Tetanus

Author: Louise Thwaites, MD

Section Editor: Daniel J Sexton, MD
Deputy Editor: Jennifer Mitty, MD, MPH

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Aug 2024. | This topic last updated: May 10, 2024.

INTRODUCTION

Tetanus is a nervous system disorder characterized by muscle spasms that is caused

by the toxin-producing anaerobe Clostridium tetani, which is found in the soil. The
clinical features of tetanus and its relationship to traumatic injuries were well known
among the ancient Greeks and Egyptians and to many clinicians before the
introduction of vaccination with tetanus toxoid in the 1940s. The term "lockjaw" (or
trismus) lives in modern parlance as a reminder of one of the cardinal features of
tetanus: intense, painful spasms of the masseter muscles, and an inability to open the
mouth.

Tetanus can present in one of four clinical patterns:

● Generalized
● Local
● Cephalic
● Neonatal

Although tetanus is now rare in resource-rich settings, the disease remains a threat to
all unvaccinated people, particularly in resource-limited countries. Since C. tetani
spores cannot be eliminated from the environment, immunization and proper
treatment of wounds and traumatic injuries are crucial for tetanus prevention. The
epidemiology, pathogenesis, clinical features, diagnosis, and management of tetanus
will be reviewed here. The principles of prevention of tetanus and management of
tetanus-prone wounds are discussed separately. (See "Tetanus-diphtheria toxoid
vaccination in adults" and "Diphtheria, tetanus, and pertussis immunization in
children 6 weeks through 6 years of age" and "Diphtheria, tetanus, and pertussis
immunization in children 7 through 18 years of age" and "Infectious complications of
puncture wounds" and "Animal bites (dogs, cats, and other mammals): Evaluation and
management".)

EPIDEMIOLOGY

Resource-rich countries
● United States — Because of almost universal vaccination of children with tetanus
toxoid in resource-rich countries, the incidence of tetanus in these regions has
dropped dramatically and steadily since 1940. During the period between 2009
and 2017, the United States Centers for Disease Control and Prevention (CDC)
reported that there were 264 cases of tetanus in the United States [1]. Sixty cases
(23 percent) were in individuals ≥65 years of age and only 36 (13 percent) were
individuals younger than 20 years. Twelve percent of patients with tetanus had
diabetes mellitus and another 8 percent of patients were injection drug users.
The case-fatality rate was 7.2 percent overall and all deaths occurred in
individuals ≥55 years of age. In 2019, 26 cases of tetanus and 2 deaths were
reported in the United States through the national tetanus surveillance system
[2].Only two cases of neonatal tetanus were reported between 2009 and 2017 [1].

Most patients with tetanus lack a history of receipt of a full series of tetanus
toxoid immunization and receive inadequate prophylaxis following a wound [3-5].
Approximately three-fourths of patients who acquired tetanus in the United
States between 2001 and 2008 recalled an acute injury prior to the onset of their
symptoms, but approximately two-thirds of these individuals did not seek
medical care [3]. Among 51 patients who sought care for an acute wound and
had a sufficiently thorough surveillance report to allow evaluation, 49 (96 percent)
did not receive adequate tetanus toxoid prophylaxis or tetanus toxoid prophylaxis
plus tetanus immune globulin [3]. However, occasional patients with pre-existing
antitetanus antibodies (as measured by guinea pig or mouse protection assays)
have developed tetanus [6]. (See "Tetanus-diphtheria toxoid vaccination in adults"
and "Diphtheria, tetanus, and pertussis immunization in children 6 weeks
 through 6 years of age", section on 'Schedules' and "Diphtheria, tetanus, and
pertussis immunization in children 7 through 18 years of age", section on
'Indications'.)

Despite the low rate of clinical disease in the United States, many adults are
inadequately vaccinated against tetanus. Anti-tetanus toxoid antibody
concentrations were measured for participants of the 2015 to 2016 National
Health and Nutrition Examination Survey (NHANES), and protective levels of anti-
tetanus antibody (>0.1 international units/mL) were present in 93.8 percent of the
United States population aged ≥6 years but declined in those >69 years old. Older
age was significantly associated with lower prevalence of sero-immunity [7]. Not
surprisingly, protective antibody levels are more likely in adults with a history of
military service, higher levels of education, and higher incomes [8].
● Other resource-rich countries – The annual incidence of tetanus in other
resource-rich countries is also low and declining due to vaccination programs. In
England and Wales, 11 cases were identified in 2021, with six cases occurring in
those born before the introduction of routine childhood vaccination [9]. Of note,
despite tetanus being a notifiable disease, only one of these cases had been
reported. A study of hospital records between 2001 and 2014 estimated that
approximately 88 percent of cases in England were under-reported [10].

