Tetanus …

Infectious Disorders

Updated 03.30.2023
Released 02.25.1994
Expires For CME 03.30.2026

Tetanus

Authors: Wanakorn Rattanawong MD, Anan Srikiatkhachorn MD, Thiravat Hemachudha MD

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Editor: John E Greenlee MD

Tetanus

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Introduction

Overview

Despite an effective immunization method, tetanus is still a threat in developing countries worldwide. In developed countries, this condition affects certain population groups, especially the elderly. In this article, the authors describe the clinical features of tetanus, which are characterized by sustained muscle rigidity and reflex spasm. Tetanospasmin, a toxin of Clostridium tetani, is responsible for these clinical symptoms. Besides symptomatic treatment, neutralization of this toxin is a mainstay for treating this condition. The beneficial effect of intrathecal immunoglobulin in conjunction with intramuscular administration has been proven in a randomized controlled clinical trial, and tetanus toxoid is considered very safe, even for immunodeficient individuals.

Key points

	• Tetanus is caused by the neurotoxin tetanospasmin, produced by an anaerobic motile gram-positive rod, Clostridium tetani.
	• This toxin interferes with the release of inhibitory neurotransmitter causing excessive excitation of spinal and bulbar motor neurons.
	• The hallmarks of tetanus are sustained muscular rigidity and, in severe cases, reflex spasms.
	• Autonomic instability, mostly hypersympathetic state, may occur in severe cases.
	• Elimination of the source of toxin, toxin neutralization, control of muscle rigidity and spasms, and ventilatory support are the main strategies in treatment of tetanus.

Historical note and terminology

The earliest record of tetanus dates back to Egyptian civilization. It was demonstrated in case seven in the Edwin Smith Surgical Papyrus, which involved a patient with trismus and nuchal rigidity after a penetrating skull injury (15). In 1890, a strychnine-like toxin, later known as tetanospasmin, was isolated from anaerobic soil bacteria and was proved to be responsible for clinical tetanus in experimental animals. Immunization with an inactivated derivative of this bacterial extract results in protection from clinical tetanus (56; 07).

Clinical manifestations

Presentation and course

	• Tetanus is classified into local and generalized forms.
	• Manifestations of generalized tetanus include muscular rigidity and reflex spams. Autonomic manifestations may be evident in later stages of the disease.
	• Localized tetanus presents with fixed rigidity confined to the affected limb that contains the wound. Cephalic tetanus, a special type of localized tetanus, presents with trismus plus paralysis of one or more cranial nerves.
	• The incubation period varies from days to weeks.
	• Prognosis depends on the temporal progression, degree of clinical severity, presence of autonomic instability, portal of entry, and age.
	• Complications include pneumonia, fractures, muscle ruptures, rhabdomyolysis, and renal failure.

The hallmarks of tetanus are sustained muscular rigidity and, in severe cases, reflex spasms. In most cases, a portal of entry can be identified; however, the lack of a defined wound does not exclude tetanus.

Clinically, tetanus can be classified into local and generalized forms (21; 12). The interval between the time of spore inoculation and development of first symptoms is referred as “incubation period,” which may vary from a few days to weeks. The time from the first symptoms to reflex spasms is known as period of onset. This temporal progression of symptoms determines the disease severity.

Early manifestations of generalized tetanus are rigidity of the masseter muscles (trismus, or lockjaw) and facial muscles, with straightening of the upper lip (grimace, or risus sardonicus).

Trismus in tetanus

Early manifestations of generalized tetanus are rigidity of the masseter muscles (lockjaw) and facial muscles, with straightening of the upper lip or risus sardonicus. (Contributed by Dr. Thiravat Hemachudha.)

Localized stiffness near the injury may be present. These symptoms are soon followed by rigidity of axial musculatures with predominant involvement of neck, back muscles (opisthotonos), and abdomen. Frequently, rigidity of axial parts precedes or appears simultaneously with lockjaw. As the disease progresses, stiffness of limb muscles also becomes evident with relative sparing of distal parts. Paroxysmal, violent contractions of the involved muscles (reflex spasms) appear repetitively only in severe cases in response to attempts at voluntary movement and to even slight external and internal (fear, hunger, etc.) stimuli. Trismus and spasms of deglutition muscles (in severe cases) cause difficulties in swallowing and in verbal expression. Generalized spasms, as well as laryngospasm, contribute to ventilatory insufficiency and asphyxia. The alteration of consciousness and true convulsive seizures are the consequence of severe cerebral hypoxia rather than the disease per se. The severity of symptoms continues to increase for 10 to 14 days after onset, and recovery usually begins after 4 weeks.

Autonomic instability, mostly hypersympathetic state, may complicate severe cases (75). Fluctuations of blood pressure and heart rate are cardinal features. These may be followed by arrhythmias and circulatory failure. Profuse sweating, hypersalivation, and extreme hyperpyrexia are also commonly present.

Patients who have an incubation period between 10 to 14 days and a period of onset of over 3 to 6 days with infrequent reflex spasms are classified as having a moderate degree of severity. A shorter incubation period and period of onset accompanied by respiratory compromise and frequent and violent spasms with severe dysphagia are regarded as evidence of severe generalized form.

Neonatal tetanus usually occurs as a generalized form and carries a high mortality. The disorder usually develops during the first 2 weeks in children born to inadequately immunized mothers and frequently follows umbilical stump infection. Some birth practices performed in developing countries, such as application of clarified butter (ghee) heated with contaminated dung fuel on an umbilical wound or wrapping an infant in sheepskin after dry cow dung is applied (bundling), are risk factors for neonatal tetanus (09; 08; 77). Failure to suck and twitching are the most frequent symptoms of neonatal tetanus.

