Tetanus is an acute, often fatal, disease caused by an exotoxin
produced by Clostridium tetani. It is characterized by generalized
rigidity and convulsive spasms of skeletal muscles. The muscle
stiffness usually involves the jaw (lockjaw) and neck and then
becomes generalized.
Although records from antiquity (5th century B.C.) contain clinical
descriptions of tetanus, it was Carle and Rattone who first produced
tetanus in animals by injecting them with pus from a fatal human
tetanus case in 1884. During the same year, Nicolaier produced
tetanus in animals by injecting them with samples of soil. In 1889,
Kitasato isolated the organism from a human victim, showed that it
produced disease when injected into animals, and reported that the
toxin could be neutralized by specific antibodies. In 1897, Nocard
demonstrated the protective effect of passively transferred antitoxin,
and passive immunization in humans was used during World War I.
Tetanus toxoid was developed by Descombey in 1924, and the effectiveness
of active immunization was demonstrated in World War II.

CLOSTRIDIUM TETANI
C. tetani is a slender, gram-positive, anaerobic rod that may develop
a terminal spore, giving it a drumstick appearance. The organism is
sensitive to heat and cannot survive in the presence of oxygen. The
spores, in contrast, are very resistant to heat and the usual antiseptics.
They can survive autoclaving at 121 degrees C for 10-15 minutes. The
spores are also relatively resistant to phenol and other chemical
agents.
The spores are widely distributed in soil and in the intestine and
feces of horses, sheep, cattle, dogs, cats, rats, guinea pigs, and chickens.
Manure-treated soil may contain large numbers of spores. In
agricultural areas, a significant number of human adults may harbor
the organism. The spores can also be found on skin surfaces and in
contaminated heroin.
Clostridium tetani produces two exotoxins, tetanolysin and
tetanospasmin. The function of tetanolysin is not known with certainty.
Tetanospasmin is a neurotoxin and causes the clinical manifestations
of tetanus. Tetanospasmin is one of the most potent toxins
known on a weight basis. The estimated minimum human lethal
dose is 2.5 nanograms per kilogram of body weight (a nanogram is
one billionth of a gram), or 175 nanograms for a 70 kg human.

PATHOGENESIS
C. tetani usually enters the body through a wound. In the presence
of anaerobic (low oxygen) conditions, the spores germinate. Toxins
are produced, and disseminated via blood and lymphatics. Toxins
act at several sites within the central nervous system, including
peripheral motor end plates, spinal cord, brain, and sympathetic
nervous system. The typical clinical manifestations of tetanus are
caused when tetanus toxin interferes with release of neurotransmitters,
blocking inhibitor impulses. This leads to unopposed muscle
contraction and spasm. Seizures may occur, and the autonomic
nervous system may also be affected.

CLINICAL FEATURES
The incubation period varies from 3 to 21 days, usually about 8
days. In general the further the injury site is from the central nervous
system, the longer the incubation period. The shorter the
incubation period, the higher the chance of death. In neonatal
tetanus, symptoms usually appear from 4 to 14 days after birth,
averaging about 7 days.
On the basis of clinical findings, three different forms of tetanus
have been described.
Local tetanus is an uncommon form of the disease, in which
patients have persistent contraction of muscles in the same
anatomic area as the injury. These contractions may persist for
many weeks before gradually subsiding. Local tetanus may
precede the onset of generalized tetanus, but is generally milder.
Only about 1% of cases are fatal.
Cephalic tetanus is a rare form of the disease, occasionally occurring
with otitis media (ear infections) in which C. tetani is present
in the flora of the middle ear, or following injuries to the head.
There is involvement of the cranial nerves, especially in the facial
area.
The most common type (about 80%) of reported tetanus is generalized
tetanus. The disease usually presents with a descending
pattern. The first sign is trismus or lockjaw, followed by stiffness of
the neck, difficulty in swallowing, and rigidity of abdominal muscles.
Other symptoms include a temperature rise of 2 degrees -4 degrees C above
normal, sweating, elevated blood pressure, and episodic rapid heart
rate. Spasms may occur frequently and last for several minutes.
Spasms continue for 3-4 weeks. Complete recovery may take
months.
Neonatal tetanus is a form of generalized tetanus that occurs in
newborn infants. Neonatal tetanus occurs in infants born without
protective passive immunity, because the mother is not immune. It
usually occurs through infection of the unhealed umbilical stump,
particularly when the stump is cut with an unsterile instrument.
Neonatal tetanus is common in some developing countries (estimated
>215,000 deaths worldwide in 1998), but very rare in the
United States.

