TETANUS

Moderator:

Dr. Prakash G.M

By,

Dr. Shamshuddin Patel Sr.

Introduction

• Tetanus is an illness characterized by an acute onset of hypertonia, painful muscular

contractions (usually of the muscles of the jaw and neck), and generalized muscle

spasms due to an infection of anaerobic bacilli, Clostridium tetani.

• Tetanos – a Greek word – to stretch

• First described by Hippocrates & Sushruta

• It is caused by a powerful neurotoxin produced by the bacterium Clostridium tetani and is completely preventable by vaccination. C. tetani is found throughout

the world, and tetanus commonly occurs where the vaccination coverage rate is low.

History

• Tetanus was first described in Egypt over 3000 years ago (Edwin smith papyrus).

• Carle and Rattone in 1884 who first noticed tetanus in animals by injecting them with pus from a fatal human tetanus case.

• During the same year , Nicolaier produced tetanus in animals by injecting them with samples of soil.

• Nocard demonstrated the protective effect of passively transferred antitoxin, and passive immunization in humans

• Tetanus Toxoid was first widely used during World War II

Epidemiology

• Tetanus is important endemic infection in India

• Factors contributing for endemicity are:

• Unhygienic Hand washing

• Unhygienic delivery practices

• Traditional birth customs

• Less Interest of people towaerds immunization

• Prior to the National Immunization Programme an estimated 3.5 lac children die annually.

• 70,000 cases continue to occur largely in the BIMAROU states (Empowered Action Group States) where TT Immunization coverage is less than national average (70%).

Distribution

Epidemiology

• More common in areas where soil is cultivated, in rural areas, in warm climates, during summer, among males.

• Reservoir : Organisms are found primarily in the soil and intestinal tracts of animals and humans.

• Mode of Transmission : is primarily by,

• Contaminated Wounds

• Tissue injury(Surgery, Burns, Deep Puncture Wounds, Crush Wounds, Otitis Media, Dental Infection, Animal bites, Abortion, and Pregnancy).

Epidemiology

• Communicability : Tetanus is not contagious from person to person .It is

the only vaccine-preventable disease that is,

“infectious but not contagious”.

• Temporal pattern : Peak in winter and summer season.

• Incubation Period : 8 DAYS ( 3-21 DAYS)

Host Factors

• Age : It is the disease of active age (5-40 years), New born baby, female during delivery or abortion

• Sex : males > females

• Occupation : Agricultural workers are at higher risk

• Rural > Urban areas

• Immunity : Herd immunity(community immunity) does not protect the individual.

• Environmental and social factors : Unhygienic custom habits , Unhygienic delivery practices.

Causative Organism

Acridine orange stain of

Clostridium tetani with

endospores wider than bacterial

body giving the characteristic

drumstick shape.

Clostridium tetani

• It’s a slender gram-positive, anaerobic bacilli that may develop a terminal spore giving it a drumstick appearance.

• It is sensitive to heat and cannot survive in the presence of oxygen.

• It produces Two Exotoxins :

• Tetanolysin : its function of is not known with certainty.

• Tetanospasmin : is a neurotoxin and causes the clinical manifestations of tetanus.

• Tetanospasmin estimated Human lethal dose is 2.5ng/Kg Body Wt.

Clostridium tetani

Gram Stain of C. tetani with spores giving

Drumstick or Tennis Racket Appearance.

Clostridium tetani

Electron Micrograph

of C. tetani with

Spores

C. tetani Spores

• It’s very resistant to heat and the usual antiseptics.

• They can not survive Autoclaving at 121°C for 20 minutes.

• Relatively resistant to phenol & other chemical agents.

• Widely distributed in soil and in the intestines and feces of horses, sheep, cattle, dogs, cats, rats, guinea pigs, and chickens.

• Manure-treated soil may contain large numbers of spores. Spores may persist for months to years.

C. tetani Spores

C. tetani Sporesmagnified to

about 4000 times

their actual size

Pathogenesis

• C. tetani usually enters the body through a wound.

• In the presence of anaerobic conditions, the spores germinate and start to produce toxin and disseminated via blood and lymphatic system.

• Toxin reaches the CNS by passing along the motor nerves to the anterior horn cells of the spinal cord .

• The shortest peripheral nerves are the first to deliver the toxin to the CNS, which leads to the early symptoms of facial distortion and back and neck stiffness.

• Toxins act at several sites within the central nervous system, including :

• Peripheral motor end plates,

• Spinal cord,

• Brain,

• Sympathetic nervous system.

Pathogenesis

• How Tetanospasmin reaches CNS?

