Clostridium tetani (Tetanus) 188
188 Clostridium tetani (Tetanus)
Itzhak Brook
Tetanus is caused by a neurotoxin produced by Clostridium tetani. It
is common in warmer climates. The worldwide incidence of tetanus
is approximately 1 million cases annually. Although a major cause of
morbidity and mortality in developing countries, tetanus is rare in the
United States, with approximately 35 to 70 cases reported annually
to the Centers for Disease Control and Prevention (CDC).1 Reported
cases are estimated to represent 60% of actual cases. Tetanus remains
a likely diagnosis in certain clinical situations even in developed coun-
tries, and individual patients suffer severe morbidity. The decline in
tetanus in developed countries is the result of an effective immunization
program.
Most cases of tetanus occur in unvaccinated people and in adults;
people older than 60 years of age account for 60% of the cases and for
75% of deaths from tetanus in the US. In the US, the current average
annual incidence of tetanus is 0.1 cases/million and 0.023 cases/million
among people ≥65 years of age.1 The case-fatality rate is 13.2% overall
but 31.3% in people ≥65 years of age. Approximately 15% of cases occur
in diabetic patients or intravenous drug users. Approximately 75% of
cases of tetanus in the US follow acute injuries, with less than one half
of these injuries occurring outdoors. Chronic wounds and abscesses,
wounds associated with a foreign body (e.g., splinters, thorns), surgical
wounds, major trauma, parenteral drug abuse, and animal-related inju-
ries are responsible for 25% of tetanus-associated injuries; approximately
) E 1 @ 0., .1 1AA1@ A C 1 1 0 D @A F .CA
@ @A 1 CA F @ CA A E C @ AA
20% of wounds are from unknown circumstances, and in 5% of cases of
tetanus, no wound source can be identified. Rare causes of tetanus are
burns and otitis media.2
MICROBIOLOGY AND PATHOGENESIS
C. tetani is a slender, gram-positive, nonencapsulated, motile, obligatively
anaerobic bacillus that exists in vegetative and sporulated forms. The
genome of the organism has been sequenced.3 The sporulated form has
a characteristic drumstick microscopic appearance because of the termi-
nal position of spores. Spores are highly resistant to disinfection by
chemicals or heat, but vegetative forms are susceptible to the bactericidal
effect of heat (autoclaving at 121°C and 103 kPa [15 psi] for 15 minutes),
to chemical disinfectants (iodine, glutaraldehyde, hydrogen peroxide),
and to certain antibiotics.4
Spores are ubiquitous in soil and the gut of mammals; they are
dormant and nonpathogenic in soil or contaminated tissue until condi-
tions are favorable for transformation to the vegetative, pathogenic form.
Such conditions are those of locally decreased oxygen reduction potential
as created in devitalized tissue by a foreign body, trauma (especially crush
injury), or suppurative infection.
C. tetani is noninvasive and does not cause an inflammatory response
or tissue destruction. Disease is initiated by exotoxins. Two toxins are
995
, A1 @ ( 1 F 2F A D @ .1@
( F@ A D @, @ A @ A @D
 PART III Etiologic Agents of Infectious Diseases
SECTION A Bacteria
produced, tetanolysin (of uncertain importance) and tetanospasmin (a
potent neurotoxin responsible for clinical tetanus). Tetanospasmin, often
referred to as “tetanus toxin,” is encoded on a plasmid present in all
toxigenic strains,5 and it is released with growth of C. tetani at the site of
infection. Tetanospasmin affects the neuromuscular end plates and the
motor nuclei of the central nervous system, thereby causing skeletal
muscle spasm and convulsions. Mechanisms of absorption and transport
of tetanospasmin are not understood completely, but 2 mechanisms are
speculated.6 If a large amount of tetanospasmin is produced, spread to
neurons through the bloodstream and lymphatic system occurs, causing
spasm at sites distant from the site of infection that first affect muscles
with the shortest neural pathway. Lockjaw and risus sardonicus, often
seen in generalized tetanus, reflect this pathophysiologic process and are
associated with rapidly progressive, severe disease. From the site of pro-
duction, small amounts of neurotoxin also can ascend the neural axis
(and sometimes the spinal axis cranially) to cause localized tetanus. The
timing of onset of muscle involvement is proportional to the neural
distance from the site of injury.
Tetanospasmin primarily gains access to the nervous system through
the neuromuscular junction, where it migrates in retrograde fashion
transsynaptically, protected from neutralizing antitoxin, to affect inhibi-
tory synapses, where it prevents release of acetylcholine.5 Uninhibited
lower motor neurons increase tone of agonist and antagonist muscles,
thereby causing characteristic localized spasms and rigidity.