COMPLICATIONS
Laryngospasm (spasm of the vocal cords) and/or spasm of the
muscles of respiration leads to interference with breathing.
Fractures of the spine or long bones may result from sustained
contractions and convulsions. Hyperactivity of the autonomic
nervous system may lead to hypertension and/or an abnormal
heart rhythm.
Nosocomial infections are common because of prolonged hospitalization.
Secondary infections, which may include sepsis from
indwelling catheters, hospital-acquired pneumonias, and decubitus
ulcers. Pulmonary embolism is particularly a problem in drug
users and elderly patients. Aspiration pneumonia is a common
late complication of tetanus, found in 50%-70% of autopsied cases.
In recent years, tetanus has been fatal in approximately 11% of
reported cases. Cases most likely to be fatal are those occurring in
persons age >60 years (18%), and unvaccinated persons (22%). In
about 20% of tetanus deaths, no obvious pathology is identified
and death is attributed to the direct effects of tetanus toxin.

LABORATORY DIAGNOSIS
There are no laboratory findings characteristic of tetanus. The
diagnosis is entirely clinical and does not depend upon bacteriologic
confirmation. C. tetani is recovered from the wound in only 30%
of cases, and can be isolated from patients who do not have
tetanus. Laboratory identification of the organism depends most
importantly on the demonstration of toxin production in mice.

MEDICAL MANAGEMENT
All wounds should be cleaned. Necrotic tissue and foreign material
should be removed. If tetanic spasms are occurring, supportive
therapy and maintanence of an adequate airway are critical.
Tetanus immune globulin (TIG) is recommended for persons with
tetanus. TIG can only help remove unbound tetanus toxin. It cannot
effect toxin bound to nerve endings. A single intramuscular
dose of 3000 to 5000 units is generally recommended for children
and adults, with part of the dose infiltrated around the wound if it
can be identified. Intravenous immune globulin (IVIG) contains
tetanus antitoxin and may be used if TIG is not available.
Due to the extreme potency of the toxin, tetanus disease does not
result in tetanus immunity. Active immunization with tetanus
toxoid should begin or continue as soon as the person’s condition
has stabilized.

WOUND MANAGEMENT
Antibiotic prophylaxis against tetanus is neither practical nor useful
in managing wounds; proper immunization plays the more important
role. The need for active immunization, with or without passive
immunization, depends on the condition of the wound and the
patient’s immunization history. Rarely have cases of
tetanus occurred in persons with a documented primary series of
tetanus toxoid.
Persons with wounds that are neither clean nor minor, and who
have had 0-2 prior doses or have an uncertain history of prior
doses, need tetanus immune globulin (TIG) as well as Td toxoids.
This is because early doses of toxoid do not induce immunity, but
only prime the immune system. The TIG provides temporary
immunity by directly providing antitoxin. This ensures that protective
levels of antitoxin are achieved even if an immune response has
not yet occurred.

EPIDEMIOLOGY
OCCURRENCE
Occurrence is worldwide, but is most frequently encountered in
densely populated regions in hot, damp climates with soil rich in
organic matter.

RESERVOIR
Organisms are found primarily in the soil and intestinal tracts of
animals and humans.

MODE OF TRANSMISSION
Transmission is primarily by contaminated wounds (apparent and
inapparent). The wound may be major or minor. In recent years,
however, a higher proportion of cases had minor wounds, probably
because severe wounds are more likely to be properly managed.
Tetanus may follow elective surgery, burns, deep puncture wounds,
crush wounds, otitis media (ear infections), dental infection,
animal bites, abortion, and pregnancy.

COMMUNICABILITY
Tetanus is not contagious from person to person. It is the only
vaccine-preventable disease that is infectious, but not contagious.

