D R M A L L U M C . B

S E N I O R R E G I S T R A R

N E U R O L O G Y U N I T

L U T H

TETANUS

HISTORICAL NOTE

Earliest record dates back to Egyptian civilization.

In 1890,tetanospasmin was extracted from anaerobic soil bacteria and found to be responsible for clinical tetanus.

EPIDEMIOLOGY

Occurs worldwide but more prevalent in developing countries.

About 1 million cases (18 per 100,000) are said to occur annually.

Case fatality ratio ranges between 20 to over 50 percent.

Neonatal tetanus is the second leading cause of death from vaccine preventable disease in children worldwide.

Half of the deaths from tetanus occur in children.

Tetanus is rare in developed countries as a result of immunization.(36 cases of tetanus reported in the US in 1994)

PATHOPHYSIOLOGY

Clostridium enters the body through a wound.

Spores germinate in anaerobic conditions.

Toxins are produced and disseminated through blood and lymphatics.

Toxins act at various sites in the nervous system including the peripheral end plate,spinal cord,brain, and sympathetic nervous system.

PATHOPHYSIOLOGY

Toxins gain access to the CNS via retrograde axonal transport in motor nerves.

Toxins move into the presynaptic inhibitory interneurons with resulting inhibition of release of inhibitory neurotransmitters (GABA in the brain, glycine in the spinal cord).

This results in heightened muscular activity.

Loss of glycine inhibition occurs in the intermediolateral grey matter of the spinal cord results in increased sympathetic activity.

PATHOPHYSIOLOGY

Reduction of release of acetylcholine from motor neurons may result in paralysis of cranial nerves in cephalic tetanus.

Clostridium Tetani

Found primarily in the soil and intestinal tracts of animals and humans.

Clostridium tetani is a slender, motile,gram positive, anaerobic rod that may develop a terminal spore giving it a drumstick appearance.

The organism is sensitive to heat and cannot survive in the presence of oxygen.

Clostridium Tetani

The spores,however, are very resistant to heat and usual antiseptics.

Spores may survive several years and are resistant to various disinfectants and to boiling for 20minutes. They are relatively resistant to phenol. Spores may survive autoclaving at 121 degrees C for 10-15 mins.

Spores are found in soil, intestines of animals and on skin surfaces and contaminated heroin.

Manure treated soil may contain large numbers of spores.

Under anaerobic conditions, spores begin to germinate and proliferate.

Spores produce two exotoxins: Tetanolysin and Tetanospasmin.

The clinical significance of Tetanolysin is still uncertain.

Tetanospasmin is a neurotoxin and is responsible for the clinical manifestations of tetanus.

The estimated human lethal dose of tetanospasmin is 2.5 ng per kg body weight.

MODE OF TRANSMISSION

Primarily from contaminated wounds.

May follow elective surgery,burns,deep puncture wounds, crush wounds,otitis media,dentalinfection,animal bites, abortion.

Tetanus is infectious but not contagious(no person to person transmission)

CLASSIFICATION

Localized tetanus

Generalized tetanus

Neonatal tetanus

Cephalic tetanus

CLINICAL FEATURES

The hall marks of tetanus are sustained muscular rigidity, and in severe cases, reflex spasms.

The interval of time between spore innoculation and development of the first symptom is the incubation period .usu 3 and 21 days,range 0-60days

The time from the first symptom to reflex spasms is the period of onset.

Incubation period less than 10-14 days and period of onset less than 3-6 days is indicative of severe disease.

CLINICAL FEATURES

The earliest manifestations of generalized tetanus are rigidity of the masseter muscle (lockjaw or trismus ) and facial muscles , with straightening of the upper lip(Grimace or Risus Sardonicus).

This is soon followed by rigidity of axial muscles with prominent involvement of the neck and back muscles(Opisthotonus).

Rigidity of axial muscles may precede or accompany trismus.

Stiffness of the limb muscles may be evident with sparing of distal muscles.

CLINICAL FEATURES

Reflex spasms are violent, paroxysmal contractions of the muscles in response to attempts at voluntary movement and to external and internal(fear,hunger) stimuli.

Spasms of the deglutition muscles in severe cases may result in difficulties in swallowing and verbal expression.

Laryngospasm may also occur leading to asphyxiation.

CLINICAL FEATURES

Disease severity continues for 10-14 days and is usually followed by recovery.

Autonomic instability may manifest by fluctuations of heart rate and blood pressure,arrhythmias,profusesweating, hyper salivation,extreme hyperpyrexia. They reflect a hypersympathetic state and complicate severe cases.

CLINICAL FEATURES(Localized tetanus )

Localized stiffness near the injury

Fixed muscular rigidity confined to wound-bearing extremity may persist for months.

Localized tetanus usually precedes generalized tetanus.

Cephalic tetanus:

Usually associated with infections of paracranialstructures eg chronic otitis media and dental infection.

Presents as trismus and paralysis of one or more cranial nerves.

Facial paresis and dysphagia.

Abnormal ocular movements – bilateral trochlear nerve palsy(ophthalmoplegic tetanus) and downbeat nystagmus.

INVESTIGATIONS

Diagnosis is entirely clinical.

Clostridium tetani is isolated from the wound in only 30% of patients and may be present in individuals without tetanus.

Serum antitoxin levels >0.01u/ml make the diagnosis unlikely.

Ancillary investigations like FBC,U&E,CR

DIFFERENTIAL DIAGNOSIS

Strychnine intoxication- trismus is absent,abdominalmuscle is less rigid.

