tetanus toxin

prevents the release of the neurotransmitter GABA from inhibitory

presynaptic inputs terminating at neurons that supply
skeletal muscles. Unchecked excitatory inputs to these neurons
result in uncontrolled muscle spasms. Th ese spasms occur especially
in the jaw muscles early in the disease, giving rise to the
common name of lockjaw for this condition. Later, they progress
to the muscles responsible for breathing, at which point
death occurs.
Sherwood p 91

Tetanus Immunization
The reported incidence of tetanus in the United States in 2005 was
0.011 per 100,000 population (27 cases reported).78 Most tetanus
patients in the United States are older than 50 years. Immunization
status needs to be considered in all patients with wounds,
regardless of severity. Forty percent of all cases of tetanus occur in
individuals who have either minor wounds or no recollection of
injury. These numbers raise serious questions regarding the validity
of separating immunization recommendations according to
clean and tetanus-prone wounds. Studies show that many people
are inadequately immunized, especially patients older than 70
years, immigrants, and people with no education beyond grade
school.79 Also, patient immunization histories are often unreliable.
Given the inability to predict which wounds are at high risk, all
wounds are approached with suspicion.
The usual incubation period for tetanus is 7 to 21 days (range,
3-56 days). Immunization is given as soon as possible but can be
given days or weeks after the injury. The dose of tetanus toxoid
(T) or diphtheria, pertussis, and tetanus toxoids (DTaP) is 0.5 mL
intramuscularly, regardless of the patients age. Inadequately
immunized patients need a dose of DTaP and tetanus immune
globulin (TIG). The TIG dose is 250 IU for all ages 7 years or older
and 4 IU/kg IM up to 250 IU for ages younger than 7 years (Table
59-3). A single injection of TIG provides protective levels of
passive antibodies for at least 4 weeks. The immune globulin
and toxoid may be given during the same visit but should
be administered with a different syringe at separate sites. The literature
suggests that emergency physicians need to be more diligent
administering TIG, because it is often not provided when
indicated.80
rosen p 765 , 1699-1704
TETANUS
Perspective
Background
Tetanus is a toxin-mediated disease characterized by severe uncontrolled
skeletal muscle spasms. Involvement of the muscles of respiration
leads to hypoventilation, hypoxia, and death. Dramatic
descriptions of this disease date to ancient Egypt, when physicians
recognized a frequent relationship between tissue injury and subsequent
fatal spasm.25
In 1884, Carle and Rattone produced tetanus in rabbits by
injecting material from an acne pustule that came from an infected
human. In the same year, Nicolaier isolated the strychnine-like
toxin from anaerobic soil bacteria. In 1889, Kitasato obtained pure
cultures of spore-forming bacteria that caused tetanus on introduction
into animals. One year later, Faber proved that tetanus is
a toxin-mediated disease when he induced the illness by injecting
animals with bacteria-free filtrates of Clostridium tetani cultures.
In the 1890s, von Behring and Kitasato discovered tetanus antitoxin
in the serum of immune animals and demonstrated its efficacy
in preventing disease. Prophylactic injection of this antitoxin
provided passive immunity to wounded soldiers during World
War I. It was not until 1924 that an effective vaccine was developed
by Descombey. Large-scale testing during World War II indicated
that the tetanus toxoid confers a high degree of protection
against disease.25-27
Epidemiology
Despite the availability of an effective vaccine, tetanus remains
endemic worldwide. It is more common in warm, damp climates
and relatively rare in cold regions. The global annual incidence of
reported cases of tetanus has declined steadily with the introduction
of vaccination programs (Fig. 129-3A). The World Health
Organization reported 9836 cases of tetanus in 2009, but it is
estimated that 800,000 to 1 million unreported cases occur a year,
with half occurring in neonates. Eighty percent of these cases
occur in Africa and Southeast Asia because of low immunization
rates and poor hygiene.27
Since the introduction of vaccination programs in the United
States, the incidence of tetanus has steadily declined from 4 cases
per million population in the 1940s to 0.095 case per million
population in 2005 (Fig. 129-3B).28 The highest incidence occurs
in people older than 65 years (0.23 case per million population),
and the incidence in Hispanic Americans is almost twice that in
non-Hispanics.28,29 Fifteen percent of cases occur in injection drug
users. The overall case fatality rate is 18% but approaches 50% in
patients older than 70 years (Fig. 129-4). Cases have been reported
in patients who had been fully vaccinated, but in the eight patients
from 1998 to 2000, no deaths occurred.29
Tetanus typically occurs as a result of a deep penetrating wound.
A history of injury is present in more than 70% of patients, but
the injury may be trivial in 50% of patients and unapparent in up
to 30% of patients.25-29 The most common portals of entry for the
organism are puncture wounds, lacerations, and abrasions.
Tetanus has also been reported in association with chronic skin
ulcers, abscesses, and otitis media as well as with foreign bodies,
corneal abrasions, childbirth, and dental procedures.26 Postoperative
tetanus has been reported in patients who have undergone
intestinal operations and abortions. In these cases the source of
bacteria is probably endogenous as up to 10% of humans harbor
C. tetani in the colon.
Inadequate primary immunization and waning immunity continue
to be the primary risk factors for tetanus in the United States.
As tetanus vaccination of children has improved, older people
have accounted for an increasing percentage of reported cases.
Etiology
C. tetani is a spore-forming, motile, slender, rod-shaped, obligate
anaerobic bacillus. It stains gram positive in fresh culture but has
a variable staining pattern in old cultures and tissue samples. The
bacillus can form a single spherical terminal endospore that
swells the end of the organism to produce a characteristic drumstick
appearance. C. tetani is ubiquitous in soil and dust and is
also found in the feces of animals and humans.25 Mature bacilli
are highly susceptible to heat and other adverse environmental
conditions. Spores are resistant to heating and chemical disinfectants
and can survive in soil for months to years. When they are
introduced into a wound, spores may not germinate for weeks
because of unfavorable tissue conditions. When injury favors
anaerobic growth, the spores germinate into mature bacilli.
Only these mature bacilli produce the tetanus toxin that causes
clinical disease.25-27
Principles of Disease
C. tetani is a noninvasive organism. The development of clinical
tetanus requires a portal of entry for the infecting spores as
well as tissue conditions that promote germination and growth
in an immunologically susceptible host. Tetanus-prone wounds
are those with damaged or devitalized tissue, foreign bodies, or
other bacteria. Under these conditions, C. tetani produces the
neurotoxin that causes clinical illness. Germination and replication
of C. tetani can occur without clinical signs of a local wound
infection.
C. tetani produces the neurotoxin tetanospasmin (TS) at the site
of tissue injury. TS first binds the motor nerve ending and then
moves by retrograde axonal transport and trans-synaptic spread
to the CNS.30,31 It binds preferentially to inhibitory (GABAergic
and glycinergic) neurons and blocks the presynaptic release of
these neurotransmitters. Interneurons afferent to alpha motor
neurons are affected first.30 Without inhibitory control, the motor
neurons undergo sustained excitatory discharge, resulting in the
muscle spasm characteristic of tetanus.26
TS may also affect preganglionic sympathetic neurons and
parasympathetic centers, resulting in autonomic nervous system
dysfunction.31,32 The clinical manifestations include dysrhythmias
and wide fluctuations in blood pressure and heart rate. The
binding of TS at the synapse is irreversible; recovery occurs only
when a new axonal terminal is produced.25
Clinical Features
Symptoms and Signs
The incubation period for tetanus ranges from 1 day to several
months. A shorter incubation period portends a worse prognosis.
26 The duration of the incubation period is not useful in making