SECULAR TRENDS IN THE UNITED STATES
A marked decrease in mortality occurred from the early 1900s to
the late 1940s. In the late 1940s, tetanus toxoid was introduced
into routine childhood immunization and tetanus became nationally
notifiable. At that time, there were 500-600 cases reported per
year (approximately 0.4 cases per 100,000 population).
After the 1940s, reported tetanus incidence rates fell steadily.
Since the mid-1970s, 50-100 cases have been reported annually
(~ 0.05 cases per 100,000). The death-to-case ratio has declined
from 30% to approximately 10% in recent years. An all-time low
of 25 cases (0.01 cases per 100,000) were reported in 2002.
From 1980 through 2000, 70% of reported cases of tetanus were
among persons 40 years of age or older. From 1980 through 1990,
a median of 21% of reported cases were age <40 years. The age
distribution of reported cases shifted to a younger age group in the
last half of the 1990s. Persons <40 years increased from 28% of
cases during 1991-1995 to 42% of cases during 1996-2000. This
change in age distribution is a result of both an increase in cases in
persons <40 years and a decrease in cases in older people. The
increase in cases among younger persons is related in part to an
increased number of cases among young injection drug users in
California in the late 1990s.
Almost all reported cases of tetanus are in persons who have either
never been vaccinated, or who completed a primary series, but have
not had a booster in the preceding 10 years.
Heroin users, particularly persons 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.
Neonatal tetanus is rare in the United States, with only 2 cases
reported since 1989. Neither of the infants' mothers had ever
received tetanus toxoid.
During 1998-2000 (the most recent years data are available) acute
injuries or wounds preceded tetanus in 94 (73%) of the 129 cases
for which information was available. Among the most frequent
wound types were puncture wounds (50%), lacerations (33%), and
abrasions (9%). The most common puncture wound was from stepping
on a nail (15 cases). Other puncture wounds involved barbed
wire, splinters, animal or insect bites, self-piercing, and self-performed
tattoos. The environment in which acute injuries occurred
was indoors or at home in 45%, in the yard, garden, or farm in
31%, and other outdoor locations in 23%.
Five percent of reported cases were intravenous drug users without
other known injury, and 11% had chronic wounds.Twenty patients
were reported to have received at least a primary series of tetanus
toxoid; 18 had an outcome reported. Of these 18 patients, one (6%)
death occurred; the death was in an injection-drug user (IDU)
whose last dose of tetanus toxoid was 11 years before the onset of
tetanus. A total of 110 patients reported <3 doses of tetanus toxoid
or had an unknown vaccination history; 95 of these patients had an
outcome reported. Nineteen deaths (20%) occurred among these 95
patients.

TETANUS TOXOID
CHARACTERISTICS
Tetanus toxoid was first produced in 1924. Tetanus toxoid immunizations
were used extensively in the armed services during World
War II. Tetanus cases among this population dropped from 70 in
World War I (13.4/100,000 wounds and injuries) to 12 in World War
II (0.44/100,000). Of the 12 cases, half had received no prior toxoid.
Tetanus toxoid consists of a formaldehyde-treated toxin. The toxoid
is standardized for potency in animal tests according to Food and
Drug Administration (FDA) regulations. Occasionally, potency is
mistakenly equated with Lf units, which are a measure of the
quantity of toxoid, not its potency in inducing protection.
There are two types of toxoid available — adsorbed (aluminum salt
precipitated) toxoid and fluid toxoid. Although the rates of seroconversion
are about equal, the adsorbed toxoid is preferred because
the antitoxin response reaches higher titers and is longer lasting than
following the fluid toxoid.
Tetanus toxoid is available as a single antigen preparation, combined
with diphtheria as pediatric DT or adult Td, and with both diphtheria
toxoid and acellular pertussis vaccine as DTaP. Pediatric
formulations (DT and DTaP) contain a similar amount of tetanus
toxoid as adult Td, but contain 3-4 times as much diphtheria toxoid.
Children younger than 7 years of age should receive either
DTaP or pediatric DT. Persons 7 years of age or older should
receive the adult formulation (adult Td), even if they have not
completed a series of DTaP or pediatric DT. There is virtually no
reason to use single antigen tetanus toxoid. Tetanus toxoid should
be given in combination with diphtheria toxoid, since periodic
boosting is needed for both antigens.

