Materiały źródłowe

• #1 Chapter 21: Tetanus | Pink Book | CDC

  https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-21-tetanus.html

  Tetanus is an acute, often fatal, disease caused by an exotoxin produced by the bacterium Clostridium tetani. It is characterized by generalized rigidity and convulsive spasms of skeletal muscles. The muscle stiffness usually begins in the jaw (lockjaw) and neck and then becomes generalized. […] C. tetani usually enters the body through a wound. In the presence of anaerobic conditions, the spores germinate. Toxins are produced and disseminated via blood and lymphatics. Tetanospasmin, also referred to as tetanus toxin, acts at several sites within the central nervous system, including peripheral motor end plates, the spinal cord, and the brain, and in the sympathetic nervous system. The typical clinical manifestations of tetanus are caused when tetanus toxin interferes with the release of neurotransmitters, blocking inhibitor impulses. This leads to unopposed muscle contraction and spasm. Seizures may occur, and the autonomic nervous system may also be affected.

• #2 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Tetanus-Pathophysiology.aspx

  Tetanus is an infectious disease caused by Clostridium tetani bacteria. The active anaerobic bacteria lead to the production of a tetanus toxin, which enters the nervous system via lower motor neurons and travels up to the spinal cord and brain stem. […] The presence of the toxin can lead to the initiation of characteristic symptoms of tetanus, such as jaw tightness (lockjaw), dysphagia, opisthotonus and other muscular spasms. This is due to the effect the toxin exhibits on certain parts of the nervous system and neurotransmitters, which interfere with muscular contraction in the body. […] It is the tetanus toxin tetanospasmin, which is produced by the causative bacteria in the organism, that is responsible for the symptoms of muscular rigidity and spasms that characterize the disease.

• #3 Tetanus – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/anaerobic-bacteria/tetanus

  Tetanus is acute poisoning resulting from a neurotoxin produced by Clostridium tetani. […] Manifestations of tetanus are caused by an exotoxin (tetanospasmin) produced when bacteria lyse. The toxin enters peripheral nerve endings, binds there irreversibly, then travels retrograde along the axons and synapses, and ultimately enters the central nervous system (CNS). As a result, release of inhibitory transmitters from nerve terminals is blocked, thereby causing unopposed muscle stimulation by acetylcholine and generalized tonic spasticity, usually with superimposed intermittent tonic seizures. Disinhibition of autonomic neurons and loss of control of adrenal catecholamine release cause autonomic instability and a hypersympathetic state. Once bound, the toxin cannot be neutralized. […] Tetanus toxin binds irreversibly to nerve terminals, and once bound, it cannot be neutralized.

• #4 Tetanus: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/229594-overview

  Clostridium tetani is an obligate, anaerobic, motile, gram-positive bacillus. It is nonencapsulated and forms spores that are resistant to heat, desiccation, and disinfectants. Since the colorless spores are located at one end of the bacillus, they cause the organism to resemble a turkey leg. They are found in soil, house dust, animal intestines, and human feces. Spores can persist in normal tissue for months to years. […] To germinate, the spores require specific anaerobic conditions, such as wounds with low oxidation-reduction potential (eg, dead or devitalized tissue, foreign body, active infection). Under these conditions, upon germination, they may release their toxin. Infection by C tetani results in a benign appearance at the portal of entry because of the inability of the organism to evoke an inflammatory reaction unless coinfection with other organisms develops.

• #5 Tetanus – UpToDate

  https://www.uptodate.com/contents/tetanus

  Heavy chains are further cleaved by pepsins into specific fragments, which individually mediate binding to specific types of neural cells. […] Presynaptic inhibition of neurotransmitter release is mediated via light chains. […] Tetanolysin is another toxin produced by C. tetani during its early growth phase. It has hemolytic properties and causes membrane damage in other cells, but its role in clinical tetanus is uncertain. […] Because C. tetani will not grow in healthy tissues, a convergence of factors must be present in order for tetanus toxin to be elaborated in the human host. […] This combination of factors usually includes absence of antibodies (ie, from inadequate vaccination) plus two or more of the following: a penetrating injury resulting in the inoculation of C. tetani spores, coinfection with other bacteria, devitalized tissue, a foreign body, localized ischemia.