the diagnosis of tetanus because many patients have no history of

an antecedent wound. Four types of clinical tetanus have been
described.
Generalized Tetanus. Generalized tetanus is the most common
form of the disease and results in spasms of agonist and antagonist
muscle groups throughout the body. The classic initial presenting
symptom of trismus (lockjaw) is caused by masseter muscle
spasm and is present in 50 to 75% of patients. As the other facial
muscles become involved, a characteristic sardonic smile (risus
sardonicus) appears. Other early symptoms include irritability,
weakness, myalgias, muscle cramps, dysphagia, hydrophobia, and
drooling. As the disease progresses, generalized uncontrollable
muscle spasms can occur spontaneously or as a result of minor
stimuli, such as touch or noise. Spasms may result in vertebral
and long bone fractures and tendon rupture. Opisthotonos is a
prolonged tonic contraction that closely resembles decorticate
posturing. Spasms of laryngeal and respiratory muscles can lead
to ventilatory failure and death. Autonomic dysfunction is the
major cause of death in patients who survive the acute phase and
is manifested by tachycardia, hypertension, temperature elevation,
cardiac dysrhythmias, and diaphoresis. The illness is progressive,
with an increase in symptoms during the first 3 days, persistence
of symptoms for 5 to 7 days, and reduction of spasms after 10
days. If the patient survives, recovery is complete after 4 weeks or
more. Throughout the course of this horrific illness, patients
remain completely lucid unless they are chemically sedated.25-27
Localized Tetanus. Localized tetanus is a form of the disease
characterized by persistent muscle spasms close to the site of
injury. Symptoms may be mild or severe, but mortality is lower
than with generalized tetanus. Local tetanus may progress to generalized
disease. This form of illness may probably reflect partial
immunity to TS and may be present for weeks to months before
resolution.25
Cephalic Tetanus. Cephalic tetanus is a rare variant of localized
tetanus that results in cranial nerve palsies and muscle spasms. The
palsies precede the spasm in 42% of cases, resulting in frequent
misdiagnosis. The most commonly involved cranial nerve is the
facial nerve (VII), mimicking Bells palsy. Most of these cases occur
after facial trauma or otitis media. Patients have trismus and
palsies of cranial nerve III, IV, VII, IX, X, or XII ipsilateral to the
site of local infection. The clinical course is variable. In one
third of cases, resolution of symptoms is complete. The remainder
progress to generalized tetanus with an overall mortality rate of
15 to 30%.25-29
Neonatal Tetanus. Neonatal tetanus is generalized tetanus of the
newborn and occurs almost exclusively in developing countries
where maternal immunization is inadequate and contaminated
material is used to cut and dress umbilical cords. Symptoms begin
during the first week of life and include irritability and poor
feeding. Mortality approaches 100% because of the high toxin
load for body weight and inadequate medical support in developing
countries. Even with limited resources, mortality can be
reduced to less than 50% with basic medication and experienced
medical and nursing personnel.33 The CDC reported one case of
neonatal tetanus in the United States between 1998 and 2000. The
infant was born at home to an unimmunized mother. The umbilical
cord had been treated with bentonite clay. The child was treated
and recovered after 19 days of hospitalization.
Complications
Acute respiratory failure, the main cause of morbidity and mortality
in tetanus, results from respiratory muscle spasms or laryngospasms
and airway obstruction. If the patient survives the acute
onset of illness and has adequate ventilatory support, autonomic
dysfunction becomes the leading cause of death. Autonomic instability
occurs several days after the onset of generalized spasms.
Disinhibition of the sympathetic nervous system predominates
and causes dysrhythmias, hypertension, myocarditis, and pulmonary
edema.34 Dysrhythmias and myocardial infarction are the
most common fatal events during this phase.
Forceful tetanic muscle spasms can cause vertebral subluxations
and fractures, long bone fractures, and shoulder and
temporomandibular joint dislocations. Rhabdomyolysis occasionally
occurs and can cause acute renal failure. Renal failure may
also result from dehydration and sympathetic nervous system
hyperactivity. Renal vein thrombosis may cause renal failure in
neonatal tetanus.
Secondary infection may occur in the initial inoculating wound
or as a complication arising from invasive treatment modalities,
such as mechanical ventilation.35 Hyperthermia may also result
from muscle spasms and sympathetic hyperactivity. Prolonged
immobility can lead to deep venous thrombosis and pulmonary
embolism. Gastrointestinal complications include peptic ulcers,
ileus, intestinal perforation, and constipation. The syndrome of
inappropriate secretion of antidiuretic hormone occurs in a small
number of patients. Hemolysis has also been reported.
Mortality is a function of the previous immunization status,
incubation period, severity and rapidity of onset of symptoms,
comorbid disease, age, and sophistication of medical treatment
available. With appropriate intensive care treatment, elder patients
may fare as well as their middle-aged counterparts.36 Long-term
physical complications in survivors are rare. The most common
persistent problem may be psychological trauma related to the
disease and its treatment.25
Diagnostic Strategies
The diagnosis of tetanus should be made on clinical grounds
alone. Wound cultures for C. tetani are of little value as they are
positive in only one third of cases. Even if a positive culture is
obtained, it does not indicate whether the bacterium is a toxinproducing
strain. There are no laboratory tests to confirm or to
exclude the diagnosis of tetanus.25 In 1990 the CDC adopted a
clinical case definition for the public health surveillance of generalized
tetanus: acute onset of hypertonia or painful muscular
contractions (usually of the muscles of the jaw and neck) and
generalized muscle spasms without other apparent medical cause
(as reported by a health care professional).29
Lumbar puncture may be indicated to exclude meningitis in the
neonate when the diagnosis of tetanus is uncertain. A computed
tomography scan is helpful in assessment for intracranial disease.
A serum calcium level is helpful to exclude hypocalcemia. Electromyography
may be useful if the diagnosis of cephalic or localized
tetanus is in doubt.25
The spatula test involves touching of the oropharynx with a
tongue blade. With a negative test result, the patient gags and
expels the tongue blade. With a positive test result, the patient has
reflex masseter muscle spasm and bites the spatula. This test is
94% sensitive and 100% specific for tetanus.27
Differential Considerations
Strychnine poisoning is the only clinical condition that truly
mimics generalized tetanus. Strychnine, like TS, antagonizes
glycine release, but unlike TS, it has no effect on -aminobutyric
acid (GABA) release. Patients have opisthotonos while remaining
alert. The annual incidences of tetanus and strychnine poisoning
are similar in the United States, and serum and urine tests for
strychnine should be performed when tetanus is considered. 25
In patients who present with diffuse generalized spasm, the
diagnosis of tetanus is less likely to be missed, but ideally the
disease should be considered and diagnosed in the early stages
to minimize complications and to decrease mortality. Some conditions
with clinical similarities to tetanus are listed in Box 129-3.
Trismus is most commonly caused by intraoral infections. These
can be excluded with careful history and physical examination
of the oral cavity and teeth. Mandibular dislocation can be ruled
out with appropriate radiographs of the mandible and temporomandibular
joints. Dystonic reactions can be differentiated from
tetanus by medication history and symptoms that are alleviated
by benztropine or diphenhydramine. Patients with encephalitis
usually exhibit an altered mental status. Meningitis can be
excluded by examination of the cerebrospinal fluid (CSF). Rabies
should be considered when there are symptoms of brainstem
dysfunction, including dysphagia and respiratory muscle dysfunction.
A history of exposure to secretions of an infected
animal is the most helpful historical point. In addition, rabies
does not cause trismus.
Cephalic tetanus is especially difficult to diagnose when the
cranial nerve palsy precedes trismus. The differential diagnosis of
cephalic tetanus also includes Bells palsy, botulism, cranial nerve
palsies, and facial cellulitis with facial nerve compression and
ophthalmoplegia.
Management
Acute Treatment
The four treatment strategies for patients with tetanus should be
undertaken simultaneously: aggressive supportive care, elimination
of unbound TS, active immunization, and prevention of
further toxin production.25-27
Supportive Care. Supportive care begins with control of the
muscle spasms. Reflex spasms can result from stimulation of the
patient, such as that caused by any movement of the patient or
loud noises. Avoidance of unnecessary stimulation is recommended.
Benzodiazepines are the mainstay of symptomatic
therapy for tetanus. These drugs are GABA agonists and indirectly
antagonize many of the effects of TS. They have no effect on the
inhibition of glycine release by TS. Diazepam is the most extensively
studied of these agents, but lorazepam and midazolam are
equally effective. Diazepam has a rapid onset of action and a wide
margin of safety, and it can be given orally, rectally, or intravenously.
It is inexpensive and thus available in most parts of the
world. It has a long cumulative half-life and active metabolites that
can cause prolonged sedation and respiratory depression. The
intravenous formulations of diazepam and lorazepam contain
propylene glycol, which, at high doses, can produce lactic acidosis.
Gastrointestinal delivery of these agents is limited by motility
problems associated with tetanus. Midazolam has a short half-life
and does not contain propylene glycol, but it should be given by
continuous infusion and is cost-prohibitive in most areas of the
world. Propofol infusion is effective, but it is also expensive, and
patients may not tolerate the lipid vehicle. Neuroleptics, barbiturates,
and intrathecal baclofen have no advantage over benzodiazepines.
Dantrolene is a direct muscle relaxant without CNS
activity. It has been reported as an adjunctive agent for muscle
spasms and may decrease the need for mechanical ventilation.37
Magnesium sulfate infusion has been advocated as both adjuvant
and first-line therapy for tetanus. Alone or in combination with
other agents, it improves spasm control and may alleviate some of
the autonomic instability associated with tetanus toxicity.38
If spasm cannot be controlled with these regimens or if any
signs of airway compromise develop, the patient should receive
neuromuscular blockade and mechanical ventilation. Although
succinylcholine can be used in the initial phase of the disease, the
clinician should be aware of the risk of severe hyperkalemia resulting
from its use in any neuromuscular disease. This effect does not
begin until about 4 days after the onset of disease.25 Long-acting
nondepolarizing agents are preferred, even in the initial phase.
Pancuronium has traditionally been used, but it is an inhibitor of
catecholamine reuptake and may worsen autonomic instability.25
Vecuronium and rocuronium are shorter acting and are without
significant cardiovascular side effects but require continuous infusion.
Whichever agent is used, adequate sedation should be provided,
and neuromuscular blockade should be withheld at least
once a day to assess the patients status. All intubated patients
should be considered for early tracheostomy to decrease reflex
spasms caused by the endotracheal tube.32
Autonomic instability requires monitoring and aggressive
treatment. Sympathetic hyperactivity can be treated with combined
alpha- and beta-adrenergic antagonists, such as labetalol
and propranolol. The use of beta-antagonists alone can lead to
unopposed alpha-activity, resulting in severe hypertension.34 If
beta-antagonists are necessary, a short-acting agent such as
esmolol should be used.26 Because the episodes of the autonomic
crises in tetanus are due to catecholamine excess, the use of pure
beta-antagonism can result in unopposed alpha-agonism. Clonidine
has shown variable success at modulation of sympathetic
outflow in these cases.34 Morphine and magnesium sulfate infusions
as well as spinal anesthesia and intrathecal baclofen have
been shown to improve autonomic dysfunction.25 Diuretics should
be avoided for blood pressure control as volume depletion can
worsen autonomic instability. Bradydysrhythmia should be treated
with temporary pacing. Atropine and sympathomimetic drugs
should be used with caution as the autonomic instability is essentially
due to catecholamine excess.26,27,34
Elimination of Unbound Tetanospasmin and Active Immunization.
Human tetanus immune globulin (HTIG) and Td should be
administered as soon as possible to all patients with suspected
tetanus. Tetanus immune globulin (TIG) does not neutralize toxin
already present in the nervous system, nor does it treat any existing
symptoms. HTIG neutralizes any circulating toxin as well as toxin
at the site of production and reduces mortality. TIG should be
administered at a site separate from the toxoid. Dosage recommendations
vary (500-10,000 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 injections. Administration of a portion of the TIG proximal
to the site of inoculation is often recommended but has not
been studied.25-27 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. The preparation of TIG
available in the United States is not licensed for intrathecal administration,
which is of no proven benefit.25,27,32
Prevention of Further Toxin Production. Toxin production is eliminated
by treatment of the C. tetani infection. Wound dbridement
and antibiotic administration can cause a transient release of TS,
so these measures should be delayed until after the HTIG is
administered. Metronidazole (500 mg orally or IV every 6 hours)
is the antibiotic of choice for C. tetani. Pediatric doses of metronidazole
depend on age and weight26,27:
Neonates < 1200 g and 0-7 days: 7.5 mg/kg IV or orally every
24 hours
Neonates < 1200 g and 8-28 days: 7.5 mg/kg IV or orally every
12 hours
Neonates > 1200 g and 0-7 days: 7.5 mg/kg IV or orally every
12 hours
Neonates > 1200 g and 8-28 days: 25-30 mg/kg/day IV or orally
every 12 hours
Infants and children: 30 mg/kg/day IV divided every 6 hours,
maximum 4 g/day
Penicillin has traditionally been used to treat tetanus and has
good in vitro and in vivo activity against C. tetani, but it also has
GABA antagonistic activity and may potentiate the effects of TS.
Metronidazole has better penetration than penicillin into devitalized
tissue and abscesses and is superior in terms of recovery time
and effect on mortality. Macrolides, doxycycline, chloramphenicol,
and tetracycline are effective alternatives in metronidazoleallergic
patients.25-27
Vaccination
Tetanus toxoid is an inactivated form of TS, and vaccination
confers protective antibody levels in nearly 100% of people who
receive three doses. Immunity wanes between 5 and 10 years after
completion of the series. In high-risk patients such as elders, injection
drug users, and patients with human immunodeficiency virus
(HIV) infection and other causes of immunocompromise, immunity
wanes more quickly and the response to vaccine is less brisk.
Adults with an uncertain history of a complete primary immunization
series should receive a primary series. The standard vaccination
program consists of a primary series of three tetanus
toxoid doses, followed by booster doses every 10 years. Age-specific
guidelines for tetanus prophylaxis have been developed by the
ACIP and published by the CDC (Tables 129-1 and 129-2).
Tetanus vaccination should be updated for all patients who
come to the emergency department for management of a wound,
even if the presenting complaint is not wound related. Patients
with unknown or uncertain immunization status should be considered
to have no previous tetanus immunization. Those younger
than 7 years should receive diphtheria-tetanus or DTaP. Patients 7
years of age or older should receive Tdap instead of DTaP because
adverse reactions from the larger doses of diphtheria toxoid in
DTaP are more common in older individuals.
HTIG prophylaxis (250 units IM) is recommended for unimmunized
and underimmunized patients with wounds at high risk
for tetanus (>6 hours old, >1 cm deep, contaminated, stellate,
denervated, ischemic, infected).27 When tetanus toxoid and HTIG
are given concurrently, separate injection sites should be used. The
only contraindication to tetanus and diphtheria toxoids is a history
of a neurologic or severe hypersensitivity reaction to a previous
dose. Adverse reactions to tetanus toxoid and tetanus-diphtheria
toxoids occur commonly and may be the result of the preservative
thimerosal. The most common side effects are minor: local swelling,
pain, erythema, pruritus, fever, nausea, vomiting, malaise, and
nonspecific rash. Local reactions do not preclude future use of
toxoid. Serious anaphylactic reactions are rare. If a patient who
requires immunoprophylaxis gives a history suggestive of a neurologic
or severe anaphylactic reaction, HTIG should be administered
alone to protect the patient from development of tetanus
as a result of the present injury. HTIG does not confer active
immunity, and such patients should be referred to an allergist for
measurement of antibody levels, antitoxin desensitization, and
immunization. No evidence exists that tetanus and diphtheria
toxoids are teratogenic. HTIG is not contraindicated in pregnancy.
For inadequately immunized patients of any age, referral should
be made to ensure that the patient receives the remainder of the
immunizations required.38

