Sensory nerves may also become invaded by tetanus toxin [ 4 , 26 ], causing altered sensation, such as pain and allodynia [ 9 , 27 ]. It is unclear where this effect takes place, since experimental evidence suggests that the toxin is unable to pass spinal sensory ganglia [ 3 ]. Therefore, a sensory effect of the toxin should be peripheral. However, the vesicular release of neurotransmitters from sensory neurons occurs centrally, in the spinal cord or brainstem [ 28 ].
This apparent paradox may reflect the fact that altered sensation in tetanus is predominantly seen in the region of the head [ 9 , 27 ], i. It is not known whether tetanus toxin that arrives in the brainstem spreads to structures involved in higher functions, such as cognition and mood regulation.
Such symptoms are rarely reported. In a recent survey of 68 patients from Ethiopia, altered mentation was noted at an early stage in three patients, but it was not stated whether such symptoms could be attributed to the tetanus itself [ 18 ]. Sequelae of tetanus in the newborn include intellectual disability [ 29 ], which may suggest an effect of tetanus toxin on higher cerebral functions.
Animal studies show clear effects of tetanus toxin on neuronal activity after focal application to the cerebral cortex [ 30 ], implying that if the toxin reaches the brain in tetanus victims, higher cerebral functions may become affected.
Acute treatment of tetanus is based on wound cleaning and antibiotic eradication of Clostridium tetani, e. Treatment is continued for seven to ten days. The notion that one should avoid penicillin because of a possible inhibition of the GABAA receptor, which could increase muscle rigidity, does not seem to be supported by studies [ 31 ].
Tetanus antitoxin is given once intramuscularly; doses of IU, IU, or higher have been used, but it is debatable whether the higher doses are more effective [ 33 ]. The antitoxin is given to inactivate any free tetanus toxin. The toxin that has been taken up into nerve terminals is probably not available to the antitoxin. Therefore, muscle symptoms may develop further, although the clostridia have been eradicated and antitoxin has been given, because tetanus toxin continues to be transported axonally and trans-synaptically and to cleave VAMP.
Intrathecal administration of antitoxin, e. Because immunity may not develop after an episode of tetanus, vaccination is included in the treatment. Treatment of the muscular rigidity and spasms in tetanus is of vital importance, since this feature of the disease often interferes with respiration and is a likely cause of death [ 1 , 18 ].
Rigidity and spasms also cause severe pain, which stimulates muscle activity. Baclofen, which acts on GABAB receptors, may also be effective; when given intrathecally its sedative effect is avoided [ 36 ]. In the setting of an intensive care unit, propofol, another GABAA receptor modulator, may be used [ 37 ], as may non-depolarizing muscle relaxants pancuronium, pipecuronium [ 38 ], which act directly on the muscle motor end plates by competing for the acetylcholine binding site.
Magnesium, a calcium antagonist that acts both by reducing acetylcholine release and by reducing the muscle response to acetylcholine [ 39 , 40 , 41 ], may be effective in relieving rigidity and spasms [ 42 ]. Magnesium also seems to reduce autonomic dysfunction [ 42 , 43 ], which is of importance, because anti-adrenergic drugs, especially beta-blockers, may produce untoward effects, including cardiac arrest [ 24 ].
Dantrolene, which binds to the ryanodine receptor in muscle and reduces calcium mobilization and thereby muscle contraction, is also in use [ 44 , 45 ]. Tetanus patients should be in a calm environment to avoid the triggering of spasms by noise or other sensory stimulation.
This objective must be balanced against the need to avoid sensory deprivation, which predisposes to delirium, a condition that tetanus patients are prone to, given their often lengthy stays in intensive care units with mechanical ventilation and treatment with neuroactive drugs such as benzodiazepines and propofol [ 46 ].
Prophylaxis against tetanus consists of immunization with formaldehyde-inactivated tetanus toxin toxoid and measures to achieve good hygiene. For instance contamination of the umbilical stump of the newborn is a primary cause of neonatal tetanus.
These issues are interrelated: a good immunization status in pregnant women leads to reduction in the prevalence of neonatal tetanus [ 47 ], because maternal anti-tetanus toxin antibodies are transferred across the placenta to the child in utero [ 48 ]. Botulinum toxins enter nerve terminals of lower motor neurons [ 6 , 7 ]. The toxins are zinc metalloproteinases that attack synaptic vesicle proteins, but they do so differentially: botulinum toxin A cleaves synaptosomal-associated protein SNAP , botulinum toxins B, D, F, and G cleave synaptobrevin which is also attacked by tetanus toxin ; botulinum toxin C cleaves SNAP and syntaxin [ 7 ].