Italy reported the highest number of cases among countries in Europe, but the
annual incidence decreased from 0.5 to 0.02 per 100,000 between the 1970s and
2018 [11]. The overall case fatality rate of the 49 European cases with known
outcome was 26.5 percent.

Resource-limited countries — In contrast with resource-rich nations where tetanus

is rare, tetanus remains endemic in resource-limited settings, and the incidence often
increases following natural disasters such as earthquakes and tsunamis [12].
According to data from the global burden of disease survey, an estimated 48,000 to
80,000 deaths occurred from tetanus worldwide in 2016 [13]. True disease incidence
is unknown, since tetanus is not a notifiable disease in most countries. National
hospital admissions data in Uganda revealed a total of 4750 cases of tetanus in 2014
(125 cases per million population) [14]. The majority of these cases were in individuals
>5 years of age.

Case-fatality rates in many resource-limited settings remain high and have not
changed significantly in the past several decades. The pooled fatality rate of 3043
adult African patients reported in 27 studies was 43 percent (95% CI 37 to 50 percent)
[15]. The high fatality rate likely reflects the fact that mechanical ventilation was often
not accessible in many of the included medical facilities.

Neonatal tetanus, which the World Health Organization targeted for elimination by
1995, accounted for approximately 34,000 deaths in 2015 [16]. While this represents a
decrease in mortality of 96 percent compared with 1988 [16], as of December 2023, 11
countries had still not eliminated maternal and neonatal tetanus [16]. (See 'Neonatal
tetanus' below.)

PATHOGENESIS

Tetanus occurs when spores of C. tetani, an obligate anaerobe normally present in the
gut of mammals and widely found in soil, gains access to damaged human tissue.
After inoculation, C. tetani transforms into a vegetative rod-shaped bacterium and
produces the metalloprotease tetanus toxin (also known as tetanospasmin).

After reaching the spinal cord and brainstem via retrograde axonal transport within
the motor neuron, tetanus toxin is secreted and enters adjacent inhibitory
interneurons, where it blocks neurotransmission by its cleaving action on the
membrane proteins involved in neuroexocytosis [17-20]. The net effect is inactivation
of inhibitory neurotransmission that normally modulates anterior horn cells and
muscle contraction. This loss of inhibition (ie, disinhibition) of anterior horn cells and
autonomic neurons results in increased muscle tone, painful spasms, and widespread
autonomic instability.

Muscular rigidity in tetanus occurs though a complex mechanism that involves an

increase in the resting firing rate of disinhibited motor neurons and lack of inhibition
of reflex motor responses to afferent sensory stimuli [21]. Lack of neural control of
adrenal release of catecholamines induced by tetanus toxin produces a
hypersympathetic state that manifests as sweating, tachycardia, and hypertension.
(See 'Generalized tetanus' below.)

Tetanus toxin-induced effects on anterior horns cells, the brainstem, and autonomic
neurons are long lasting because recovery requires the growth of new axonal nerve
terminals. (See 'Duration of illness' below.)

The mechanisms of binding to and inhibition of neural cells are related to specific
portions of the tetanus toxin molecule. Tetanus toxin is produced initially as an
inactive polypeptide chain by actively growing organisms. This synthesis is controlled
by genes located in an intracellular plasmid.

After the toxin is released, it is activated by bacterial or tissue proteases into its active
form, which contains a heavy chain necessary for binding and entry into neurons and
a light chain responsible for its toxic properties [20-23]. Heavy chains are further
cleaved by pepsins into specific fragments, which individually mediate binding to
specific types of neural cells. Presynaptic inhibition of neurotransmitter release is
mediated via light chains.

Tetanolysin is another toxin produced by C. tetani during its early growth phase. It has
hemolytic properties and causes membrane damage in other cells, but its role in
clinical tetanus is uncertain.