Tetanospasmin is taken up by motor neurons in the peripheral nerve endings through endocytosis. It then travels along the axons until it reaches the motor neuron cell bodies in the spinal cord, by fast retrograde transport.

The toxin travels via intra axonal transport at a rate of 75 -250 mm/day. A process which takes 2 -14 days to reach the CNS.

Pathogenesis

The typical clinical manifestations of tetanus are caused when tetanus toxin interferes with release of neurotransmitters, blocking inhibitory impulses. This leads to unopposed muscle contraction and spasm. Seizures may occur, and the autonomic nervous system may also be affected.

Pathogenesis

• The blocking of neurotransmitter release by Tetanospasmin involves cleavage of Synaptobrevin – essential for proper functioning of synaptic vesicle release apparatus

• With diminished inhibition – resting firing rate of alpha motor neurons increases –causes Muscle Rigidity

• Lessened activity of reflexes which limit polysynaptic spread of impulses, causing agonists & antagonists getting recruited – thereby causes Muscle spasms

• Loss of inhibition of preganglionic sympathetic neurons – causes Sympathetic Hyperactivity

Why there is no Sensory Deficit?

• No loss in sensory function because it only affects inhibitory pathways.

• However, the disease is very painful because it affects our natural way to control pain. The natural pain controlling mechanism uses inhibitory pathways, and if those inhibitory receptors are blocked the Neurotransmitters can’t bind to control pain.

Grand Synaptic Potential

• Each motor neuron is stimulated

by a large number of presynaptic

endings releasing either excitatory

or inhibitory chemical messages.

• If the SUM of the potentials of all

inhibitory and excitatory synapses

do not reach threshold an action

potential will not be triggered.

So,

• When no inhibitory messages are being received by the motor neuron, the

excitatory potentials add up to reach threshold and send action potentials much

more frequently.

• Our ability to move smoothly relies upon inhibitory chemical messages as well as

excitatory ones. When one muscle contracts the opposing muscle must relax to

allow the movement.

• When all excitatory neurons are firing and no inhibitory neurons are counteracting

them, all of the muscles are contracted and movement becomes jerky or impossible.

Analogy of Tetanospasmin

• Think of the Inhibitory pathway as your parents, and the Excitatory pathway as your

friends.

• If a group of your parents’ friends take them away for a weekend out, the friends are

like tetanospasmin because they are removing your inhibitory control.

• When your friends come over for the party you’re throwing. your excitatory pathway is

uncontrolled because your inhibitory pathway has been incapacitated.

• This results in muscle spasms, and potentially death.

Clinical Features

• The further the injury site is from the CNS, the longer the Incubation Period.

• The shorter the Incubation Period, the higher the chance of death.

• In Neonatal Tetanus, symptoms usually appear from 4 to 14 days after birth, averaging about 7 days.

• On the basis of clinical features, 3 types of tetanus has been described,

• Local Tetanus

• Cephalic Tetanus

• Generalized Tetanus

Other Types of Tetanus

• Traumatic Tetanus

• Puerperal Tetanus

• Otogenic Tetanus

• Idiopathic Tetanus

• Tetanus Neonatarum

Local Tetanus

• Local tetanus is an uncommon form of the disease, in which patients have persistent contraction of muscles in the same anatomic area of the injury.

• Local tetanus may precede the onset of generalized tetanus but is generally milder. Only about 1%of cases are fatal.

Cephalic Tetanus

Cephalic tetanus is a rare form of

the disease, occasionally occurring with otitis media(ear infections) in

which C. tetani is present in the flora

of the middle ear , or following injuries to the head .

There is involvement of the cranial nerves, especially in the facial area.

Generalized Tetanus

• It is the most common type (about 80%) of reported tetanus.

• The disease usually presents with a descending pattern.

• Neonatal tetanus is a form of generalized tetanus

• Increased muscle tone & generalized spasms

• Median time of onset after injury – 7 days

• Patient first notices increased tone in masseter muscles causing Trismus, called as lock jaw

• Dysphagia

• Stiffness/pain in neck, shoulder, back muscles appear concurrently/or soon thereafter

• Rigid abdomen & stiff proximal limb muscles.

• Hands, feet spared.

Neonatal Tetanus

• Form of generalized tetanus that occurs in newborn infants born without protective passive immunity because the mother is not immune.

• Usually occurs through infection of the unhealed umbilical stump, particularly when the stump is cut with an unsterile instrument.

• During 1st 2 weeks of life.

• Usually fatal if untreated

• Poor feeding, rigidity and spasms usually occur.