Tetanospasmin also can prevent transmission at neuromuscular junc-
tions and thus cause paralysis. The effect of the toxin on the brain is
controversial; direct inoculation can cause seizures, but spasms of tetanus
probably result from the spinal rather than the supraspinal action of teta-
nospasmin. Affected patients are fully conscious. Some clinical manifes-
tations of tetanus suggest involvement of the sympathetic nervous
system. The effect of tetanospasmin is permanent; recovery depends on
ultrasprouting of neurons.
CLINICAL MANIFESTATIONS
Tetanus is divided into clinical patterns that reflect host factors and the
site of inoculation: generalized, localized, cephalic, and neonatal. In most
cases, the site of injury, which often is minor, can be determined. Inability
to identify a portal of entry does not exclude the diagnosis, especially in
unimmunized people. The appearance of a wound is not helpful in
diagnosis, but circumstances of occurrence are (e.g., severity of crush
injury and soil contamination). In the US, most cases of tetanus occur
after puncture wounds, farming or gardening activities,2 or the use of
illicit drugs.
The interval between the time of injury and the appearance of symp-
toms has important prognostic significance; the shorter the interval (<7
days), the worse the prognosis. The frequency and severity of clinical
manifestations depend on the amount of toxin that reaches the nervous
system. The portal of entry also is an important prognostic factor. Certain
injuries (e.g., compound fracture, puncture wound in a drug user) or
infections (e.g., that following abortion, infection of a neonate’s umbili-
cal stump, burn wound) have poor prognoses. Involvement of the
autonomic nervous system portends a poor prognosis. Such data have
been used to develop scoring systems to predict severity and
prognosis.5
Generalized Tetanus
Generalized tetanus, which is a neurologic disease manifesting as
trismus, dysphagia, and severe muscular spasms, is the most common
manifestation of tetanus, usually occurring as a complication of localized
tetanus that is recognized only in retrospect. The onset can be insidious
over a period of 1 to 7 days. Trismus (lockjaw), the most common
presenting symptom, commonly is mistaken as a manifestation of para-
pharyngeal infection or temporomandibular joint problems. A history
of stiffness of the back or rigidity of the neck or abdomen frequently
is recognized in retrospect. A subtle “sarcastic smile” (risus sardonicus)
may be noticed, and rigidity of the abdominal muscles is detectable on
examination.
As the disease progresses, additional muscle groups become involved,
the most striking involvement being of the paraspinal musculature. The
most dramatic feature of generalized tetanus is the very painful,
996
) E 1 @ 0., .1 1AA1@ A C 1 1 0 D @A F .CA
@ @A 1 CA F @ CA A E C @ AA
FIGURE 188.1 The patient is displaying opisthotonic posturing caused by Clos-
tridium tetani exotoxin. (Courtesy of US Centers for Disease Control and
Prevention.)
generalized tetanic, opisthotonic spasm manifest as arching of the back
(sometimes with just head and feet touching the bed) to resemble
decorticate posturing (Fig. 188.1). The force can produce fractures of the
vertebrae or other bones and hemorrhage into muscles. The periodicity
of tetanic spells can cause confusion with seizures; however, patients with
tetanus, unlike patients with seizures, do not lose consciousness. Spasms
often are triggered by sensory stimuli. Respiratory compromise during
tetanic spells can be life-threatening; upper airway obstruction is
common, and with additional involvement of abdominal and diaphrag-
matic muscle, apnea can occur.
Symptoms of autonomic overactivity generally are manifest in early
phases as irritability, restlessness, sweating, and tachycardia. In later
phases, profuse sweating, cardiac arrhythmias, labile hypertension or
hypotension, and fever commonly are present.7 Episodes of bradycardia
and hypotension can lead to cardiac arrest. Cardiac arrest also has been
attributed to myocardial damage caused by the high catecholamine level,8
as well as by toxic damage to the brainstem.9 Fever can result from
sympathetic overactivity or from superinfections, such as pneumonia.10
Spasms and cardiovascular complications occur most commonly during
the first week and resolve slowly during the ensuing 2 to 4 weeks.
Even with available treatment, generalized tetanus usually worsens in
the first 2 weeks after diagnosis, with recovery occurring over the subse-
quent 3 to 5 weeks. If antitoxin is not given, disease persists for weeks to
months until cessation of production and binding of tetanospasmin and
the formation of new neuromuscular junctions.
Localized Tetanus
Localized tetanus is an unusual presentation. Muscles near the entry
wound become painful and weak within 2 to 3 days after the injury and
then become rigid; deep tendon reflexes are hyperactive. Rigidity usually
persists for weeks to months and resolves spontaneously without pro-
gressing, although disease can progress to generalized tetanus.11 Localized
tetanus has a mortality rate <1%. In partially immune patients, neutral-
ization of local toxin and heightened production of antitoxin can prevent
generalized tetanus.