Tetanus
ESSENTIALS OF DIAGNOSIS
History of wound and possible contamination.
Jaw stiffness followed by spasms of jaw muscles
(trismus).
Stiffness of the neck and other muscles, dysphagia,

irritability, hyperreflexia.
Finally, painful convulsions precipitated by minimal

stimuli.
General Considerations
Tetanus is caused by the neurotoxin tetanospasmin, elaborated
by C tetani. Spores of this organism are ubiquitous in
soil and may germinate when introduced into a wound.
The vegetative bacteria produce tetanospasmin, a zinc
metalloprotease that cleaves synaptobrevin, a protein
essential for neurotransmitter release. Tetanospasmin
interferes with neurotransmission at spinal synapses of
inhibitory neurons. As a result, minor stimuli result in
uncontrolled spasms, and reflexes are exaggerated. The
incubation period is 5 days to 15 weeks, with the average
being 812 days.
Most cases occur in unvaccinated individuals. Persons at
risk are the elderly, migrant workers, newborns, and injection
drug users. While puncture wounds are particularly
prone to causing tetanus, any wound, including bites or
decubiti, may become colonized and infected by C tetani.
Clinical Findings
A. Symptoms and Signs
The first symptom may be pain and tingling at the site of
inoculation, followed by spasticity of the muscles nearby.
Stiffness of the jaw, neck stiffness, dysphagia, and irritability
are other early signs. Hyperreflexia develops later, with
spasms of the jaw muscles (trismus) or facial muscles and
rigidity and spasm of the muscles of the abdomen, neck,
and back. Painful tonic convulsions precipitated by minor
stimuli are common. Spasms of the glottis and respiratory
muscles may cause acute asphyxia. The patient is awake
and alert throughout the illness. The sensory examination
is normal. The temperature is normal or only slightly
elevated.
B. Laboratory Findings
The diagnosis of tetanus is made clinically.
Differential Diagnosis
Tetanus must be differentiated from various acute central
nervous system infections such as meningitis. Trismus may
occasionally develop with the use of phenothiazines.
Strychnine poisoning should also be considered.
Complications
Airway obstruction is common. Urinary retention and
constipation may result from spasm of the sphincters.
Respiratory arrest and cardiac failure are late, life-threatening
events.
Prevention
Tetanus is preventable by active immunization (see
Table 307). For primary immunization of adults, Td
(tetanus and diphtheria toxoids vaccine) is administered as
two doses 46 weeks apart, with a third dose 612 months
later. For one of the doses, Tdap (tetanus toxoid, reduced
dose diphtheria toxoid, acellular pertussis vaccine) should
be substituted for Td. Booster doses are given every 10 years
or at the time of major injury if it occurs more than 5 years
after a dose. A single dose of Tdap is preferred to Td for
wound prophylaxis if the patient has not been previously
vaccinated with Tdap.
Passive immunization should be used in nonimmunized
individuals and those whose immunization status is
uncertain whenever a wound is contaminated or likely to
have devitalized tissue. Tetanus immune globulin, 250 units,
is given intramuscularly. Active immunization with tetanus
toxoid is started concurrently. Table 332 provides a guide
to prophylactic management.
Treatment
A. Specific Measures
Human tetanus immune globulin, 500 units, should be
administered intramuscularly within the first 24 hours of
presentation. Whether intrathecal administration has any
additional benefit is controversial. An unblinded, randomized
trial comparing intramuscular tetanus immune globulin
to intramuscular plus intrathecal tetanus immune
globulin found more rapid resolution of spasms, fewer days
B. General Measures
Minimal stimuli can provoke spasms, so the patient should
be placed at bed rest and monitored under the quietest
conditions possible. Sedation, paralysis with curare-like
agents, and mechanical ventilation are often necessary to
control tetanic spasms. Penicillin, 20 million units intravenously
daily in divided doses, is given to all patientseven
those with mild illnessto eradicate toxin-producing
organisms.
Prognosis
High mortality rates are associated with a short incubation
period, early onset of convulsions, and delay in treatment.
Contaminated lesions about the head and face are more
dangerous than wounds on other parts of the body.
CMDT 1421-1422

TETANUS
_
_ Localized or generalized muscle stiffness
_ Superimposed paroxysmal tonic spasms (tetanospasms)
_ Autonomic instability

_ Normal mental status

ESSENTIALS OF DIAGNOSIS
_ General Considerations
Tetanus is caused by a neurotoxin produced at the site of
injury by Clostridium tetani, an anaerobic, gram-positive
bacillus. Spores of C tetani are present in soil worldwide.
Portals of entry resulting in human disease include traumatic
and surgical wounds, injection sites (especially among parenteral
drug abusers), skin ulcers, burns, and infected
umbilical cords. Tissue necrosis and suppuration allow the
bacteria to germinate and produce the toxin (tetanospasmin),
which is taken up by peripheral nerve terminals and ascends
intra-axonally to the spinal cord or brainstem. Tetanospasmin
blocks inhibitory interneurons, resulting in excessive discharge
of motor neurons and, in severe cases, autonomic
dysfunction. In the United States, 5070 cases of tetanus are
reported yearly, most from acute or chronic wounds. In
developing countries lacking adequate vaccination programs,
1 million cases of neonatal tetanus occur annually as a result
of nonsterile birthing technique.
_ Prevention
Acute immunization of infants and children with DPT
(diphtheria and tetanus toxoids and pertussis adsorbed) is
recommended at 2, 4, 6, and 15 months, and 46 years, with
booster immunization every 10 years thereafter. Passive
immunization with human tetanus immune globulin (HTIG)
is recommended for tetanus-prone wounds (eg, wounds
contaminated by dirt, feces, or saliva; puncture or missile
wounds; avulsions; burns) in patients with uncertain immunization
history.
_ Clinical Findings
A. Symptoms and Signs
The usual incubation period from injury to first symptoms is
721 days. Trismus (lockjaw) and stiffness of the neck and
paraspinal muscles are prominent early symptoms, spreading
as the disease progresses to the limbs. Stiffness of facial
muscles produces risus sardonicus, and paraspinal rigidity
can produce opisthotonus. Superimposed paroxysmal painful
tonic spasms (tetanospasms) occur spontaneously or are
triggered by tactile stimuli or sound. Pharyngeal muscle
spasm causes dysphagia, and laryngeal and respiratory muscle
spasms cause asphyxia. Autonomic dysfunction can cause
fever, blood pressure swings, severe diaphoresis, and cardiac
arrhythmia even when body spasms are controlled. Most
patients remain mentally clear. Partially immunized subjects
can develop localized tetanus confined to the injured limb or
to cephalic muscles after a head injury or otitis.
B. Laboratory Findings
CSF analysis shows normal findings. There are no specific
laboratory tests to confirm the diagnosis, which is based on
the characteristic signs. A wound may not be apparent, and
even when it is present, C tetani may not be identified.
_ Differential Diagnosis
Diagnostic considerations include neuroleptic-induced dystonia,
meningitis, dental abscess, status epilepticus, subarachnoid
hemorrhage, hypocalcemic tetany, ethanol, sedative
or opiate withdrawal, strychnine poisoning, black widow
spider bite, stiff-person syndrome, and rabies.
_ Treatment
Patients should be treated in an intensive care unit. The
wound is debrided after administration of HTIG (human
tetanus immune globulin, 30006000 units) into one limb
and tetanus toxoid into another. (Tetanus toxoid is required
because infection with C tetani does not confer its own
immunity.) Because penicillin use can exacerbate spasms
as it antagonizes the inhibitory neurotransmitter
-aminobutyric acid, metronidazole, 2 g/day for 710 days, is
the antimicrobial of choice. Patients with tetanospasms require
ventilatory support and, because endotracheal intubation
provokes spasms, tracheostomy is usually indicated.
Benzodiazepines, often titrated to very high doses, are given to
control spasms and provide sedation, but neuromuscular
blockade (eg, vecuronium, 68 mg/h) may be necessary in
patients with severe spasms. Infusion of magnesium sulfate
may be useful as well. In patients with autonomic instability,
labetalol, 0.251.0 mg/min, can be given for hypertension, and
verapamil is used for tachycardia. Pressors may be necessary
for hypotension, and bradycardia may require a pacemaker.
_ Prognosis
The disease may progress for 2 weeks even after administration
of antitoxin, and severe tetanus may require several
weeks more for recovery. Mortality is up to 25% even in
modern intensive care units. Complications include bone
fractures, dehydration, pneumonia, and pulmonary emboli.
Current neurology p 424-425