Symptoms

• Tetanic seizures (painful, powerful bursts of muscle contraction)

• If the muscle spasms affect the larynx or chest wall, they may cause asphyxiation

• Stiffness of jaw (also called lockjaw)

• Stiffness of abdominal and back muscles

• Contraction of facial muscles

• Fast pulse

• Fever

• Sweating

Symptoms

• The contractions by the muscles of the back and extremities may become so violent and strong that bone fractures may occur.

• The affected individual is conscious throughout the illness, but cannot stop these contractions

• Some patients develop paroxysmal, violent, painful, generalized muscle spasms and cyanosis. Spasms occur repetitively & may be spontaneous/provoked by slightest stimulation.

• Constant threat during generalized spasm is reduced ventilation, apnea/laryngospasm.

Signs

• Risus Sardonicus : Spasm of

facial muscles ( frontalis &

angle of mouth muscles )

producing grinning facies

Signs

• Opisthotonus : Painful spasms

of neck, trunk and extremity

producing characteristic bowing

and arching of back

• The back muscles are more

powerful, thus creating the arc

backward

Signs

Lock Jaw : Increased tone in

masseter muscles causing Trismus,

and called as Lock Jaw.

Signs

• Neck Rigidity & Retraction :

Stiffness/pain in neck,

shoulder, back muscles

Complications

• Laryngospasms

• Fractures

• Hypertension

• Nosocomial Infections

• Pulmonary Embolism

• Aspiration Pneumonia

• Death

Diagnosis

• There are no laboratory findings characteristic of tetanus.

• The diagnosis is entirely clinical and does not depend upon bacteriologic

confirmation.

• C. tetani is recovered from the wound in only 30% of cases and can be

isolated from patients who do not have tetanus.

• As a result, diagnosis is made on the basis of clinical findings and history

Indirect Investigations

• Done Rarely.

• Wound cultures : In suspected cases, C. tetani can be isolated from wounds of patients without tetanus & frequently cannot be isolated from wounds of those with tetanus

• Electromyograms : Continuous discharge of motor units, shortening / absence of silent interval seen after AP.

• Muscle enzymes : Raised

• Serum Anti toxin levels >= 0.1 IU/ml : Protective & makes tetanus unlikely .

Clinical Diagnosis

• Clinically it is confirmed by noticing the following features,

• Risus Sardonicus or fixed sneer.

• Lock jaw.

• Opisthotonus (extension of lower extremities, flexion of upper extremities and

arching of the back. The examiners hand can be passed under the back of the patient

when he lies on the bed in supine position.)

• Neck rigidity

Bedside Diagnostic Tests

• Spatula Test :

• Apet and Kamad described a simple bedside test to diagnose tetanus

• The posterior pharyngeal wall is touched with a spatula and a reflex spasm of the masseters indicates a positive test.

• This test shows 94 % sensitivity and 100 % specificity.

• The altered whistle :

• This explained as an early effect of increased tone in facial muscles which causes the classical Risus Sardonicus.

Grading and Prognosis

• Give One point for each of the following 7 items if present:

• Incubation Period < 7 days (period between injury and 1st symptom.)

• Period of onset < 48 hours (period between 1st symptom and 1st spasm. )

• Acquired from burns, surgical wounds, compound fractures, or septic abortion .

• Addiction (Narcotics)

• Generalized tetanus

• Temperature greater than 104°F (40°C)

• Tachycardia greater than 120 beats per minute (>150 beats per min in neonates)

Grading and Prognosis

• Total score indicates the severity and the prognosis as follows,

SCORE GRADE PROGNOSIS (in terms

of MORTALITY)

0-1 MILD <10%

2-3 MODERATE 10-20%

4 SEVERE 20-40%

5-6 VERY SEVERE >50%

Albett Classification of Severity

• Grade I (mild):

• Mild to Moderate Trismus

• General Spasticity

• No Respiratory Problems

• No Spasms

• Little or No Dysphagia

Albett Classification of Severity

• Grade II (moderate):

• Moderate Trismus

• Well-marked Rigidity

• Mild to Moderate but short-lasting Spasms

• Moderate Respiratory Failure with Tachypnea of 30-35/min

• Mild Dysphagia

Albett Classification of Severity

• Grade III (severe):

• Severe Trismus

• Generalized Spasticity

• Spontaneous prolonged Spasms

• Respiratory failure with tachypnea >40/min and apneic spells

• Severe Dysphagia

• Tachycardia >120/min.

Albett Classification of Severity

• Grade IV (very severe):

• Features of Grade III + Violent Autonomic disturbances involving the CVS.

