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33SECTION TWO: Licensed vaccines
Tetanus is unique among vaccine-preventable diseases in thatit
is not communicable. Clostridium tetani, the causative agentof
tetanus, is widespread in the environment; many animals inaddition
to humans can harbor and excrete the organism and itsspores. When
spores ofC. tetani are introduced into the anaer-obic conditions
found in devitalized tissue or punctures, theygerminate to
vegetative bacilli that elaborate toxin. The clinicalpresentation
results from the actions of this toxin on the centralnervous system
(CNS). Many animal species besides humansare susceptible to the
disease.
The clinical characteristics of tetanus were recognized
asdistinct early in human history because of the constancy
andseverity of the symptoms in animals and humans. A descrip-
tion of tetanus was found as early as 1550 BC in the medi-cal
papyri of ancient Egypt, and detailed descriptions wereincluded in
the writings of Hippocrates and other ancientGreeks.1,2The etiology
of tetanus was unknown until 1884,when Carle and
Rattone3demonstrated that injecting the con-tents of a pustule from
a fatal human case into the sciaticnerve of a rabbit resulted in
the typical symptoms of tetanus.The disease could subsequently be
passed to other rabbitsfrom infected nervous tissue. Inoculation of
soil samples intoanimals also resulted in tetanus. Gram-positive
bacilli wereoften noted in the exudate at the inoculation site but
gener-ally not in nervous tissue, leading Nicolaier4 to
hypothesizethat a poison produced at the site of inoculation caused
thenervous system symptoms. In 1886, spore-forming bacilliwere
observed in the exudate obtained from a human patient.5
In 1889, the spores ofC. tetani, in contrast to the
vegetativeorganisms, were shown to survive heating and to
germinateunder anaerobic conditions; injection of pure cultures
repro-ducibly caused the disease in animals.6After
identificationand purification of the toxin in 1890, repeated
inoculation ofanimals with minute quantities of toxin led to the
productionof antibodies in survivors that neutralized the effects
of thetoxin.7 Preparations of antibodies derived from animal
sera,particularly from horses, became the first means to preventand
treat tetanus. These efforts culminated in the preparationof an
anatoxina chemically inactivated toxin, now termed atoxoidin
1924.8Toxoid induced active immunity against thedisease before
exposure.
The impetus to prevent tetanus through immunization wasthe
striking and highly fatal disease in both industrialized and
developing nations, predominantly associated with injuries
tootherwise healthy persons, and particularly during military
con-flicts. In the developing world, tetanus in neonates
continuesto represent a substantial proportion of the health burden
fromtetanus. Prevention of tetanus is now almost universally
achiev-able by use of highly immunogenic and safe
toxoid-containing
vaccines. Tetanus also can be prevented or modified by
properwound care, sterile surgical and obstetric practices, and use
ofexogenous antibody.
Clinical description
Although the incubation period for tetanus varies from 1 dayto
several months after a wound, the majority of cases occurwithin 3
days to 3 weeks after inoculation of spores. In theUnited States
during 1972 to 2001, the median intervalbetween the injury and
onset of tetanus was 7 days (range, 0 to178 days) for 1,191
non-neonatal cases with reported informa-
tion. The time between injury and the onset of symptoms was30
days or less for 97% of the cases, and 2 days or less for 10%of the
cases.9
A direct relationship exists between the site of inoculationand
the incubation period: the longest intervals occur after inju-ries
farthest from the CNS; injuries of the head and trunk aregenerally
associated with the shortest incubation periods.10,11The incubation
period is inversely related to severity of ill-ness1218 and has
historically been considered one of the bestprognostic
indicators.19,20Incubation periods of 10 days or moretend to result
in milder disease, whereas incubation periodswithin 7 days of
injury tend to result in more severe disease.
Three clinical syndromes are associated with tetanus infec-tion:
(1) localized, (2) generalized, and (3)
cephalic.10Localizedtetanus, which is uncommon, consists of spasm
of muscles in
a confined area surrounding the site of the injury.
21,22Painfulcontractions may persist for several weeks to months
beforegradually subsiding. Localized disease is thought to occur
whentransport of toxin produced at the site of the injury is
restrictedto the local nerves.11The symptoms can be produced
experi-mentally by simultaneously injecting toxin into a muscle
andantitoxin into blood to prevent hematogenous
dissemination.11Although localized tetanus per se is generally
mild, with fatal-ity rates of less than 1%, progression to
generalized tetanus andits complications can occur.21
More than 80% of cases of tetanus are generalized. The
mostcommon initial sign is spasm of the muscles of
masticationtrismus, or lockjawoccurring in up to 90% of patients
onpresentation.10,23,24Spasm of the facial muscles produces a
char-acteristic facial expressionrisus sardonicusconsisting of
raised eyebrows, tight closure of the eyelids, wrinkling of
theforehead, and extension of the corners of the mouth
laterally.Other early presentations of tetanus include pain and
musclespasm of the neck, shoulders, back, and abdomen. Dysphagiacan
be the initial symptom, particularly in the elderly.25,26Initially,
spasms are triggered by external stimuli such as touch
Tetanus toxoidMartha H. Roper
Steven G. F. Wassilak
Tejpratap S. P. Tiwari
Walter A. Orenstein