Fixed muscular rigidity confined to a wound-bearing extremity is the characteristic of local tetanus and may persist for months. However, it is more common that local tetanus is a forerunner of the generalized form. Cephalic tetanus is a specialized form of local tetanus, presenting as trismus plus paralysis of one or more cranial nerves. Facial paresis and dysphagia are common presentations. Abnormal ocular movements including bilateral trochlear nerve palsy (ophthalmoplegic tetanus) and downbeat nystagmus can be present (59). Cephalic tetanus is usually associated with infections of paracranial structures, especially chronic otitis media and dental infection (12).

Prognosis and complications

Prognosis depends on the temporal progression, degree of clinical severity, presence of autonomic instability, portal of entry, and age. Burns, infected umbilical stumps, septic abortion, intramuscular injection, and compound fractures are often related to poor outcome. Tetanus that follows intramuscular quinine injection carries high mortality with a rapidly fatal course (80). Poor prognostic factors for neonatal tetanus includes age less than 10 days on admission, symptom duration less than 5 days on admission, risus sardonicus, fever, infant weight of less than 2500 g, and increase in white blood cells (33; 24; 42).

Complications include pneumonia, fractures, muscle ruptures, rhabdomyolysis, and renal failure. Tetanus-induced acute renal failure is probably related to adrenergic overactivity (22). Phrenic and laryngeal neuropathies as well as toxic axonal polyneuropathy have also been found as consequences (48).

Clinical vignette

A 32-year-old previously healthy male was brought to the emergency room because of difficulty in swallowing and chewing. He reported having punctured his right foot with a nail 7 days previously. He did not receive any antitetanus antiserum or tetanus toxoid. His immunization record showed that he had completed primary immunization program during childhood but had received no booster. Physical examination revealed trismus and rigidity involving facial and trunk muscles. The wound at the right sole was infected. He was diagnosed as having tetanus and was admitted to the hospital.

Human tetanus immune globulin was given intramuscularly. The wound was cleansed thoroughly. Amoxicillin-clavulanate (1.2 g every 8 hours intravenously) and metronidazole (500 mg every 6 hours intravenously) were given and continued for 10 days. A nasogastric tube was inserted. Diazepam was administered intravenously to control muscle rigidity.

Despite such treatments, his condition deteriorated in the following days. Rigidity spread to the limbs and torso. Spasms occurred spontaneously and in response to external stimuli. Rigidity and spasm were severe enough to compromise respiration. An endotracheal tube was inserted after administration of pancuronium. Tracheostomy was performed thereafter, and respiration was assisted by mechanical ventilator. Pancuronium was given intravenously every 2 to 3 hours and was continued for 4 weeks. Substantial improvement was evident at the end of the fourth week. Rigidity improved, requiring fewer doses of pancuronium. In the sixth week, rigidity was controlled by diazepam alone. He recovered uneventfully and was discharged after 8 weeks.

Biological basis

	• Tetanus is caused by the neurotoxin tetanospasmin, which is produced by an anaerobic motile gram-positive rod, Clostridium tetani.
	• Tetanus produces two exotoxins: tetanolysin and tetanospasmin. Only tetanospasmin is directly involved in the production of neurologic signs.
	• Wounds that provide an anaerobic condition and are associated with a severe degree of tissue necrosis, foreign bodies, or active infection with other organisms are more prone to produce tetanus.
	• Tetanus toxin gains access to the CNS by retrograde axonal transport within motor nerves from the site of infection. Within the CNS, the toxin moves transsynaptically into presynaptic inhibitory interneurons where inhibition of the release of neurotransmitters (mainly GABA in brainstem and glycine in spinal cord) takes place, resulting in tetanus presentations.

Etiology and pathogenesis

Tetanus is caused by the neurotoxin tetanospasmin, produced by an anaerobic motile gram-positive rod, Clostridium tetani. The mature form has a slender shape with a terminal spherical spore. Spores may survive several years and are resistant to various disinfectants and to boiling for 20 minutes. Under an appropriate anaerobic condition, contaminated spores start to germinate and proliferate to easily inactivated vegetative cells with subsequent production of two exotoxins: tetanolysin and tetanospasmin. The clinical relevance of tetanolysin in tetanus is still uncertain. The complete genome sequence of Clostridium tetani has been reported (16).

The thermolabile neurotoxin tetanospasmin, a zinc metalloprotease, which is responsible for the clinical tetanus, is a single 1315-amino acid polypeptide chain of 151 kd, formed in vegetative cells under plasmid control. The native nonvirulent or low-virulent molecule becomes toxic after being cleaved at serine-458 by a bacterial protease resulting in a heterodimer of one heavy (100-kd) and one light (50-kd) chain connected by a disulfide bridge (10). This bridge as well as a second bridge on the heavy chain is required for the toxin activity (40). By using papain that cleaves the heavy chain at lysine-865, this toxin molecule can be divided into three fragments. C fragment is a 50-kd carboxy-terminal polypeptide. The remaining A-B fragment is the light chain and the amino-terminal end of the heavy chain, joined by a disulfide bridge. The C fragment is responsible for attachment and internalization of toxin, whilst the A-B fragment involves the inhibition of neurotransmitter release. Tetanus toxin entry into vertebrate motoneurons may involve binding of neuronal surface gangliosides containing the “1b” substructure (70). This toxin internalizes the lumen of synaptic vesicles via the process of vesicular reuptake. Vesicle acidification is essential for the toxin translocation in the cytosol where it exerts its neurotoxic effect (50).