Predisposing factors — Because C. tetani will not grow in healthy tissues, a

convergence of factors must be present in order for tetanus toxin to be elaborated in
the human host. This combination of factors usually includes absence of antibodies
(ie, from inadequate vaccination) plus two or more of the following:
● A penetrating injury resulting in the inoculation of C. tetani spores
● Coinfection with other bacteria
● Devitalized tissue
● A foreign body
● Localized ischemia

The above factors explain why tetanus-prone injuries include splinters and other
puncture wounds, gunshot wounds, compound fractures, burns, and unsterile
intramuscular or subcutaneous injections (that often occur in injection drug users).
These predisposing factors can also explain why tetanus can develop in unusual
clinical settings such as in:
● Neonates (due to infection of the umbilical stump)
● Obstetric patients (after septic abortions)
● Postsurgical patients (with necrotic infections involving bowel flora)
● Adolescents and adults undergoing male circumcision in sub-Saharan Africa [24]
● Patients with dental infections
● Diabetic patients with infected extremity ulcers
● Patients who inject illicit and/or contaminated drugs [25]

Tetanus in patients without an identifiable cause — An identifiable antecedent

cause for tetanus is obvious in most patients presenting with tetanus, but no cause
can be identified in up to a quarter of patients with classic signs and symptoms of
tetanus. Presumably, minor unnoticed abrasions or skin injuries are responsible for
most or all of these "cryptogenic" cases. Tetanus has occurred rarely in patients who
have received a timely and correct series of tetanus immunizations [26].

CLINICAL FEATURES

Incubation period — The incubation period of tetanus is approximately 8 days but

ranges from 3 to 21 days [27]. The incubation period is typically shorter in neonatal
tetanus than in non-neonatal tetanus [23]. (See 'Neonatal tetanus' below.)

Generalized tetanus — The most common and severe clinical form of tetanus is
generalized tetanus. The presenting symptom in more than 80 percent of such
patients is trismus (lockjaw), although patients with generalized tetanus sometimes
present initially with cephalic or localized tetanus. Patients with generalized tetanus
typically have symptoms of autonomic overactivity that may manifest in the early
phases as sweating and tachycardia. In later phases of illness, profuse sweating,
cardiac arrhythmias, labile hypertension or hypotension, and fever are often present.

Patients with generalized tetanus characteristically have tonic contraction of their

skeletal muscles and intermittent intense muscular spasms. Since patients with
tetanus have no impairment of consciousness or awareness, both the tonic
contractions and spasms are intensely painful. Tetanic spasms may be triggered by
loud noises or other sensory stimuli such as physical contact or light. Tonic and
periodic spastic muscular contractions are responsible for most of the classic clinical
findings of tetanus such as:
● Stiff neck
● Opisthotonus
● Risus sardonicus (sardonic smile)
● A board-like rigid abdomen
● Periods of apnea and/or upper airway obstruction due to vise-like contraction of
the thoracic muscles and/or glottal or pharyngeal muscle contraction,
respectively
● Dysphagia

During generalized tetanic spasms, patients characteristically clench their fists, arch
their back, and flex and abduct their arms while extending their legs, often becoming
apneic during these dramatic postures.

Local tetanus — Rarely, tetanus presents with tonic and spastic muscle contractions
in one extremity or body region. Local tetanus often but not invariably evolves into
generalized tetanus. Diagnosis in local tetanus can be difficult. For example, rarely
patients with early tetanus may develop board-like abdominal rigidity that mimics an
acute surgical abdomen.

Cephalic tetanus — Patients with injuries to the head or neck may present with
cephalic tetanus, involving initially only cranial nerves. Like other forms of local
tetanus, patients with cephalic tetanus often subsequently develop generalized
tetanus. Prior to the appearance of the typical features of generalized tetanus,
patients with cephalic tetanus may manifest confusing clinical findings including
dysphagia, trismus, and focal cranial neuropathies that can lead to a misdiagnosis of
stroke [28]. The facial nerve is most commonly in cephalic tetanus [29], but
involvement of cranial nerves VI, III, IV, and XII may also occur either alone or in
combination with others.

Neonatal tetanus — Neonatal tetanus occurs as a result of the failure to use aseptic
techniques in managing the umbilical stump in offspring of mothers who are poorly
immunized. The application of unconventional substances to the umbilical stump (eg,
ghee or clarified butter, juices, and cow dung) have been implicated as common
cultural practices that contribute to neonatal tetanus [30]. Neonatal tetanus can also
result from unclean hands and instruments or contamination by dirt, straw, or other
nonsterile materials in the delivery field.

Neonatal tetanus typically occurs in infants 5 to 7 days following birth (range 3 to 24

days) [23]. The onset of illness is typically more rapid in neonatal tetanus than in older
individuals and may progress over hours rather than days, probably because axonal
length is proportionately shorter in infants [31].

