TETANUS

ABSTRACT

Objectives: Although tetanus is now uncommon in Oman (The Expanded Program on

Immunization was introduced in 1981), patients continue to present from time to time at an
average rate of 6 cases per year. Worldwide, the mortality rate for tetanus remains high
(ranging from 15-20% in developed countries). At the Sultan Qaboos University Hospital,
Muscat, Oman, prolonged Intensive Care Unit treatment and multi-disciplinary management
is invariably required for tetanus patients. This study was carried out to evaluate our results
over the past decade.

Methods: All tetanus patients admitted to the Sultan Qaboos University Hospital from 1991
up to the end of 1999 were retrospectively reviewed. Patients were diagnosed early, and
aggressive treatment in the Intensive Care Unit was instituted, with a coordinated
multidisciplinary management.

Results: Ten cases were identified and included in the review, comprising 9 adults and one
infant aged 2 weeks. Adult patients were aged 36-75 years (mean 59 years), and the average
Intensive Care Unit stay of the 9 surviving patients was 5.5 weeks (range 3-7 weeks). All
patients presented with severe generalized tetanus. Two patients with traditional cautery
marks developed tetanus. A focus of infection could not be found in 2 patients. All patients
had early tracheostomy and assisted ventilation with appropriate sedation. One patient
required almost 45 gm of diazepam throughout his Intensive Care Unit stay. One adult patient
died on the 6th day of admission following myocardial infarction. The neonatal case survived
after 35 days care in the Intensive Care Unit. The mortality rate for our patients was therefore
10%.

Conclusion: Tetanus in Oman remains an infrequent but important disease requiring costly
and prolonged Intensive Care Unit treatment. We attribute the comparatively low mortality
rate (10%) in this study, to early diagnosis, institution of aggressive treatment, good nursing
as well as a well-coordinated multi-disciplinary management.

Tetanus is a potentially preventable disease caused by a potent neurotoxin produced by

Clostridium tetani. The disease was first described in the 14th century by John of Arderne.
Tetanospasmin is responsible for its pathogenesis. After the toxin of botulism, it is the most
potent neurotoxin known to man, with an estimated lethal dose of 2.5 ng/kg body
weight.Tetanus is one of the target diseases of the World Health Organization (WHO)
Expanded Program on Immunization (EPI). The overall annual incidence worldwide is 0.5-1
million cases. It is estimated that there are 140,000 fatal neonatal cases per annum. The
disease is more common in tropical and developing countries, where immunization is
deficient and opportunities for penetrating contaminated wounds is higher. In Oman, tetanus
toxoid was first included in the EPI in 1981 and accordingly the majority of adults are not
immunized. Most Omanis live in rural areas and are involved in subsistence agriculture and
livestock farming, subsequently, exposure to tetanus is common. Sultan Qaboos University
Hospital (SQUH) is a tertiary care teaching hospital in Muscat and patients with tetanus are
referred from regional and district hospitals.
Methods. All patients referred to, or presenting at, the SQUH from 1991 to 1999 were
included in this study. One or more of the authors had treated each patient. A retrospective
evaluation of all the patients was undertaken to determine the results of treatment during this
time. Medical records were reviewed to collect demographic information, circumstances of
injury, anatomic site and type of injury, treatment and outcomes. Ten cases were identified
including a neonate, 9 males and one female (Table 1). All but one patient, a Bangladeshi,
were Omanis. All patients had full clinical examinations, including identification of the focus
of infection. Severe generalized tetanus was the main diagnosis in all the cases thus early
ventilatory support and tracheostomy together with intensive nursing care, were instituted.
The diagnosis of tetanus is purely clinical, as there are no specific laboratory tests. However,
the basic initial investigations have included full blood count, erythrocyte sedimentation rate,
serum glucose, serum, . calcium, arterial blood gases, urea and electrolytes,
electrocardiogram, chest x-ray and wound cultures. All the patients received antibiotics, anti-
tetanus toxoid and human tetanus immunoglobulin (TIG). Generalized muscle spasms, which
occurred in all patients, were well controlled with a combination of sedative drugs and
muscle relaxants. Initially parenteral then enteral nutrition was instituted in all patients.

