TETANUSDiana May U. Baclay, M.D.

Medical Resident II

TETANUS

• An acute bacterial disease caused by the neurotoxin tetanospasmin elaborated by Clostridium tetani and characterized by a prolonged contraction of skeletal muscle fibers

• “lockjaw”

definition

• CDC“ the acute onset of hypertonia or… painful

muscular contractions (usually of the muscle of the jaw and neck) and generalized muscle spasms without other apparent medical cause”

definition

• Maternal Tetanus (WHO)“tetanus ocurring during pregnancy or within 6

weeks after the conclusion of pregnancy (whether with birth, miscarriage, or abortion)”

epidemiology

• Tetanus is an international health problem, as spores are ubiquitous and occurs almost exclusively in persons who are unvaccinated or inadequately immunized – developing countries

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

• 2006: ~ 290,000 people died of tetanus, mostly in Southeast Asia and Africa

epidemiology

• Rare disease in developed countries• 2007: ~ 28 cases in the US

• High risk groups:• >60 years of age –antibody levels decrease over time• Injection drug users• Incomplete vaccination/unvaccinated individuals

 

      14,132 reported cases

     61,000 estimated deaths in <5 years (in 2008)

      83% estimated DTP3 coverage

2011 global figuresWHO

etiology

• Clostridium tetani is a Gram-positive, obligate anaerobic, spore bearing and flagellate organism.

• produce 2 exotoxins: • tetanolysin – no role in pathogenesis of the disease• Tetanospasmin – potent neurotoxin

spores are resistant to heat and most disinfectants

etiology

• Clostridium tetani• The organism is widely distributed in soil and in

intestine of horses, sheep, cattle, dogs, cats, rats, chickens and nearly 10% of humans

• The spores can also be found on skin surfaces and in contaminated heroin

• Grow, multiply and release exotoxin once in a suitable anaerobic environment

• Very low concentration of toxin can result in symptoms (minimum lethal human dose, 2.5 ng/mg)

• ~ 20% of cases of tetanus – no puncture entry wound

• Common infection sites: superficial abrasions to the limbs

• Deeper infections: associated with more severe disease and worse outcome

pathogenesis

• Tetanus toxin – single 150-kDa protein that is cleaved to produce heavy (100-kDa) and light (50-kDa) chains linked by disulfide bonds and noncovalent forces

• Toxin → transported by intra-axonal transport to motor nuclei of the cranial nerves or ventral horns of the spinal cord

• Carboxyl terminal of the c-chain binds to specific membrane components in presynaptic α-motor nerve terminals → toxin internalization and uptake into the nerves

pathogenesis

• Inside the neuron:

• Toxin enters a retrograde transport pathway, whereby it is transported proximally towards the neuron body

• pH-neutral environment of neurons prevents conformational change of the toxin

pathogenesis

• Tetanus toxin :

• escapes normal lysosomal degradation processes, undergoing translocation across the synapse to the GABA-ergic presynaptic inhibitory interneuron terminals

• > prevents transmitter release and effectively blocks inhibitory interneuron discharge

pathogenesis

• Results:• Unregulated activity in the motor neuron system• Autonomic system disturbance

• Recovery: • Little is known about the process of recovery• Can take several weeks• Some evidence suggest: toxin degradation as a mechanism

of recovery

Incubation period

Usually incubation period ranges from 3-21 days but can range from the day of injury to several months

Average incubation period is 10 days

Depends on character, location, and extent of wound

(Wound to first symptom)

Clinical manifestations

• Pain and tingling at the site of wound• Pain in neck, back and abdomen• Opisthotonus position• Risus sardonicus (Mouth kept slightly open)• Spasm of pharyngeal muscles• Lock jaw (reflex trismus)• Dysphasia• Acute asphyxia• Refusal of feeding and excessive crying• Other symptoms like fever, headache, etc