Neuroleptic Malignant syndrome- lack of reflex spasms

Acute dystonic reactions(extrapyramidal side effects of dopamine blocking agents)- lack of reflex spasms.

Stiff-person syndrome- insidious onset, less involvement of face,jaw muscles;muscle rigidity reduced by sleep.

DIFFERENTIAL DIAGNOSIS

Hypocalcemic tetany- involves extremities more than trunk;chvostek and trousseau’s sign.

Meningoencephalitis- also has abnormal tone and nuchal rigidity but this does not have normal sensorium as in tetanus.

Dental abscess- may mimic trismus

Subarachnoid haemorrhage,

Hysteria

COMPLICATIONS OF TETANUS

Laryngospasm and/or spasms of muscles of respiration.

Fractures of spine and /or long bones from sustained contraction.

Hypertension and/or abnormal heart rhythm- due to hyperactivity of autonomic nervous system.

Nosocomial infections- sepsis from indwelling catheters,decubitus ulcers,hospital-aquiredpneumonia.

COMPLICATIONS OF TETANUS

Pulmonary embolism especially in elderly and IV drug users.

Aspiration pneumonia-

Death in 11% of reported cases more common in persons older 60yrs,unvaccinated persons.

Causes include larygnospasm,cardiac arrest.

Renal insufficiency

MANAGEMENT

The principles of management are:

1.Elimination of source of toxin

2.Toxin neutralization

3.Control of muscular rigidity and spasms.

4.Supportive care

ElIMINATION OF THE SOURCE OF TOXIN

Wound exploration, cleansing and debridement are important to reduce the bacterial load.

Antibiotic therapy is given. Iv metronidazole 500mg 8hrly,

IV penicillin is usually given but may worsen the spasm because it has a central GABA antagonistic effect.

TOXIN NEUTRALIZATION

Neutralization of circulating toxin is done by giving Sc ATS anti tetanus serum(ATS) at 10,000 IU stat after a negative test dose

An alternative is IM Human tetanus Immunoglobin500 IU stat where available.

CONTROL OF SPASMS

Benzodiazepines such as diazepam,lorazepam,midazolam

IV diazepam is given in infusion IV 5% dextrose water in 0.9%normal saline .

Dose of diazepam to titrated in response to spasm frequency and to be reduced in event of any drowsiness.

IV diazepam 20mg every 2hours via intravenous push can be given for breakthrough spasms.

CONTROL OF SPASMS

Barbiturates such as IV phenobarbital are second line drugs.

Neuromuscular blockade with atracurium,vecuronium or pancuronium is required in severe cases with violent spasms and respiratory depression.

Other alternatives are morphine,fentanyl,clonidine, atropine, continuous spinal anaesthesia.

Supportive care

Autonomic instability has been treated with combined alpha and beta blockers eg labetalol with varying success

Patient is to be nursed in a dark, quiet room.

NPO

A spasm chart is to be kept.

DVT prophylaxis with SC clexane or heparin.

Feeding can be recommenced once patient is spasm free

Physiotherapy may assist in mobilization once patient is spasm free.

ICU admission + tracheostomy may be required in severe cases

IMMUNIZATION SCHEDULE ON DISCHARGE

IM TT 0.5mls stat is given on presentation

A Repeat dose is given 6 weeks after the first

The 3rd dose is given 6 months afterwards.

PROGNOSIS

Poor prognostic factors:

-short incubation period

-short period of onset

-cephalic tetanus

-neonatal tetanus

-poor prior vaccination

-dysautonomia

PREVENTION

Appropriate wound care and immunization

Especially for wounds with severe tissue necrosis,suppuration,retained foreign bodies.

Eg burns,umbilical stumps,compoundfractures,septic abortion,intramuscular injections.

Antibiotic prophylaxis has no place in the management of tetanus

PREVENTION

Prophylaxis is antibody dependent and can be either passive(Tetanus-specific immunoglobulin) or active(tetanus toxoid)

Patients should receive antitetanus globulin as well as tetanus toxoid.

Wounds that are neither clean nor minor

0-2 prior doses of tetanus toxoid

Uncertain history of prior doses.

IMMUNIZATION

The only reliable immunity against tetanus is achieved by vaccination with tetanus toxoid.

Tetanus toxoid can safely be given in pregnancy and in immunocompromised individuals.

1st dose=IgM + small IgG) insufficient protection

2nd dose = 90% protection but after 1 yr drops to 80%

3rd dose = 98% protection and lasts several years

IMMUNIZATION

Length of protection after 5-6 doses = 20-25 yrs.

WHO recommends that 5 doses of tetanus toxoid be given over 12-15 yrs , starting at infancy, with a sixth dose often given in adulthood to ensure long lasting protection.

MCQS

Regarding spores of causative organism of tetanus , which is true?

- Highly susceptible to heat and disinfectants

Survive for less than 24 hours

Require high oxygen tension to grow

Aquired from contamination of deep wounds by rusty implements or dust

Susceptible to autoclaving when present on surgical instruments

MCQS

Complications of tetanus include the following

- Acute renal failure

-fractures

-Respiratory failure

Sympathetic overactivity

Sudden cardiac death

MCQS

In the diagnosis of tetanus, which of the following is confirmatory?

ESR

Serum antitoxin levels

Serum tetanus toxin levels

CSF tetanolysin antibody test

No laboratory test is required

MCQS

The following are poor prognostic features in tetanus:

-Presence of autonomic features

-short incubation period

-short period of onset

- More cephalic presentation of culprit wound

- Presence of difficulty opening mouth as the first symptom