Compared to tetanus toxin, the botulinum toxins undergo less axonal and trans-synaptic transport, although some transport does seem to occur [ 53 , 54 ]. Therefore, the effects of botulinum toxins remain fairly confined to the nerve terminals of lower motor neurons, inhibiting release of acetylcholine and activation of voluntary muscles.
For this reason they may have a role in reducing the muscular hyperactivity in tetanus patients. In six reported cases of tetanus, all with symptom severity that amounted to grade 3 in the Ablett symptom severity grading system, botulinum toxin A was used successfully to control muscle rigidity and spasms [ 9 , 45 , 49 , 50 , 51 ].
In three cases the tetanus was cephalic or fairly local; in three it was generalized Table 1. In all cases beneficial effects of treatment were seen. However, only in one patient was the treatment given within the first week after admission to the hospital; in the remainder, botulinum toxin was given two to eight weeks after admission, although symptom severity was greatest in the earlier phase of the disease.
Therefore, one cannot rule out the possibility that the improvement seen after treatment with botulinum toxin to some extent reflected the natural history of tetanus, including spontaneous resolution of muscle rigidity. In some cases [ 45 , 50 , 51 ] botulinum toxin was used to treat residual muscle rigidity that proved especially resistant to other muscle-relaxing therapies.
Summary of case reports on the use of botulinum toxin against tetanus-induced muscle rigidity and spasms. In the four reports that give details on onset of action, improvement of rigidity was noted within one to four days. Maximal effect was reached after one to three weeks, except in one case, in which maximal effect was seen one day after injection of botulinum toxin Table 1.
The activity of botulinum toxin is reported to be increased by neuronal activity [ 55 , 56 ]. Theoretically, the action of botulinum toxin could be more rapid in tetanus, in which the activity of the lower motor neurons is much increased. Dosage varied somewhat Table 1 , but resembled those commonly used to treat dystonia [ 57 ].
Only in one patient was treatment repeated two months after the initial injection [ 51 ]. In the remaining cases, the effect of botulinum toxin apparently outlasted the symptoms of tetanus. Only in one case was a side effect noted: a certain atrophy of the masseter muscles after botulinum toxin injection for trismus [ 49 ].
Trismus and dysphagia are early and common symptoms of tetanus, both generalized and cephalic. They constitute major hazards for the patient, irrespective of the threats of respiratory failure and autonomic dysfunction described above. Normal salivation predisposes to aspiration in a patient who cannot swallow normally or evacuate the mouth, wherefore aspiration and pneumonia commonly occur in tetanus [ 58 , 59 ].
Trismus further interferes with eating and with oral hygiene, which is an important issue, because the condition may last for many weeks, endangering dental health. Lastly, trismus is associated with involuntary tongue biting, which may be very painful [ 9 ].
The use of botulinum toxin to ameliorate tetanus-induced trismus must be considered a safe procedure, given that the masseter and temporalis muscles are at some distance from the larynx; injection into the cricopharyngeal muscles to alleviate dysphagia, in contrast, requires electromyographic guidance [ 45 ]. Treatment of trismus and dysphagia with botulinum toxin should probably be considered at an early stage in tetanus, because it may contribute to a more favorable course of the disease, reducing the risk of aspiration and pneumonia, allowing dental care, and, possibly, food intake.
Injections into the trapezius, splenius capitis, levator scapulae and sternocleidomastoid muscles may alleviate painful neck rigidity; care must be taken to avoid neighboring vital structures, such as the carotid artery, and spread of botulinum toxin to the larynx.
No information exists on the use of botulinum toxin on large truncal muscles in tetanus, such as the abdominal and erector spinae muscles, which are affected in generalized tetanus. Botulinum toxin has been used for back pain syndromes with injection of the toxin into several levels of the erector spinae muscles in the L1—L5 area [ 62 ]. From such reports it seems feasible to use botulinum toxin in large truncal muscles affected by tetanus, although it must be emphasized that no clinical experience with such treatment has been published.
Disadvantages of the botulinum toxin approach to tetanus include the difficulty of treating all affected muscle groups in generalized tetanus. Even so, botulinum toxin should be considered in generalized tetanus, in which the rigidity of certain muscle groups may pose a special therapeutic challenge.