• These include,

• Episodes of severe hypertension and tachycardia alternating with relative hypotension and

bradycardia

• Severe persistent hypertension (diastolic >110 mmHg)

• Severe persistent hypotension (systolic <90)

Differential Diagnosis

• Mandible dislocations

• Stroke

• Encephalitis

• Subarachnoid Hemorrhage

• Hypocalcaemia

• Dystonic Reactions

• Meningitis

• Peri-tonsillar Abscess

• Rabies

Other Problems to Be Considered,

Intraoral disease

Odontogenic infections

Globus hystericus

Hepatic encephalopathy

Hysteria

Strychnine poisoning

Treatment

• It includes,

• General Measures

• Wound Management

• Medical Management

• Control of Spasms

• Neutralizing remaining Toxin

• Elimination of Source of toxin (Elimination of C. tetani from body)

• Prevention of Tetanus

General Measures

• Goal is to eliminate the source of toxin, Neutralize the unbound toxin & prevent muscle spasm & providing support especially respiratory support.

• Admit in a dark and quiet room in ICU.

• Continuous careful observation & cardiopulmonary monitoring.

• Minimize stimulation.

• Protect airway

• Explore wounds – debridement

• Seriously consider prophylactic intubation with succinylcholine in all patients with moderate-to-severe clinical manifestations. Intubation and ventilation are required in 67% of patients.

Wound Management

• All wounds should be cleaned with Hydrogen Peroxide & Antiseptics.

• Necrotic tissue and foreign material should be removed.

• Wound is then lightly bandaged to prevent formation of local anaerobic

environment which is conducive for growth of C. tetani.

Control of Spasms

• Nurse in a quiet dark room

• Avoid noise & other stimuli

• IV Diazepam/Lorazepam/Midazolam – 1st Drug of Choice.

• Barbiturates & Chlorpromazine –2nd line drugs

• Continued spasms : Intubate & ventilate

• Propofol, Dantrolene, Intrathecal Baclofen, Succinylcholine & Magnesium Sulfate can be tried.

Control of Spasms

• Sedative-hypnotic agents are the mainstays of tetanus spasms treatment.

• Diazepam (Valium):

Depresses all levels of CNS, including limbic and reticular formation, possibly by increasing activity of GABA(γ-Amino-butyric acid ), a major inhibitory neurotransmitter.

Adult Dose:

Mild spasms: 5-10 mg PO /4-6h Moderate spasms: 5-10 mg IV(diluted in 8 ml glucose 5% or saline) Severe spasms: Mix 50-100 mg in 500 mL D5W and infuse at 40 mg/h

Pediatric Dose:

Mild spasms: 0.1-0.8 mg/kg/d PO divided tid/qidModerate or severe spasms: 0.1-0.3 mg/kg IV q4-8h

Control of Spasms

• Phenobarbital: used to

• Prolong effects of diazepam

• Treat severe muscle spasms.

Adult Dose: 1 mg/kg IM q4-6h; not to exceed 400 mg/day

Pediatric Dose: 5 mg/kg/d IV/IM divided tid/qid.

Control of Spasms

• Skeletal Muscle Relaxants:

• These agents can inhibit both monosynaptic and polysynaptic reflexes at spinal level, possibly by hyperpolarization of afferent terminals.

• Baclofen (Lioresal), a physiological GABA agonist

• Adult Dose:

<55 years: 1000 mcg IT(intrathecal)>55 years: 800 mcg IT

• Pediatric Dose:

<16 years: 500 mcg IT>16 years: Administer as in adults

Neutralizing remaining Toxin

• Tetanus immune globulin (TIG) (passive immunization) :

• Recommended for treatment of tetanus.

• TIG can only help remove unbound tetanus toxin, but it cannot affect toxin bound to nerve endings.

• A single IM. dose of 3000-5000 units is generally recommended for children and adults, with part of the dose infiltrated around the wound if it can be identified.

• Dosage recommendations vary (500–10,000 units of TIG), but multiple injections are stimuli for spasm and most authorities note that 500 units is as effective as higher doses.

• Adult and pediatric doses are the same. If the larger doses are used, they should be given in divided doses.

• Protective antibody levels are achieved 48 to 72 hours after administration of TIG.

Neutralizing remaining Toxin

• Recovered individuals do not necessarily develop “natural Immunity” against

the infection because of extreme potency of the toxin and very small

amount produced during the infection. It does not elicit a strong, protective

immune response which would produce enough antibodies against future re-

infection.

• So, Active immunization with tetanus toxoid should begin or continue as

soon as the person’s condition has stabilized.