algorithm

Wound infection,

multiplication of C. tetani

Tetanus toxin uptake into

nervous system cleavage in GABA inhibitory neurons

Further toxin effects causing widespread

disinhibition of motor and

autonomic nervous system

Toxin degradation

No symptoms

Initial symptoms: muscle aches,

trsimus, myalgia

Muscle spasm: local and generalized

Cardiovascular instability: labile BP, tachy- or bradycardia

Pyrexia, increased respiratory and GI

secretions

Cessation of spasm,

restoration of normal muscle

tone

Cardiovascular and autonomic

control

7-10 days

24-72 hrs

4-6 weeks

Ablett Classification of the Severity of Tetanus

Grade Clinical FeaturesI Mild Mild to moderate trismus; general

spasticity; no respiratory embarrassment; no spasms; little or no dysphagia

II Moderate Moderate trismus; well-marked

rigidity; mild to moderate but short

spasms; moderate respiratory

embarrassment with an increased

respiratory rate greater than 30,

mild dysphagia

Ablett Classification of the Severity of Tetanus

Grade Clinical Features• III Severe Severe trismus; generalized

spasticity; reflex prolonged spasms;

respiratory rate greater than 40;

apneic spells, severe dysphagia;

tachycardia > 120• IV Very Severe Grade III and violent autonomic

disturbances involving the

cardiovascular system. Severe

hypertension and tachycardia

alternating with relative hypotension

and bradycardia, either of which

may be persistent

Autonomic Disturbances Seen in Tetanus

• Sustained or labile hypertension• Progressive and refractory hypotension• Peripheral vasoconstriction• Tachycardia (episodic commonly)• Bradycardia and asystole• Arrythmias• Fever• Profuse diaphoresis, salivation• Increased bronchial secretions• Gastric stasis and ileus• Urinary retention

Clinical manifestations

Autonomic disturbance:• Maximal during the 2nd week of severe tetanus• BP labile• Bradycardia/tachycardia/heart block• Gastrointestinal stasis, sweating, increased tracheal

secretions and acute renal failure• Death – secondary to cardiovascular event

COMPLICATIONS

(modified from Cook et al 12)

Body system Complication• Airway Aspiration, laryngospasm

sedative associated obstruction• Respiratory Apnoea, hypoxia, Type I and Type II

respiratory failure, ARDS,complications of prolonged assistedventilation (eg. pneumonia)tracheostomy complications,

• Cardiovascular Tachycardia, hypertension, ischemia,hypotension, bradycardia,arrythmias,asystolic, cardiac failure

• Renal Renal failure, urinary infectionand stasis

• Gastrointestinal Stasis, ileus, hemorrhage• Miscellaneous Weight loss, thromboembolism

sepsis, multiorgan dysfunctionsyndrome, fracture due to spasm

DIAGNOSIS

• CLINICAL• Injury/presence of wound• portal of entry is not evident: • a careful search for signs of parentral drug abuse, otitis media,

instrumentation, injections or minor surgical procedures should be inquired

• Culture of C. tetani from wound – supportive evidence

TREATMENT

• Entry wound should be identified, cleaned, and debrided of necrotic material to remove anaerobic foci of infection

• ~infection sec to other organisms induces further toxin production

• Admit @ quiet, calm environment• Secure airway - tracheostomy

TREATMENT

• Metronidazole: 400mg rectally or 500mgIV q6h for 7 days• Alternative: penicillin (100,000-200,000 IU/kg per day)

• Antitoxin• HTIG 3000-6000 IU as single dose IM• Equine antitoxin (ATS) 10,000-20,000 as single dose IM

TREATMENT

• Spasms:• Heavy sedation: benzodiazepines• Chlorpromazine, phenobarbital and magnesium sulfate• Propofol – control spasm and provide sedation

prognosis

• Incubation period: time form wound to first symptom

• Period of Onset: time from first symptom to generalized spasm

Factors associated with poor prognosis

• Adult tetanus:• Age >70 yo• Incubation period <7days• Short time from first symptom to admission• Puerperal, IV, postsurgery, burn entry site• Period of onset <48H• Heart rate >140bpm• SBP>140mmHg• Severe disease or spasms• Temperature >38.5C

PREVENTION

• Good wound care

• Immunization

Afshar et al., Ann Intern Med. 1 March 2011;154(5):329-335: Narrative Review: Tetanus—A Health Threat After Natural Disasters in Developing Countries

IMMUNIZATION

IMMUNIZATION

• WHO recommendations (maternal tetanus):• Prevention of maternal and neonatal tetanus call for

administration of two doses of TT at least 4 weeks apart to the previously unimmunized pregnant woman

• Safe delivery and postnatal practices

• If with tetanus prone wounds:• Immunized if their vaccination status is incomplete or

unknown, or their last booster was given >10years ago

Any questions ???