• #6 Tetanus – UpToDate

  https://www.uptodate.com/contents/tetanus

  The above factors explain why tetanus-prone injuries include splinters and other puncture wounds, gunshot wounds, compound fractures, burns, and unsterile intramuscular or subcutaneous injections. […] These predisposing factors can also explain why tetanus can develop in unusual clinical settings such as in neonates (due to infection of the umbilical stump), obstetric patients (after septic abortions), postsurgical patients (with necrotic infections involving bowel flora), adolescents and adults undergoing male circumcision in sub-Saharan Africa, patients with dental infections, diabetic patients with infected extremity ulcers, patients who inject illicit and/or contaminated drugs. […] An identifiable antecedent cause for tetanus is obvious in most patients presenting with tetanus, but no cause can be identified in up to a quarter of patients with classic signs and symptoms of tetanus. […] Presumably, minor unnoticed abrasions or skin injuries are responsible for most or all of these „cryptogenic” cases.

• #7 Tetanus: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/229594-overview

  Clostridium tetani is an obligate, anaerobic, motile, gram-positive bacillus. It is nonencapsulated and forms spores that are resistant to heat, desiccation, and disinfectants. Since the colorless spores are located at one end of the bacillus, they cause the organism to resemble a turkey leg. They are found in soil, house dust, animal intestines, and human feces. Spores can persist in normal tissue for months to years. […] To germinate, the spores require specific anaerobic conditions, such as wounds with low oxidation-reduction potential (eg, dead or devitalized tissue, foreign body, active infection). Under these conditions, upon germination, they may release their toxin. Infection by C tetani results in a benign appearance at the portal of entry because of the inability of the organism to evoke an inflammatory reaction unless coinfection with other organisms develops.

• #8 Tetanus – UpToDate

  https://www.uptodate.com/contents/tetanus

  Heavy chains are further cleaved by pepsins into specific fragments, which individually mediate binding to specific types of neural cells. […] Presynaptic inhibition of neurotransmitter release is mediated via light chains. […] Tetanolysin is another toxin produced by C. tetani during its early growth phase. It has hemolytic properties and causes membrane damage in other cells, but its role in clinical tetanus is uncertain. […] Because C. tetani will not grow in healthy tissues, a convergence of factors must be present in order for tetanus toxin to be elaborated in the human host. […] This combination of factors usually includes absence of antibodies (ie, from inadequate vaccination) plus two or more of the following: a penetrating injury resulting in the inoculation of C. tetani spores, coinfection with other bacteria, devitalized tissue, a foreign body, localized ischemia.

• #9 Tetanus: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/229594-overview

  When the proper anaerobic conditions are present, the spores germinate and produce the following 2 toxins: Tetanolysin This substance is a hemolysin with no recognized pathologic activity […] Tetanospasmin This toxin is responsible for the clinical manifestations of tetanus; by weight, it is one of the most potent toxins known, with an estimated minimum lethal dose of 2.5 ng/kg body weight. […] Tetanospasmin is synthesized as a 150-kd protein consisting of a 100-kd heavy chain and a 50-kd light chain joined by a disulfide bond. The heavy chain mediates binding of tetanospasmin to the presynaptic motor neuron and also creates a pore for the entry of the light chain into the cytosol. The light chain is a zinc-dependent protease that cleaves synaptobrevin. […] After the light chain enters the motor neuron, it travels by retrograde axonal transport from the contaminated site to the spinal cord in 2-14 days. When the toxin reaches the spinal cord, it enters central inhibitory neurons. The light chain cleaves the protein synaptobrevin, which is integral to the binding of neurotransmitter containing vesicles to the cell membrane.