Teta n u s
The cause o f this disease i s the anaerobic, spore-forming
rod Clostridium tetani. The organisms are found in the
feces of some humans and many animals, particularly
horses, from which they readily contaminate the soil. The
spores may remain dormant for many months or years,
but when they are introduced into a wound, especially if
a foreign body or purulent bacteria are present, they are
converted into their vegetative forms, which produce the
exotoxin tetanospasmin. In developing countries, tetanus
is still a common disease, particularly in newborns, in
whom the spores are introduced via the umbilical cord
(tetanus neonatorum). In the United States, the incidence
rate of tetanus is about 1 per million people per year.
Injection of contaminated heroin is a significant cause.
Approximately 67 percent of all injuries leading to tetanus
occur from deep scratches and puncture wounds in
the home, and approximately 20 percent from deep
scratches and puncture wounds in gardens and on farms.
Since 1903, when Morax and Marie proposed their
theory of centripetal migration of the tetanus toxin,
it has been taught that spread to the nervous system
occurs via the peripheral nerves, the toxin ascending
in the axis cylinders or the perineural sheaths. Modern
studies, using fluorescein-labeled tetanus antitoxin, have
disclosed that the toxin is also widely disseminated
via blood or lymphatics, probably accounting for the
generalized form of the disease. However, in local tetanus
(see Chap. 55), the likely mode of spread to the CNS is
indeed by retrograde axonal transport.
M o d e of Act i o n of Teta n u s Tox i n
Like botulinum toxin, the tetanus toxin is a zinc-dependent
protease. It blocks neurotransmitter release by
cleaving surface proteins of the synaptic vesicles, thus
preventing the normal exocytosis of neurotransmitter.
The toxin interferes with the function of the reflex arc by
the blockade of inhibitory transmitters, mainly GABA, at
presynaptic sites in the spinal cord and brainstem. The
Renshaw cell, the source of recurrent inhibition of spinal
and brainstem motor neurons, is preferentially affected.
Elicitation of the jaw jerk, for example, is normally followed
by the abrupt suppression of motor neuron activity,
manifested in the electromyogram (EMG) as a "silent
period" (see further on) . In the patient with tetanus, there
is a failure of this inhibitory mechanism, with a resulting
increase in activation of the neurons that innervate
the masseter muscles (trismus, or lockjaw). Of all neuromuscular
systems, the masseter innervation seems to
be the most sensitive to the toxin. Not only do afferent
stimuli produce an exaggerated effect, but they also abolish
reciprocal innervation, allowing both agonists and
antagonists to contract, giving rise to the characteristic
muscular spasm of tetanus (see below) . In addition to its
generalized effects on the motor neurons of the spinal
cord and brainstem, there is evidence that the toxin acts
directly on skeletal muscle at the point where the axon
forms the endplate (accounting perhaps for localized
tetanus) and also upon the cerebral cortex and the sympathetic
nervous system in the hypothalamus.
The incubation period varies greatly, from a day or
two to a month or longer. Long incubation periods are
associated with mild and localized types of the disease.
C l i n i c a l Featu res
There are several clinical types of tetanus, usually designated
as local, cephalic, and generalized.
Generalized Tetanus This is the most common form.
It may begin as local tetanus that becomes generalized
after a few days, or it may be diffuse from the beginning.
Trismus is frequently the first manifestation. In some cases
this is preceded by a feeling of stiffness in the jaw or neck,
slight fever, and other general symptoms of infection. The
localized muscle stiffness and spasms spread quickly to
other bulbar muscles as well as those of the neck, trunk,
and limbs. A state of unremitting rigidity develops in
all the involved muscles: the abdomen is board-like,
the legs are rigidly extended, and the lips are pursed or
retracted (risus sardonicus); the eyes are partially closed by
contraction of the orbicularis oculi, or the eyebrows are
elevated by spasm of the frontalis. Superimposed on this
persistent state of enhanced muscle activity are paroxysms
of tonic contraction or spasm of muscles (tetanic seizures
or "convulsions"), which occur spontaneously or in
response to the slightest external stimulus. They are
agonizingly painful. Consciousness is not lost during these
paroxysms. The tonic contraction of groups of muscles
results in opisthotonos or in forward flexion of the trunk,
flexion and adduction of the arms, clenching of the fists,
and extension of the legs. Spasms of the pharyngeal,
laryngeal, or respiratory muscles carry the constant
threat of apnea or suffocation. Fever and pneumonia are
common complications. Large swings in blood pressure
and heart rate as well as profuse diaphoresis are typical,
mainly in response to the intense muscular contractions
but they may also be related to the action of the toxin on
the CNS. Death is usually attributable to asphyxia from
laryngospasm, to heart failure, or to shock, the latter
resulting from the action of the toxin on the hypothalamus
and sympathetic nervous system.
Generalized spasms and rigidity of trunk and limbs
developing in a neonate a few days after birth should
always suggest the diagnosis of tetanus. This form of
tetanus occurs when there has been inadequate sterile
treatment of the umbilical cord stump in a neonate born
to an unimmunized mother.
Local Tetanus This is the most benign form. The
initial symptoms are stiffness, tightness, and pain in
the muscles in the neighborhood of a wound, followed
by twitchings and brief spasms of the affected muscles.
Local tetanus occurs most often in relation to a wound
of the hand or forearm, rarely in the abdominal or
paravertebral muscles. Gradually, some degree of
continuous involuntary spasm becomes evident. There is
sustained tautness of the affected muscles and resistance
of the part to passive movement. Superimposed on this
background of more or less continuous motor activity
are brief, intense spasms, lasting from a few seconds to
minutes and occurring spontaneously or in response to all
variety of stimulation (Struppler et al) . Early in the course
of the illness there may be periods when the affected
muscles are palpably soft and appear to be relaxed. A
useful diagnostic maneuver at this stage is to have the
patient perform some repetitive voluntary movements,
such as opening and closing the hand, in response
to which there occurs a gradual increase in the tonic
contraction and spasms of the affected muscles, followed
by spread to neighboring muscle groups (recruitment
spasm) . Even with mild localized tetanus there may be
slight trismus, a useful diagnostic sign.
Symptoms may persist in localized form for several
weeks or months. Gradually the spasms become less
frequent and more difficult to evoke, and they finally
disappear without residue. Complete recovery is to be
expected, as there are no pathologic changes in muscles,
nerves, spinal cord, or brain, even in the most severe
generalized forms of tetanus.
Cephalic Tetanus This form of tetanus follows
wounds of the face and head. The incubation period is
short, 1 or 2 days as a rule. The affected muscles (most
often facial) are weak or paralyzed. Nevertheless, during
accessions of tetanic spasm, the palsied muscles are seen
to contract. Apparently, the disturbance in the facial
motoneurons is sufficient to prevent voluntary movement
but insufficient to prevent the strong reflex impulses that
elicit facial spasm. The spasms may involve the tongue
and throat, with persistent dysarthria, dysphonia, and
dysphagia. Ophthalmoparesis is known to occur but is
difficult to verify because of severe blepharospasm. In a
strict sense, these cephalic forms of tetanus are examples
of local tetanus that frequently becomes generalized.
Many cases prove fatal.
Diagnosis
This i s made from the clinical features and a history of
preceding injury. The latter is sometimes disclosed only
after careful questioning, the injury having been trivial,
forgotten and entirely healed. The organisms may or
may not be recovered from the wound by the time the
patient receives medical attention; other laboratory tests,
apart from the EMG, are of little value. Serum CK may
be moderately elevated if the rigidity is generalized. The
EMG recorded from muscles in spasm shows continuous
discharges of normal motor units like those recorded
from a forceful voluntary muscle contraction. Most characteristic
of tetanus, as mentioned earlier, is a loss of the
physiologic silent period that occurs 50 to 100 ms after
reflex contraction. This pause, normally produced by
the recurrent inhibition of Renshaw cells, is blocked by
tetanus toxin. In generalized tetanus the loss of the silent
period can almost always be demonstrated in the masseter,
and it is found in a muscle affected by local tetanus.
Interestingly, the silent period is preserved in the stiff
man syndrome (see Chap. 55) .
Tetany caused by hypocalcemia, the spasms of
strychnine poisoning or black widow spider bite, trismus
as a result of painful conditions in and around the jaw,
the dysphagia of rabies, hysterical spasms, rigidity and
dystonic spasms caused by neuroleptic drugs, and the
spasms of the stiff man syndrome all resemble the spasms
of tetanus but should not be difficult to distinguish when all
aspects of these disorders are considered. Nonetheless, the
diagnosis is difficult to bring to mind in a nonendemic area.
The death rate from tetanus is approximately 50 percent
overall; it is highest in newborns, heroin addicts, and
patients with the cephalic form of the disease. The patient
usually recovers if there are no severe generalized muscle
spasms during the course of the illness or if the spasms
remain localized.
Treat m e nt
This is directed along several lines. At the outset, a single
dose of antitoxin (3,000 to 6,000 U of tetanus immune
human globulin) should be given along with a 10-day
course of penicillin ( 1 .2 million U of procaine penicillin
daily), metronidazole (500 mg q6h intravenously or
400 mg rectally), or tetracycline (2 g daily) . These drugs
are effective against the vegetative forms of C. tetani.
Immediate surgical treatment of the wound (excision or
debridement) is imperative, and the tissue around the
wound should be infiltrated with antitoxin.
Survival depends on expert and constant nursing
in an intensive care unit and may be necessary for
weeks. Tracheostomy is a requisite in all patients with
recurrent generalized tonic spasms and should not be
delayed until apnea or cyanosis has occurred. The patient
must be kept as quiet as possible to avoid stimulusinduced
spasms. This requires a darkened, quiet room
and the judicious use of sedation. The benzodiazepines
are the most useful drugs for both sedation and muscle
relaxation; diazepam 120 mg / d or more can be given
in frequent divided doses if ventilatory support is
available; alternatively midazolam or propofol can be
used in a continuous intravenous infusion. Short-acting
barbiturates and chlorpromazine may also be useful, as
may be morphine. Intrathecal baclofen and continuous
atropine infusions have been used with success in severe
cases, and intramuscular injections of botulinum toxin
may be used for trismus and local spasm. The aim of
therapy is to suppress muscle spasms and to keep the
patient drowsy to avoid the horrible discomfort of the
spasms. All treatments and manipulations should be kept
to a minimum and coordinated so that the patient may be
sedated beforehand.
Failure of these measures to control the tetanic
paroxysms requires that intravenous administration of
neuromuscular blocking agents such as pancuronium
or vecuronium be used to abolish all muscle activity;
appropriate sedative medication is instituted for as long
as necessary, breathing being maintained by a positivepressure
respirator. Many intensive care units favor
the use of neuromuscular paralytic drugs in all but the
mildest cases. Further details concerning treatment can
be found in the review by Farrar and colleagues.
All persons should be immunized against tetanus
and receive a booster dose of toxoid every 10 years-a
practice that is frequently neglected in the elderly. Injuries
that carry a threat of tetanus should receive toxoid if
the patient has not received a booster injection in the
preceding year, and a second dose of toxoid is needed
6 weeks later. If the injured person has not received a
booster injection since the original immunization, he
should receive an injection of both toxoid and human
antitoxin; the same applies to the injured person who has
never been immunized. An attack of tetanus does not
confer permanent immunity and persons who recover
should be actively immunized.
Adam 1215-1217

the mechanism of
action of tetanus toxin. In the ventral horn of the
spinal cord, negative feedback loop neurons (Renshaw
cells) limit the activity of the -motoneurons.
Tetanus toxin prevents the release of the inhibitory
neurotransmitter glycine from these cells, which
allows uncontrolled spasms of skeletal muscle. Strychnine
(and brucine) compete with glycine for its
receptors on the -motoneurons and thus cause a
very similar clinical picture. Acute dystonic reactions
(oculogyric crises) may also mimic tetanus
p. 300.
For the role of the Renshaw cell in tetanus and strychnine
poisoning Figure 14.1.
The clinical features of tetanus can progress slowly
over as much as 2 weeks. In the usual order of appearance
they are as follows:
Stiff muscles near the wound (or injection site)
Jaw stiffness and trismus (lock-jaw)
Abdominal rigidity
Progressive painful muscle spasms (the fixed
mocking grin caused by facial muscle tightening
is known as the risus sardonicus and extensor
spasms of the back, neck and limbs are called
opisthotonus)
Dysphagia and respiratory difficulty
Autonomic dysfunction.
Tx Supportive therapy is essential with special
attention given to the airway, respiration and autonomic
activities. IV benzodiazepines or even general
anaesthesia may be required to control spasms.
The tetanus bacillus is sensitive to both benzylpenicillin
and metronidazole. Immunoglobulin against
tetanus toxin (HTIg) 150 IU/kg is given intramuscularly
in multiple sites (a range of doses from 30 IU/kg
to 300 IU/kg has been suggested.) Tetanus immunoglobulin
for IV use is also available on a namedpatient
basis. The dose is 500010 000 IU by IV
infusion. Surgical debridement of wounds may help
to reduce the toxin load. Suspicion of tetanus infection
should provoke a discussion with a specialist in
infectious diseases. Strychnine poisoning is treated
with similar supportive and relaxant therapy.