Cephalic Tetanus
Cephalic tetanus is a rare presentation, the result of decreased neuromus-
cular transmission of the lower cranial nerves affected because of wounds
on the head and neck. Clinical manifestations usually occur 1 to 2 days
after injury and can include facial palsy, dysphagia, paresis of extraocular
muscles (ophthalmoplegic tetanus),12 and supranuclear oculomotor
palsies.1,13 The mechanism of the last clinical manifestation is not clear.
Usually, cephalic tetanus has a poor prognosis, although some patients
have good outcome. Cephalic tetanus has been reported in patients after
complete immunization. Cephalic tetanus can precede generalized
tetanus.
, A1 @ ( 1 F 2F A D @ .1@
( F@ A D @, @ A @ A @D

FIGURE 188.2 This infant with neonatal tetanus is displaying body rigidity pro-
duced by Clostridium tetani exotoxin. (Courtesy of US Centers for Disease Control
and Prevention.)
Neonatal Tetanus
Neonatal tetanus is a generalized form of the disease that occurs only in
infants born to inadequately immunized mothers. Tetanus usually follows
infection of the umbilical stump, which can result from poor obstetric
procedures, delivery outside a healthcare environment, inadequate
postnatal care, or cultural practices such as application of cow dung or
soil to the umbilical stump. Immunization of adolescent girls and women
of childbearing age, appropriate training of midwives, and topical appli-
cation of antibiotics can reduce the risk of neonatal tetanus. Neonatal
tetanus is rare in developed countries but remains a significant problem
in developing countries.1,14
Weakness and inability to suck are the most common manifestations,
often appearing between 5 and 7 days of age (range, 3–24 days). Later,
generalized tetanic spasms, rigidity, and opisthotonus occur (Fig. 188.2).
The mortality rate is >90%, and death can be secondary to a hypersym-
pathetic state. The major causes of death are apnea in the first week and
septicemia in the second week, generally as a result of infection that
originated at the umbilical stump. Other complications are pneumonia,
pulmonary or central nervous system hemorrhage, and laryngeal spasm.
Poor prognosis is associated with risus sardonicus, fever, age <10 days,
and delayed presentation for medical care.15
Improvement is heralded by defervescence (usually within 3–7 days),
decrease in the number of episodes of spasm, and slow resolution of
rigidity. Complete resolution can take up to 6 weeks. Developmental
disability often occurs in survivors.
DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS
The diagnosis of tetanus is made from clinical findings in a setting
of risk and by excluding other causes of tetanic spasms. Recovery of
C. tetani from wounds is not helpful because the presence of this
organism does not necessarily indicate toxin production. Laboratory
tests are useful only to exclude other diseases; management cannot be
delayed until test results are available. Although generalized tetanus and
cephalic tetanus are recognized easily, the diagnosis can be unsuspected
if no portal of entry is identified. Given the clinical suspicion, a history
should be elicited regarding chronic otitis media, otitis externa, recent
intramuscular injection, a minor surgical procedure, intravenous drug
abuse, and rectal or vaginal instrumentation. Neonatal tetanus becomes
apparent shortly after initial manifestations. Localized tetanus can be
unrecognized until generalized manifestations occur. Trismus must be dif-
ferentiated from manifestations of parapharyngeal and retropharyngeal
infections.
The differential diagnosis of generalized tetanus includes stiff man
syndrome,16 pseudotetanus,17 meningitis, encephalitis, hypocalcemic
tetany, seizures, rabies, dystonic reactions to neuroleptic drugs or other
central dopamine antagonists (for which treatment with an anticholin-
ergic agent is rapidly effective), hysterical conversion reaction, and
strychnine poisoning. Although strychnine poisoning is the most com-
monly confused intoxication, patients with such poisoning lack trismus
and abdominal rigidity between spasms. Biochemical analysis of blood
and urine for strychnine is performed in patients with suspected
) E 1 @ 0., .1 1AA1@ A C 1 1 0 D @A F .CA
@ @A 1 CA F @ CA A E C @ AA
Clostridium tetani (Tetanus) 188
generalized tetanus. Conversely, tetanus always should be considered
when strychnine poisoning is suspected.
TREATMENT AND OUTCOME
The goals of management of tetanus are eradication of C. tetani, neutral-
ization of toxin, and provision of specific supportive care.18
Providing aggressive, yet restrained, supportive care with a minimum
of stimulation is challenging. Transfer to an optimal setting should be
accomplished early in the disease, before the severity of spasms precludes
moving the patient. Survival depends on minimizing morbid or fatal
spasms over a prolonged period. The patient is protected from stimuli by
isolation in a noise-free, darkened room, with a nurse in the room at all
times, monitors silenced, and a sentry nurse positioned outside the door
to limit entry and to reinforce minimal examination and manipulation
of the patient.
