Tetanus: Vaccine preventable deadly disease

Tetanus: The vaccine preventable deadly disease

Tetanus as its name suggests is a disease in which those who are affected show characteristic tetany like feature that is contraction of limbs and lock jaw. It caused spastic paralysis making breathing and mouth opening difficult leading to death in some days. It is an infectious illness. Tetanus is easily prevented by tetanus vaccine. Let us discus here about this deadly disease and its vaccine is cheaper which prevents the disease very effectively.

Etiology of Tetanus disease:

Tetanus is infectious disease. That means it is caused by infective agent. Clostridium tetani is the infective agent causing the Tetanus disease. This is gram positive motile bacterium. The shape of this bacterium is tennis racket shape. It is able to produce the spores that can survive in soil for years. This ia not a very invasive bacterium. It produces toxin tetanospasmin. Tetanospasmin is also called as Tetanus toxin. Tetanospasmin is very potent toxin and extremely small dose of this toxin is able to produce the symptoms and can lead to death. Lethal dose of this Tetanus toxin is very small and estimated to be 0.000001 mg. Botulinum toxin is the only toxin which is more potent than this Tetanus toxin. The spores of this Clostridium tetani go to injury site with soil from environment. They germinate there and infect the wound. Clostridium tetani multiply there and produces the most potent Tetanus toxin.

Epidemiology of Tetanus disease:

Tetanus disease occurs worldwide and is endemic in 90 countries including the developing countries. Tetanus disease affecting the neonates is called as neonatal tetanus. This form of disease kills 3 lakh infants each year. Mothers of these infants are unimmunized for TT. In addition approximately 15000-30000 mothers die of Tetanus disease. 80 percent of these deaths occur in poor developing Asian and African countries. Most of these mothers die after postpartal, postabortal or postsurgical wound infections. In developed world majority of cases occur in children whose parents refused vaccinations.

Tetanus disease occurs when Clostridium tetani infects the wound. These wound can be very trivial to be remembered. Penetrating wound infected by dirty objects like nails and splinter are common culprit. Unsterile injection and illicit drug abuse are becoming leading cause across the world. Contaminated suture material can be the cause if suture material is contaminated. Intramuscular injections with unsterile needle can lead to Tetanus. The tetanus disease can occur after animal bites, abscesses, body and ear piercing, chronic skin ulceration and burns, gangrene, frostbite, ritual scarring and circumcision.

Pathogenesis of Tetanus disease:

Tetanus is infectious disease. Tetanus occurs when the wound is infected with Clostridium tetani bacterium. The spores of Clostridium tetani are found in environment and soil. When these spores of Clostridium tetani reach the wound with soil they germinate there. They grow to Clostridium tetani bacterium. These Clostridium tetani multiply in wounds where oxygen supply is low. They produce tetanospasmin toxin also called as tetanus toxin. Tetanus toxin in released outside the cell when Clostridium tetani undergo lysis. Tetanus toxin is made up of two chains. Heavy chains and light chain are joined by disulfide bonds. Tetanus toxin is a protein compound. This tetanus toxin when comes in contact with neuromuscular junction it is taken inside the nerve cell by endocytosis. Tetanus toxin after endocytosis travels across the length of the alpha motor neurons. After travelling across the length of alpha motor neuron, tetanus toxin is released out of nerve into the spinal cord. Here in spinal cord tetanus toxin enters the inhibitory neuron. Inhibitory neurons release inhibitory neurotransmitters GABA and glycine. This release of inhibitory neurotransmitters is inhibited by the Tetanus toxin. The inhibitory signals are removed by Tetanus toxins leading to continuous stimulation of antagonistic muscles leading to loss of voluntary movements with contractions of muscles. In other nerves Autonomic nerves are affected in Tetanus. The patients of this disease may show autonomic nervous system imbalance leading to irregular heart rate and fluctuation in blood pressure.

Heavy chain of Tetanus toxin helps the toxin to attach to neurons and get inside it. Light chain of the Tetanus toxin is endoprotease enzyme and its target is synaptobrevin. Synaptobrevin is a protein which helps the synaptic vesicles to fuse the membrane of the neurons to the terminal site where synaptic vesicle releases the material inside it in to the synapse. Thus here in case of Tetanus toxin the inhibitory neurotransmitters glycine and GABA are not released leading to continuous excitation of the nerves which is uninhibited.

What are clinical features of Tetanus?

Tetanus is of two forms generalized and localized. Most common form is generalized. Trismus that is lock jaw or masseter muscles spasm is the most common feature of the generalized form of disease and is found in almost half the cases affected by the disease. Early symptoms are characterized by headache, restlessness and irritability and these symptoms are followed by muscles spasm, and stiffness, difficulty in chewing and dysphagia, neck muscles spasm. 

