Clostridium Tetani

CLOSTRIDIUM TETANI o Clostridium tetani appears as slight slender rod of 3 - 5 µ by 0.4µ with rounded ends due to the presence of spherical and terminal spare. o The fully developed spore gives the organism the appearance of drumstick o Obligate anaerobe – motile by peritrochous flagella o Spores are highly resistant to a number of injurious agents including boiling, phenol, cresol and autoclaving for 15 minutes at 120˚C o The organism is widely distributed in nature as saprophyte in the intestine of human and animal particularly horse and is cultivates in manured soil. NEONATAL TETANUS (NNT) o It occurs mainly due to the hygienic birth practices especially when delivered in non aseptic conditions, umbilical cord is cut with unclear instruments or when the umbilical stump is dressed with ash, soil or cow dung. o The umbilical stump gets infected and the first being seen about 7 days o Tetanus is known as 8th day disease in Punjab o Neonatal tetanus kills about 80% of these infected o Pregnant women receive atleast 2 doses of tetanus vaccine o Neonatal tetanus called as “ End – of – the roadside – disease” because its more prevalent in the areas where lack of hygiene, inefficient and non existent health service combine to provide ideal condition for causative agents. TYPES OF TETANUS 1. LOCAL TETANUS: o Its very rare type and characterized by spasticity of a group of muscles near the wound o It may persist for weeks or month and then subside or mild trismes may follow

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2. CEPHALIC TETANUS: •

Due to wound of head especially near eyebrow, its marked by trimus, facial paralysis on one side and pronounced dysplasia.

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Usually unilateral but can be bilateral

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The facial on the cranial nerve gets affected

3. TRAUMATIC TETANUS •

Trauma is a major and important cause of tetanus

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Tetanus may result from trivial or even unnoticed wounds.

4. PUERPERAL TETANUS •

Tetanus follows abortion more frequently than a normal labours

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A post-abortal uterus is a favorite site for the germination of tetanus spores.

5. OTOGENIC TETANUS •

A pediatric problem but cases may occur in adults also

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Foreign bodies such as infected pencils, matches and beads may introduce the infection.

6. IDIOPATHIC TETANUS •

Microscopic trauma or absorption of tetanus toxin from the intestinal tract or inhalation of tetanus spores.

TETANUS TOXIN •

C.Tetani itself causes no disease

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Disease due to the production of a potent neurotoxin which is synthesized intracellularly by C.Tetani

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The tetanus toxin consists of two components

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a) TETANOSPASMIN → A neurotoxin which acts on the motor end plates → Isolated in pure crystalline form and 1gm contains 6 million lethal dose for mice → Extremely powerful poison b) TETANOLYSIN → It has hemolytic effect, O2 liable and antigenic when infected into animals. → Adsorbed by a suspension of red cells → Tetanus toxin is a single polypeptide chain of 1,50,000 Da → After cell lysis the toxin is released into the medium and cleaved by endogenous protease to give an NH2 – terminal light chain of 52,300Da (Fragment A)and a COOH terminal heavy chain of 98,300 Da (Fragment B - C) → The light and heavy chains are held together by disulphide bridge → Treatment of the toxin with Papain yields NH2 – terminal fragment A-B of 99,000Da and a COOH terminal fragment C of 51,500 Da

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STRUCTURE A

B

C

NH2

COOH INTRA CELLULAR

A NH2

B-C COOH

S-S EXTRA CELLULAR (Papain Treatment) A-B

C

NH2

COOH

ACTION Tetanus toxin binds to gangliosides and portions of peripheral nerve terminals through COOH terminal fragment C It is then internalized and transported to spinal cord neurons, where they produce spastic paralysis accompanied by convulsions Purified fragments A and B are non toxic if they are re-associated, the toxicity is restored A –B fragments produce flaccid paralysis The light chain tetanus is a zinc metallo protease that cleaves synaptobrevin an integral membrane protein of presynaptic vesicle Once it is cleaved the vesicles are unable to fuse with the cell membrane and release neurotransmitters.

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TETANUS TOXOID •

Tetanus toxoid is prepared by inactivation of clarified culture supernatants followed by partial purification

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Both formaldehyde in concentration of 0.5% and gluteraldehyde in the concentration of 0.2% are used as detoxifying agents

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During detoxification the following reactions take place, 1) Reaction with amino group of lysine which is rapid and reversible 2) Reaction of one of the above form unstable product with the 2nd molecule containing an amino group, imidazole ring or a phenol ring

The final result involves a cross linkage between an amino group of lysine, these reactions can occur between amino acids of same toxin molecules resulting in internal cross linkage of the proteins between 2 toxin molecules, resulting in dimerisation or between a small peptide in the medium and a toxin molecule.

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