The child with tetanus should be sedated, and human tetanus immune
globulin (TIG) should be administered immediately. TIG neutralizes
circulating tetanospasmin. Recommended dosage and administration of
TIG are shown in Table 188.1.19,20 Local infiltration of part of the dose
around the wound is recommended. However, the efficacy of this tech-
nique has not been proven. In countries where TIG is not available,
equine tetanus antitoxin (TAT) is an alternative. It is administered after
adequate testing for sensitivity and desensitization if needed. Immune
globulin intravenous (IGIV) can be given if TIG is not available.
Local wound care is essential. Foreign bodies, if present, are removed;
the wound is irrigated vigorously and debrided to remove devitalized
tissue. Extensive debridement of puncture wounds is not needed. Exci-
sion of necrotic tissue may be required, but excision of the umbilical
stump is no longer recommended in cases of neonatal tetanus.
C. tetani is susceptible to penicillins, cephalosporins, metronidazole,
macrolides, tetracyclines, and imipenem.21 Although the utility of anti-
microbial therapy in tetanus is controversial, specific therapy should be
given (see Table 188.1). Oral or intravenous metronidazole or parenteral
penicillin G is appropriate. Oral tetracycline and intravenous vancomycin
are effective against C. tetani, but the cephalosporins are not reliably
active. When a polymicrobial infection is present, broad antimicrobial
coverage may be necessary.
A single, nonblinded clinical study performed in Indonesia compared
oral metronidazole with intramuscular penicillin for treatment of
tetanus.22 Patients treated with metronidazole had less progression of
disease (i.e., severity and frequency of spasms), shorter hospital stays, and
better overall survival rates. The validity of these findings may have been
compromised by an inadequate dose of penicillin given intramuscularly,
TABLE 188.1 Treatment of Tetanus
Agent Dosage and Administration
Tetanus immune Single dose, 3,000–6,000 U IMa
globulin, human (TIG)
Tetanus antitoxin (TAT)b Single dose, 50,000–100,000 U after
appropriate testing is performed for sensitivity
and desensitization if necessary; part of dose
(20,000 U) is given IV, and the remainder IM
Immune globulin Single dose of 200–400 mg/kg IV can be
intravenous (IGIV) considered if TIG is not available; not
approved for this indication
Metronidazole 30 mg/kg/day (maximum, 4 g/day) divided into
q6h doses PO or IV for 10–14 days
Penicillin G 100,000 units/kg/day (maximum, 12 million U/
day) divided into q6h doses IV for 10–14
days
Tetracycline 25–50 mg/kg/day; an alternative; not approved
for children <8 years old
a
Some experts recommend a single dose of 500 units IM, which appears to be as effective
and causes less discomfort.14,15
b
TAT is not available in the United States; it should be used elsewhere only if TIG is not
available.
IM, intramuscularly; IV, intravenously; PO, orally.
997
, A1 @ ( 1 F 2F A D @ .1@
( F@ A D @, @ A @ A @D
 PART III Etiologic Agents of Infectious Diseases
SECTION A Bacteria

the administration of which can increase the severity and frequency of

tetanic spasms. Although theoretically penicillin could act synergistically TABLE 188.3 Prevention of Tetanus
with tetanospasmin to worsen neuromuscular effects,23 extensive experi- PRIMARY IMMUNIZATIONa
ence has been accrued for penicillin treatment of tetanus.24
Age Vaccine
Sedation and muscle relaxation in patients with mild cases should be
accomplished, generally with diazepam, 0.1 to 0.2 mg/kg given intrave- 2 mo DTaP
nously every 4 to 6 hours. Ventilatory assistance is imperative at higher 4 mo DTaP
doses. Other benzodiazepines (lorazepam or midazolam) are equally
6 mo DTaP
effective. Additional sedation with a phenothiazine drug is appropriate;
use of phenothiazine alone is less effective than sedation with diazepam. 12–18 mo DTaP
If spasms are not controlled effectively, therapeutic paralysis is necessary. 4–6 yr DTaP
Neuromuscular blockade can be achieved with curariform drugs. The
agents used most often are pancuronium and vecuronium. ≥11–12 yr Tdap once
Suppression of excessive catecholamine release (which induces the Every 10 yr (booster) Td
autonomic dysfunction) can control the dysautonomia. Labetalol SECONDARY IMMUNIZATIONb
(0.25–1.0 mg/min) frequently has been administered because of its dual
α- and β-blocking potential. β-Blockade alone (i.e., with propranolol) History or Dose of Clean Minor All Other
should be avoided because of the danger of sudden death.25 Morphine Tetanus Toxoid Wound Woundsc
sulfate (0.5–1.0 mg/kg/hr by continuous intravenous infusion) is used Administration
TIG Tdd TIG Tdd
commonly to induce sedation and to control autonomic dysfunction by
<3 doses or unknown No Yes Yes Yes
reducing sympathetic tone in the heart and the vascular system, thus
controlling cardiac instability without causing cardiac compromise.26 ≥3 dosese No Nof No Nog
Other agents available for the treatment of various autonomic events are a
If an infant has contraindications to pertussis vaccine, diphtheria and tetanus toxoids (DT)
atropine, clonidine, and epidural bupivacaine.27 are given on the same schedule; if primary immunization is begun at 7 years, Td/Tdap is
Of the foregoing drugs only magnesium sulfate was evaluated in a used (see Chapter 162).