ETIOLOGY
Tetanus is an acute, spastic paralytic illness historically called
lockjaw that is caused by the neurotoxin produced by Clostridium
tetani, a motile, gram-positive, spore-forming obligate anaerobe
whose natural habitat worldwide is soil, dust, and the
alimentary tracts of various animals. C. tetani forms spores terminally,
producing a drumstick or tennis racket appearance
microscopically. Tetanus spores can survive boiling but not autoclaving,
whereas the vegetative cells are killed by antibiotics, heat,
and standard disinfectants. Unlike many clostridia, C. tetani is
not a tissue-invasive organism and instead causes illness through
the effects of a single toxin, tetanospasmin, more commonly
referred to as tetanus toxin. Tetanospasmin is the 2nd most poisonous
substance known, surpassed in potency only by botulinum
toxin. The human lethal dose of tetanus toxin is estimated
to be 105 mg/kg.
EPIDEMIOLOGY
Tetanus occurs worldwide and is endemic in approximately 90
developing countries, although its incidence varies considerably.
The most common form, neonatal (or umbilical) tetanus, kills
approximately 500,000 infants each year, with about 80% of
deaths in just 12 tropical Asian and African countries. It occurs
in infants whose mothers are not immunized. In addition, an
estimated 15,000-30,000 unimmunized women worldwide die
each year of maternal tetanus, which results from postpartum,
postabortal, or postsurgical wound infection with C. tetani.
Approximately 50 cases of tetanus are reported each year in
the USA, mostly in persons >60 yr of age, although cases also
occur in toddlers and neonates. Approximately 20% of children
in the USA 10-16 yr of age lack a protective antibody level.
The majority of childhood cases of tetanus in the USA have
occurred in unimmunized children whose parents objected to
vaccination.
Most non-neonatal cases of tetanus are associated with a
traumatic injury, often a penetrating wound inflicted by a dirty
object such as a nail, splinter, fragment of glass, or unsterile injection.
Tetanus occurring after illicit drug injection is becoming
more common. The disease also occurs after the use of contaminated
suture material and after intramuscular injection of medicines,
most notably quinine for chloroquine-resistant falciparum
malaria. The disease may also occur in association with animal
bites, abscesses (including dental abscesses), ear and other body
piercing, chronic skin ulceration, burns, compound fractures,
frostbite, gangrene, intestinal surgery, ritual scarification, infected
insect bites, and female circumcision. Rare cases have no history
of trauma.
PATHOGENESIS
Tetanus occurs after introduced spores germinate, multiply, and
produce tetanus toxin in the low oxidation-reduction potential
(Eh) of an infected injury site. A plasmid carries the toxin gene.
Toxin is released after vegetative bacterial cell death and lysis.
Tetanus toxin (and the botulinum toxins) is a 150-kd simple
protein consisting of a heavy chain (100 kd) and a light (50 kd)
chain joined by a single disulfide bond. Tetanus toxin binds at the
neuromuscular junction and enters the motor nerve by endocytosis,
after which it undergoes retrograde axonal transport to the
cytoplasm of the "-motoneuron. In the sciatic nerve, the transport
rate was found to be 3.4 mm/hr. The toxin exits the motoneuron
in the spinal cord and next enters adjacent spinal inhibitory interneurons,
where it prevents release of the neurotransmitters glycine
and #-aminobutyric acid (GABA). Tetanus toxin thus blocks the
normal inhibition of antagonistic muscles on which voluntary
coordinated movement depends; in consequence, affected muscles
sustain maximal contraction and cannot relax. The autonomic
nervous system is also rendered unstable in tetanus.
The phenomenal potency of tetanus toxin is enzymatic in
nature. The light chain of tetanus toxin (and of several botulinum
toxins) is a zinc-containing endoprotease whose substrate is synaptobrevin,
a constituent protein of the docking complex that
enables the synaptic vesicle to fuse with the terminal neuronal
cell membrane. The heavy chain of the toxin contains its binding
and internalization domains.
Because C. tetani is not an invasive organism, its toxinproducing
vegetative cells remain where introduced into the
wound, which may display local inflammatory changes and a
mixed bacterial flora.
CLINICAL MANIFESTATIONS
Tetanus is most often generalized but may also be localized. The
incubation period typically is 2-14 days but may be as long as
months after the injury. In generalized tetanus, the presenting
symptom in about half of cases is trismus (masseter muscle
spasm, or lockjaw). Headache, restlessness, and irritability are
early symptoms, often followed by stiffness, difficulty chewing,
dysphagia, and neck muscle spasm. The so-called sardonic smile
of tetanus (risus sardonicus) results from intractable spasms of
facial and buccal muscles. When the paralysis extends to abdominal,
lumbar, hip, and thigh muscles, the patient may assume an
arched posture of extreme hyperextension of the body, or opisthotonos,
with the head and the heels bent backward and the
body bowed forward with only the back of the head and the heels
touching the supporting surface. Opisthotonos is an equilibrium
position that results from unrelenting total contraction of opposing
muscles, all of which display the typical boardlike rigidity of
tetanus. Laryngeal and respiratory muscle spasm can lead to
airway obstruction and asphyxiation. Because tetanus toxin does
not affect sensory nerves or cortical function, the patient unfortunately
remains conscious, in extreme pain, and in fearful anticipation
of the next tetanic seizure. The seizures are characterized
by sudden, severe tonic contractions of the muscles, with fist
clenching, flexion, and adduction of the arms and hyperextension
of the legs. Without treatment, the seizures range from a few
seconds to a few minutes in length with intervening respite
periods, but as the illness progresses, the spasms become sustained
and exhausting. The smallest disturbance by sight, sound,
or touch may trigger a tetanic spasm. Dysuria and urinary retention
result from bladder sphincter spasm; forced defecation may
occur. Fever, occasionally as high as 40C, is common because of
the substantial metabolic energy consumed by spastic muscles.
Notable autonomic effects include tachycardia, dysrhythmias,
labile hypertension, diaphoresis, and cutaneous vasoconstriction.
The tetanic paralysis usually becomes more severe in the 1st wk
after onset, stabilizes in the 2nd wk, and ameliorates gradually
over the ensuing 1-4 wk.
Neonatal tetanus, the infantile form of generalized tetanus,
typically manifests within 3-12 days of birth as progressive difficulty
in feeding (sucking and swallowing), associated hunger,
and crying. Paralysis or diminished movement, stiffness and
rigidity to the touch, and spasms, with or without opisthotonos,
are characteristic. The umbilical stump may hold remnants of
dirt, dung, clotted blood, or serum, or it may appear relatively
benign.
Localized tetanus results in painful spasms of the muscles
adjacent to the wound site and may precede generalized tetanus.
Cephalic tetanus is a rare form of localized tetanus involving the
bulbar musculature that occurs with wounds or foreign bodies in
the head, nostrils, or face. It also occurs in association with
chronic otitis media. Cephalic tetanus is characterized by retracted
eyelids, deviated gaze, trismus, risus sardonicus, and spastic
paralysis of the tongue and pharyngeal musculature.
DIAGNOSIS
The picture of tetanus is one of the most dramatic in medicine,
and the diagnosis may be established clinically. The typical setting
is an unimmunized patient (and/or mother) who was injured or
born within the preceding 2 wk, who presents with trismus, other
rigid muscles, and a clear sensorium.
Results of routine laboratory studies are usually normal. A
peripheral leukocytosis may result from a secondary bacterial
infection of the wound or may be stress induced from the sustained
tetanic spasms. The cerebrospinal fluid is normal, although
the intense muscle contractions may raise intracranial pressure.
Neither the electroencephalogram nor the electromyogram shows
a characteristic pattern. C. tetani is not always visible on Gram
stain of wound material and is isolated in only about 30% of
cases.
DIFFERENTIAL DIAGNOSIS
Fully developed, generalized tetanus cannot be mistaken for any
other disease. However, trismus may result from parapharyngeal,
retropharyngeal, or dental abscesses or, rarely, from acute encephalitis
involving the brainstem. Either rabies or tetanus may follow
an animal bite, and rabies may manifest as trismus with seizures.
Rabies may be distinguished from tetanus by hydro phobia,
marked dysphagia, predominantly clonic seizures, and pleocytosis
(Chapter 266). Although strychnine poisoning may result in
tonic muscle spasms and generalized seizure activity, it seldom
produces trismus, and unlike in tetanus, general relaxation
usually occurs between spasms. Hypocalcemia may produce
tetany that is characterized by laryngeal and carpopedal spasms,
but trismus is absent. Occasionally, epileptic seizures, narcotic
withdrawal, or other drug reactions may suggest tetanus.
TREATMENT
Management of tetanus requires eradication of C. tetani and the
wound environment conducive to its anaerobic multiplication,
neutralization of all accessible tetanus toxin, control of seizures
and respiration, palliation, provision of meticulous supportive
care, and, finally, prevention of recurrences.
Surgical wound excision and debridement are often needed to
remove the foreign body or devitalized tissue that created anaerobic
growth conditions. Surgery should be performed promptly
after administration of human tetanus immunoglobulin (TIG)
and antibiotics. Excision of the umbilical stump in the neonate
with tetanus is no longer recommended.
Tetanus toxin cannot be neutralized by TIG after it has begun
its axonal ascent to the spinal cord. TIG should be given as soon