IMMUNOGENICITY AND VACCINE EFFICACY
After a primary series of three properly spaced doses of tetanus toxoid
in persons >7 years of age and four doses in children <7 years
of age, essentially all recipients achieve antitoxin levels considerably
greater than the minimal protective level of 0.01 IU/ml.
Efficacy of the toxoid has never been studied in a vaccine trial. It
can be inferred from protective antitoxin levels that a complete
tetanus toxoid series has a clinical efficacy of virtually 100%; cases
of tetanus occurring in fully immunized persons whose last dose was
within the last 10 years are extremely rare.
Following a properly administered primary series, almost all persons
develop a protective level of antitoxin. Antitoxin levels decrease
with time. While some persons may be protected for life, most persons
have antitoxin levels that approach the minimal protective level
by 10 years after the last dose. As a result, routine boosters are recommended
every 10 years.
In a small percentage of individuals, antitoxin levels fall below the
minimal protective level before 10 years have elapsed. To ensure
adequate protective antitoxin levels in individuals who sustain a
wound that is other than clean and minor, a booster is recommended
for these persons if more than 5 years have elapsed since their
last dose. (See Wound Management for details on persons who
previously received fewer than three doses.)

VACCINATION SCHEDULE AND USE
DTaP (diphtheria and tetanus toxoids and acellular pertussis vaccine)
is the vaccine of choice for children 6 weeks through 6 years
of age. The usual schedule is a primary series of 4 doses at 2, 4, 6,
and 15-18 months of age. The first, second, and third doses of
DTaP should be separated by a minimum of 4 weeks. The fourth
dose should follow the third dose by no less than 6 months, and
should not be administered before 12 months of age.
If a child has a valid contraindication to pertussis vaccine, pediatric
DT should be used to complete the vaccination series. If the child
was less than 12 months old when the first dose of DT was administered
(as DTaP or DT), the child should receive a total of four
primary DT doses. If the child was 12 months of age or older at
the time that the first dose of DT was administered, three doses
(third dose 6-12 months after the second) completes the primary
DT series.
If the fourth dose of DTaP, DTP, or DT is administered before the
fourth birthday, a booster dose is recommended at 4-6 years of
age. The fifth dose is not required if the fourth dose was given on
or after the fourth birthday.
Because of waning antitoxin titers, most individuals have antitoxin
levels below the optimal level 10 years after the last dose of DTaP,
DTP, DT, or Td. As a result, additional booster doses of tetanus
and diphtheria toxoids (as Td) are required every 10 years to maintain
protective antitoxin titers. The first booster dose of Td may
be given at 11-12 years of age, if at least 5 years have elapsed since
the last dose of DTaP, DTP, or DT. If a dose is given sooner as
part of wound management, the next booster is not needed for 10
years thereafter. More frequent boosters are not indicated and have
been reported to result in an increased incidence and severity of
local adverse reactions.
Td is the vaccine of choice for children 7 years and older, and for
adults. A primary series is three or four doses, depending on
whether the person has received prior doses of diphtheria-containing
vaccine, and the age these doses were administered. The number
of doses recommended for children who received one or more
doses of DTP, DTaP, or DT before age 7 years is discussed above.
For unvaccinated persons 7 years and older (including persons who
cannot document prior vaccination), the primary series is three
doses. The first two doses should be separated by at least 4 weeks,
and the third dose given 6 to 12 months after the second.
A booster dose of Td should be given every 10 years.
Interruption of the recommended schedule or delay of subsequent
doses does not reduce the response to the vaccine when the series
is finally completed. There is no need to restart a series regardless
of the time elapsed between doses.
Tetanus disease does not confer immunity because of the very
small amount of toxin required to produce illness. Persons recovering
from tetanus should begin or complete active immunization
with tetanus toxoid (Td) during convalescence.