Neonatal tetanus presents with refusal to feed and difficulty opening the mouth due
to trismus in an infant previously able to feed and cry normally [23]. Sucking then
stops and facial muscles spasm, which may result in risus sardonicus (sardonic smile).
The hands are often clenched, the feet become dorsiflexed, and muscle tone
increases. As the disease progresses, neonates become rigid and opisthotonus
(spasm of spinal extensors) develops.

Severity of illness — The severity and frequency of the clinical features of tetanus
may vary from case to case, depending upon the amount of tetanus toxin that
reaches the central nervous system. Symptoms and signs may progress for up to two
weeks after the disease onset. The severity is related to the incubation period of the
illness and the interval from the onset of symptoms to the appearance of spasms [32];
the longer the interval, the milder the clinical features of tetanus. More severe illness
is seen in those with deep penetrating wounds [32].

Duration of illness — Tetanus toxin-induced effects are long lasting because

recovery is believed to require the growth of new axonal nerve terminals. The usual
duration of clinical tetanus is four to six weeks.

DIAGNOSIS

The diagnosis of tetanus is usually obvious and can generally be made based upon
typical clinical findings outlined above. Tetanus should especially be suspected when
there is a history of an antecedent tetanus-prone injury and a history of inadequate
immunization for tetanus. However, tetanus can sometimes be confused with other
processes, as discussed in the following section.

DIFFERENTIAL DIAGNOSIS

Tetanus can sometimes be confused with the following mimics.

Drug-induced dystonias such as those due to phenothiazines — Drug-induced

dystonias often produce pronounced deviation of the eyes, writhing movements of
the head and neck, and an absence of tonic muscular contraction between spasms.
By contrast, tetanus does not produce eye deviations, and the muscles are
characteristic tonically contracted between spasms. Finally, administration of an
anticholinergic agent such as benztropine mesylate will usually immediately reverse
the spasms seen in drug-induced dystonias. Such therapy has no effect on patients
with tetanus.

Trismus due to dental infection — Dental infections may produce trismus that may
rarely be confused with cephalic forms of tetanus. However, the presence of an
obvious dental abscess and the lack of progression or superimposed spasms usually
make the distinction between the two diseases apparent after initial evaluation
and/or a period of observation. (See "Deep neck space infections in adults" and
"Complications, diagnosis, and treatment of odontogenic infections".)

Strychnine poisoning due to ingestion of rat poison — Accidental or intentional

strychnine poisoning may produce a clinical syndrome similar to tetanus. Supportive
care for both conditions is critical; thus, the initial treatment of both conditions is
identical. Assays of blood, urine, and tissue for strychnine can be performed in special
reference laboratories. Such tests should be obtained when there is any suspicion of
accidental or intentional poisoning or when a typical history of an antecedent injury
or infection for tetanus is lacking or the patient has been adequately immunized for
tetanus. (See "Strychnine poisoning".)

Malignant neuroleptic syndrome — Patients with malignant neuroleptic syndrome

can present with striking symptoms of autonomic instability and muscular rigidity.
However, the presence of fever, altered mental status, and recent receipt of an agent
with a propensity to cause this complication usually makes the distinction from
tetanus relatively easy. (See "Neuroleptic malignant syndrome".)

Stiff-person syndrome — Stiff-person syndrome (SPS) is a rare neurologic disorder

characterized by severe muscle rigidity. Spasms of the trunk and limbs may be
precipitated by voluntary movements or auditory, tactile, or emotional stimulation, all
of which can also occur in tetanus. The absence of trismus or facial spasms and rapid
response to diazepam distinguish SPS from true tetanic spasms [33]. In addition, SPS
is associated with autoantibodies against glutamic acid decarboxylase. (See "Stiff-
person syndrome".)

TREATMENT

Overview — Treatment of tetanus is best performed in the intensive care unit in

consultation with an anesthesiologist or critical care specialist trained in the
management of the complications of this disease, including early and aggressive
airway management. The goals of treatment include:
● Halting the toxin production
● Neutralization of the unbound toxin
● Airway management
● Control of muscle spasms
● Management of dysautonomia
● General supportive management

Unfortunately, little evidence exists to support any particular therapeutic intervention

in tetanus. There are only six randomized trials reported in the literature over the past
20 years [34].

Halting toxin production

Wound management — All patients with tetanus should undergo wound

debridement to eradicate spores and necrotic tissue, which could lead to conditions
ideal for germination.