randomized clinical trial,28 as well as in clinical series for controlling b
See text for important details.
spasms.29–32 The results of these studies brought about the use of magne- c
Such as, but not limited to, the following: wounds contaminated with dirt, feces, soil, or
sium titrated to clinical end points as a first-line agent in the management saliva; puncture wounds; avulsions; and wounds resulting from missiles, crushing, burns,
of tetanus. Magnesium is a vasodilator, and it reduces catecholamine and frostbite.
release from the adrenal medulla33 and adrenergic nerve endings.34 d
For children <7 years old, DTaP (DT if pertussis vaccine is contraindicated) is preferred to
In a randomized, double-blind study of 256 patients, magnesium tetanus toxoid alone; for persons >7 years old, Td is preferred to tetanus toxoid alone. For
sulfate infusion (loading dose 40 mg/kg over 30 minutes, followed by children and adolescents, Tdap should be used when Td is indicated if the patient has not
continuous infusion of 2 g/hr for patients >45 kg or 1.5 g/hr for patients already received Tdap.
e
≤45 kg) was compared with placebo.28 Magnesium sulfate significantly If the patient has received only 3 doses of fluid toxoid, a fourth dose of toxoid, preferably an
adsorbed toxoid, should be given.
reduced the need for other drugs to control muscle spasms, and patients f
Yes, if >10 years since last dose.
were 4.7 times (95% confidence interval, 1.4–15.9) less likely to require g
Yes, if >5 years since last dose (more frequent boosters are not needed and can
verapamil to treat cardiovascular instability than were subjects in the
accentuate side effects).
placebo group. DTaP, diphtheria and tetanus toxoids and acellular pertussis; Td, tetanus and diphtheria
Hypotension, if present, is treated initially with saline solution; if toxoids; Tdap, tetanus and diphtheria toxoids and reduced acellular pertussis; TIG, tetanus
hypotension remains unresolved, a pulmonary catheter is placed for immune globulin.
monitoring, and fluid, dopamine, or norepinephrine is administered as
indicated.
Nutritional support should be initiated as soon as possible to sustain
the patient’s high caloric and protein needs. Enteral feeding is preferred;
a percutaneous endoscopic gastrostomy tube is used commonly to limit
PREVENTION
gastroesophageal reflux compared with a nasogastric tube. Prevention of No reliable natural immunity to tetanus exists. Prevention consists of
thromboembolism can be attained with heparin, low-molecular-weight providing neutralizing antibody to tetanospasmin in case C. tetani con-
heparin, or other anticoagulants, and it should be begun early. Because taminates and multiplies in a wound.
patients often become disabled because of the drug-induced paralysis
and immobilization, physical therapy should be initiated as soon as
spasms have abated.
Primary Prevention
Complications of tetanus are shown in Table 188.2. Primary prevention is pre-exposure immunization, consisting of primary
immunization followed by booster doses of tetanus toxoid–containing
vaccines (TT) throughout life.35 Schedules are shown in Table 188.3.36
TABLE 188.2 Complications of Tetanus The goal of immunization is to provide a continuous serum concentra-
tion of 0.01 IU/mL of neutralizing antitoxin.37,38 Protection between
Complications Comments levels of 0.01 and 1.0 IU/mL is not absolute; some authorities consider
Cardiomyopathy Direct toxic effect an antibody level of 0.15 IU/mL or greater as protective.39
Several longterm follow-up studies indicated that protective antitoxin
Phrenic nerve palsy Direct toxic effect
levels persist in 91% to 96% of people 10 years after receipt of the initial
Laryngeal nerve palsy Direct toxic effect 3-dose series of TT as infants.40–42 In 1 study, 70% of the subjects >6 years
Respiratory compromise Secondary to spasms of age and living in the US had antibody levels ≥0.15 IU/mL.43 The
presence of protective antibody dropped with age from >90% in children
Rhabdomyolysis Secondary to spasms
6 to 9 years of age to 80% in children 10 to 16 years of age, to <28% in
Myositis ossificans circumscripta Secondary to spasms adults ≥70 years of age. Rates of seronegativity reflect the time since
Vertebral compression fracture Secondary to spasms immunization or the lack of immunization.