Results. Most patients presented with progressive difficulty in swallowing, back pain and
stiffness of the back and neck, of 2 days to one-week duration. Tetanic spasms were observed
in only one patient. On admission, all patients were alert, agitated, had trismus, generalized
rigidity associated with hyperreflexia and exhibited plantar withdrawal, their sensorium was
otherwise normal. A focus of infection could not be found in 2 patients. Risus sardonicus and
opisthotonos were noted in 2 patients. Two patients with traditional cautery burns developed
tetanus. One of them was a female patient with an unreported, infected cautery lesion on her
scalp, which was found by chance by the nursing staff when being washed. The other one had
multiple traditional cautery marks on the neck and the trunk. We obtained only one positive
culture out of the 8 cases with a known focus of infection and the basic initial investigations
were unremarkable. Our neonatal case was delivered by an old blind woman at home in a
remote village (mother Gravida 7, Para 6 and sera confirmed non-immunized state). An
unsterile knife cut the umbilical cord. On the 5th day the baby showed failure of sucking,
vomiting and looked unwell. On the 6th day, he presented to the nearest hospital. He was
dehydrated, showing tetanic spasms, risus sardonicus, opisthotonos with an infected
umbilical cord. As the tetanus diagnosis was evident, the neonate was sedated, intubated and
transferred to our hospital. All patients had early tracheostomy and assisted ventilation with
appropriate sedation. It has been noted generally, the further distant the focus of infection
from the central nervous system (CNS) the longer the incubation period. The average
Intensive Care Unit (ICU) stay of the 9 surviving patients was lengthy, 5.5 weeks (range 3-7
weeks). In this small sized sample the mortality rate of our patients was therefore 10%. The
following major complications were encountered. All patients developed multiple chest
infections (pneumonia) and 2 patients contracted urinary tract infections. One patient
developed right subclavian vein thrombosis probably secondary to continuous diazepam
infusion. One patient with severe aortic stenosis (pressure gradient across the aortic valve 70-
80mmHg) was revived from cardiac arrest (asystole) and underwent a successful aortic valve
replacement after a full recovery from tetanus. Unsuccessful resuscitation of cardiac arrest
occurred in a patient with non-insulin dependent diabetes mellitus who sustained myocardial
infarction on the 6th day of his admission. Myocardial infarction is a rarely observed
complication of tetanus.4 All patients showed one or more manifestations of autonomic
dysfunction e.g. hypertension, hypotension, tachycadia, bradycardia and dysrhythmias
particularly in the 2nd and the 3rd week. On discharge there were no major sequele to any
patient and outpatient follow-up showed no major long-term complications.
Discussion. Tetanus remains an important cause of morbidity and mortality despite the wide
implementation of the EPI. The WHO estimated in 1990 that worldwide, there were about
715,000 deaths from neonatal tetanus.2 In Oman, tetanus is a notifiable disease, and there
were 2 neonatal and 52 adult cases (on average 6 cases per year) reported over the period
from 1991 up to the end of 1999. Tetanus is primarily a disease of the elderly in developed
countries. Active immunization and better hygiene, wound care and management of
childbirth have diminished its incidence. Mortality has been reduced to 15% with the active
employment of intensive care facilities for the treatment of this condition.5 Our mortality rate
is comparatively low at 10%. The diagnosis of tetanus is purely clinical, as there are no
specific laboratory tests. It has been estimated that wound cultures are positive in only 32%
of cases.6 Only one positive culture was obtained. A simple bedside test, the "spatula test" (a
reflex spasm of the masseters on touching the posterior pharyngeal wall leading to biting of
the spatula rather than a gag reflex), was described by Apte et al. In 400 patients, this test had
a sensitivity of 94% and a specificity of 100%.7 Pain and stiffness of the back are the most
common presenting symptoms, followed by trismus and dysphagia. Spasms may be
precipitated by minimal stimuli such as noise, light or touch and may last from seconds to
minutes. They can be painful or dangerous, causing apnea, fractures or rhabdomyolysis and
thus our patients were kept in a quiet room and stimuli kept at a minimum until satisfactory
sedation was achieved. Sera can be analyzed for tetanus antitoxin, the presence of more than
0.01 antitoxin unit per ml is regarded as protective against clinical tetanus, although cases
have occurred in patients with antibody concentrations at least 10-fold higher than this. In
this study, tetanus serology was only performed for the mother of the neonatal case, which
confirmed her non-immunized state. The major differential diagnoses which were excluded in
our cases are hypocalcemia, meningitis, encephalitis, subarachnoid hemorrhage, peritonsilar
abscess, dystonic reactions, rabies, spider envenomatoin (widow), strychnine poisoning and
hysteria. There are 4 clinical forms of tetanus:
neonatal, localized, cephalic and generalized. All the adult tetanus cases studied were of the