Antimicrobial therapy — Although antibiotics probably play a relatively minor role

in the management of tetanus, they are universally recommended. However, it is
important to emphasize that appropriate antimicrobial therapy may fail to eradicate
C. tetani unless adequate wound debridement is performed. This was illustrated by
one study in which 45 isolates of C. tetani were obtained at the time of wound
debridement from 84 Vietnamese patients with severe tetanus [35]. All 45 isolates
were susceptible by disc diffusion and E-test to penicillin and metronidazole, and all
were resistant to trimethoprim-sulfamethoxazole. However, C. tetani was isolated
from the wounds of two patients who underwent debridement after more than two
weeks of high doses of penicillin.

Metronidazole (500 mg intravenously [IV] every six to eight hours) is the preferred
treatment for tetanus, but penicillin G (2 to 4 million units IV every four to six hours) is
a safe and effective alternative [12]. We suggest a treatment duration of 7 to 10 days.

The first study to compare penicillin and metronidazole found a greater reduction in
mortality in the metronidazole group (7 versus 24 percent) [36]. However, in three
subsequent studies, there was no difference in mortality in patients treated with
penicillin and those treated with metronidazole [37-39]. In one of the former studies,
patients receiving metronidazole required fewer muscle relaxants and sedatives [37].
It is possible that the observed difference in outcomes may not be due to differences
in the antimicrobial activity of the two agents but rather may be explained by the
GABA antagonist effect of penicillins and third-generation cephalosporins, which may
lead to central nervous system (CNS) excitability.

If a mixed infection is suspected, a first-, second-, or third-generation cephalosporin

such as cefazolin (1 to 2 g IV every 8 hours), cefuroxime (2 g IV every 6 hours), or
ceftriaxone (1 to 2 g IV every 24 hours) can be used.

An alternative agent is doxycycline (100 mg every 12 hours); other agents with activity
against C. tetani are macrolides, clindamycin, vancomycin, and chloramphenicol
[12,40]. The efficacy of these agents has not been evaluated but, based upon in vitro
susceptibility data, it is likely that they are effective.

Neutralization of unbound toxin — Since tetanus toxin is irreversibly bound to

tissues, only unbound toxin is available for neutralization. The use of passive
immunization (ie, antitoxin) to neutralize unbound toxin is associated with improved
survival and it is considered to be standard of care [41].
● Intramuscular antitoxin – Human tetanus immune globulin (HTIG) is the
antitoxin of choice to neutralize unbound toxin. The United States Centers for
Disease Control and Prevention (CDC) recommends a single dose of 500 units
intramuscularly (IM) [42,43]. The previously recommended dose range was 3000
to 6000 units.

HTIG should be administered as soon as the diagnosis of tetanus is considered,

with part of the dose infiltrated around the wound [42,43]. HTIG should be
administered at different sites than tetanus toxoid. (See 'Active immunization'
below.)

If HTIG is not available, human immunoglobulin or equine antitoxin are

reasonable alternatives. In a blinded, randomized trial of 215 adults with tetanus
in Vietnam that compared intramuscular equine antitoxin (21,000 international
units) with HTIG (3000 international units), there were no differences in
mechanical ventilation rate, hospital/intensive care unit (ICU) length of stay,
mortality, or adverse events [44].

When equine antitoxin is used, an intradermal test dose of 0.1 mL in a 1:10

dilution should be administered prior to giving the full dose in order to evaluate
for hypersensitivity reactions [12]. In contrast, antecedent skin testing is not
needed if a human preparation is to be used.
● Role of intrathecal antitoxin – In general, there is no role for intrathecal
antitoxin in addition to IM antitoxin since intrathecal therapy is of unclear benefit.
As an example, in the trial of 215 patients from Vietnam described above, the rate
of mechanical ventilation among those who received intrathecal antitoxin in
addition to IM antitoxin was similar to those who received IM antitoxin alone (43
versus 50 percent, respectively; relative risk 0.87, 95% CI 0.66 to 1.13) [44]. In
another trial of 120 patients from Brazil evaluating the use of intrathecal
immunoglobulin in addition to intramuscular therapy, patients receiving
intrathecal therapy had a shorter duration of spasms, shorter hospital stay, and a
decreased requirement for respiratory assistance; however, mortality was not
significantly affected [45].
Active immunization — Since tetanus is one of the few bacterial diseases that does
not confer immunity following recovery from acute illness, all patients with tetanus
should receive active immunization with a full series (eg, three doses in adults and
children >7 years old) of tetanus and diphtheria toxoid-containing vaccines,
commencing immediately upon diagnosis. Such vaccines should be administered at a
different site than tetanus immune globulin. Specific recommendations on vaccine
formulations and vaccination schedules are discussed in detail separately:
● (See "Tetanus-diphtheria toxoid vaccination in adults", section on 'Routine adult
immunization'.)
● (See "Immunizations during pregnancy", section on 'Tetanus, diphtheria, and
pertussis vaccination'.)
● (See "Diphtheria, tetanus, and pertussis immunization in children 6 weeks
through 6 years of age", section on 'Schedules'.)
● (See "Diphtheria, tetanus, and pertussis immunization in children 7 through 18
years of age", section on 'Schedule'.)