as possible in order to neutralize toxin that diffuses from the
wound into the circulation before the toxin can bind at distant
muscle groups. The optimal dose of TIG has not been determined.
A single intramuscular injection of 500 U of TIG is sufficient to
neutralize systemic tetanus toxin, but total doses as high as
3,000-6,000 U are also recommended. Infiltration of TIG into
the wound is now considered unnecessary. If TIG is unavailable,
use of human intravenous immunoglobulin (IVIG) may be necessary.
IVIG contains 4-90 U/mL of TIG; the optimal dosage of
IVIG for treating tetanus is not known, and its use is not approved
for this indication. Another alternative is equine- or bovinederived
tetanus antitoxin (TAT). The usual dose of TAT is 50,000-
100,000 U, with half given intramuscularly and half intravenously,
but as little as 10,000 U may be sufficient. TAT is not available
in the USA. Approximately 15% of patients given the usual
dose of TAT experience serum sickness. When TAT is used, it
is essential to check for possible sensitivity to horse serum;
desensitization may be needed. The human-derived immunoglobulins
are much preferred because of their longer half-lives (30
days) and the virtual absence of allergic and serum sickness
adverse effects. Intrathecal TIG, given to neutralize tetanus toxin
in the spinal cord, is not effective.
Penicillin G (100,000 U/kg/day divided every 4-6 hr IV for
10-14 days) remains the antibiotic of choice because of its effective
clostridiocidal action and its diffusibility, which is an important
consideration because blood flow to injured tissue may be compromised.
Metronidazole (500 mg every 8hr IV for adults) appears
to be equally effective. Erythromycin and tetracycline (for persons
>8 yr of age) are alternatives for penicillin-allergic patients.
All patients with generalized tetanus need muscle relaxants.
Diazepam provides both relaxation and seizure control. The
initial dose of 0.1-0.2 mg/kg every 3-6 hr given intravenously is
subsequently titrated to control the tetanic spasms, after which
the effective dose is sustained for 2-6 wk before a tapered withdrawal.
Magnesium sulfate, other benzodiazepines (midazolam),
chlorpromazine, dantrolene, and baclofen are also used. Intrathecal
baclofen produces such complete muscle relaxation that
apnea often ensues; like most other agents listed, baclofen should
be used only in an intensive care unit setting. The highest survival
rates in generalized tetanus are achieved with neuromuscular
blocking agents such as vecuronium and pancuronium, which
produce a general flaccid paralysis that is then managed by
mechanical ventilation. Autonomic instability is regulated with
standard "- or $- (or both) blocking agents; morphine has also
proved useful.
SUPPORTIVE CARE
Meticulous supportive care in a quiet, dark, secluded setting is
most desirable. Because tetanic spasms may be triggered by minor
stimuli, the patient should be sedated and protected from all
unnecessary sounds, sights, and touch, and all therapeutic and
other manipulations must be carefully scheduled and coordinated.
Endotracheal intubation may not be required, but it should
be done to prevent aspiration of secretions before laryngospasm
develops. A tracheostomy kit should be immediately at hand for
unintubated patients. Endotracheal intubation and suctioning
easily provoke reflex tetanic seizures and spasms, so early tracheostomy
should be considered in severe cases not managed by
pharmacologically induced flaccid paralysis. Therapeutic botulinum
toxin has been used for this purpose, that is, to overcome
trismus.
Cardiorespiratory monitoring, frequent suctioning, and maintenance
of the patients substantial fluid, electrolyte, and caloric
needs are fundamental. Careful nursing attention to mouth, skin,
bladder, and bowel function is needed to avoid ulceration, infection,
and obstipation. Prophylactic subcutaneous heparin may be
of value but must be balanced with the risk for hemorrhage.
COMPLICATIONS
The seizures and the severe, sustained rigid paralysis of tetanus
predispose the patient to many complications. Aspiration of
secretions and pneumonia may have begun before the first
medical attention was received. Maintaining airway patency often
mandates endotracheal intubation and mechanical ventilation
with their attendant hazards, including pneumothorax and mediastinal
emphysema. The seizures may result in lacerations of the
mouth or tongue, in intramuscular hematomas or rhabdomyolysis
with myoglobinuria and renal failure, or in long bone or spinal
fractures. Venous thrombosis, pulmonary embolism, gastric ulceration
with or without hemorrhage, paralytic ileus, and decubitus
ulceration are constant hazards. Excessive use of muscle relaxants,
which are an integral part of care, may produce iatrogenic
apnea. Cardiac arrhythmias, including asystole, unstable blood
pressure, and labile temperature regulation reflect disordered
autonomic nervous system control that may be aggravated by
inattention to maintenance of intravascular volume needs.
PROGNOSIS
Recovery in tetanus occurs through regeneration of synapses
within the spinal cord and thereby the restoration of muscle
relaxation. However, because an episode of tetanus does not
result in the production of toxin-neutralizing antibodies, active
immunization with tetanus toxoid at discharge with provision for
completion of the primary series is mandatory.
The most important factor that influences outcome is the
quality of supportive care. Mortality is highest in the very young
and the very old. A favorable prognosis is associated with a long
incubation period, absence of fever, and localized disease. An
unfavorable prognosis is associated with onset of trismus <7 days
after injury and with onset of generalized tetanic spasms <3 days
after onset of trismus. Sequelae of hypoxic brain injury, especially
in infants, include cerebral palsy, diminished mental abilities, and
behavioral difficulties. Most fatalities occur within the 1st wk of
illness. Reported case fatality rates for generalized tetanus are
5-35%, and for neonatal tetanus they extend from <10% with
intensive care treatment to >75% without it. Cephalic tetanus has
an especially poor prognosis because of breathing and feeding
difficulties.
PREVENTION
Tetanus is an entirely preventable disease. A serum antibody titer
of %0.01 U/mL is considered protective. Active immunization
should begin in early infancy with combined diphtheria toxoid
tetanus toxoidacellular pertussis (DTaP) vaccine at 2, 4, and
6 mo of age, with a booster at 4-6 yr of age and at 10-yr intervals
thereafter throughout adult life (tetanus and reduced diphtheria
toxoid [Td] or tetanus, and reduced diphtheria and pertussis
toxoids [Tdap]). Immunization of women with tetanus toxoid
prevents neonatal tetanus, and the World Health Organization is
currently engaged in a global campaign for elimination of neonatal
tetanus through maternal immunization with at least 2
doses of tetanus toxoid. For unimmunized persons >7 yr of age,
the primary immunization series consists of 3 doses of Td toxoid
given intramuscularly, with the 2nd given 4-6 wk after the 1st
and the 3rd given 6-12 mo after the 2nd.
Arthus reactions (type III hypersensitivity reactions), a localized
vasculitis associated with deposition of immune complexes and
activation of complement, are reported rarely after tetanus vaccination.
Mass immunization campaigns in developing countries
have occasionally provoked a widespread hysterical reaction.
Wound Management
Tetanus prevention measures after trauma consist of inducing
active immunity to tetanus toxin and of passively providing antitoxic
antibody (Table 203-1). Tetanus prophylaxis is an essential
part of all wound management, but specific measures depend on
the nature of the injury and the immunization status of the
patient. Regrettably, prevention of tetanus must now be included
in planning for the consequences of bombings and other possible
civilian mass-casualty events.
Tetanus toxoid should always be given after a dog or other
animal bite, even though C. tetani is infrequently found in canine
mouth flora. All non-minor wounds require human TIG except
those in a fully immunized patient. In any other circumstance
(e.g., patients with an unknown or incomplete immunization
history; crush, puncture, or projectile wounds; wounds contaminated
with saliva, soil, or feces; avulsion injuries; compound
fractures; or frostbite), TIG 250 U should be given intramuscularly,
with 500 U for highly tetanus-prone wounds (i.e., unable
to be debrided, with substantial bacterial contamination, or
>24 hr since injury). If TIG is unavailable, use of human IGIV
may be considered. If neither of these products is available, then
3,000-5,000U of equine- or bovine-derived TAT may be given
intramuscularly after testing for hypersensitivity. Even at this
dose, serum sickness may occur.
The wound should undergo immediate, thorough surgical
cleansing and debridement to remove foreign bodies and any
necrotic tissue in which anaerobic conditions might develop.
Tetanus toxoid should be given to stimulate active immunity and
may be administered concurrently with TIG (or TAT) if given in
separate syringes at widely separated sites. A tetanus toxoid
booster (preferably Td or Tdap) is administered to all persons
with any wound if the tetanus immunization status is unknown
or incomplete. A booster is administered to injured persons who
have completed the primary immunization series if (1) the wound
is clean and minor but %10 yr have passed since the last booster
or (2) the wound is more serious and %5 yr have passed since the
last booster. Persons who experienced an Arthus reaction after a
dose of tetanus toxoidcontaining vaccine should not receive Td
more frequently than every 10 yr, even for tetanus prophylaxis
as part of wound management. In a situation of delayed wound
care, active immunization should be started at once. Although
fluid tetanus toxoid produces a more rapid immune response than
the absorbed or precipitated toxoids, the absorbed toxoid results
in a more durable titer.
Nelson 991-993

