TETANU S

dr. Masliani

Introduction.

Definition

Tetanus is an acute , often fatal disease caused by an exotoxin produced by the bacterium Clostridium tetani. But prevented by immunization with tetanus toxoid.
It is characterized by generalized rigidity and convulsive spasms of skeletal muscles . The muscle stiffness usually involves the jaw (lockjaw)and neck and then becomes generalized.
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Introduction (con ). History:

Tetanus was first described in Egypt over 3000 years ago(Edwin smith papyrus). It was again described by Hippocrates 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.
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Introduction(con).

History:

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.

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

Passive immunization and prophylaxis for tetanus during World War I

Tetanus Toxoid was first widely used during world war II

Causative Organism Clostridium tetani

Acridine orange stain of characteristic C tetani with endospores wider than the characteristic drumstick shape.
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Clostridium tetani
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[Link] is : * a slender gram-positive, anaerobic rod 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 : 1) tetanolysin . its function of is not known with certainty. 2) tetanospasmin is a neurotoxin and causes the clinical manifestations of tetanus.

Courtesy : Google Image on tetanus

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SPORES:

*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 faces 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.

rabiezahran@[Link]

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Epidemiology: a:Occurrence. b:Reservoir . c:Mode of transmission d:Communicability

Epidemiology:
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Tetanus - Greek Word -- Tetanos -to Contract

Tetanus Remains a Major Public Health Problem in the Developing World and Is Still Encountered in the Developed World. There Are about 800 000 : 1 Million Deaths Due to Tetanus Each Year.80% of These Deaths Occur in Africa and South East Asia and It Remains Endemic in 90 Countries World Wide.

1998 - U.K,USA 7 Cases, 41 Cases Including

Epidemiology(con):

Occurrence: Tetanus occurs worldwide but is most frequently encountered in densely populated regions in hot , damp climates with soil rich in organic matter. 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).
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EPIDEMIOLOGY (CONTU ): Communicability

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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 :
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Age : I t 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.

Pathogenesis .

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*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 lymphatics. *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 : 1) peripheral motor end plates, 2) spinal cord, 3) brain, 4) sympathetic nervous system.

Pathogenesis

How tetanospasmin reaches the 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.

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SPEED OF TOXIN TRANSPORT:

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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 (con )

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

Mechanism of Action of Tetanus Toxin

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Why there is no loss of sensory function ?

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 Neuro-Ts cant 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.

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Grand Synaptic Potential

If the SUM of the potentials of all inhibitory and excitatory synapses do not reach threshold an action potential will not be triggered.
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SO :
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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.

Clinical Features

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INCUBATION PERIOD :

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I P. ranges from 3 to 21 days, usually about 8 days. In general : *The further the injury site is from the CNS, the longer the I P. *The shorter the I P, the higher the chance of death. * In neonatal tetanus, symptoms usually appear from 4 to 14 days after birth, averaging about 7 days.

TYPES OF TETANUS: (ON THE BASIS OF CLINICAL FINDINGS, THREE DIFFERENT FORMS OF TETANUS HAVE BEEN DESCRIBED).

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1) 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.

TYPES OF TETANUS (CON)

rabiezahran@[Link]

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2)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.

TYPES OF TETANUS (CONT)

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3) 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

Sequence of events
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Lock Jaw Stiff Neck Difficulty Swallowing Muscle Rigidity Spasms

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rabiezahran@[Link]

Risus Sardonicus in Tetanus Patient

A person suffering from tetanus undergoes convulsive muscle contractions of the jaw--called LOCKJAW 32

Opisthotonos in Tetanus Patient

The contractions by the muscles of the back and extremities may become 33 so violent and strong that bone fractures may occur

Opisthotonos in Tetanus Patient

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rabiezahran@[Link]

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Neck rigidity & retraction.

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

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Rusty nail may cause prick & transmit tetanus

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Traumatic T.

Puerperal T.

TYPE OF TETANUS

Otogenic T. Idiopathic T.

T. Neonatorum

Complications .

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Diagnosis

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LABORATORY 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. Laboratory identification of the organism depends most importantly on the demonstration of toxin production in mice.

Clinically it is confirmed by noticing the following features:

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1. 2. 3.

4.

Risus sardonicus or fixed sneer. Lock jaw. Opisthotonos (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

DIAGNOSTIC TESTS FOR TETANUS:

Spatula Test :
Apet and Kamad discribe a simple bedside test to diagnose tetanus : the posterior pharyngeal wall is touched with a

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spatula and a reflex spasm of the masseters indicates a +[Link]. This test shows 94 % sensitivity . and 100 % specificity. The altered whistle : This explained as an early effect of tone in facial muscles which causes the classic R . sardonicus

scale for the severity and the prognosis of tetanus: Score :

One point for each of the following 7 items: I P. < 7 days
(period between injury and [Link].)

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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 104F (40C) Tachycardia greater than 120 beats per minute (>150 beats per min in neonates)

Total score indicates the severity and the prognosis as follows:

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Score
0 -1

Severity
mild moderate

Prognosis (mortality rate)

< 10 % 10 : 20 %

2 -3 4
5:6

severe
very severe
rabiezahran@[Link]

20 : 40 %
> 50 %

Grading of tetanus severity(OXFORD )

Ablett Classification
Grade I (mild):

* mild to moderate trismus; * general spasticity; * no respiratory problems; * no spasms; * little or no dysphagia.
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ABLETT CLASSIFICATION

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Grade II (moderate):
* moderate trismus; * well-marked rigidity; *mild to moderate but short-lasting spasms; * moderate respiratory failure with tachypnoea 30-35/min; * mild dysphagia.