Subsequent tetanus doses, in the form of tetanus and diphtheria toxoid or tetanus,
diphtheria, acellular pertussis, are recommended at 10-year intervals throughout
adulthood in many countries including the United States [46]. Tetanus toxoid alone
should be given only to those patients with documented allergy or untoward
reactions to diphtheria toxoid. (See "Tetanus-diphtheria toxoid vaccination in adults".)

Control of muscle spasms — Generalized muscle spasms are life threatening since
they can cause respiratory failure, lead to aspiration, and induce generalized
exhaustion in the patient. Several drugs may be used to control these spasms.
Attention to placement of the patient and control of light or noise in the room in an
effort to avoid provoking muscle spasms was an important component of care for
patients with tetanus in the past before the availability of drugs to prevent spasms.
These measures are still vital in regions where the availability of neuromuscular
blocking agents may be limited [12].

Benzodiazepines and other sedatives

● Benzodiazepines – Benzodiazepines have been used traditionally and are
generally effective in controlling the rigidity and spasms associated with tetanus
 [12]. They also provide a sedative effect. Diazepam has been used most
frequently, but other benzodiazepines are as effective as diazepam.

For tetanus, the usual starting dose of diazepam for an adult is 10 to 30 mg IV

and is repeated as needed every 1 to 4 hours. Patients with tetanus often show
tolerance to the sedating effects of benzodiazepines and may remain awake and
alert after receiving doses that would sedate or cause anesthesia in other
patients [26].

Since benzodiazepines may be required for a prolonged period of time (often

weeks), they should be tapered gradually to avoid withdrawal reactions and
ventilator weaning.

The properties, usual dosing regimens for sedation, and adverse effects of
benzodiazepines are discussed in greater detail separately. (See "Sedative-
analgesia in ventilated adults: Medication properties, dose regimens, and adverse
effects", section on 'Benzodiazepines' and "Sedative-analgesia in ventilated
adults: Medication properties, dose regimens, and adverse effects", section on
'Dosing and administration' and "Sedative-analgesia in ventilated adults:
Medication properties, dose regimens, and adverse effects", section on
'Propylene glycol toxicity'.)
● Other sedatives – Infusion of the anesthetic propofol may also control spasms
and rigidity. Its prolonged use has been associated with lactic acidosis,
hypertriglyceridemia, and pancreatic dysfunction.

Neuromuscular blocking agents — Neuromuscular blocking agents are used when

sedation alone is inadequate. Options depend on availability. Vecuronium or other
cardiovascularly inert neuromuscular blockers are preferred. Pancuronium, a long-
acting agent, has been traditionally used, but it may worsen autonomic instability
because it is an inhibitor of catecholamine reuptake. Neuromuscular blocking agents
are generally given as continuous infusions. Monitoring of patients on these drugs is
extremely important to avoid or recognize complications.

Baclofen, which stimulates postsynaptic GABA beta receptors, has been used in a few
small studies. The preferred route is intrathecal, and it may be given either in a bolus
of 1000 mcg or by continuous intrathecal infusion [47]. Intrathecal baclofen given as
an initial bolus in a dose ranging from 40 to 200 mcg followed by a continuous
infusion of 20 mcg/hour was found to control spasms and rigidity in 21 out of 22
patients with grade III tetanus in a retrospective outcome study from a single medical
center in Portugal. One of 22 patients developed meningitis secondary to infection of
the intrathecal catheter despite the fact that most patients required such therapy for
at least three weeks (range 8 to 30 days) [48]. In some cases, baclofen has been used
without the need for mechanical ventilation [49]. Phenothiazines and barbiturates
were used in the past to control spasms but have largely been displaced by
neuromuscular blocking agents.

Management of autonomic dysfunction — Several drugs have been used to

produce adrenergic blockade and suppress autonomic hyperactivity; only treatment
with magnesium sulfate has been studied in a randomized clinical trial in tetanus [50]
because of its use in clinical series for the management of autonomic dysfunction and
as adjunctive treatment for controlling spasms [50-53].