Any breach in skin or mucosal barrier may result in the inoculation of C tetani spores. Wounds that provide an anaerobic condition (low oxidation-reduction potential), eg, those associated with a severe degree of tissue necrosis, foreign bodies, or active infection with other organisms, are more prone to produce tetanus. Toxin released in the wound binds to the peripheral nerve terminals directly, as in the case of local tetanus, or may disseminate via the bloodstream to neuromuscular junctions throughout the body before binding in generalized form (61). The toxin gains access to the CNS by retrograde axonal transport along the motor nerves. Within the CNS, the toxin moves transsynaptically into presynaptic inhibitory interneurons where inhibition of the release of neurotransmitters (mainly GABA in brainstem and glycine in spinal cord) takes place, resulting in heightened muscular activity (53). By a similar process, loss of glycine inhibition may affect preganglionic sympathetic neurons in the intermediolateral gray matter of the spinal cord and produce increased sympathetic activity with markedly increased catecholamine levels. This inhibitory action is mediated by protease activity of light chain on synaptobrevin at Gln 76 to Phe 77 (43; 69). Synaptobrevin (also known as vesicle-associated membrane protein or VAMP) is an integral membrane protein of small synaptic vesicles and is essential for docking vesicles into release site on synaptic membrane. Motor neurons can also be similarly affected causing the reduction in the release of acetylcholine at the motor end plate. This may account for the paralysis of cranial nerves observed in cephalic tetanus. However, in general, this prejunctional effect on the neuromuscular junction is usually overwhelmed by the central disinhibition of motor neurons.

Prevention

	• Immunizations come in two forms: active and passive.
	• Active immunizations can be administered alone as a single toxoid (TT), in combination with diphtheria (DT, dT), or with diphtheria and pertussis (DTwP, DTaP, dTaP or dTaP).
	• The World Health Organization recommends infants receive three doses of diphtheria, tetanus, and pertussis (DTP) in the first 6 months of life. To maintain lifelong immunity, three additional doses are required at the ages of 12 to 23 months, 4 to 7 years, and 9 to 15 years of age, with a 4-year interval between each dose. In addition, the CDC also recommends a booster dose every 10 years.
	• Passive immunization comes in forms of tetanus immunoglobulin, which are used to neutralize tetanospasmin and circulating toxins.
	• In the event of injury, patients who have completed the primary vaccination within 5 years for tetanus-prone wounds and within 10 years for clean wounds do not require booster immunization. Patients with tetanus-prone wounds with incomplete immunization or no immunization within the preceding 10 years should receive human tetanus immunoglobulin 250 IU intramuscularly on a separate site with a different syringe from that used for the tetanus-containing vaccine.

Wounds with severe tissue necrosis, suppuration, and retained foreign bodies (eg, burns, umbilical stumps, compound fractures, septic abortion, intramuscular injection) are associated with high risk of tetanus. Appropriate wound care and immunization are the main preventive strategies.

In preventing tetanus, certain immunizations are available in forms of both active (tetanus toxoid) and passive (tetanus specific immunoglobulin) immunizations. Active immunizations come in forms of toxoid that can rather be administered alone as single toxoid (TT) or in combination with diphtheria (DT, dT) or diphtheria with acellular pertussis (DTwP, DTaP, dTaP or dTaP). In some countries, combining tetanus with hepatitis B, Haemophilus influenzae type b, and poliomyelitis may be used. It is advised that combination vaccines should be selected first rather than tetanus toxoid alone. DT vaccines are recommended to be use in children younger than 7 years of age whereas dT vaccines for those 7 and older are recommended. A WHO expert consultation panel concluded that dT could be used in children aged 4 to 7 years as a second booster dose in the 6-dose series and that this regimen could provide adequate protection to tetanus and diphtheria (27). Passive immunizations come in forms of tetanus immunoglobulin (TIG) used to neutralize tetanospasmin and circulating toxins.

The DTP combination (primarily for children aged less than 1 year) has been part of The World Health Organization’s Expanded Program on Immunization since its inception in 1974. The primary set of DTP consists of three doses (DTP3) that should be given to infants in their first 6 months of life with at least 4-week intervals for each dose. This primary series is the fundamental requirement in building a lifelong immunity. WHO suggests that in maintaining a lifelong immunity, three additional doses are required at the age of 12 to 23 months, 4 to 7 years, and 9 to 15 years of age with a 4-year interval to each dose (78). This practice is also recommended by the Centers for Disease Control and Prevention but with an additional recommendation of a single booster every 10 years (17; 18; 20). Prophylactic administration of antipyretic drugs at the time of vaccination to prevent febrile reaction can minimize the antibody response and, therefore, is not recommended as routine practice (62).

Preterm infants have a similar antibody response after completion of the primary series of regular vaccines (23). Reduction of vaccine dosage for preterm infants may result in inadequate immunity (11). The antibody titer to routine tetanus immunization can be reduced in preterm infants who receive dexamethasone, but the level is still above protective level. Therefore, additional booster vaccination for these infants is not necessary (64). Breastfeeding (more than 6 months) can increase immunity against tetanus (60).

Unvaccinated adults or those with incomplete history of primary prevention vaccination should undergo a primary prevention of three doses tetanus-containing vaccine; administer the first two doses at least 4 weeks apart and the third dose 6 to 12 months after the second. Further recommendation suggests that for maintaining a lifelong immunity, an additional two doses are preferred. A booster dose of tetanus-containing vaccines is given to individuals in whom childhood primary vaccination was completed and last dose was given 10 years or more previously (78).

Specific risk patients may need reimmunization; this includes recipients of bone marrow transplantation because of the loss in protective immunity (45). HIV patients have been reported to have a lower response to tetanus vaccination as its disease progresses, but they still show a positive response compared with other vaccinations (66). Antibody monitoring after tetanus immunization may be necessary in special groups of patients, such as those receiving hemodialysis, because a high percentage of recipients do not show documentable seroconversion after standard immunization (41). For previously immunized travelers to endemic areas and healthcare workers, there is no evidence that revaccination is needed. Another group of patients that might need attention are diabetic patients. Diabetic patients have a lower level of tetanus antitoxin compared to nondiabetic people. In addition, patients with diabetic foot are more prone to tetanus (38; 35).

