxin intraperitoneally die rapidly.  The antigenic type of toxin is identified by neutralization with specific antitoxin in mice.  C botulinum may be grown from food remains and tested for toxin production.  In infant botulism, C botulinum and toxin can be demonstrated in bowel contents but not in serum.  Toxin may be demonstrated by passive hemagglutination or radioimmunoassay.
  • 11. Potent antitoxins to three types of botulinum toxins have been prepared in horses.  Since the type responsible for an individual case is usually not known, trivalent (A, B, E) antitoxin must be promptly administered intravenously with customary precautions.  Adequate ventilation must be maintained by mechanical respirator, if necessary.  These measures have reduced the mortality rate from 65% to below 25%.  Although most infants with botulism recover with supportive care alone, antitoxin therapy is recommended.
  • 12. Botulinum toxin is considered to be a major agent for bioterrorism and biologic warfare.  Since spores of C botulinum are widely distributed in soil, they often contaminate vegetables, fruits, and other materials.  A chief risk factor for botulism lies in home-canned foods, particularly string beans, corn, peppers, olives, peas, and smoked fish or vacuum-packed fresh fish in plastic bags.  Toxic foods may be spoiled and rancid, and cans may "swell," or the appearance may be innocuous.  When such foods are canned or otherwise preserved, they either must be sufficiently heated to ensure destruction of spores or must be boiled for 20 minutes before consumption.