Immunodeficient people may not acquire adequate response to TT
Hypoxic cerebral injury Secondary to respiratory and require passive immunization. Stem cell or bone marrow transplant
compromise
recipients must be revaccinated with at least 2 doses.44 In 1 study, although
Acute renal failure Secondary to rhabdomyolysis only 38% of human immunodeficiency virus–infected children and
Psychological effects Most prominent after recovery
adolescents had protective tetanus antibody levels, most developed
and maintained protective levels after booster administration.45 Severe

998
) E 1 @ 0., .1 1AA1@ A C 1 1 0 D @A F .CA , A1 @ ( 1 F 2F A D @ .1@
@ @A 1 CA F @ CA A E C @ AA ( F@ A D @, @ A @ A @D
anaphylactic reactions, brachial neuritis, and Guillain-Barré syndrome
following TT administration have been reported rarely.
Secondary Prevention
Secondary prevention consists of administration of vaccine and antitoxin
(TIG) after a tetanus-prone injury (see Table 188.3), with the need
determined by the type of injury and the patient’s immunization history.
Although wounds with major tissue injury are most tetanus prone, any
type of wound, if contaminated, can lead to tetanus.14 Immunization is
given immediately if the patient’s tetanus immunization history is not
available or is uncertain or if 60 months or more have elapsed since the
last TT booster dose. When indicated by immunization history, TIG is
given intramuscularly in a dose of 250 units (regardless of age or weight).
Immune globulin intravenous or equine tetanus antitoxin is recom-
mended if TIG is unavailable. Decisions on the need for TIG for infants
<6 months of age who have not received a full 3-dose primary vaccine
series should be based on the mother’s TT immunization status at the
time of delivery. Additional circumstances warrant the use of TIG in
immunized people, including anticipated impairment of response to
vaccine, and in certain wounds, such as major burns, frostbite, crush
injury, or injury by avulsion, puncture, or missile.
Hyperimmunization (multiple booster doses of toxoid over a short
time) can cause severe local reactions at the injection site, such as swelling
of the entire arm. Patients with such reactions have high antitoxin levels.46
Preformed antitoxin forms complexes with administered toxoid and
induces an Arthus type II hypersensitivity response. The use of tetanus
toxoid in situations where it is not indicated is inappropriate.
) E 1 @ 0., .1 1AA1@ A C 1 1 0 D @A F .CA
@ @A 1 CA F @ CA A E C @ AA
Tertiary Prevention
Tertiary prevention consists of antitoxin and immunization given after
clinical tetanus is manifest. Tetanus does not provide protective immu-
nity, probably because the minute amount of toxin produced is insuffi-
cient to elicit an immune response.47 All patients should complete a series
of immunizations with tetanus toxoid, beginning at presentation.
All references are available online at www.expertconsult.com.
KEY REFERENCES
6. Turton K, Chaddock JA, Acharya KR. Botulinum and tetanus neurotoxins: structure,
function and therapeutic utility. Trends Biochem Sci 2002;27:552–558.
14. Roper M, Vandelaer J, Gasse F. Maternal and neonatal tetanus. Lancet
2007;370:1947–1959.
15. Lam PK, Trieu HT, Lubis IN, et al. Prognosis of neonatal tetanus in the modern
management era: an observational study in 107 Vietnamese infants. Int J Infect Dis
2014;33C:7–11.
18. Rodrigo C, Fernando D, Rajapakse S. Pharmacological management of tetanus: an
evidence-based review. Crit Care 2014;18:217.
21. Campbell JI, Lam TM, Huynh TL, et al. Microbiologic characterization and anti-
microbial susceptibility of Clostridium tetani isolated from wounds of patients with
clinically diagnosed tetanus. Am J Trop Med Hyg 2009;80:827–831.
27. Brook I. Current concepts in the management of Clostridium tetani infection. Expert
Rev Anti Infect Ther 2008;6:327–336.
36. Centers for Disease Control and Prevention. Updated recommendations for use of
tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) in
pregnant women—Advisory Committee on Immunization Practices (ACIP), 2012.
MMWR Morb Mortal Wkly Rep 2013;62:131–135.
, A1 @ ( 1 F 2F A D @ .1@
( F@ A D @, @ A @ A @D

REFERENCES
1. Centers for Disease Control and Prevention. Summary of notifiable disease—United
States, 2010. MMWR Morb Mortal Wkly Rep 2014;61:1–120.