Vaccination in pregnant women is an emerging concern in the prevention of neonatal tetanus and will be discussed in the pregnancy section.

In case of injuries, patients who have completed the primary vaccination within 5 years for tetanus-prone wounds and within 10 years for clean wounds do not require booster immunization. Patients with tetanus-prone wounds with incomplete immunization or no immunization within the preceding 10 years should receive human tetanus immunoglobulin 250 IU intramuscularly on a separate site with a different syringe from that used for the tetanus containing vaccine (78). Patients with immunodeficient states should also receive passive immunization after injuries unless adequate immunity to tetanospasmin has been demonstrated (12).

Tetanus toxoid is considered very safe, even for use in immunodeficient individuals. Adverse effects of tetanus toxoid are usually mild (local tenderness and edema). In general, both local and systemic reactions increase with increasing numbers of doses. Granuloma formations at the injection sites and Arthus reactions especially after boosters have been reported. Therefore, tetanus-diphtheria toxoid boosters should not be given to anyone who has either completed a primary series or received a booster dose within the previous 5 years. On rare occasions, nervous system complications, eg, acute radiculomyelitis parkinsonism, brachial neuritis, or Guillain-Barré syndrome, can develop following the administration of tetanus toxoid (72; 06; 34; 63). Tetanus vaccination is not associated with an elevated risk of multiple sclerosis exacerbation (46).

Management

	• Key strategies for the management of tetanus include elimination of the source of toxin, toxin neutralization, control of muscle rigidity and spasms, and ventilator support.
	• Prophylactic intubation should be considered in moderate to severe tetanus.
	• Portal of entry identification with appropriate wound care is necessary to eliminate the source of toxin.
	• Metronidazole is the antibiotic of choice in tetanus.
	• Toxin neutralization with human tetanus immunoglobulin should be administered in all cases.
	• Severe muscle rigidity and spasms are frequently found during the disease. Several drugs are proven to be beneficial, including benzodiazepines.

Elimination of the source of toxin, toxin neutralization, control of muscle rigidity and spasms, and ventilator support are the main strategies in treatment of tetanus (21; 12).

The first step of tetanus management is to consider prophylactic intubation and mechanical ventilation, particularly in moderate to severe tetanus. Intubation may still be necessary even in the absence of severe or frequent spasms, especially in patients with severe generalized rigidity within a few days after the first clinical symptoms and in patients whose incubation periods are shorter than 10 days (severity continues for 10 to 14 days after onset). The drawback of an endotracheal tube is that it stimulates spasms; as a result, tracheostomy should be considered to prevent further damage (55).

Identification of the portal of entry and wound dressing are necessary in every tetanus patient. In cases without an apparent source, careful examination for signs of parenteral drug abuse, otitis, or rectal or vaginal instrumentation should be attempted. Improper wound care with retaining of foreign body may result in continuous toxin production. Antibiotic therapy is usually recommended despite the controversy of its benefit. Metronidazole (500 mg intravenously every 6 hours for 7 to 10 days) is the drug of choice and has shown better survival, shorter hospital stays, and less disease progression compared with the alternative penicillin (02). Parenteral administration of penicillin (10 to 12 million U daily for 10 days) is an alternative. Because penicillin has central GABA antagonistic effect; however, it may act synergistically with tetanospasmin and worsen spasms. Clindamycin and erythromycin are also alternatives for penicillin-allergic patients.

Neutralization of circulating (unbound) toxin by antitoxin will shorten the course of disease and lower mortality. Human tetanus immune globulin should be administered promptly before manipulating the wound. The recommended dose is 500 U intramuscularly. Combined intrathecal (1000 U) and intramuscular antitetanus immunoglobulin administration gives better clinical outcomes than intramuscular administration alone (51). A meta-analysis based on results from 12 clinical trials confirmed the benefit of using intrathecal therapy over intramuscular administration. The combined relative risk of mortality for intrathecal versus intramuscular therapy was 0.71 (95%CI, 0.62-0.81) (36). In addition to clinical outcome, intrathecal immunoglobulin also reduces cost by preventing a worsening of disease severity and shortening hospital stay (52). Equine antitetanus serum (doses up to 10,000 to 100,000 U) is an alternative in case human tetanus immune globulin is not available, but it should be used after testing and desensitization. A primary immunization series is also required in addition to human tetanus immune globulin.

For control of muscle spasms and rigidity, several drugs have been proven to be beneficial. Benzodiazepines are key medications for controlling spasms because of their action as GABA agonists. Diazepam is the most preferable drug of its kind due to its widely studied benefits. A dose of 5 mg is given intravenously with an incremental dose of up to 600 mg until spasm is controlled but without ventilatory depression (76). Lorazepam and midazolam have no solid evidence of efficacy compared with diazepam but can be used as alternatives (65). Phenobarbitone and chlorpromazine have also been used worldwide, but a study shows that diazepam alone is more effective than combination of phenobarbitone and chlorpromazine (57). In patients whose spasms could not be controlled with benzodiazepine or in severe cases with ventilation failure, neuromuscular junction blockade using agents such as atracurium, vecuronium, or pancuronium, are preferred. Propofol has also proven to be effective, but its side effects, including metabolic acidosis, rhabdomyolysis, and cardiac arrhythmia, should be considered (58). Intravenous magnesium sulphate alone has been reported to effectively control both muscle spasms and autonomic dysfunction in a prospective study of 40 patients (05).