There is intractable spasm of the facial and buckle muscles. The face of the Tetanus patients may be characterized by the typical smile that smile is called as sardonic smile of Tetanus or Risus sardonicus. 

When there is extreme contraction of the abdominal muscles with lumbar, hip and back muscles patients go into hyperextended body position. This leads to arching of the body leading to ophisthotonus position. In this position back is bowed backwards and the head and heals touching the surface. In ophisthotonus position all the muscles are continuously contracting at the same time as result body achieves position where all the muscle forces are in equilibrium. In this position all muscles are contracting and rigid like a hard board.

Laryngeal and airway muscles also contract leading to the airway obstruction and asphyxia. this disease does not affect the consciousness so unfortunately patient suffers the entire course consciously. Muscle spasm leads to seizure. Muscle spam in stimulated by the environment. Slightest disturbance in sound, sight leads to clenching of fists, flexion abduction of the arms, hyperextension of the legs. 

If treatment is not provided, these spasms can stay for few seconds to few minutes. Patient is conscious and suffers extreme pain. There is resting period in between the spam episodes. Gradually spasm become frequent and the severity may increase too. Urinary bladder sphinctor too may get spasm leading to urinary spasm and urinary retention. Involuntary defecation may occur due to spasms. 

Body temperature may rise and fever may reach to 104F. This is fever is due to muscle spasm and autonomic imbalance caused by the the disease. Tachycardia, arrhythmia, diaphoresis, skin vasoconstrictions, hypertension these are some findings of autonomic dysfunctions and sometimes deadly. These manifestations of Tetanus are most sever in first week of illness and they stabilize for next 2-3 weeks followed by recovery in next 1-2 weeks if patient survives the earlier stages of the disease. 

Neonatal Tetanus may manifest at age 3-12 days in neonates of mother who were unimmunized for the TT. First manifestations of the neonatal disease are feeding difficulty by the baby cries for hunger. Paralysis, decreased movements with muscle spasm on touch or stimulationcan found. Slowly muscle spasm sets it sometimes leading to ophisthotonus. The remnants of dirt, dung may be found on the umbilicus.

Localised Tetanus is spasm of the muscles near the wound site. This may be the form preceding the generalized for of Tetanus. 

Cephalic Tetanus is rare form of disease in which bulbar muscles contract with spasms. This may occur after wound and foreign bodies in face, head or nostrils. Retracted eyelids, deviated gaze, trismus, risus sardonicus, spastic paralysis of the tongue and pharyngeal musculature are the findings in cephalic form of disease.

How the Tetanus disease is diagnosed?

Tetanus is diagnosed clinically. Common picture is unimmunized patient who got injured or borne in last 2 weeks before onset of symptoms. Sometimes the injury is so trivial that it is forgotten. Trisms and risus sardonicus are early and classic findings usually. When established fully it does not mimic with other illness and diagnosis is clear. Culture taken from wound is positive for Clostridium tetani only for 30 percent times.

What is treatment of Tetanus?

Management of the this disease include:

· Eradication of the Clostridium tetani from the wound.

· Healing of the wound supporting the multiplication of bacteria and spore production.

· Neutralizing the toxin in body.

· Providing respiratory support throughout the illness.

· Providing the palliation support during the illness.

· Prevention of the recurrences.

· Providing meticulous support during the autonomic imbalance.

Surgical excision of the wound may be needed to remove the foreign body and debris from the wound. The surgical excision should be done after adequate dose of Tetanus immunoglobulin is provided and antibiotic is provided.

TIG ( Tetanus immunoglobulin) is to be given as soon as possible. It can neutralize the toxin that is getting released from the wound or circulation in the blood. It can not neutralize the Tetanus toxin that is already in the axons and ascending in the axons. The dose is thought to be 500 units but some experts recommend doses 3000 to 6000 units.

If TIG is not available IV immunoglobilins may be needed. IVIg contains antibodies in Tetanus toxin too but in varied quantity. Dose of the IVIg for these purpose is unknown yet so the use for this purpose is not yet approved.

If TIG is not available bovine derived TAT (Tetanus antitoxin) is used in doses 50000-100000 units. TAT frequently causes serum sickness like reaction. It should be tested for reactions before injection and desensitization may be needed. 

Penicillin is drug of choice for the disease. Metronidazole is equally effective. Erythromycin and tetracyclines are the alternatives of the penicillins.

