A Case Study and Clinical Review of Clostridium tetani
Tetanus isn't necessarily a thing of the past in the United States
By Troy M. Smith, DO
Tetanus is an illness characterized by an acute onset of hypertonia, painful muscle contractions (usually of the neck and jaw) and generalized muscle spasms without other apparent medical etiologies.
The toxin, tetanospasmin, which is released by the germinating spores of the bacterium, Clostridium tetani, causes the disease. This obligate anaerobic gram-positive bacillus forms spores, which are resistant to heat, desiccation and disinfectants. If the spores enter a wound that penetrates the skin under anaerobic conditions, they germinate and release the tetanospasmin toxin, which ranks with botulism toxin as the most potent known microbial poison.
An estimated one million infants die of tetanus in developing countries each year because of poor hygiene. Since childhood immunization laws were passed in the United States in the 1970s, only about 50 cases a year are reported in this country.(1) Presently, tetanus is a severe disease of primarily older adults who are unvaccinated or inadequately vaccinated. The following case study involves an individual who was eventually diagnosed and treated for a tetanus infection in March of 2004.
Case Study
This 75 year-old Caucasian male was driving back to Michigan following a six-month stay in New Mexico. He began to notice difficulty holding a coffee cup and some weakness in his left arm. He wasn’t concerned, because he had experienced on-and-off weakness since experiencing a CVA three years prior. Four days later, he began to experience twitching in his left arm, with spasms to the left side of his face. Retrospectively, he gave history of having fallen twice, and of progressive weakness of his upper extremities. He then presented to an emergency room for evaluation.
His medical history was significant for mild emphysema with a 20-pack-per year history of cigarette smoking, hyperlipidemia, a prior cerebral vascular accident in 2001, and partial gastric resection for peptic ulcer disease in 1965. He related a history of moderate alcohol use. He lived in a suburban area of Detroit, Michigan, and traveled every winter to New Mexico. He related no known recent immunizations or previous military service.
Physical examination revealed a temperature of 101° F, heart rate of 104 bpm, blood pressure 124/64 and respiratory rate of 18. The patient was alert and oriented times three and was in no acute respiratory distress. His cardio-pulmonary exam was unremarkable. His neurological exam revealed intermittent, involuntary muscle spasms of the left upper extremity of approximately five seconds in duration. He demonstrated an occasional left facial grimace with the spasms. He also had diffuse weakness of the left upper extremity. His deep tendon reflexes were symmetric and sensation was intact.
He was admitted to the hospital, and evaluated by the neurology and infectious disease services. He underwent extensive diagnostic studies, which revealed normal CBC, VDRL and CSF studies. His metabolic labs were normal, except for a low sodium finding of 131. His serologies including Lyme and West Nile antibodies, and others were negative. His chest x-ray and CT of the head were negative. His EEG was reported as mildly abnormal, non-specific cerebral dysfunction with mild encephalopathy. His clinical condition deteriorated and he developed progressive dysarthria and dysphagia. He continued to have dystonic movements to his face and upper extremeties. He required intubation with mechanical ventilation as well as a PEG tube placement. He was also treated for an upper GI bleed and developed PSVT and atrial flutter.
The etiology for his progressive neurologic decline was uncertain. He was suspected to have had a possible toxin exposure. On further questioning of his family, they revealed he had dental work performed in Mexico two weeks prior to his admission. The neurologist suspected generalized tetanus, and empirically treated him with a diphtheria-tetanus vaccination and 6,000 units of tetanus immune globulin.
During the next few days, the patient’s clinical status began to improve. He required continued supportive care and inpatient rehabilitation. After a prolonged recovery, he was eventually discharged to home with near- full recovery of his previous functional ability.
As this near-fatal case illustrates, it is important to consider tetanus in the differential diagnosis of cases with unexplained neurological symptoms. The balance of this article provides an overview of the pathophysiology, history and clinical features, management and prevention of tetanus.
Pathophysiology
The toxin, tetanospasmin, which is released by the germinating spore of the tetanus bacillus to underlying tissue, circulates via the lymphatic and vascular circulation, where it diffuses to the end plates of all nerves. The circulating toxin cannot cross the blood-brain barrier, and therefore does not enter the central nervous system directly, except at the fourth ventricle.(2) The toxin binds to the gangliosides at the neuromuscular junction, and is transported along the axon in a retrograde direction into the neurons of the central nervous system. The transport in the motor nerve takes from two to 14 days to reach the CNS.(2)
The toxin affects the inhibitory neurons, preventing the release of GABA and glycine, leading to failure of inhibition of motor reflex responses to sensory stimulation. This causes muscle rigidity and the characteristic generalized contractions of a tetanic spasm, along with autonomic instability. Once the toxin binds to neurons, it cannot be neutralized by antitoxin. The length and course of illness is influenced by the amount and location of the bound toxin. The usual clinical course of tetanus usually ranges from two to four weeks, and is influenced by the age of the patient and the development of complications.(3)
History and Clinical Features
The diagnosis of tetanus requires a high index of clinical suspicion, as there are no specific laboratory tests for its diagnosis. In 15 to 30 percent of cases, there is neither a history of injury, nor a source of infection.(4) The mechanism of injury is commonly contamination of a wound, burn or animal bite but atypical cases from middle ear infection, dental caries, septic abortion and intramuscular injections have been reported.(2)
Tetanus may occur in three clinical forms: localized, generalized or cephalic. Local tetanus is characterized by muscle spasm near the site of inoculation. It may precede generalized tetanus, but by itself, is usually resolved without sequelae after several weeks. Cephalic tetanus is a rare manifestation that involves introduction of the Clostridium tetani bacterium in the head and neck region. The most common affected cranial nerve is the facial nerve.
