Download Tetanus toxin

Biology of Toxin
Spring 2007
Thu Pham
Nghi Tran
Hong Nguyen
Basic Background
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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.
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
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Clostridium tetani produces 2 exotoxins:
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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.
Sites and Source of Infection
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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.
Source distribution of Tetanus 19982000
Infection Pathway
Image.google.com
Mechanism
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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.
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
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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.
Signs & Symptoms
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Symptoms of tetanus
usually begin 8 days
after infection.
First symptoms of
Tetanus infection are:
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Headache
Spasms
Cramping of the jaw
muscles
image.google.com
Signs & Symptoms
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Muscular irritability
Sensitivity to touch
High fever
Sore throat
Rapid heartbeat
Difficulty breathing
Severe sweat
Hypertension
image.google.com
Levels of Severity
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Laryngospasm
Fractures
Nosocomial infections
Bleeding inside the
bowels.
Severe may lead to death.
image.google.com
Tetanus surveillance (U.S.)
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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.
**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.**
**The increase is related
to an increased number of
injection-drug users (IDU)
among younger people.
1. Reported cases of tetanus during 1991-1995 and
1996-2000 were highest among people 40 years
of age or older.
2. 28% cases of people younger than 40 years of
age during 1991-1995 has increased to 42%
from 1996 to 2000.**
Epidemiology
Range:
-Dark red= widespread
-Light yellow= few cases
-Gray=no 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.
Prevention
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Vaccination
Recommendation:
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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.
Treatments
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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.
Treatment for severe cases
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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.
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/clostet.html
Klein, J. and Ho, W. 2003. Tetanus. Kidshealth. Retrieved on April 29, 2007 from
http://www.kidshealth.org/parent/infections/bacterial_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