2. Centers for Disease Control and Prevention. Tetanus surveillance—United States,
2001–2008. MMWR Morb Mortal Wkly Rep 2011;60:365–369.
3. Bruggemann H, Baumer S, Fricke WF, et al. The genome sequence of Clos-
tridium tetani: the causative agent of tetanus disease. Proc Natl Acad Sci USA
2003;100:1316–1321.
4. Stevens D, Bryant A, Berger A, von Eichel-Streiber C. Clostridium. In: Versalovic J,
Carroll K, Funke G, et al. (eds) Manual of Clinical Microbiology, 10th ed. Washing-
ton, DC, ASM Press, 2011, pp 834–857.
5. Ernst ME, Klepser ME, Fouts M, et al. Tetanus: pathophysiology and management.
Ann Pharmacother 1997;31:1507–1513.
6. Turton K, Chaddock JA, Acharya KR. Botulinum and tetanus neurotoxins: structure,
function and therapeutic utility. Trends Biochem Sci 2002;27:552–558.
7. Henriques Filho GT, Lacerda HR, Albuquerque A, Ximenes RA. Sympathetic overac-
tivity and arrhythmias in tetanus: electrocardiographic analysis. Rev Inst Med Trop
Sao Paulo 2007;49:17–22.
8. Pomara C, Neri M, Riezzo I, et al. Autonomic nervous system instability, tetanic
necrosis of the heart and myocardial TNFalpha expression in a tetanus fatal case.
Int J Cardiol 2009;136:e54–e57.
9. Hollow VM, Clarke GM. Autonomic manifestations of tetanus. Anaesth Intensive
Care 1975;3:142–147.
10. Loan HT, Parry J, Nga NT, et al. Semi-recumbent body position fails to prevent
healthcare-associated pneumonia in Vietnamese patients with severe tetanus. Trans
R Soc Trop Med Hyg 2012;106:90–97.
11. Amare A, Melkamu Y, Mekonnen D. Tetanus in adults: clinical presentation, treat-
ment and predictors of mortality in a tertiary hospital in Ethiopia. J Neurol Sci
2012;317:62–65.
12. Fezza JP, Howard J, Wiley R, et al. The effects of tetanus toxin on the orbicularis oculi
muscle. Ophthal Plast Reconstr Surg 2000;16:101–113.
13. González-Forero D, Morcuende S, Alvarez FJ, et al. Transynaptic effects of tetanus
neurotoxin in the oculomotor system. Brain 2005;128:2175–2188.
14. Roper M, Vandelaer J, Gasse F. Maternal and neonatal tetanus. Lancet
2007;370:1947–1959.
15. Lam PK, Trieu HT, Lubis IN, et al. Prognosis of neonatal tetanus in the modern
management era: an observational study in 107 Vietnamese infants. Int J Infect Dis
2014;33C:7–11.
16. Duddy ME, Baker MR. Stiff person syndrome. Front Neurol Neurosci
2009;26:147–165.
17. Barnes V, Ware MR. Tetanus, pseudotetanus, or conversion disorder: a diagnostic
dilemma? South Med J 1993;86:591–592.
18. Rodrigo C, Fernando D, Rajapakse S. Pharmacological management of tetanus: an
evidence-based review. Crit Care 2014;18:217.
19. American Academy of Pediatrics. Tetanus (lockjaw). In: Kimberlin DW, Brady MT,
Jackson MA, Long SS (eds) Red Book: 2015 Report of the Committee on Infectious
Diseases, 30th ed. Elk Grove Village, IL, American Academy of Pediatrics, 2015, pp
773–778.
20. Strikas RA. Advisory Committee on Immunization Practices recommended
immunization schedules for persons aged 0 through 18 years—United States, 2015.
MMWR Morb Mortal Wkly Rep 2015;64:93–94.
21. Campbell JI, Lam TM, Huynh TL, et al. Microbiologic characterization and anti-
microbial susceptibility of Clostridium tetani isolated from wounds of patients with
clinically diagnosed tetanus. Am J Trop Med Hyg 2009;80:827–831.
22. Ahmadsyah I, Salim A. Treatment of tetanus: an open study to compare the efficacy
of procaine penicillin and metronidazole. Br Med J (Clin Res Ed) 1985;291:648–650.
23. Clarke G, Hill RG. Effects of a focal penicillin lesion on responses of rabbit cortical
neurones to putative neurotransmitters. Br J Pharmacol 1972;44:435–441.
24. Reddy VG. Pharmacotherapy of tetanus: a review. Middle East J Anaesthesiol
2002;16:419–442.