ADVERSE REACTIONS FOLLOWING VACCINATION
Local adverse reactions (e.g., erythema, induration, pain at the
injection site) are common, but are usually self-limited and require
no therapy. A nodule may be palpable at the injection site of
adsorbed products for several weeks. Abscess at the site of injection
has been reported. Fever and other systemic symptoms are not
common.
Exaggerated local (Arthus-like) reactions are occasionally
reported following receipt of a diphtheria-or tetanus-containing vaccine.
These reactions present as extensive painful swelling, often
from shoulder to elbow. They generally begin from 2 to 8 hours
after injections, and are reported most often in adults, particularly
those who have received frequent doses of diphtheria or tetanus toxoid.
Persons experiencing these severe reactions usually have very
high serum antitoxin levels; they should not be given further routine
or emergency booster doses of Td more frequently than every 10
years. Less severe local reactions may occur in persons who have
multiple prior boosters.
Severe systemic reactions such as generalized urticaria (hives),
anaphylaxis, or neurologic complications have been reported after
receipt of tetanus toxoid. A few cases of peripheral neuropathy and
Guillain-Barré Syndrome (GBS) have been reported following
tetanus toxoid administration. Following a recent review, the
Institute of Medicine (IOM) concluded that the available evidence
favors a causal relationship between tetanus toxoid and both
brachial neuritis and GBS, although these reactions are very rare.

CONTRAINDICATIONS AND PRECAUTIONS TO
VACCINATION
A severe allergic reaction (acute respiratory distress or collapse)
following a prior dose of tetanus toxoid is a contraindication to
receipt of tetanus toxoid. If a generalized reaction is suspected to
represent allergy, it may be useful to refer an individual for appropriate
skin testing before discontinuing tetanus toxoid immunization.
A moderate or severe acute illness is reason to defer
routine vaccination, but a minor illness is not.
If a contraindication to using tetanus toxoid-containing preparations
exists, passive immunization with tetanus immune globulin (TIG)
should be considered whenever an injury other than a clean minor
wound is sustained.

VACCINE STORAGE AND HANDLING
DTaP, DT (pediatric),Td, DTP/Hib, and tetanus toxoid should be
stored continuously at 2 degrees – 8 degrees C (35 degrees  - 46 degrees F). 
The vaccine may be out of refrigeration for up to 4 days, but should be refrigerated
immediately when received. Freezing reduces the potency of the
tetanus component.
Tetanus
SELECTED REFERENCES
American Academy of Pediatrics.Tetanus. In Pickering L, ed. Red
Book 2003: Report of the Committee on Infectious Diseases. 26th ed.
Elk Grove Village, IL: American Academy of Pediatrics, 2003:
611-16.
CDC. Diphtheria, tetanus, and pertussis: Recommendations for
vaccine use and other preventive measures: Recommendations of
the Advisory Committee on Immunization Practices (ACIP).
MMWR 1991;40(RR-10):1-28.
CDC. Pertussis vaccination: use of acellular pertussis vaccines
among infants and young children. Recommendationd of the
Advisory Committee on Immunization Practices (ACIP). MMWR
1997;46(RR-7):1-25.
CDC.Tetanus surveillance--United States, 1998-2000. MMWR
2003;52(SS-3):1-12.
Orenstein WA, Hadler S,Wharton M. Trends in vaccine-preventable
diseases. Semin Pediatr Infect Dis 1997;8:23-33.
Sutter RW, Cochi SL, Sirotkin B, et al. Assessment of vital statistics
and surveillance data for monitoring tetanus mortality, United
States, 1979-1984. Am J Epidemiol 1990;131:132-42.
Sutter RW, Orenstein WA,Wassilak SGF. In: Evans AS and
Brachman PS, eds. Bacterial Infections of Humans: Epidemiology
and Control. 3rd ed. New York, NY: Plenum Medical Book
Company, 1998:741-57.
Wassilak SGF, Roper MH, Murphy TV, Orenstein WA.Tetanus. In:
Plotkin SA, Orenstein WA, eds. Vaccines. 4th ed. Philadelphia, PA:
Saunders, 2003:745-81.
World Health Organization. The “high-risk” approach: the WHOrecommended
strategy to accelerate elimination of neonatal
tetanus. Wlky Epidemiol Rec 1996;71:33-36.