Magnesium sulfate — Magnesium sulfate acts as a presynaptic neuromuscular

blocker, blocks catecholamine release from nerves, and reduces receptor
responsiveness to catecholamines [54]. It has the advantage of worldwide experience
in the treatment of eclampsia.

In a randomized, double blind trial in 256 hospitalized patients with severe tetanus in
Vietnam, magnesium sulfate infusion compared with placebo controlled autonomic
dysfunction [50]. The patients were randomly assigned to magnesium sulfate (loading
dose 40 mg/kg over 30 minutes, followed by continuous infusion of either 2 g per
hour for patients over 45 kg or 1.5 g per hour for patients ≤45 kg) versus placebo (5
percent glucose in water) infusion. Magnesium infusion significantly reduced the
requirement for other drugs to control muscle spasms, and patients treated with
magnesium were 4.7 times (95% CI 1.4 to 15.9) less likely to require verapamil to treat
cardiovascular instability than those in the placebo group. Magnesium sulfate
infusion did not reduce the need for mechanical ventilation.

Magnesium may also have the benefit of reducing muscle spasm. In two small
unblinded trials, magnesium sulfate infusion (with infusion rate titrated against
patella reflex) reduced spasm compared with diazepam [55,56].
Beta blockade — Labetalol (0.25 to 1 mg/min) has frequently been administered
because of its dual alpha- and beta-blocking properties. Beta blockade alone with
propranolol, for example, should be avoided because of reports of sudden death [57].
Morphine sulfate (0.5 to 1 mg/kg per hour by continuous intravenous infusion) is
commonly used to control autonomic dysfunction as well as to induce sedation.

Other drugs — Other drugs for the treatment of various autonomic events, which
have been reported to be useful, are dexmedetomidine, atropine, clonidine, and
epidural bupivacaine.

Airway management and other supportive measures — Since tetanus toxin cannot
be displaced from the nervous system once bound to neurons, supportive care is the
main treatment for tetanus. In patients with severe tetanus, prolonged immobility in
the intensive care unit is common, much of which is on mechanical ventilation and
may last for weeks. Such patients are predisposed to nosocomial infections, decubitus
ulcers, tracheal stenosis, gastrointestinal hemorrhage, and thromboembolic disease.

Endotracheal intubation is justified initially, but early tracheostomy is frequently

indicated because of the likelihood of prolonged mechanical ventilation. The latter
allows better tracheal suctioning and pulmonary toilet.

Energy demands in tetanus may be extremely high, so early nutritional support is

mandatory. Enteral feeding is preferred. Prophylactic treatment with sucralfate or
acid blockers may be used to prevent gastroesophageal hemorrhage from stress
ulceration.

Prophylaxis of thromboembolism with heparin, low molecular weight heparin, or

other anticoagulants should be administered early.

Physical therapy should be started as soon as spasms have ceased, since tetanus
patients often are left with disability from prolonged muscle wasting and contractures
[58].

Considerations in resource-limited settings — Critical care services are often

unavailable or rudimentary in many resource-limited countries [12]. When ICUs are
not available, acute respiratory failure is a leading cause of death from tetanus. In the
absence of an ICU, ideally a separate ward or room should be designated for patients
with tetanus, and sensory stimuli should be kept to a minimum since loud noises,
physical contact, and light can trigger tetanic spasms [12]. Other options include eye
shades and ear plugs to reduce stimuli. Nondepolarizing paralytic agents, such as
vecuronium and pancuronium, are not safe to use in the absence of ventilatory
support. However, benzodiazepines and baclofen can be used in such situations if
doses are carefully titrated to avoid respiratory depression. Magnesium sulfate may
be used to manage autonomic dysfunction and as an adjunctive for muscle spasm.
(See 'Control of muscle spasms' above and 'Magnesium sulfate' above.)

PROPHYLAXIS

Tetanus prophylaxis following a puncture wound is discussed in detail separately. The

following table summarizes the approach to tetanus prophylaxis ( table 1). (See
"Infectious complications of puncture wounds", section on 'Tetanus immunization'.)

Immunization of women who are pregnant or of childbearing age reduces neonatal

tetanus mortality by approximately 94 percent [23]. Improving hygiene during home
births in resource-limited settings is also likely to play an important role in preventing
neonatal tetanus.

PROGNOSIS

Case-fatality rates for non-neonatal tetanus in resource-limited countries range from

5 to 50 percent [23,31,58], whereas the majority of patients with tetanus recover
when modern supportive care is available [59]. Long-term functional outcome in adult
survivors can be impaired, particularly in older adults [58,60,61]. In Japan, 290 out of
465 survivors of tetanus were discharged home and the remainder to other facilities
[61]. In France, only 61.5 percent of 70 patients surviving an intensive care unit stay
for tetanus were reported to have no functional disability [60].