The slow onset of action and gradual increase in effect over one to three weeks necessitates simultaneous treatment with other muscle-relaxing drugs. The possibility of overdosing, the evidence of which may become manifest days after injection of botulinum toxin, makes it important to monitor patients closely.
The protracted effect of botulinum toxin [ 64 ] implies that such side effects may be of some duration. A main obstacle to the use of botulinum toxin for tetanus may prove to be the cost of treatment, especially in generalized tetanus, in which large doses may be needed to reduce rigidity and spasms of large muscles.
There is limited experience with the use of botulinum toxin for the treatment of muscle rigidity and spasms in tetanus. However, from a few published case reports it would seem that such treatment is useful. This may be especially true for trismus, which constitutes a major problem in itself, predisposing to pulmonary aspiration, painful, involuntary tongue biting, anorexia, and dental caries. The treatment of trismus with botulinum toxin is probably a fairly safe procedure, since injection into the masseter and temporalis muscles can be achieved without endangering neighboring vital structures.
However, the possibility of complications caused by distant spread of the toxin must be kept in mind. There is a general lack of randomized clinical trials with respect to both antibiotic [ 31 , 32 ] and muscle-relaxing therapies [ 35 ] in tetanus. It is to be hoped that the potential usefulness of botulinum toxin in the treatment of tetanus will lead to its evaluation in clinical trials. National Center for Biotechnology Information , U.
Journal List Toxins Basel v. Toxins Basel. Published online Jan 8. Author information Article notes Copyright and License information Disclaimer. This article has been cited by other articles in PMC. Abstract Tetanus toxin, the product of Clostridium tetani , is the cause of tetanus symptoms. Keywords: tetanus, tetanospasmin, Clostridium tetani , botulinum toxin, trismus, lockjaw, dysphagia. Introduction The muscular rigidity and spasms of tetanus are caused by tetanus toxin tetanospasmin , which is produced by Clostridium tetani , an anaerobic bacillus, whose spores survive in soil and cause infection by contaminating wounds [ 1 ].
Pathophysiology of Tetanus Toxin By a mechanism similar to that of botulinum toxin, tetanus toxin is taken up into nerve terminals of lower motor neurons, the nerve cells that activate voluntary muscles [ 4 , 5 , 6 ].
Symptomatology of Tetanus Tetanus toxin causes hyperactivity of voluntary muscles in the form of rigidity and spasms. Treatment of Tetanus Acute treatment of tetanus is based on wound cleaning and antibiotic eradication of Clostridium tetani, e.
Table 1 Summary of case reports on the use of botulinum toxin against tetanus-induced muscle rigidity and spasms. Two injection sites per muscle. Proper treatment and cleaning of wounds can also help prevent the infection. Without treatment, tetanus can be fatal. Death is more common in young children and older adults. According to the CDC , roughly 11 percent of reported cases of tetanus have been fatal in recent years.
This rate was higher in people who were older than 60 years, reaching 18 percent. In people who were unvaccinated, 22 percent of cases were fatal. Prompt and proper treatment will improve your outlook. Go to your doctor or emergency room right away if you think you may have tetanus. The vaccine is extremely effective, according to the CDC. Reports of tetanus occurring in fully immunized people who have received a vaccine or booster within the last 10 years are very rare.
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Shigellosis is a bacterial infection that affects the digestive system. The Shigella bacterium is spread through contact with contaminated feces. In there were only 4 cases of tetanus reported in England.
The number is low because an effective tetanus vaccine is given as part of the NHS childhood vaccination programme. Most people who get tetanus have either not been vaccinated against it or did not complete the entire vaccination schedule. Tetanus bacteria can survive for a long time outside the body and are commonly found in soil and the manure of animals such as horses and cows.
If the bacteria enter the body through a wound they can quickly multiply and release a toxin that affects the nerves, causing symptoms such as muscle stiffness and spasms. The symptoms of tetanus usually start around 4 to 21 days after infection. On average, they start after around 10 days. Contact a GP or visit your nearest minor injuries unit if you're concerned about a wound, particularly if:. A doctor will assess the wound and decide whether you need treatment and whether you need to go to hospital.
If a doctor thinks there's a chance you could develop tetanus from a wound, but you do not yet have any symptoms, they'll make sure your wound is thoroughly cleaned. They may also give you an injection of tetanus immunoglobulin. If you have not been fully immunised for tetanus, or you're not sure whether you have, you may be given a dose of the tetanus vaccine. You may also be given antibiotics. Tetanus immunoglobulin is a medicine containing antibodies that prevent the tetanus toxin working, stopping its effects on the nerves.
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