Elimination of C. tetani

• Penicillin G:

• Adult Dose:

• 10-24 million U/d. ( IV/IM/6h)

• Pediatric Dose:

• 100,000-250,000 U/kg/d. (IV/IM/6h)

• 10 to 14 day course of treatment is recommended.

Elimination of C. tetani

• Metronidazole :

• Considered as a drug of choice by many as it has a better safety profile, better tissue penetrability and negligible CNS excitability. (penicillin can cause seizures at high doses).

• It can also be given rectally

• Adult Dose:

• 500 mg orally/6h or 1 g IV /12h; not to exceed 4 g/d

• Pediatric Dose:

• 15-30 mg/kg/d IV divided /8-12h; not to exceed 2 g/d

• 10 to 14 day course of treatment is recommended.

Elimination of C. tetani

• Doxycycline:

• Used when there is contraindication to penicillin or metronidazol.

• Adult Dose:

• 100 mg orally/IV /12h

• Pediatric Dose:

• <8 years: Not recommended<45 kg : 4.4 mg/kg/d) PO/IV divided bid

• > 45 kg: Administer as in adults

Management Protocol

Management Protocol

Prevention

• It includes,

• Active Immunization

• Passive Immunization

• Elimination of Spores

Active Immunization

Tetanus Toxoid:

• Tetanus toxoid was developed by Descombey in 1924,

• Tetanus toxoid immunizations were used extensively in the armed services during World War II.

• Tetanus toxoid consists of a formaldehyde-treated toxin.

• There are two types of toxoid available —

• Adsorbed (aluminum salt precipitated) toxoid

• Fluid toxoid.

• Although the rates of seroconversion are about equal, the adsorbed toxoid is preferred because the antitoxin response reaches higher titers and is longer lasting than that following the fluid toxoid.

Active Immunization

Tetanus Toxoid:

• Tetanus Toxoid Adsorbed, for intramuscular use, is a sterile suspension of

alum-precipitated (aluminum potassium sulfate)toxoid in an isotonic

sodium chloride solution containing sodium phosphate buffer to control pH.

The vaccine, after shaking, is a turbid liquid, whitish-gray in color.

• Each 0.5 mL dose is formulated to contain 5 Lf (flocculation units)of tetanus toxoid and not more than 0.25 mg of aluminum.

Active Immunization

Tetanus Toxoid:

• Immunization requires at least 3 doses of Td.

• 1st dose at First visit

• 2nd dose after 4-8 weeks

• 3rd dose after 6 months

• Booster dose throughout life every 10 years.

Active Immunization

Tetanus Toxoid Schedule for Young infants:

Passive Immunization

• ATS (equine) Immunoglobulin - 1500 IU/ Subcutaneously,

• After sensitivity test

• ATS (human)Immunoglobulin - 250-500 IU/ Subcutaneously,

• No anaphylactic shock, very safe

• Very Costly

Elimination of Spores

• How to kill Spores:

• Spores are extremely stable, but killed by,

• Immersion in boiling water for 15 minutes.

• Autoclaving for 15-20 minutes at 121°c.

• Sterilization by dry heat for 1 -3 hrs. at 160 °C.

• Ethylene oxide sterilization is sporocidal.

Prevention of Neonatal Tetanus

• 2 doses of T.T to all pregnant women between 16 to 36 weeks of pregnancy with an interval of 1 to 2 months between the two doses.

• The first dose as early as possible & the second dose a month later preferably 3 weeks before delivery.

• If the pregnant woman is previously immunized, a booster dose is sufficient.

• If the pregnant woman is not immunized, then the new born should be protected against tetanus by giving tetanus human immunoglobulin 750 IU within 6 hours of birth.

References

• Centre For Disease Control, Atlanta, USA

• Management and Prevention of Tetanus, Richard F. Eldritch, MD PhD, Lisa Hill, Chandra A Mahler, Larry Jude Cox, MD, Daniel G Becker MD, Jed H Horowitz, MD 4 Larry S Nichter MD MS,4 Marcus L Martin, MD 5 &William C Lineweaver MD6

• Current Medical Diagnosis & Treatment, 2011

• Harrison’s Principles of Medicine, 22nd Edition.

• Text of Emergency Medicine, S. David, 1st Edition

• Manson’s Tropical diseases 21st edition

• Txt book of preventive and social medicine 18th edition by K.PARK

• http://www.who.int/immunization_monitoring/diseases/Tetanus_map_cases.jpg

• Tetanus By J J Farrara b, L M Yenc, T Cookd, N Fairweathere, N Binhc, J Parrya b, C M Parrya b

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