Wednesday, July 07, 2021

DETERMINANTS OF PATHOGENICITY FOR CLOSTRIDIUM TETANI

Introduction:  Tetanus toxin is one of the most poisonous substances known and for technical reasons, there is no in vitro test to detect its activity.  Toxicity is observed by assaying the toxin in experimental animals.  There are two products liberated by C.tetani and one is a classical neurotoxin known as tetanospasmin while the other is a haemolysin known as tetanolysin.  The haemolysin is heat labile and inactivated by oxygen.  It is liberated by those strains which do not produce neurotoxin.

Kinetics of the toxin:  The toxin is relatively heat labile being destroyed at 65°C in 5 minutes however, it is stable in dry state.  It is not absorbed from the gastrointestinal tract and may be inactivated by gastric juice meaning that there are no receptors for it in the GIT lumen, and the chemical makeup of the toxin cannot withstand acidic pH.  Treatment of  this toxin with formaldehyde results in polymerization of toxin and results into formation of a product (toxoid) which is non-toxic but antigenic.  This is one basis for prevention of tetanus, where the polymer is formed between formaldehyde and tetanus toxoid.

Mode of action of the toxin:  The molecular basis for the action of tetanospasmin is not clearly known. The site of action is the nerve endings that are high in toxin fixing capacity.  The toxin specifically affects the synaptic junction of nerves by preventing the inhibition or erasing of nerve impulses once they have crossed the synaptic junctions.  In this case, the nerve continues to send impulses, a condition that results in spasmodic contraction (tetany) of the involved muscles.  

Symptoms of toxicity by clostridium tetani:  Early symptoms are muscle stiffness with the muscles of the jaw often developing spasms first.  This condition gives the disease its common name of lockjaw.   As the disease progresses, spasms develop in other muscles.  The spasms may be brief but can occur frequently and cause great pain and exhaustion.  Respiratory complications are many and death rate is high, especially in young children and elderly persons.

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