• #10 Tetanus pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Tetanus_pathophysiology

  The pathogenesis of tetanus is as follows: C. tetani gains access to the human body through a wound contaminated with the organism or through an umbilical stump (in cases of neonatal tetanus) by contact with contaminated medical tools. […] The spores germinate in the wound because of their anaerobic character. […] Toxins are produced and spread through the blood and lymphatics. […] C. tetani produces two exotoxins: Tetanolysin, the function of which, is not well understood; Tetanospasmin, a metalloprotease, which is a neurotoxin responsible for the spasticity associated with tetanus. Tetanospasmin is among the most potent toxins known to man. […] The toxin uses retrograde transport along the nerve axon to reach the spinal cord and the brainstem. […] The toxins binds irreversibly with the receptors.

• #11 Tetanus: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/229594-overview

  When the proper anaerobic conditions are present, the spores germinate and produce the following 2 toxins: Tetanolysin This substance is a hemolysin with no recognized pathologic activity […] Tetanospasmin This toxin is responsible for the clinical manifestations of tetanus; by weight, it is one of the most potent toxins known, with an estimated minimum lethal dose of 2.5 ng/kg body weight. […] Tetanospasmin is synthesized as a 150-kd protein consisting of a 100-kd heavy chain and a 50-kd light chain joined by a disulfide bond. The heavy chain mediates binding of tetanospasmin to the presynaptic motor neuron and also creates a pore for the entry of the light chain into the cytosol. The light chain is a zinc-dependent protease that cleaves synaptobrevin. […] After the light chain enters the motor neuron, it travels by retrograde axonal transport from the contaminated site to the spinal cord in 2-14 days. When the toxin reaches the spinal cord, it enters central inhibitory neurons. The light chain cleaves the protein synaptobrevin, which is integral to the binding of neurotransmitter containing vesicles to the cell membrane.

• #12 Tetanus

  https://www.pediatriconcall.com/articles/infectious-diseases/tetanus/tetanus-introduction

  Tetanospasmin is a 150 kD protein constitutes of two units of proteins 100 kD heavy chain and 50 kD light chain both linked by a disulfide bond. Among them, the heavy chain has two functions one binding of tetanospasmin to presynaptic motor neuron the other is creating pore which facilitates the access of light chain in the cytosol. The light chain is a kind of Zn2+ dependant protease which cleaves synaptobrevin. On the entry of the light chain into the motor neuron, it movements by retrograde axonal transport from the location of infection to the spinal cord in 2-14 days. In the spinal cord, it enters the central inhibitory neurons. The light chain cuts the synaptobrevin protein, which is essential for binding the neurotransmitter comprising vesicles to the cell membrane resulting in non-release of GABA (gamma-aminobutyric acid) and glycine from vesicles. Further, this leads to loss of central inhibition, creating automatic hyper action resulting in uncontrolled muscle contraction in response to normal stimuli. The passage of the toxin is through the central nervous system which uses motor neurons as a transport cell. Fixed toxins on to neurons cannot be neutralized by antitoxin. Recovery requires new nerve terminals and new synapses formation.

• #13 Structure and mechanism of action of botulinum and tetanus neurotoxins: A review – Skryabina – Epidemiology and Infectious Diseases

  https://rjeid.com/1560-9529/article/view/321328

  Tetanus and botulinum neurotoxins are proteins consisting of a light chain (L, molecular weight 50 kDa) and a heavy chain (H, molecular weight 100 kDa) connected by a disulfide bridge and folded into four domains, each playing a specific role in affecting nerve endings. […] Both tetanus toxin and botulinum neurotoxin affect their specific targets, presynaptic nerve endings, through a similar mechanism related to their modular structure and consisting of five main steps binding to the presynaptic membrane, internalisation of bound toxin into the cytosol via endocytosis, translocation of the L-chain into the cytosol via the HN domain, disruption of the inter-chain disulfide bond with release of the L-chain to express its catalytic activity (as a metalloprotease) in the cytosol and selective cleavage of one or more SNARE complex proteins with subsequent blockade of neurotransmitter release.