Intrathecal baclofen (infusion or intermittent injections) may be effectively used as a single therapy in moderately severe cases (67; 29). However, risk of developing central depression with coma and respiratory failure after frequent injections precludes its use as a routine in tetanus treatment. Flumazenil has been used to counteract these adverse effects (68).

Autonomic instability has been a troublesome problem due to its lack of positive response to medication. Combined alpha- and beta-adrenergic blocking agents such as labetalol, have been tried with some success. Beta-adrenergic blockade is rarely used because hypotension and sudden cardiac arrest may occur. Only esmolol was proved to be effective in a case report (39). Other alternatives include parenteral administration of morphine, fentanyl, magnesium sulfate, clonidine, atropine, and continuous spinal anesthesia (12; 32). Magnesium infusion can reduce the requirement for other drugs to control muscle spasms and cardiovascular instability but does not reduce the need for mechanical ventilation in adults with severe tetanus (74). In medication-refractory autonomic instability cases, stellate ganglion blocks were reported to show control over autonomic storm, but further study is needed (03).

Special considerations

Pregnancy

Maternal tetanus is tetanus occurring during pregnancy or within 6 weeks after any type of pregnancy. Approximately 15,000 to 30,000 cases of maternal tetanus occur in developing countries each year (31). No further data have been reported thus far, but incidence of maternal tetanus is likely to have fallen due to maternal vaccine coverage (73). Neonatal tetanus is defined as any neonate with normal sucking in the first 2 days who then cannot suck normally between 3 to 28 days and has spasm and stiffness (78).

In preventing both maternal and neonatal tetanus, safe deliveries, umbilical cord care, and maternal immunization are of extreme importance. However, the most cost-effective prevention is complete vaccination. Studies suggest that a complete set of six doses of tetanus-containing vaccine in childhood or five doses at adolescence can prevent both maternal tetanus and neonatal tetanus, with no need for further immunization (26). For countries where tetanus is endemic, at least two doses of tetanus-containing vaccines are recommended. Each dose should be 4 weeks apart with the last dose at least 2 weeks before delivery. For those with only three doses in childhood, an additional two doses are recommended (78). A study showed that antepartum Tdap vaccination produces no adverse pregnancy outcomes for either mother or child (54). The mortality associated with postpartum tetanus is comparable to nonpostpartum cases, and early hysterectomy has no effect on its outcome (37).

Immunization for pregnant women is also effective in preventing cases of and deaths from neonatal tetanus. A meta-analysis showed that immunization of pregnant women or women of childbearing age with at least two doses of tetanus toxoid is estimated to reduce mortality from neonatal tetanus by 94% (95% confidence interval 80% to 98%) (13). Tetanus toxoid immunogenicity as well as maternal-fetal antibody transfer can be affected by various factors, including maternal vitamin A deficiency, maternal HIV infection, and placental infection with falciparum malaria (14; 25; 28). Freezing tetanus toxoid has been shown to decrease its potency, but its impact on immunogenicity needs more evaluation.

