Biology%20of%20Toxin

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• Biology of Toxin
• Spring 2007
• Thu Pham
• Nghi Tran
• Hong Nguyen

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Basic Background

• Tetanus is an acute, often fatal, disease.
• Described by Hippocrates in 5 BCE.
• In 1884, Carle and Rattone successfully
  introduced tetanus in animals.
• Tetanus toxoid was widely used in World War II
  for prevention of tetanus.

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Four types of tetanus

• Local tetanus uncommon, in which patients have
  persistent contraction of muscles
• Cephalic tetanus rare, associating with ear
  infections
• Generalized tetanus common (80), the disease
  usually presents with a descending pattern.
• Neonatal tetanus similar to generalized tetanus
  excepts that it affects a baby less than one
  month.

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The Bacteria

• Clostridium tetani produces 2 exotoxins
• Tetanolysin-unknown
• Tetanospasmin- known to cause Tetanus
• C. tetani is a Gram-positive, anaerobic,
  rod-shaped bacterium that may be developed into
  terminal spore.
• C. tetani is sensitive to heat, while its spore
  is extremely resistant to heat, to usual
  antiseptics, even to some degrees of autoclave
  process.

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Sites and Source of Infection

• C. tetani spores are widely distributed in soil,
  in the intestines and feces of horses, sheep,
  cattle, dogs, cats, and etc.
• Humans usually acquire the bacteria through deep
  puncture wounds great anaerobic environment for
  the bacteria.
• Infants neonatal form born without protective
  passive immunity and/or infection of unhealed
  umbilical stump.

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Source distribution of Tetanus 1998-2000
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Infection Pathway
Image.google.com
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Mechanism

• Tetanus neurotoxin (TeNT) works as an A-B type
  toxin.
• TeNT binds irreversibly to presynaptic membrane
  at the interneuronal junction in the spinal cord.
• It blocks inhibitory neurotransmitter from
  releasing by the use of A or active portion of
  the toxin.

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Mechanism (cont.)

• Active (A) portion is a zinc dependent
  metalloprotease.
• (A) portion cleaves protein components, which are
  required for docking and fusing of synaptic
  vesicles.
• ? Inhibitory neurotransmitters cannot be
  released.
• ? Prevent opposing muscle to relax when the other
  muscle contracts.
• ? Opposing pairs of muscles contract at the same
  time.
• ? Spastic paralysis.

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Effects of C. tetani infection

• Spasms may cause pain in the muscles of the
  neck, shoulders and back.
• Tetanus affects the muscle in the jaw, a
  condition known as lockjaw.
• Affects the nerves which control body muscle
  activities.
• Affects the chest and airways, which may lead to
  respiratory failure.

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Signs Symptoms

• Symptoms of tetanus usually begin 8 days after
  infection.
• First symptoms of Tetanus infection are
• Headache
• Spasms
• Cramping of the jaw muscles

image.google.com
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Signs Symptoms

• Muscular irritability
• Sensitivity to touch
• High fever
• Sore throat
• Rapid heartbeat
• Difficulty breathing
• Severe sweat
• Hypertension

image.google.com
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Levels of Severity

• Laryngospasm
• Fractures
• Nosocomial infections
• Bleeding inside the bowels.
• Severe may lead to death.

image.google.com
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Tetanus surveillance (U.S.)

• Approximately 500-600 cases reported per year in
  the late 1940s.
• Steadily decreased since 1947
• Mortality rates declined from 30 to 10 in
  recent years.

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The zigzag pattern shown in the graph MIGHT due
to immunization taken by choice

1. Reported tetanus incidence rates declined from
   1980 to 2004.
2. The decline was due to the introduction of
   childhood immunization and tetanus toxoid.

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The increase is related to an increased number
of injection-drug users (IDU) among younger
people.

• Reported cases of tetanus during 1991-1995 and
  1996-2000 were highest among people 40 years of
  age or older.
• 28 cases of people younger than 40 years of age
  during 1991-1995 has increased to 42 from 1996
  to 2000.

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Epidemiology
Range -Dark red widespread -Light yellow few
cases -Grayno case

1. Tetanus cases reported worldwide from 1990 to
   2004.
2. It is estimated that one million cases reported
   worldwide.
3. Approximately 300,000-500,000 deaths occurred
   each year.

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Prevention

• Vaccination
• Recommendation
• One booster every ten years in adults.
• Administer as a combined vaccine TDap or DTaP
  which is against diphtheria and pertussis for
  children less than 7 years old.
• The TD vaccine (tetanus and diphtheria) is
  commonly used in adults and children over seven.

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Treatments

• Clean infected wound.
• Surgical debridement remove dead and infected
  tissues.
• Metronidazole treatment decrease number of
  infective bacteria.
• Tetanus immune globulin IV or IM.
• Tetanus vaccination.

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Treatment for severe cases

• Tetanus immune globulin IV or IM.
• Magnesium infusion to prevent muscle spasm.
• Mechanical ventilation to maintain airway.
• Due to an increase in muscular activity,
  maintaining nutrition in the body is required.

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Reference

• Clostridium tetani. 2006. Office of Medical
  Informatics. College of Medicine. University of
  Florida. Retrieved on April 29, 2007 from
  http//medinfo.ufl.edu/year2/mmid/bms5300/bugs/clo
  stet.html
• Klein, J. and Ho, W. 2003. Tetanus. Kidshealth.
  Retrieved on April 29, 2007 from
  http//www.kidshealth.org/parent/infections/bacter
  ial_viral/tetanus.html
• Montecucco, C. and Schiavo, G. 1994. Mechanism
  of action of tetanus and botulinum neurotoxins.
  Molecular Microbiology. Vol 13, No 1 1-8.
• Tetanus. 2007. CDC. Retrieved on April 29,
  2007 from http//www.cdc.gov/Nip/publications/pink
  /tetanus.pdf
• "Tetanus." 2007. Wikipedia Foundation. Retrieved
  on May 2, 2007 from http//en.wikipedia.org/wiki/
  Tetanus