TETANUS

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HISTORY During the same year, Nicolaier

produced tetanus in animals by

injecting them with samples of soil.

In 1889, Kitasato isolated the

organism from a human victim,

showed that it produced disease

when injected into animals, and

reported that the toxin could be

neutralized by specific antibodies.

In 1897, Nocard demonstrated the

protective effect of passively

transferred antitoxin, and passive

immunization in humans was used for

treatment and prophylaxis during

World War I.

A method for inactivating tetanus

toxin with formaldehyde was

developed by Ramon in the early

1920's which led to the development

of tetanus toxoid by Descombey in

1924. It was first widely used during

World War II.

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What is Tetanus?

An infectious disease caused by contamination of wounds from the bacteria Clostridium tetani, or the spores they produce that live in the soil, and animal feces.

Greek words -“tetanosand teinein”,meaning rigid and stretched, which describe the condition of the muscles affected by the toxin, tetanospasmin, produced by Clostridium tetani.

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The usual locations for the bacteria to enter the

body:

Puncture wounds (such as those caused by rustynails, splinters, or insect bites.).

Burns, any break in the skin, and IV drug accesssites are also potential entryways for the bacteria.

Route of Entryi. Apparently trivial injuries.

ii. Animal bites/human bites.

iii. Open fractures.

iv. Burns.

v. Gangrene.

vi. In neonates usually via infected umbilical stumps.

vii. Abscess.

viii.Parenteral drug abuse.

Incubation Period

Varies from 1 day to several months. It is

defined as the time from injury to the

first symptom.

Period of onset It is the time from first symptoms to the reflex

spasm.

An incubation period of 4 days or less

or A period of onset of less than 48 hr is

associated with the development of severe

tetanus.

Clostridium Causing TetanusCl. tetani

Gram positive, straight, slender rod with rounded ends.

All species form endospore. (drumstick with a large round end)

Fermentative.

Obligate anaerobe.

Motile by peritrichous flagella.

Grows well in cooked meat broth and produces a thin spreading film when grown on enriched blood agar.

Spores are highly resistant to adverse conditions.

Iodine (1%) in water is able to kill the spores within a few hours.

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Clostridium tetani — agent of tetanus

Morphology and Physiology- • long thin gram-positive organism that stains gram negative in old cultures • round terminal spore gives drumstick appearance • motile by peritrichous flagella • grow on blood agar or cooked meat medium with swarming • beta-hemolysis exhibited by isolated colonies • spores resist boiling for 20 minutes

Antigenic Structure- flagella (H), somatic (0), and spore antigens. Single antigenic toxin characterizes all strains.

Pathogenicity Determinants" • play a role in local infection only in conjunction with other bacteria that create suitable

environment for their invasion • systemic-acting, plasmid-mediated A-B neurotoxin (tetanospasmin) produced intracellularly Mode of Action — one of most poisonous substances

• binds gangliosides in synaptic membranes (synapses of neuronal cells) and blocks release of inhibitory neurotransmitters; continuous stimulation by excitatory transmitters

• muscle spasms (spastic paralysis) (trismus (lockjaw), risus sardonicus, opisthotonos), cardiac arrhythmias, fluctuations in blood pressure

Lab Identification" • use characteristics of resistance to heat, motility, and toxin production to help identify

Diagnosis/Treatment/Prevention • empirical diagnosis on basis of clinical manifestations • treat to prevent elaboration and absorption of toxin clean wound (debridement), control spasms metronidazole administered to eliminate vegetative bacteria that produce neurotoxin passive immunity (human tetanus immunoglobulin); vaccination (active) as preventative antitoxin administered to bind free tetanospasmin

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ToxinsCl. tetani produces two types of

toxins:Tetanolysin, which causes lysis of RBCs.

Tetanospasmin , is neurotoxin and essential

pathogenic product. Heat-labile (65℃, 30min).

Tetanospasmin is toxic to humans and various

animals when injected parenterally, but it is not toxic

by the oral route.