References

01: Abrahamian FM, Pollack CV Jr, LoVecchio F, Nanda R, Carlson RW. Fatal tetanus in a drug abuser with "protective" antitetanus antibodies. J Emerg Med 2000;18:189-93. PMID 10699520
02: Ahmadsyah I, Salim A. Treatment of tetanus: an open study to compare the efficacy of procaine penicillin and metronidazole. Br Med J 1985;291:648-650. PMID 3928066
03: Altiparmak B, Uysal Aİ, Yaşar E, Demirbilek S. [Alternative approach to autonomic instability of very severe tetanus: stellate ganglion block]. Rev Bras Anestesiol 2018;68(2):209-11. PMID 28551062
04: Apte NM, Karnad DR. Short report: the spatular test: a simple bedside test to diagnose tetanus. Am J Trop Med Hyg 1995;53:386-7. PMID 7485691
05: Attygalle D, Rodrigo N. Magnesium as first line therapy in the management of tetanus: a prospective study of 40 patients. Anesthesia 2002;57:778-817. PMID 12133096
06: Bakshi R, Graves MC. Guillain-Barré syndrome after combined tetanus-diphtheria toxoid vaccination. J Neurol Sci 1997;147:201-2. PMID 9106128
07: Behring E, Kitasato S. Ueber das zustandekommen der diphtherie-immunitat und der tetanus-immunitat bei thieren. Dtsch Med Wochenschr 1890;16:1113-4.
08: Bennett J, Ma C, Traverso H, Agha SB, Boring J. Neonatal tetanus associated with topical umbilical ghee: covert role of cow dung. Int J Epidemiol 1999;28:1172-5. PMID 10661665
09: Bennett J, Schooley M, Traverso H, Bano Agha S, Boring J. Bundling, a newly identified risk factor for neonatal tetanus: implication for global control. Int J Epidemiol 1996;25:879-84. PMID 8921470
10: Bergey GK, Habig WH, Bennett JI, Lin CS. Proteolytic cleavage of tetanus toxin increases activity. J Neurochem 1989;53:155-61. PMID 2656915
11: Bernbaum J, Daft A, Samuelson J, Polin RA. Half-dose immunization for diphtheria, tetanus, pertussis: response of preterm infants. Pediatrics 1989;83:471-6. PMID 2538797
12: Bleck TP, Brauner JS. Tetanus. In: Scheld WM, Whitley RJ, Durack DT, editors. Infections of the central nervous system. 2nd ed. Philadelphia: Raven, 1997:629-53.
13: Blencowe H, Lawn J, Vandelaer J, Roper M, Cousens S. Tetanus toxoid immunization to reduce mortality from neonatal tetanus. Int J Epidemiol 2010;39 Suppl 1:i102-9. PMID 20348112
14: Brair ME, Brabin BJ, Milligan P, Maxwell S, Hart CA. Reduced transfer of tetanus antibodies with placental malaria. Lancet 1994;343:208-9. PMID 7904669
15: Breasted JH. The Edwin Smith surgical papyrus. Chicago: University Chicago Press, 1930.
16: Bruggemann H, Baumer S, Fricke WF, et al. The genome sequence of Clostridium tetani, the causative agent of tetanus disease. Proc Natl Acad Sci U S A 2003;100(3):1316-21. PMID 12552129
17: Centers for Disease Control and Prevention. Recommended adult immunization schedule---United States, 2009. MMWR 2008a;57(53).
18: Centers for Disease Control and Prevention. Recommended immunization schedules for persons aged 0 through 18 years---United States, 2009. MMWR 2008b;57(51&52).
19: Centers for Disease Control and Prevention. Tetanus surveillance --- United States, 2001-2008. MMWR Morb Mortal Wkly Rep 2011;60:365-9. PMID 21451446
20: Centers for Disease Control and Prevention. Adult vaccination coverage--United States, 2010. MMWR Morb Mortal Wkly Rep 2012;61:66-72. PMID 22298302
21: Cole L, Youngman H. Treatment of tetanus. Lancet 1969;1:1017-20. PMID 4181173
22: Daher EF, Abdulkader RC, Motti E, Marcondes M, Sabbaga E, Burdmann EA. Prospective study of tetanus-induced acute renal dysfunction: role of adrenergic overactivity. Am J Trop Med Hyg 1997;57:610-4. PMID 9392604
23: D'Angio CT, Maniscalco WM, Pichichero ME. Immunologic response of extremely premature infants to tetanus, Haemophilus influenzae, and polio immunization. Pediatrics 1995;96:18-22. PMID 7596716
24: Davies-Adetugbo AA, Torimiro SE, Ako-Nai KA. Prognostic factors in neonatal tetanus. Trop Med Int Health 1998;3:9-13. PMID 9484962
25: de Moraes-Pinto MI, Almeida AC, Kenj G, et al. Placental transfer and maternally acquired neonatal IgG immunity in human immunodeficiency virus infection. J Infect Dis 1996;173(5):1077-84. PMID 8627057
26: Demicheli V, Barale A, Rivetti A. Vaccines for women for preventing neonatal tetanus. Cochrane Database Syst Rev 2015;(7):CD002959 PMID 26144877
27: Desai S, Scobie HM, Cherian T, Goodman T. Use of tetanus-diphtheria (Td) vaccine in children 4–7 years of age: World Health Organization consultation of experts. Vaccine 2020;38(21):3800-7. PMID 31983584
28: Dietz V, Galazka A, van Loon F, Cochi S. Factors affecting the immunogenicity and potency of tetanus toxoid: implications for the elimination of neonatal and non-neonatal tetanus as public health problems. Bull World Health Organ 1997;75(1):81-93. PMID 9141753
29: Dressnandt J, Konstanzer A, Weinzierl FX, Pfab R, Klingelhofer J. Intrathecal baclofen in tetanus: four cases and a review of reported cases. Intensive Care Med 1997;23:896-902. PMID 9310810
30: Edsall G. Introduction. In: Edsall G, editor. Proceedings of the fourth international conference on tetanus. Dakar: Foundation Murieux, 1975:19-20.
31: Fauveau V, Mamdani M, Steinglass R, Koblinsky M. Maternal tetanus: magnitude, epidemiology and potential control measures. Int J Gynaecol Obstet 1993;40:3-12. PMID 8094347
32: Gregorakos L, Kerezoudi E, Dimopoulos G, Thomaides T. Management of blood pressure instability in severe tetanus: the use of clonidine. Intensive Care Med 1997;23:893-5. PMID 9310809
33: Gurses N, Aydin M. Factors affecting prognosis of neonatal tetanus. Scand J Infect Dis 1993:353-3. PMID 8362232
34: Hamati-Haddad A, Fenichel GM. Brachial neuritis following routine childhood immunization for diphtheria, tetanus, and pertussis (DTP): report of two cases and review of the literature. Pediatrics 1997;99:602-3. PMID 9093307
35: Hoseini Tavassol Z, Sajjadpour Z, Hasani-Ranjbar S, Pejman Sani M, Aghaei Meybodi H, Larijani B. Do patients with diabetic foot ulcer need booster dose of tetanus vaccine? J Diabetes Metab Disord 2022;21(1):1023-7. PMID 35673424
36: Kabura L, Ilibagiza D, Menten J, Van den Ende J. Intrathecal vs. intramuscular administration of human antitetanus immunoglobulin or equine tetanus antitoxin in the treatment of tetanus: a meta-analysis. Trop Med Int Health 2006;11:1075-81. PMID 16827708
37: Khajehdehi P, Rezaian GR. Puerperal tetanus and hysterectomy. Int J Gynaecol Obstet 1997;58:211-5. PMID 9252257
38: Kilic D, Kaygusuz S, Saygun M, Cakmak A, Uzer H, Doğanci L. Seroprevalence of tetanus immunity among noninsulin-dependent diabetes mellitus patients. J Diabetes Complications 2003;17(5):258-63. PMID 12954154
39: King WW, Cave DR. Use of esmolol to control autonomic instability of tetanus. Am J Med 1991;91(4):425-8. PMID 1683152
40: Kreiglstein K, Henschen A, Weller U, Habermann E. Arrangement of disulfide bridges and positions of sulfhydryl groups in tetanus toxin. Eur J Biochem 1990;188:39-45. PMID 2108021