177
Tetanus
C. Louise Thwaites, Lam Minh Yen
Tetanus is an acute disease manifested by skeletal muscle
spasm and autonomic nervous system disturbance. It is caused
by a powerful neurotoxin produced by the bacterium
Clostridium tetani and is completely preventable by vaccination. C.
tetani is found throughout the world, and tetanus commonly occurs
where the vaccination coverage rate is low. In developed countries, the
disease is seen occasionally in individuals who are incompletely vaccinated.
In any setting, established tetanus is a severe disease with a
high mortality rate.
DEFINITION
Tetanus is diagnosed on clinical grounds (sometimes with supportive
laboratory confirmation of the presence of C. tetani; see Diagnosis,
below), and case definitions are often used to facilitate clinical and
epidemiologic assessments. The Centers for Disease Control and
Prevention (CDC) defines tetanus as the acute onset of hypertonia or
painful muscular contractions (usually of the muscles of the jaw and
neck) and generalized muscle spasms without other apparent medical
cause. Neonatal tetanus is defined by the World Health Organization
(WHO) as an illness occurring in a child who has the normal ability to
suck and cry in the first 2 days of life but who loses this ability between
days 3 and 28 of life and becomes rigid and has spasms. Given the
unique presentation of neonatal tetanus, the history generally permits
accurate classification of the illness with a high degree of probability.
Maternal tetanus is defined by the WHO as tetanus occurring during
pregnancy or within 6 weeks after the conclusion of pregnancy
(whether with birth, miscarriage, or abortion).
ETIOLOGY
C. tetani is an anaerobic, gram-positive, spore-forming rod whose
spores are highly resilient and can survive readily in the environment
throughout the world. Spores resist boiling and many disinfectants. In
addition, C. tetani spores and bacilli survive in the intestinal systems
of many animals, and fecal carriage is common. The spores or bacteria
enter the body through abrasions, wounds, or (in the case of neonates)
the umbilical stump. Once in a suitable anaerobic environment, the
organisms grow, multiply, and release tetanus toxin, an exotoxin that
enters the nervous system and causes disease. Very low concentrations
of this highly potent toxin can result in tetanus (minimum lethal
human dose, 2.5 ng/kg).
In 2030% of cases of tetanus, no puncture entry wound is found.
Superficial abrasions to the limbs are the commonest infection sites in
adults. Deeper infections (e.g., attributable to open fracture, abortion,
or drug injection) are associated with more severe disease and worse
outcomes. In neonates, infection of the umbilical stump can result
from inadequate umbilical cord care; in some cultures, for example,
the cord is cut with grass or animal dung is applied to the stump.
Circumcision or ear-piercing also can result in neonatal tetanus.
EPIDEMIOLOGY
Tetanus is a rare disease in the developed world. Two cases of neonatal
tetanus have occurred in the United States since 1989. Between 2001
and 2008, a total of 231 cases of tetanus were reported to the U.S.
national surveillance system. Most cases occur in incompletely vaccinated
or unvaccinated individuals. Vaccination status is known in
50% of cases reported in the United States between 1972 and 2009;
among these cases, only 16% of patients had had three or more doses
of tetanus toxoid.
Persons >60 years of age are at greater risk of tetanus because antibody
levels decrease over time. One-third of recent cases in the United
States were in persons >65 years old. Injection drug usersparticularly
those injecting heroin subcutaneously (skin-popping)
are increasingly recognized as a high-risk group (15% of all cases in
20012008). In 2004, an outbreak of tetanus occurred in the United
Kingdom, which had previously reported low rates among drug users.
The reasons for this outbreak remain unclear but are thought to
involve a combination of heroin contamination, skin-popping, and
incomplete vaccination. Since then, only seven sporadic cases have
been reported in the United Kingdom.
PATHOGENESIS
Genome sequencing of C. tetani has allowed identification of several
exotoxins and virulence factors. Only those bacteria producing tetanus
toxin (tetanospasmin) can cause tetanus. Although closely related to
the botulinum toxins in structure and mode of action, tetanus toxin
undergoes retrograde transport into the central nervous system and
thus produces clinical effects different from those caused by the botulinum
toxins, which remain at the neuromuscular junction.
Toxin is transported by intra-axonal transport to motor nuclei of
the cranial nerves or ventral horns of the spinal cord. Tetanus toxin is
produced as a single 150-kDa protein that is cleaved to produce heavy
(100-kDa) and light (50-kDa) chains linked by a disulfide bond and
noncovalent forces. The carboxy terminal of the heavy chain binds
to specific membrane components in presynaptic -motor nerve
terminals; evidence suggests binding to both polysialogangliosides
and membrane proteins. This binding results in toxin internalization
and uptake into the nerves. Once inside the neuron, the toxin enters a
retrograde transport pathway, whereby it is transported proximally to
the motor neuron body in what appears to be a highly specific process.
Unlike other components of the endosomal contents, which undergo
acidification following internalization, tetanus toxin is transported in
a carefully regulated pH-neutral environment that prevents an acidinduced
conformational change that would result in light-chain expulsion
into the surrounding cytosol.
The next stage in toxin trafficking is less clearly understood 985
but involves tetanus toxins escaping normal lysosomal degradation
processes and undergoing translocation across the synapse to the
GABA-ergic presynaptic inhibitory interneuron terminals. Here the
light chain, which is a zinc-dependent endopeptidase, cleaves vesicleassociated
membrane protein 2 (VAMP2, also known as synaptobrevin).
This molecule is necessary for presynaptic binding and release
of neurotransmitter; thus tetanus toxin prevents transmitter release
and effectively blocks inhibitory interneuron discharge. The result is
unregulated activity in the motor nervous system. Similar activity in
the autonomic system accounts for the characteristic features of skeletal
muscle spasm and autonomic system disturbance. The increased
circulating catecholamine levels in severe tetanus are associated with
cardiovascular complications.
Relatively little is known about the processes of recovery from
tetanus. Recovery can take several weeks. Peripheral nerve sprouting
is involved in recovery from botulism, and similar central nervous
system sprouting may occur in tetanus. Other evidence suggests toxin
degradation as a mechanism of recovery.
APPROACH TO THE PATIENT:
Tetanus
The clinical manifestations of tetanus occur only after tetanus
toxin has reached presynaptic inhibitory nerves. Once these effects
become apparent, there may be little that can be done to affect disease
progression. Treatment should not be delayed while the results
of laboratory tests are awaited. Management strategies aim to neutralize
remaining unbound toxin and support vital functions until
the effects of the toxin have worn off. Recent interest has focused on
intrathecal methods of antitoxin administration to neutralize toxin
within the central nervous system and limit disease progression (see
Treatment, below).
CLINICAL MANIFESTATIONS
Tetanus produces a wide spectrum of clinical features that are broadly
divided into generalized (including neonatal) and local. In the usually
mild form of local tetanus, only isolated areas of the body are affected
and only small areas of local muscle spasm may be apparent. If the cranial
nerves are involved in localized cephalic tetanus, the pharyngeal
or laryngeal muscles may spasm, with consequent aspiration or airway
obstruction, and the prognosis may be poor. In the typical progression
of generalized tetanus (Fig. 177-1), muscles of the face and jaw often
are affected first, presumably because of the shorter distances toxin
must travel up motor nerves to reach presynaptic terminals. Neonates
typically present with inability to suck.
In assessing prognosis, the speed at which tetanus develops is
important. The incubation period (time from wound to first symptom)
and the period of onset (time from first symptom to first generalized
spasm) are of particular significance; shorter times are associated with
worse outcome. In neonatal tetanus, the younger the infant is when
symptoms occur, the worse the prognosis.
The commonest initial symptoms are trismus (lockjaw), muscle
pain and stiffness, back pain, and difficulty swallowing. In neonates,
difficulty in feeding is the usual presentation. As the disease progresses,
muscle spasm develops. Generalized muscle spasm can be very painful.
Commonly, the laryngeal muscles are involved early or even in isolation.
This is a life-threatening event as complete airway obstruction may
ensue. Spasm of the respiratory muscles results in respiratory failure.
Without ventilatory support, respiratory failure is the commonest cause
of death in tetanus. Spasms strong enough to produce tendon avulsions
and crush fractures have been reported, but this outcome is rare.
Autonomic disturbance is maximal during the second week of
severe tetanus, and death due to cardiovascular events becomes the
major risk. Blood pressure is usually labile, with rapid fluctuations
from high to low accompanied by tachycardia. Episodes of bradycardia
and heart block can also occur. Autonomic involvement is evidenced
by gastrointestinal stasis, sweating, increased tracheal secretions, and
acute (often high-output) renal failure.
DIAGNOSIS
The diagnosis of tetanus is based on clinical findings. As stated above,
treatment should not be delayed while laboratory tests are conducted.
Culture of C. tetani from a wound provides supportive evidence.
Serum anti-tetanus immunoglobulin G may also be measured in a
sample taken before the administration of antitoxin or immunoglobulin.
Serum levels >0.1 IU/mL are deemed protective and do not
support the diagnosis of tetanus. If levels are below this threshold, a
bioassay for serum tetanus toxin may be helpful, but a negative result
does not exclude the diagnosis. Polymerase chain reaction also has
been used for detection of tetanus toxin, but its sensitivity is unknown.
The few conditions that mimic generalized tetanus include strychnine
poisoning and dystonic reactions to antidopaminergic drugs.
Abdominal muscle rigidity is characteristically continuous in tetanus
but is episodic in the latter two conditions. Cephalic tetanus can be
confused with other causes of trismus, such as oropharyngeal infection.
Hypocalcemia and meningoencephalitis are included in the differential
diagnosis of neonatal tetanus.
TREATMENT Teta nus
If possible, the entry wound should be identified, cleaned, and
debrided of necrotic material in order to remove anaerobic foci of
infection and prevent further toxin production. Metronidazole (400
mg rectally or 500 mg IV every 6 h for 7 days) is the preferred antibiotic.
An alternative is penicillin (100,000200,000 IU/kg per day),
although this drug theoretically may exacerbate spasms. Failure
to remove pockets of ongoing infection may result in recurrent or
prolonged tetanus.
Antitoxin should be given early in an attempt to deactivate any
circulating tetanus toxin and prevent its uptake into the nervous
system. Two preparations are available: human tetanus immune
globulin (TIG) and equine antitoxin. TIG is the preparation of choice,
as it is less likely to be associated with anaphylactoid reactions.
Recommended therapy is 30005000 IU of TIG as a single IM dose,
a portion of which should be injected around the wound. Equinederived
antitoxin is available widely and is used in low-income
countries at a dosage of 10,00020,000 U administered IM as a single
dose or as divided doses after testing for hypersensitivity. Some
evidence indicates that intrathecal administration of TIG inhibits
disease progression and leads to a better outcome. The results of
relevant studies have been supported by a meta-analysis of trials
involving both adults and neonates, with TIG doses of 501500 IU
administered intrathecally.
Spasms are controlled by heavy sedation with benzodiazepines.
Chlorpromazine and phenobarbital are commonly used worldwide,
and IV magnesium sulfate has been used as a muscle relaxant. A
significant problem with all these treatments is that the doses necessary
to control spasms also cause respiratory depression; thus, in
resource-limited settings without mechanical ventilators, controlling
spasms while maintaining adequate ventilation is problematic,
and respiratory failure is a common cause of death. In locations with
ventilation equipment, severe spasms are best controlled with a
combination of sedatives or magnesium and relatively short-acting,
cardiovascularly inert, nondepolarizing neuromuscular blocking
agents that allow titration against spasm intensity. Infusions of
propofol have also been used successfully to control spasms and
provide sedation.
It is important to establish a secure airway early in severe tetanus.
Ideally, patients should be nursed in calm, quiet environments
because light and noise can trigger spasms. Tracheal secretions are
increased in tetanus, and dysphagia due to pharyngeal involvement
combined with hyperactivity of laryngeal muscles makes endotracheal
intubation difficult. Patients may need ventilator support for
several weeks. Thus tracheostomy is the usual method of securing
the airway in severe tetanus.
Cardiovascular instability in severe tetanus is notoriously difficult
to treat. Rapid fluctuations in blood pressure and heart rate can
occur. Cardiovascular stability is improved by increasing sedation
with IV magnesium sulfate (plasma concentration, 24 mmol/L or
titrated against disappearance of the patella reflex), morphine, or
other sedatives. In addition, drugs acting specifically on the cardiovascular
system (e.g., esmolol, calcium antagonists, and inotropes)
may be required. Short-acting drugs that allow rapid titration are
preferred; particular care should be taken when longer-acting
antagonists are administered, as their use has been associated with
hypotensive cardiac arrest.
TABLE 177-
Complications arising from treatment are common and include
thrombophlebitis associated with diazepam injection, ventilatorassociated
pneumonia, central-line infections, and septicemia. In
some centers, prophylaxis against deep-vein thrombosis and thromboembolism
is routine.
Recovery from tetanus may take 46 weeks. Patients must be
given a full primary course of immunization, as tetanus toxin is
poorly immunogenic and the immune response following natural
infection is inadequate.
PROGNOSIS
Rapid development of tetanus is associated with more severe disease
and poorer outcome; it is important to note time of onset and length
of incubation period. More sophisticated modeling has revealed other
important predictors of prognosis (Table 177-1). Few studies have
formally addressed long-term outcomes of tetanus. However, it is
generally accepted that recovery is typically complete unless periods
of hypoventilation have been prolonged or other complications have
ensued. Studies of children and neonates have suggested a higher
incidence of neurologic sequelae. Neonates may be at increased risk of
learning disabilities, behavioral problems, cerebral palsy, and deafness.
PREVENTION
Tetanus is prevented by good wound care and immunization
(Chap. 148). In neonates, use of safe, clean delivery and cord-care
practices as well as maternal vaccination are essential. The WHO
guidelines for tetanus vaccination consist of a primary course of three
doses in infancy, boosters at 47 and 1215 years of age, and one
booster in adulthood. In the United States, the CDC suggests an additional
dose at 1416 months and boosters every 10 years. Catch-up
schedules recommend a three-dose primary course for unimmunized
adolescents followed by two further doses. For persons who have
received a complete primary course in childhood but no further boosters,
two doses at least 4 weeks apart are recommended.
Standard WHO recommendations for prevention of maternal and
neonatal tetanus call for administration of two doses of tetanus toxoid
at least 4 weeks apart to previously unimmunized pregnant women.
However, in high-risk areas, a more intensive approach has been successful,
with all women of childbearing age receiving a primary course
along with education on safe delivery and postnatal practices.
Individuals sustaining tetanus-prone wounds should be immunized
if their vaccination status is incomplete or unknown or if their last
booster was given >10 years earlier. Patients sustaining wounds not
classified as clean or minor should also undergo passive immunization
with TIG. It is recommended that tetanus toxoid be given in conjunction
with diphtheria toxoid in a preparation with or without acellular
pertussis: DTaP for children <7 years old, Td for 7- to 9-year olds, and
Tdap for children >9 years old and adults.
In the early 1980s, tetanus caused more than 1 million deaths
a year, accounting for an estimated 5% of maternal deaths and
14% of all neonatal deaths. In 1989, the World Health