Neonatal tetanus, once nearly always fatal, now has mortality rates of 3 to 88 percent
[23]. Patients with shorter incubation periods (eg, ≤7 days) have increased disease
severity and mortality [23,62].

Among neonatal infections, survivors may recover fully or have varying degrees of
neurologic damage ranging from minor intellectual deficits to cerebral palsy [63].
SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and

regions around the world are provided separately. (See "Society guideline links:
Tetanus infection".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond
the Basics." The Basics patient education pieces are written in plain language, at the
5th to 6th grade reading level, and they answer the four or five key questions a patient
might have about a given condition. These articles are best for patients who want a
general overview and who prefer short, easy-to-read materials. Beyond the Basics
patient education pieces are longer, more sophisticated, and more detailed. These
articles are written at the 10th to 12th grade reading level and are best for patients
who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage
you to print or e-mail these topics to your patients. (You can also locate patient
education articles on a variety of subjects by searching on "patient info" and the
keyword(s) of interest.)
● Basics topic (see "Patient education: Tetanus (The Basics)")

SUMMARY AND RECOMMENDATIONS

● Epidemiology – Although rare, tetanus remains a threat to all unvaccinated
people, particularly in resource-limited countries. Since Clostridium tetani spores
cannot be eliminated from the environment, immunization and proper treatment
of wounds and traumatic injuries are crucial for tetanus prevention. (See
'Introduction' above.)
● Clinical features/diagnosis – Tetanus is a clinical diagnosis and should be
considered in patients with an inadequate vaccination history and consistent
 clinical findings. The most common and severe clinical form of tetanus is
generalized tetanus. The presenting symptom in more than 80 percent of such
patients is trismus (lockjaw), although patients with generalized tetanus
sometimes present initially with cephalic (involving the cranial nerves) or localized
tetanus. (See 'Clinical features' above and 'Diagnosis' above.)
● Management

• Supportive care – Supportive care is the mainstay of management to avoid

complications such as respiratory failure, nosocomial infections, and
thromboembolism. (See 'Airway management and other supportive measures'
above.)

• Halting and neutralizing toxin production – Since tetanus is mediated by a

toxin, a crucial aspect of therapy is to eliminate ongoing toxin production. This
includes debriding the wound and administering antimicrobial therapy (eg,
metronidazole 500 mg intravenously every six to eight hours for 7 to 10 days).
In addition, patients should receive passive immunization with antitoxin (eg,
human tetanus immune globulin) to neutralize unbound toxin. (See 'Halting
toxin production' above and 'Neutralization of unbound toxin' above.)

• Control of muscle spasms – Muscle spasms are controlled with sedation

(usually benzodiazepines) or neuromuscular blockade. (See 'Control of muscle
spasms' above.)

• Autonomic dysfunction – Autonomic hyperactivity can be treated with

labetalol or morphine sulfate. Beta blockade without concomitant alpha
blockade should be avoided.

The use of magnesium sulfate for both autonomic dysfunction and additional
control of muscle spasms has generated considerable interest. This drug is
readily available and is used worldwide for the treatment of eclampsia. (See
'Management of autonomic dysfunction' above.)

• Active immunization – All patients with tetanus should receive active

immunization with a full vaccine series (eg, three doses in adults and children
>7 years old) of tetanus and diphtheria toxoid-containing vaccines; tetanus is
one of the few bacterial diseases that does not confer immunity following
 recovery from acute illness. Immunization should commence immediately
upon diagnosis, and vaccines should be administered at a different site than
tetanus immune globulin. (See 'Active immunization' above.)
● Prevention – Tetanus prophylaxis following a puncture wound should be
administered to those who are unvaccinated against tetanus, as well as those
who were vaccinated against tetanus previously, but who are not up to date with
their vaccines ( table 1). (See "Infectious complications of puncture wounds",
section on 'Tetanus immunization'.)

Immunization of women who are pregnant or of childbearing age dramatically

reduces neonatal tetanus mortality. Improving hygiene during home births in
resource-limited settings is also likely to play an important role in preventing
neonatal tetanus. (See 'Prophylaxis' above.)

ACKNOWLEDGMENT

UpToDate gratefully acknowledges John G Bartlett, MD, who contributed as Section

Editor on earlier versions of this topic and was a founding Editor-in-Chief for
UpToDate in Infectious Diseases.
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