41: Kruger S, Seyfarth M, Sack K, Kreft B. Defective immune response to tetanus toxoid in hemodialysis patients and its association with diphtheria vaccination. Vaccine 1999;17:1145-50. PMID 10195626
42: Lam PK, Trieu HT, Lubis IN, et al. Prognosis of neonatal tetanus in the modern management era: an observational study in 107 Vietnamese infants. Int J Infect Dis 2015;33:7-11. PMID 25499039
43: Link E, Edelmann L, Chou JH, et al. Tetanus toxin action: inhibition of neurotransmitter release linked to synaptobrevin proteolysis. Biochem Biophys Res Commun 1992;189:1017-23. PMID 1361727
44: Liu L, Oza S, Hogan D, et al. Global, regional, and national causes of child mortality in 2000–13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet 2015;385(9966):430-40. PMID 5280870
45: Ljungman P, Cordonnier C, de Bock R, et al. Immunizations after bone marrow transplantation: results of a European survey and recommendations from the infectious diseases working party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 1995;15:455-60. PMID 7599572
46: Loebermann M, Winkelmann A, Hartung HP, Hengel H, Reisinger EC, Zettl UK. Vaccination against infection in patients with multiple sclerosis. Nat Rev Neurol 2012;8(3):143-51. PMID 22270022
47: Luisto M, Seppalainen AM. Electroencephalography in tetanus. Acta Neurol Scand 1989a;80:157-61. PMID 2816278
48: Luisto M, Seppalainen AM. Electroneuromyographic sequelae of tetanus, a controlled study of 40 patients. Electromyogr Clin Neurophysiol 1989b;29:377-81. PMID 2557202
49: Mastaglia FL, Thickbroom GW, Day T, Bond R. Craniocervical tetanus presenting with dysphagia: Diagnostic value of electrophysiological studies. J Neurol 2001;248:903-4. PMID 11697530
50: Matteoli M, Verderio C, Rossetto O, et al. Synaptic vesicle endocytosis mediates the entry of tetanus neurotoxin into hippocampal neurons. Proc Natl Acad Sci U S A 1996;93:13310-5. PMID 8917587
51: Miranda-Filho DB, Ximenes RA, Barone AA, Vaz VL, Vieira AG, Albuquerque VM. Randomised controlled trial of tetanus treatment with antitetanus immunoglobulin by the intrathecal or intramuscular route. BMJ 2004;328:615. PMID 25577622
52: Miranda-Filho DB, Ximenes RA, Siqueira-Filha NT, Santos AC. Incremental costs of treating tetanus with intrathecal antitetanus immunoglobulin. Trop Med Int Health 2013;18(5):555-63. PMID 23461581
53: Montecucco C, Schiavo G. Structure and function of tetanus and botulinum neurotoxins. Q Rev Biophys 1995;28:423-72. PMID 8771234
54: Morgan JL, Baggari SR, McIntire DD, Sheffield JS. Pregnancy outcomes after antepartum tetanus, diphtheria, and acellular pertussis vaccination. Obstet Gynecol 2015;125:1433-8. PMID 2600515
55: Mukherjee DK. Tetanus and tracheostomy. Ann Otol Rhinol Laryngol 1977;86(1 Pt 1):67-72. PMID 835974
56: Nicolaier A. Ueber infectiosen tetanus. Dtsch Med Wochenschr 1884;10:842-4.
57: Okoromah CA, Lesi FE. Diazepam for treating tetanus. Cochrane Database Syst Rev 2004;1:CD003954. PMID 14974046
58: Orko R, Rosenberg PH, Himberg JJ. Intravenous infusion of midazolam, propofol and vecuronium in a patient with severe tetanus. Acta Anaesthesiol Scand 1988;32(7):590-2. PMID 2903605
59: Orwitz JI, Galetta SL, Teener JW. Bilateral trochlear nerve palsy and downbeat nystagmus in a patient with cephalic tetanus. Neurology 1997;49:894-5. PMID 9305367
60: Perin MC, Schlindwein CF, de Moraes-Pinto MI, et al. Immune response to tetanus booster in infants aged 15 months born prematurely with very low birth weight. Vaccine 2012;30(46):6521-6. PMID 22959983
61: Price DL, Griffin JW. Tetanus toxin: retrograde axonal transport of systemically administered toxin. Neurosci Lett 1977;4:61-5. PMID 19604922
62: Prymula R, Siegrist CA, Chlibek R, et al. Effect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: two open-label, randomised controlled trials. Lancet 2009;374:1339-50. PMID 19837254
63: Reijneveld JC, Taphoorn MJ, Hoogenraad TU, van Gijn J. Severe but transient parkinsonism after tetanus vaccination. J Neurol Neurosurg Psychiatry 1997;63:258. PMID 9285473
64: Robinson MJ, Heal C, Gardener E, Powell P, Sims DG. Antibody response to diphtheria-tetanus-pertussis immunization in preterm infants who receive dexamethasone for chronic lung disease. Pediatrics 2004;113:733-7. PMID 15060220
65: Rodrigo C, Fernando D, Rajapakse S. Pharmacological management of tetanus: an evidence-based review. Crit Care 2014;18(2):217. PMID 25029486
66: Roper MH, Wassilak SG, Tiwari TS, Orenstein WA. Tetanus toxoid. In: Plotkin S, Orenstein W, Offit P, editors. Vaccines. 6th ed. Philadelphia: Sauders, 2013:447-92.
67: Saissy JM, Demaziere J, Vitris M, et al. Treatment of severe tetanus by intrathecal injections of baclofen without artificial ventilation. Intensive Care Med 1992a;18:241-4. PMID 1430590
68: Saissy JM, Vitris M, Demazaire J, Seck M, Marcoux L, Gaye M. Flumazenil counteracts intrathecal baclofen-induced central nervous system depression in tetanus. Anesthesiology 1992b;76:1051-3. PMID 1599091
69: Schiavo G, Benfenati F, Poulain B, et al. Tetanus and botulinum toxin-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin. Nature 1992;359:832-5. PMID 1331807
70: Shapiro RE, Specht CD, Collins BE, Woods AS, Cotter RJ, Schnaar RL. Identification of a ganglioside recognition domain of tetanus toxin using a novel ganglioside photoaffinity ligand. J Biol Chem 1997;272:30380-6. PMID 9374528
71: Slifka AM, Park B, Gao L, Slifka MK. Incidence of tetanus and diphtheria in relation to adult vaccination schedules. Clin Infect Dis 2021;72(2):285-92. PMID 32095828
72: Tezzon F, Tomelleri P, Ferrari G, Segi A. Acute radiculomyelitis after antitetanus vaccination. Ital J Neurol Sci 1994;15:191-4. PMID 7960672
73: Thwaites CL, Beeching NJ, Newton CR. Maternal and neonatal tetanus. Lancet 2015;385(9965):362-70. PMID 25149223
74: Thwaites CL, Yen LM, Loan HT, et al. Magnesium sulphate for treatment of severe tetanus: a randomised controlled trial. Lancet 2006;368(9545):1436-43. PMID 17055945
75: Udwadia FE, Sunavala JD, Jain MC, et al. Hemodynamic studies during the management of severe tetanus. Q J Med 1992;83:449-60. PMID 1448546
76: WHO. Current recommendations for treatment of tetanus during humanitarian emergencies. WHO Emergencies Preparedness. World Health Organization, 2010.
77: WHO. Achieving and sustaining maternal and neonatal tetanus elimination. Strategic plan 2012-2015. World Health Organization, 2012.
78: WHO. Tetanus vaccines: WHO position paper. WHO weekly epidemiological record. No 6. World Health Organization 2017;92:53-76.
79: Woldeamanuel YW, Andemeskel AT, Kyei K, Woldeamanuel MW, Woldeamanuel W. Case fatality of adult tetanus in Africa: systematic review and meta-analysis. J Neurol Sci 2016;368:292-9. PMID 27538652
80: Yen LM, Dao LM, Day NP, et al. Role of quinine in the high mortality of intramuscular injection tetanus. Lancet 1994;344:786-7. PMID 7916074

