Clostridium tetani

1. Gram + rod
2. Anaerobes
3. Ubiquitous
4. Normal flora of GI - humans and animals
5. ENDOSPORES formed

1. Tetani
2. Botulinum
3. Perfringes - rarely produce spores
4. Difficile

1. Spores introduced to wound via contaminated items or soil contact
2. wounds involve puncture with LOW oxygen
3. Most cases in less developed areas
-vaccine not used
-poor sterilization during medical procedures
-umbilical stump contamination
-less than 40 cases b/c of vaccine
4. Spores germinate IN body to give vegetative cells that muptiply and produce tetanospasmin at low levels

Levels are too low to start antibody response
Still get symptoms

1. Tetanospasmin
2. Tetanolysin

Virulence factor for Clostridium tetani

Plasmid encoded

Very potent exotoxin (neurotoxin) - 1 of 3 most potent

A/B subunits - expressed as 1, gets modified and becomes 2 units

A/B bind to cell surface receptors - taken in by endocytosis

Conformational change of toxin structure once internalized

Vaccine made with Formalin to treate tetanospasmin - gives nontoxic toxoid, toxoid has antigenicity while non-toxic

1 microgram is lethal

Not understood

Inhibited by oxygen and serum cholesterol

Oxygen Labile Enotoxin - expressed invivo

Minor contributor to virulence

Multiply locally and no direct tissue damage

Tetanospasmin produced ONLY when organism in stationary growth phase

Toxin is released - it binds to specific host cell receptors
-occurs at neuromuscular junction
- 2 receptors - glycolipid and glycoprotein
- must bind to both receptors
- toxin binding is NOT reversible
- receptors and toxin move into cell - endocytosis
- A subunit interferes with NT transport and release, degrades protein synaptobrevin. Causes motor message to NOT be inhibited, does MOST damage
- B subunit used mostly for binding

Results - SPASTIC PARALYSIS
- contractions so tight they break bones

Toxin moves up and down spinal cord --> total body spasms

Ability to recover depends on - ability to regenerate new nerve endings where toxin NOT bound

Looks at symptoms because hard to culture
30% show + results

Can have localized
Systemic more common

4 days - weeks
Depends on distance from wound to CNS and # of spores

Masseter muscles = Lockjaw

Trimus - contractions that dont break

Risus sardonicus - sustained contraction of facial muscles

Sweating, drooling, irritability

Can spread
Involve large areas
Eventually muscle of respiration, swallowing, etc.
Symptoms for years in survivors

Treatment - 30%
Untreated - 100%

Months - years

No immunity provided
Amount of tetanospasmin is too small for immune response