Tetanospasmin which causes increasing excitability of

spinal cord neurons and muscle spasm. 10

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Mechanisms of tetanospasmin

toxin → peripheral nerve fibers / lymph

and blood → spinal cord and brain stem →

inhibitory interneuron → blocks the release of

neurotransmitters from the presynaptic

membrane of inhibitory interneurons→ inhibit

the motor neuron → spastic paralysis (rigid

paralysis).

excitatory transmitter: acetylcholine

inhibitory transmitter: glycine and γ–aminobutyric acid(GABA)

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Mechanisms of tetanospasmin(Contd…)

spastic paralysis (rigid paralysis)NORMAL

Mechanism of Action of Tetanus Toxin(Contd…)

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1. C. tetani enters

body from through

wound.

3. Germinates under

anaerobic conditions and

begins to multiply and

produce tetnospasmin.

2. Stays in sporulated

form until anaerobic

conditions are presented.

4. Tetnospasmin spreads using

blood and lymphatic system,

and binds to motor neurons.

5. Travels along the axons

to the spinal cord.

6. Binds to sites responsible for

inhibiting skeletal muscle

contraction.

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Laboratory Diagnosis of TetanusThe diagnosis of tetanus depends primarily upon the

clinical manifestation of tetanus including muscle spasm and rigidity.

Specimen: Wound exudates using capillary tube.

Culture:

On blood agar and incubated anaerobically.

Growth appears as a fine spreading film.

Gram stain is a good method for identifying Clostridium

Cl. tetani is Gram positive rod motile with a round terminal spore giving a drumstick appearance

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Clinical Forms of Tetanus

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Clinical features Risus sardonicus: Contraction of the muscles at the angle

of mouth and frontalis.

Trismus (Lock Jaw): Spasm of Masseter muscles.

Opisthotonus: Spasm of extensor of the neck, back and legs

to form a backward curvature.

Muscle spasticity

Prolonged muscular action causes sudden, powerful, and painful

contractions of muscle groups. This is called tetany. These

episodes can cause fractures and muscle tears.

If respiratory muscle is involved – apnoea.

Opisthotonos in Tetanus Patient

Risus Sardonicus in Tetanus

Patient

TRISMUS(LOCK JAW)

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Signs and Symptoms

TETANUS COMPLICATIONS

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Diagnosis

There are currently no blood tests that can be used

to diagnose tetanus. Diagnosis is done clinically.

Differential Diagnosis

Masseter muscle spasm due to dental abscess.

Dystonic reaction to phenothiazine.

Rabies.

Hysteria.

Principle of Treatment1. Neutralization of unbound toxin with Human tetanus immunoglobulin.

2. Prevention of further toxin production by

-Wound debridement.

-Antibiotics (Metronidazole).

3. Control of spasm

- Nursing in quiet environment

- avoid unnecessary stimuli

- Protecting the airway

4. Supportive care

- Adequate hydration

- Nutrition

- Treatment of secondary infection

- prevention of bed sores.

Prevention Tetanus is completely preventable

by active tetanus immunization.

Immunization is thought to provide

protection for 10 years.

Begins in infancy with the DPT

series of shots. The DPT vaccine is

a "3-in-1" vaccine that protects

against diphtheria, pertussis, and

tetanus.

Prevention(Contd…) Can be achieved by active immunization by tetanus

toxoid (5 doses – 0 day, 1 month, 6 month, 1 year, 1

year).

Older teenagers and adults who have sustained

injuries, especially puncture-type wounds, should

receive booster immunization for tetanus if more than

10 years have passed since the last booster.

Clinical tetanus does not produce immunity to further

attacks. Therefore, even after recovery patients must

receive a full course of tetanus toxoid.

TETANUS TOXOID

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Epidemiology Tetanus is an international health problem, as spores

are ubiquitous. The disease occurs almost exclusivelyin persons who are unvaccinated or inadequatelyimmunized.

Tetanus occurs worldwide but is more common in hot,damp climates with soil rich in organic matter.

More common in developing and under-developingcountries.

More prevalent in industrial establishment, whereagriculture workers are employed.

Tetanus neonatorum is common due to lack of MCHcare.

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