Assembly adopted a resolution to eliminate neonatal tetanus by the 987

year 2000; elimination was defined as <1 case/1000 live births in every
district in every country. By 1999, elimination was still to be achieved
in 57 countries and the deadline was extended until 2005, with the
additional target of eliminating maternal tetanus (tetanus occurring
during pregnancy or within 6 weeks of its end). Ratification of the
Millennium Development Goals, in particular goal 4 (achieving a twothirds
reduction in the mortality rate among children under 5 by
2015), has further focused attention on reducing deaths from vaccinepreventable
disease, particularly in the first 4 weeks of life.
Because vaccination reduces the incidence of neonatal tetanus by an
estimated 94%, immunization of pregnant women with two doses of
tetanus toxoid at least 4 weeks apart has been the primary method of
maternal and neonatal tetanus elimination. In some areas, all women
of childbearing age have been targeted as a means of increasing vaccination
coverage. In addition, educational programs have focused
on improving hygiene during the birth process, an intervention that
in itself is estimated to reduce neonatal tetanus deaths by up to 40%.
The latest available data show that 34 countries have yet to eliminate
maternal and neonatal tetanus, although incidence has declined significantly.
Worldwide, deaths from neonatal tetanus fell by 92% between
1990 and 2008; in the latter year, with 84% of newborns protected from
the disease by maternal vaccination, there were an estimated 59,000
neonatal tetanus deaths. Despite this relative success, immunization
programs need to be ongoing as there is no tetanus herd immunity
effect and C. tetani contamination of soil and feces is widespread.
Harrison 984-987

IPD 1799-1807

c. tetani memiliki bentuk khas, ujung sel mirip tongkat pemukul gendang
atau raket squash.
Membentuk 2 macam eksotoksin yang dihasilkan : tetanolisin dan
tetanispasmin
Tetanolisin : menghancurkan sel darah merah tetai tidak bisa
menimbulkan tetanus secara langsung, tetapi menambah optimal kondisi
lokal untuk berkembangnya bakteri.
Tetanospasmin : terdiri dari protein yang bersifat toksik terhadap sel saraf,
toksin ini diabsorbsi oleh bagian ujung saraf motoric dan diteruskan ke sel
ganglion dan ssp. Sifatnya terikat pada sel saraf dan tidak dapat
dinetralkan kembali. Saraf yang terpotong atau berdegenerasi m lambat
menyerap toksin.
Saraf sensorik sama sekali tidak menyerap
Masa inkubasi 3hari- 4 minggu, rata-rata 8 hari .
Makin pendek masa inkubasi maka prognosis penyakit makin buruk
Biasanya pada yang masa inkubasi <1 minggu, maka angka kematiannya
tinggi.
Tetanus dapat muncul sebagain tetanus lokal terutama terhadap orang
yang sudah diimunisasi. Gejala berupa kaku persisten pada daerah otot
dekat luka yang terkontaminasi basil tetanus.
Kadang pada trauma kepala timbul tetanus lokal tipe sefalik
Bisa terjadi fenomena motoric sesuai dengan serabut saraf yang terkena.
Lebih sering berupa tetanus umum, ditandai dengan kekauan pada otot
maseter yang menyebabkan sulit membuka mulut/ trismus
Timbul opistotonus disebabkan kaku kuduk, kaku leher dan kaku
punggung
Selain dinding perut menjadi keras seperti papan, timbul juga risus
sardonikus karena kaku otot wajah dan kaku ekstremitas.
Penyebab kematian merupakan kombinasi dari berbagai keadaan
sepertu : kelelahan otot nafas, infeksi sekunder di paru yang
menyebabkan gagal napas
Gangguan keseimbangan cairan dan elektrolit
Diagnosis ditegakan dengan ditemukan port dentre, trismus, risus
sardonikus, kaku kuduk, opistotonus, perut papan, kejang tanpa gangguan
kesadaran.

tetanus ringan dapat sembuh sendiri

tetanus sednag dapat sembuh dengan pengobatan baku
tetanus berat memerlukan perlakuan khusus yang intensif
progresivitas penyakit dinilai dengan melihat :
derajat kekakuan, frekuensi kejang, suhu badan, laju pernapaasan yang
dinilai tiap 12 jam
untuk mengatasi kaku otot diberikan obat yang melemaskan otot dan
sedasi digunakan fenobarbital, klorpromazin atau diazepam
pada tetanus berat kadang dilakukan paralisis otot total /kurarisasi
dengan mengambil alih pernapasan memakai respirator
pasien dengan kaku laring biasnaya ditrakeostomi unuk mengatasi
gangguan pernapasan
berikan ruangan yang optimal : tenang, jauh dari rangsangan penglihatan,
pendengaran dan perabaan
netralisasi toksin yang masih ebredar dengan serum antitetanus/ATS atau
Imunoglobun tetanus human.
ATS diberikan 20.000 IU / hari selama lima hari berturt
Pertimbangkan timbulnya reaksi alergi .
Pemberian immunoglobulin tunggal 3000-6000 U
Pemberian tidak pelru diulang karena waktu paruh antibody 3-4 minggu
Menghilangkan kuman penyebab dengan melakukan perawatan luka yang
dicurigai sebagai sumbern infeksi dengan mencuci luka dengan larutan
antiseptic, eksisi luka, pemberian antibiotic ( penisilin 3x1/2 juta U/hari,
metronidazole 3x1gr/hari)
Pencegahan : imunisasi aktif dengan menyuntikan toksoid tetanus untuk
merangsang antibody
Imunisasi pasif dengan pemberian serum yang mengandung antitoksin
heterolog / ATS atau antitoksin homologi / ig antitetanus.
Prognosis : faktor yang mempengaruhi mortalitas pasien adalah :
Masa inkubasi, periode awal pengobatan, imunisasi lokasi focus infeksi ,
penyakit lain penyerta
Cole spooner (klasifikasi prognostic)
Kelompok prognostik Periode awal Masa inkubasi
I <36 jam 6 hari
II >36 jam >6 hari
III Tidak diketahui Tidak diketahui
Prognostic terburuk I > II > III

Clostridium tetani is an obligate, anaerobic,

motile, gram-positive bacillus. It is
nonencapsulated and forms spores that are
resistant to heat, desiccation, and
disinfectants. Since the colorless spores are
located at one end of the bacillus, they
cause the organism to resemble a turkey
leg.
 produce the following 2 toxins:
Tetanolysin This substance is a hemolysin
with no recognized pathologic activity
1Tetanospasmin This toxin is responsible
for the clinical manifestations of tetanus; by
weight, it is one of the most potent toxins
known, with an estimated minimum lethal
dose of 2.5 ng/kg body weight
Tetanospasmin is synthesized as a 150-kd
protein consisting of a 100-kd heavy chain
and a 50-kd light chain joined by a disulfide
bond. reference_ids_tool_tip reference_ids [7] The heavy chain
mediates binding of tetanospasmin to the
presynaptic motor neuron and also creates a
pore for the entry of the light chain into the
cytosol. The light chain is a zinc-dependent
protease that cleaves synaptobrevin.
reference_ids_tool_tip reference_ids [8]

para, childcount:0
After the light chain enters the motor
neuron, it travels by retrograde axonal
transport from the contaminated site to the
spinal cord in 2-14 days. When the toxin
reaches the spinal cord, it enters central
inhibitory neurons. The light chain cleaves
the protein synaptobrevin, which is integral
to the binding of neurotransmitter
containing vesicles to the cell membrane.
para, childcount:1
As a result, gamma-aminobutyric acid
(GABA)-containing and glycine-containing
vesicles are not released, and there is a loss
of inhibitory action on motor and autonomic
neurons. reference_ids_tool_tip reference_ids [8] With this loss of
central inhibition, there is autonomic
hyperactivity as well as uncontrolled muscle
contractions (spasms) in response to normal
stimuli such as noises or lights.
para, childcount:0
Once the toxin becomes fixed to neurons, it
cannot be neutralized with antitoxin.
Recovery of nerve function from tetanus
toxins requires sprouting of new nerve
terminals and formation of new synapses.
para, childcount:0
Localized tetanus develops when only the
nerves supplying the affected muscle are
involved. Generalized tetanus develops
when the toxin released at the wound
spreads through the lymphatics and blood to
multiple nerve terminals. The blood-brain
barrier prevents direct entry of toxin to the
CNS.
Heroin users, particularly those who inject
themselves subcutaneously, appear to be at
high risk for tetanus. Quinine is used to
 dilute heroin and may support the growth of
C tetani.
A rating scale has been developed for
assessing the severity of tetanus and
determining the prognosis. reference_ids_tool_tip reference_ids [15]
On this scale, 1 point is given for each of the
following:
itemizedlist
listitem
para, childcount:0Incubation period shorter
than 7 days
listitem
para, childcount:0Period of onset shorter
than 48 hours
listitem
para, childcount:0Tetanus acquired from
burns, surgical wounds, compound fractures,
septic abortion, umbilical stump, or
intramuscular injection
listitem
para, childcount:0Narcotic addiction
listitem
para, childcount:0Generalized tetanus
listitem
para, childcount:0Temperature higher than
104F (40C)
listitem
para, childcount:0Tachycardia exceeding
120 beats/min (150 beats/min in neonates)
The total score indicates disease severity
 and prognosis as follows:
itemizedlist
listitem
para, childcount:00 or 1 Mild tetanus;
mortality below 10%
listitem
para, childcount:02 or 3 Moderate tetanus;
mortality of 10-20%
listitem
para, childcount:04 Severe tetanus;
mortality of 20-40%
listitem
para, childcount:05 or 6 Very severe
tetanus; mortality above 50%
para, childcount:0
Cephalic tetanus is always severe or very
severe. Neonatal tetanus is always very
severe.
A high risk of mortality is associated with
the following:
itemizedlist
listitem
para, childcount:0Short incubation period
listitem
para, childcount:0Early onset of convulsions
listitem
para, childcount:0Delay in treatment
listitem
para, childcount:0Contaminated lesions of
the head and the face
listitem
para, childcount:0Neonatal tetanus

5
4
3
2
1

10
8
4
2
0

10
8
4
2
1