generalized form. In the literature, the source of infection is from an obvious injury in 58% of
cases (8 out of 10 in our series). Two patients with traditional cautery remedy developed
tetanus. It is probable, that the source of tetanus in these cases was ash applied by the
traditional healer to accelerate the wound healing. Our treatment followed the recommended
guidelines: Neutralization of the toxin and elimination of the source of infection by careful
surgical excision and wound care. As soon as the diagnosis of tetanus was made, Human TIG
1000 units were given and repeated for an additional 2 days in most patients. This at best
neutralizes only circulating toxins, but does not affect toxins already fixed to the CNS.
Intrathecal administration of antitetanus toxin has not been used as large metaanalyses
reported it to be ineffective in reducing the morbidity and mortality.8 Once the Human TIG
has been given, the infected site should be thoroughly cleaned and all the necrotic tissue
extensively debribed. Antibiotics destroy tetanus spores. The favorite choice was
Metronidazole 500mg intravenously (IV) 8 hourly for 10 days as the drug has a spectrum of
activity against anaerobes, it is able to penetrate necrotic tissue and has been shown to be
more effective than penicillin in this situation.However, penicillin or a 3rd-generation
cephalosporin have also been used in a few patients. Natural immunity to tetanus does not
occur, tetanus may both relapse and recur, so victims of tetanus must be actively immunized.
Immunization with tetanus toxoid was given at the time of the diagnoses. A 2nd and 3rd
toxoid injection were given one and 2 months later, with planned booster injections oneyear
later and then 10 yearly intervals. In the case of a neonate, the mother also was given the
vaccine. The main aims of treatment are to relieve the patient’s distress, controlling the
spasms and rigidity and to maintain adequate respiration. If endotracheal intubation was
necessary, tracheostomy was performed within 10 days. As the endotracheal tube seems to be
a strong stimulus for spasms, in the last 3 patients a tracheostomy was carried out earlier, on
the 2nd day of ventilation. Benzodiazepines reduce anxiety, induce amnesia, sedation and
muscle relaxation as well as being anticonvulsant. These drugs are Gama-amniobutyric acid
A (GABA-A) agonists, thereby functioning as indirect antagonists of the effect of the toxin
on inhibitory systems. Diazepam or midazolam by continuous infusion have been used.
Diazepam is less expensive compared to other benzodiazepines. The disadvantages of
diazepam include slow onset, prolonged action, and irritation to tissues and thrombophlebitis
(one patient developed subclavian vein thrombosis). Most of our patients received diazepam
IV infusions ranging between 10 to 60 mg/hr. One of our patients required 4500 ampoules of
10 mg diazepam (45000 mg) throughout his ICU stay. Other antispasmodics used included
magnesium sulphate, morphine and muscle relaxants.
It is known that the mortality in tetanus associated with autonomic dysfunction is as high as
50%. Unexpected cardiac arrest is the most common cause of death in patients with tetanus
admitted to the ICU and no obvious cause of death can be found at autopsy in up to 20% of
deaths. It is general consensus that no drug singly, or in combination, has proved consistently
effective in the control of autonomic disturbances. The armamentarium of drugs used in our
patients included benzodiazepines, morphine,11 alpha blockers, beta blockers, or agents with
both properties, calcium antagonists, magnesium sulphate,12 and atropine. Physiotherapy and
nursing played a major rule in preventing contractures and deep vein thrombosis in ICU and
were the mainstay of rehabilitation in the ward. Other factors known to contribute to
morbidity and mortality in tetanus were also prevented. These include hypoxia, malnutrition,
and complications of mechanical ventilation (barotrauma), fluid and electrolytes disturbances.
Bed sores and embolic phenomena were avoided thanks to excellent nursing care. Supportive
psychotherapy was offered to both patient and family. Prevention of tetanus is the key to its
elimination and loss of life in an easily preventable disease is unacceptable. Primary care and
emergency physicians can reduce the morbidity and mortality of tetanus through proper
immunization. As a patient’s tetanus immunization history is often unreliable in routine
wound management, liberal use of tetanus toxoids and appropriate TIG is recommended.3 In
conclusion, tetanus is a potentially preventable disease. However, it remains a frequent cause
of death and hospitalization in most developing countries. Proper attention, strict adherence
to immunization schedules and appropriate wound care will reduce the incidence of this
potentially fatal disease. Active immunization is the clear solution. Early recognition of
tetanus and early use of intensive care facilities can reduce the mortality considerably.

Acknowledgments. Our sincere thanks go to all those involved in the management of these
unfortunate patients stricken by a deadly disease. Their commitment probably saved their
lives. We also like to thank Dr. Deleu, HoD of Pharmacology and Consultant Neurologist, for
his editorial advice.
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