) E 1 @ 0., .1 1AA1@ A C 1 1 0 D @A F .CA
@ @A 1 CA F @ CA A E C @ AA
Clostridium tetani (Tetanus) 188
25. Buchanan N, Smit L, Cane RD, et al. Sympathetic overactivity in tetanus: fatality
associated with propranolol. Br Med J 1978;2:254–255.
26. Rocke DA, Wesley AG, Pather M, et al. Morphine in tetanus: the management of
sympathetic nervous system overactivity. S Afr Med J 1986;70:666–668.
27. Brook I. Current concepts in the management of Clostridium tetani infection. Expert
Rev Anti Infect Ther 2008;6:327–336.
28. Thwaites CL, Yen LM, Loan HT, et al. Magnesium sulphate for treatment of severe
tetanus: a randomised controlled trial. Lancet 2006;368:1436–1443.
29. Attygalle D, Rodrigo N. Magnesium as first line therapy in the management of
tetanus: a prospective study of 40 patients. Anaesthesia 2002;57:811.
30. James MF, Manson ED. The use of magnesium sulphate infusions in the manage-
ment of very severe tetanus. Intensive Care Med 1985;11:5–12.
31. Ceneviva GD, Thomas NJ, Kees-Folts D. Magnesium sulfate for control of muscle
rigidity and spasms and avoidance of mechanical ventilation in pediatric tetanus.
Pediatr Crit Care Med 2003;4:480–484.
32. Lipman J, James MF, Erskine J, et al. Autonomic dysfunction in severe tetanus:
magnesium sulfate as an adjunct to deep sedation. Crit Care Med 1987;15:987–988.
33. Lishajko F. Releasing effect of calcium and phosphate on catecholamines, ATP, and
protein from chromaffin cell granules. Acta Physiol Scand 1970;79:575–584.
34. von Euler US, Lishajko F. Effects of Mg2+ and Ca2+ on noradrenaline release and
uptake in adrenergic nerve granules in differential media. Acta Physiol Scand
1973;89:415–422.
35. World Health Organization, United Nations Children’s Fund, and United Nations
Population Fund. Maternal and Neonatal Tetanus Elimination by 2005: Strategies for
achieving and maintaining elimination. WHO/V&B/02.09. Geneva, World Health
Organization, United Nations Children’s Fund, and United Nations Population
Fund, 2000.
36. Centers for Disease Control and Prevention. Updated recommendations for use of
tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) in
pregnant women—Advisory Committee on Immunization Practices (ACIP), 2012.
MMWR Morb Mortal Wkly Rep 2013;62:131–135.
37. Wolters KL, Dehmel H. Abschliessende Untersuchungen uber, die Tetanus Prophy-
laxe durch aktive Immunisierung. Z Hyg 1942;124:326–332.
38. Kutukculer N, Akil T, Egemen A, et al. Adequate immune response to tetanus toxoid
and failure of vitamin A and E supplementation to enhance antibody response in
healthy children. Vaccine 2000;18:2979–2984.
39. Dimache G, Croitoru M, Durbaca S, et al. Experimental study upon the efficacy
of some accelerated vaccination schedules in tetanus prophylaxis. Roum Arch
Microbiol Immunol 1993;52:247–254.
40. Pedrazzi C, Ghio L, Balloni A, et al. Duration of immunity to diphtheria and tetanus
in young kidney transplant patients. Pediatr Transplant 1999;3:109–114.
41. Christenson B, Bottiger M. Immunity and immunization of children against tetanus
in Sweden. Scand J Infect Dis 1991;23:643–647.
42. Steger MM, Maczek C, Berger P, et al. Immune reaction to tetanus in the elderly: what
is the duration of vaccine protection? Wien Klin Wochenschr 1997;109:767–770. [in
German].
43. Gergen JP, McQuillan GM, Kiely M, et al. A population-based serologic survey of
immunity to tetanus in the United States. N Engl J Med 1995;332:761–766.
44. Vance E, George S, Guinan EC, et al. Comparison of multiple immunization
schedules for Haemophilus influenzae type b-conjugate and tetanus toxoid vac-
cines following bone marrow transplantation. Bone Marrow Transplant 1998;22:
735–741.
45. Ching N, Deville JG, Nielsen KA, et al. Cellular and humoral immune responses to a
tetanus toxoid booster in perinatally HIV-1–infected children and adolescents receiv-
ing highly active antiretroviral therapy (HAART). Eur J Pediatr 2007;166:51–56.
46. Barbaud A, Deschildre A, Waton J, et al. Hypersensitivity and vaccines: an update.
Eur J Dermatol 2013;23:135–141.
47. Alhaji MA, Mustapha MG, Ashir GM, et al. Recurrent generalized tetanus: a case
report. Trop Doct 2011;41:127–128.
999.e1
, A1 @ ( 1 F 2F A D @ .1@
( F@ A D @, @ A @ A @D