tetanus discussion
TRANSCRIPT
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 ???