Generalized tetanus is the most common form seen in 80 percent of cases. The onset may be insidious, but typically presents with trismus (i.e. lock jaw) in 75 percent of the cases. Other presenting complaints include dysphagia, stiffness, neck rigidity, restlessness and reflex spasms.
As the disease progresses, muscle rigidity becomes the major manifestation. Muscle rigidity spreads from the jaw and facial muscles to the extensor muscles of the limbs during the next 24 to 48 hours. Persistent contraction of facial musculature may occur, producing the classic sneering grin expression known as risus sardonicus.(3) Reflex spasms develop in most patients, and can be triggered by minimal external stimulation such as light, touch or noise. They may last seconds to minutes, and as the disease progresses, may cause fractures, dislocations, apnea and rhabdomyolysis. In severe cases of tetanus, autonomic dysfunction occurs, which is often the cause of death.
One bedside diagnostic test is known as the spatula test.(5) A spatula or tongue blade is used to touch the posterior pharynx. This usually elicits a gag reflex and the patient tries to expel the tongue blade. This is a negative test. In tetanus, the patient develops a reflex spasm of the masseters and bites the spatula. This is a positive test. In 400 patients this test had a specificity of 100 percent, and sensitivity of 94 percent. No adverse sequelae were reported from this test. This test can be performed in a patient presenting with trismus to help aid in the early diagnosis of tetanus and to hasten appropriate therapeutic intervention.
Management
Since there is no way to remove the toxin once it is bound to nervous tissue, the only specific treatment is to eradicate the bacteria from the wound and neutralize the circulating toxin, and to provide appropriate supportive care. Specific therapy includes administration of intramuscular human tetanus immune globulin HTIg to neutralize any residual circulating antitoxin. The recommended dose is 500 to 3000 U. A patient also should receive tetanus toxoid to prevent recurrent disease. Therapy also includes antibiotics and wide wound debridement under anesthesia
when a wound is identified.
Penicillin had previously been the traditional antibiotic for tetanus, but it was shown to be a GABA antagonist, which could aggravate tetanus spasms. It has been replaced with metronidazole (Flagyl), which is bactericidal against obligate anaerobes including C. tetani.(2) The recommended dose is 500 mg intravenously every eight hours for seven to 10 days.
Patients should be monitored in an intensive care setting, and prophylactic intubation should be considered in all patients with moderate to severe clinical manifestations. Patients also require minimal external stimulation. Sedation and muscle relaxation should be instituted, usually with diazepam (0.1-0.2 mg/kg IV q 4-6 hours).(3) Maintenance of adequate hydration, nutrition and oxygenation is also required. Often, these patients require parenteral nutrition due to the lengthy disease process. The main goal of therapy is to prevent and treat complications.
New treatment options to consider reported to avoid artificial ventilation and sedation are dantrolene, baclofen and magnesium. Magnesium therapy has the advantages
of controlling spasms and sympathetic hyperactivity without sedation. Studies have concluded that magnesium should be used as
a first line therapy in the routine management of tetanus.(2)
The main predictors of prognosis are the quickness of symptom onset from exposure and the rate of progression from trismus to severe spasms. In general, shorter intervals indicate more severe tetanus and a poorer prognosis. Most patients usually survive tetanus and return to their predisease state of health, but recovery is slow and usually occurs during a two- to four-month period.
Conclusion
The best treatment for tetanus is prevention. The cost of immunization
is negligible, compared to the costs of
treating a prolonged case of tetanus. Active immunization with tetanus toxoid is the
most effective means of prevention.(6) Tetanus toxoid is one of the safest and most effective vaccines available.(7) Serious vaccine complications are rare, with anaphylaxis occurring one in one million cases.(8) The primary series of tetanus toxoid, administered as DTP vaccine at two, four and six months, and a booster 12 months later, ensures protection in childhood. Additional boosters should be given each decade throughout
life, with further tetanus prophylaxis after acute wounds.
Individuals who have received a full primary immunization and appropriate boosters need only local wound care for clean and minor wounds. However, they should receive a tetanus toxoid booster after a dirty, tetanus-prone wound if the most recent dose was received more that five years previously. Patients who have not completed a primary series require a tetanus toxoid booster after any penetrating wound, and TIG after a tetanus-prone injury. The prophylactic dose of TIG is 250-500 U, given intramuscularly.
Although tetanus is uncommon in the U.S., it could be minimized by updating and maintaining tetanus immunizations. With tetanus being such a preventable disease, it is important to ask patients about their immunization histories and to update them when possible. In addition, vaccination programs need to be expanded worldwide to decrease this highly preventable disease.
Troy M. Smith, DO, is a 1990 graduate of the University of Osteopathic Medicine and Health Sciences-College of Osteopathic Medicine and Surgery in Des Moines, Iowa. He completed a Family Practice residency at Garden City Osteopathic Hospital in 1993. He is Board-certified in Family Practice and Geriatric Medicine. He is a Clinical Assistant Professor of Family Medicine at Michigan State University, East Lansing, Michigan.
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