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Authors

Wanakorn Rattanawong MD

Dr. Rattanawong of Chulalongkorn University in Bangkok, Thailand, has no relevant financial relationships to disclose.
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Anan Srikiatkhachorn MD

Dr. Srikiatkhachorn of King Mongkut’s Institute of Technology Ladkrabang has no relevant financial relationships to disclose.
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Thiravat Hemachudha MD

Dr. Hemachudha of Chulalongkorn University Hospital in Bangkok, Thailand, has no relevant financial relationships to disclose.
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Editor

John E Greenlee MD

Dr. Greenlee of the University of Utah School of Medicine has no relevant financial relationships to disclose.
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Patient Profile

Age range of presentation: 0 month to 65+ years
Sex preponderance: male=female
Heredity: none
Population groups selectively affected: none selectively affected
Occupation groups selectively affected: none selectively affected

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Tetanus

Differential Diagnosis

strychnine intoxication
dystonia
neuroleptic malignant syndrome
stiff-person syndrome
severe hypocalcemia
- hypomagnesemia tetany
- meningoencephalitis

Also Relevant

Blepharospasm
Diphtheritic neuropathy
Intrathecal baclofen
Neurologic complications of vaccination
Vaccines for neurologic disorders
- West syndrome

Clinical Categories

Web References

Guidelines

Clinical Trials

NIH: Epilepsy

	• Strychnine intoxication produces an almost identical clinical presentation to tetanus, except trismus is absent and abdominal muscles are less rigid in strychnine intoxication.
	• Extrapyramidal side effects caused by dopaminergic-blocking agents, like dystonia and neuroleptic malignant syndrome, resemble tetanus, but the lack of reflex spasms helps differentiate these conditions from tetanus.
	• Stiff-person syndrome has an insidious onset and minimally involves facial and jaw musculatures. Sleep also lessens muscular rigidity.
	• Severe hypocalcemia or hypomagnesemia tetany is accompanied by Chvostek and Trousseau signs and mainly involves the extremities more than the trunk.
	• Meningoencephalitis is sometimes confused with tetanus due to abnormal muscle tone, nuchal rigidity, and true convulsive seizures. This diagnosis can be excluded by clear sensorium in tetanus and by spinal fluid examination.

Tetanus …

Tetanus

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Diagnostic workup

Management

Special considerations

Pregnancy

Media

References

Contributors

Authors

Editor

Patient Profile

ICD & OMIM codes

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Also in This Category

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Pneumococcal meningitis

	• Tetanus is more prevalent in developing countries. The average incidence in the United States is 0.09 per million person-years.
	• Tetanus has a high fatality rate in Africa, which is due to low-quality care and lack of mechanical ventilation.
	• Neonatal tetanus is the second leading of cause of death from vaccine-preventable diseases.

	• The diagnosis of tetanus is clinically based.
	• Laboratory investigation may aid in diagnosis, including culture positive for C tetani, polymerase chain reaction for detection of C tetani nucleic acids, and detection of tetanus toxin in serum. EMG and EEG may also provide useful information. However, all of these may be falsely negative.

Tetanus

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Diagnostic workup

Management

Special considerations

Pregnancy

Media

References

Contributors

Authors

Editor

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Neuropathies associated with cytomegalovirus infection

Genital herpes: neurologic complications

Zika virus: neurologic complications

Gram-negative bacillary meningitis

Chronic inflammatory demyelinating polyradiculoneuropathy

Amyotrophic lateral sclerosis

Amiodarone neuropathy

Pneumococcal meningitis

This is an article preview.
Start a Free Account
to access the full version.