Ablett Classification
Grade III (severe): * severe trismus; *generalized spasticity; *reflex and often spontaneous prolonged spasms; *respiratory failure with : tachypnoea >40/min; apnoeic spells; *severe dysphagia; * tachycardia >120/min.

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Ablett Classification

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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)

1) 2)

Medical Management . Wound Management .

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MEDICAL MANAGEMENT
Aim of TTT: (1) provide supportive care (until the tetano-spasmin that is fixed in tissue has been metabolized ) by: a: treatment of muscle spasm, b: prevention of respiratory complications. c: prevention of metabolic complications. (2)neutralization of circulating toxin to prevent the continued spread. (3) elimination of the source of toxin.

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1: Admit patients with Grade III (severe): to the (ICU). For risk of reflex spasms . 2: maintain a dark and quiet room for the patient. 3: Avoid unnecessary procedures .
4: Seriously consider prophylactic intubation with succinylcholine in all patients with moderate-to-severe clinical manifestations. Intubation and ventilation are required in 67% of patients.

HOW TO TREAT :

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5:Perform tracheostomy in patients requiring intubation for more than 10 days. Tracheostomy has also been recommended after onset of the first generalized seizure. 7:Tetanus immune globulin (TIG)(passive immunization) is 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.

HOW TO TREAT :

MARX: ROSEN'S EMERGENCY MEDICINE, 7TH ED.2009

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*Dosage recommendations vary (50010,000 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. * Because the half-life of TIG is 25 days, repeated doses are not needed.

How to treat :
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.
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SO Active immunization with tetanus toxoid should begin or continue as soon as the persons condition has stabilized.
HOW TO TREAT :

DRUGS:
1) Penicillin G: Adult 10-24 million U/d. ( IV/IM/6h. ) Pediatric 100,000-250,000 U/kg/d. (IV/IM/6h. )

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( 10- to 14-d course of treatment is recommended.)

2) Metronidazole :
*considered as a drug of choice by many. * 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 500 mg orally/6h or 1 g IV /12h; not to exceed 4 g/d Pediatric 15-30 mg/kg/d IV divided /8-12h; not to exceed 2 g/d
( 10- to 14-d course of treatment is recommended.)

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DRUGS:

DRUGS:
3)Doxycycline : Used when there is contraindication to penicillin or metronidazol. Adult 100 mg orally/IV /12h Pediatric <8 years: Not recommended <45 kg : 4.4 mg/kg/d) PO/IV divided bid > 45 kg: Administer as in adults

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Drugs:
Sedative-hypnotic agents are the mainstays of tetanus treatment. 1) Diazepam (Valium):

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Depresses all levels of CNS, including limbic and reticular formation, possibly by increasing activity of GABA(-Amino-butyric acid ), a major inhibitory neurotransmitter.
Adult 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 Mild spasms: 0.1-0.8 mg/kg/d PO divided tid/qid Moderate or severe spasms: 0.1-0.3 mg/kg IV q4-8h

ANTICONVULSANTS:

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2) Phenobarbital: used to * prolong effects of diazepam. * treat severe muscle spasms. Adult 1 mg/kg IM q4-6h; not to exceed 400 mg/d Pediatric 5 mg/kg/d IV/IM divided tid/qid

SKELETAL MUSCLE RELAXANTS

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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 <55 years: 1000 mcg IT(intrathecal) >55 years: 800 mcg IT Pediatric <16 years: 500 mcg IT >16 years: Administer as in adults

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DIFFERENTIAL DIAGNOSES
Mandible dislocations, Stroke , Encephalitis Subarachnoid Hemorrhage Hypocalcemia Dystonic Reactions Meningitis Peri-tonsillar Abscess Rabies
Other Problems to Be Considered

Intraoral disease Odontogenic infections Globus hystericus Hepatic encephalopathy Hysteria Strychnine poisoning

Wound Management .

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 All wounds should be cleaned with H2O2 & antiseptic. Necrotic tissue and foreign material should be removed. Passive immunization. Active immunization. Or Both.
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PREVENTION

PREVENTION How to kill spores :

Spores are extremely stable ,but killed by: Immersion in boiling water for 15 minutes. Autoclaving for 15-20 minutes at 121c. Sterilization by dry heat for 1 -3 hrs at 160 C. Ethylene oxide sterilization is sporocid.
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PREVENTION

Fumigation
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Sterilization of operation theatre by :

* 500 ml of formalin , 200gms of Potpermanganate/30 cu . meters of space *All windows and doors are closed except one . *Fissures between the panels of the doors and windows are closed with adhesive tape *After 12 hours the doors and windows are opened and the theatre is aired for 24 hours before decommissioning it.

PREVENTION:
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Active Immunization Passive Immunization Active and passive Immunization.

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Active Immunization
by using

tetanus toxoid

Passive Immunization

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Passive Immunization
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ATS(equine)I g. 1500 IU/s.c after sensitivity test (or) 2. ATS(human)I g. 250-500 IU, no anaphylactic shock, very safe and costly.
1.

Assess Wound

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