If generalized disease already set in then patients need muscle relaxants. Diazepam is good central muscle relaxant and also helps to control the seizures. 0.1-0.2 mg per kg given orally by oro gastric tube or by intravenous route every 3-6 hourly and dose is titrated upwards as per needed. The dose which is effective is maintained for 2-4 weeks. After this period diazepam is gradually tapered down. Magnesium sulfate, dantrolene, baclofen, Chlorpromazine is also used. Generalized paralysis with vecuronium and providing mechanical ventilation achieves best results. For autonomic dysfunctions alpha ans beta blocking agnets are useful.

Supportive care in Tetanus disease:

Most important in treatment of Tetanus is meticulous support. Patient’s survival depends upon both treatment of the disease and more importantly the supportive care. 

As Tetanic spams may be triggered by minor stimuli like sound and light patient is to be provided calm and darker place at least place without intense light. Patient should be sedated and no noise should be there unnecessarily. Touch stimulations are avoided as far as possible. The therapeutic interventions are co-ordinated after the dose of sedation. Endotracheal intubation is done as a prophylaxis because laryngospasm once sets in it will be difficult to intubate. Additionally intubation prevents aspiration that is possible during spasm. The kit to do tracheostomy should be ready with person with skill of tracheostomy available on call. Endotracheal intubation and suctioning easily provokes the spasms. Tracheostomy should be considered early in the course. Botulinum toxin may be used to relieve the trismus.

Cardiorespiratory monitoring, adequate suctioning, maintaining fluid electrolyte balance and calorie needs is very important. Careful nursing attention is provided to mouth, skin, bladder, bowel to avoid further complications.

Natural disease does not confer immunity to disease so the dose of Tetanus toxoid is to be given on discharge and also planned during follow up.

What are complications of Tetanus?

· Seizures and rigid paralysis related complications.

· Aspiration of secretion and pneumonia.

· Pneumothorax and mediastinal emphysema.

· Laceration of mouth and tongue.

· Hematoma and rhabdomyolysis.

· Myoglobinuria and renal failure.

· Long bone and spinal fracture.

· Venous thrombosis and pulmonary embolism.

· Gastric ulceration and paralytic ileus.

· Decubetus ulceration.

· Arrhythmia, unstable blood pressure and labile temperature regulation.

What is prognosis of Tetanus disease?

Recovery of Tetanus occurs after regeneration of affected nerves. So it takes weeks to recover. Patient needs supportive care during this period to survive. The mortality ranges from 10 percent in intensive units to more than 80 percent without treatment. 

Long incubation period, localized disease, and no fever are the factors which are favorable prognosis.

Development of trismus within 7 days of injury and generalized spasm within 3 days of trismus have worst prognosis in this disease. 

Cephalic form of this disease have worst prognosis.

Child may suffer hypoxic brain injury and behavioral issues which may be permanent. Neonate may develop cerebral palsy later on.

Tetanus toxoid (TT) vaccine:

Tetanus toxoid is a vaccine is used to prevent the disease. Nowadays all the TT doses are to be replaced by DTaP or Tdap combination vaccines depending on age of the patient. DTaP and Tdap contains diphtheria and pertusis component as well. Tetanus toxoid vaccine is very cheap and very effective and life saving preventing the Tetanus disease. Tetanus toxoid is tetanus toxin with neutralized toxicity. So immune system of host recognizes it and produces antibody against it. When the actual infection and Tetanus toxin occurs it get rapidly and very effectively neutralized by the host who received vaccination and the deadly disease is prevented.

Dose of DPT is given at 6 -10-14 weeks schedule followed by boosters at 18 months and 5 years age in routine vaccination. Thereafter Tdap can be used above age 7. At age 10 years Tdap is given and then followed every 5 years, 2 doses of Tdap 1 month apart in pregnancy are utmost important to prevent this disease in neonates.

Those who are borne to unimmunized mothers and those who are non immune or have got less than 3 doses of TT also need Tetanus immunoglobulin (TIG) additionally to prevent the disease. DPT, Tdap also contain diphtheria and pertussis componants.

History of tetatnus toxoid vaccineClean minor woundAll other wounds
Uncertain less than 3 dosesTdap or dt Yes
TIG No
Tdap or dt Yes
TIG No
3 or more dosesTdap or dt No
TIG No
Tdap or dt No
TIG No

* Even if patient has got Tetanus containing vaccine more than 3 doses but last dose more than 5 years ago repeat dose of Tdap or TT or Td after the injury.
In case of HIV infected patients administer TIG in all patients after injury along with the Tetanus toxoid containing vaccine.
DTaP vaccine is preferable over Tetanus toxoid in children less than 7 year old and Tdap or Td vaccine is preferable in all patients above 7 years old.
DTP, DTaP, and Tdap vaccines additionally contains diphtheria and pertussis components as they are combination vaccines.




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