• #14 Tetanus: Pathophysiology, Treatment, and the Possibility of Using Botulinum Toxin against Tetanus-Induced Rigidity and Spasms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3564069/

  Tetanus toxin, the product of Clostridium tetani, is the cause of tetanus symptoms. Tetanus toxin is taken up into terminals of lower motor neurons and transported axonally to the spinal cord and/or brainstem. Here the toxin moves trans-synaptically into inhibitory nerve terminals, where vesicular release of inhibitory neurotransmitters becomes blocked, leading to disinhibition of lower motor neurons. Muscle rigidity and spasms ensue, often manifesting as trismus/lockjaw, dysphagia, opistotonus, or rigidity and spasms of respiratory, laryngeal, and abdominal muscles, which may cause respiratory failure. […] 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. Tetanus toxin is a zinc-dependent metalloproteinase that targets a protein (synaptobrevin/vesicle-associated membrane proteinVAMP) that is necessary for the release of neurotransmitter from nerve endings through fusion of synaptic vesicles with the neuronal plasma membrane.

• #15 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Tetanus-Pathophysiology.aspx

  The tetanus toxin enters the nerve terminals through the lower motor neurons, which are usually responsible for activating voluntary muscular movements. It is then transported via the axons to the spinal cord and brainstem. […] The toxin then moves throughout the nervous system trans-synaptically into the nerve terminals responsible for the release of inhibitory neurotransmitters. If this vesicular process becomes blocked, the ability to inhibit lower motor neurons is disrupted, which can result in muscle rigidity and spasm. […] Tetanus toxin inhibits normal nervous function due to its action as a zinc-dependent metalloproteinase that targets VAMP, a protein that regulates the neurotransmitter release from nerve endings. […] The first symptoms to be noted by individuals affected by tetanus are usually localized to the area of the infection and may include flaccid paralysis. This is due to interference at the neuromuscular junction with the release of acetylcholine. From this point, the toxin travels across synapses to inhibitory GABAergic or glycinergic neurons that are responsible for the lower motor neuron activity. The toxin then targets VAMP to inhibit the release of neurotransmitters and affect the function of the motor neurons.

• #16 Tetanus

  https://www.pediatriconcall.com/articles/infectious-diseases/tetanus/tetanus-introduction

  Tetanospasmin is a 150 kD protein constitutes of two units of proteins 100 kD heavy chain and 50 kD light chain both linked by a disulfide bond. Among them, the heavy chain has two functions one binding of tetanospasmin to presynaptic motor neuron the other is creating pore which facilitates the access of light chain in the cytosol. The light chain is a kind of Zn2+ dependant protease which cleaves synaptobrevin. On the entry of the light chain into the motor neuron, it movements by retrograde axonal transport from the location of infection to the spinal cord in 2-14 days. In the spinal cord, it enters the central inhibitory neurons. The light chain cuts the synaptobrevin protein, which is essential for binding the neurotransmitter comprising vesicles to the cell membrane resulting in non-release of GABA (gamma-aminobutyric acid) and glycine from vesicles. Further, this leads to loss of central inhibition, creating automatic hyper action resulting in uncontrolled muscle contraction in response to normal stimuli. The passage of the toxin is through the central nervous system which uses motor neurons as a transport cell. Fixed toxins on to neurons cannot be neutralized by antitoxin. Recovery requires new nerve terminals and new synapses formation.

• #17 Clostridium tetani: Properties, Pathogenesis, Lab Diagnosis • Microbe Online

  https://microbeonline.com/clostridium-tetani-properties-pathogenesis-diagnosis/

  Tetanus toxin binds to polysialogangliosides receptors present on motor nerve terminals which results in toxin internalization. Following internalization, tetanus toxin gets transported in a retrograde way from the peripheral nervous system to the central nervous system by retrograde axonal transport. When tetanus toxin reaches inhibitory neuron terminals, it prevents the presynaptic release of inhibitory neurotransmitters glycine and gamma-aminobutyric acid (GABA). […] Lack of inhibitory signals to the motor neurons and constant release of acetylcholine to the muscle fibers leads to irreversible contraction of the muscles and spastic paralysis.

• #18 15.20F: Tetanus – Biology LibreTexts

  https://bio.libretexts.org/Bookshelves/Microbiology/Microbiology_(Boundless)/15%3A_Diseases/15.20%3A_Microbial_Diseases_of_the_Nervous_System/15.20F%3A_Tetanus

  Tetanus is a medical condition characterized by a prolonged contraction of skeletal muscle fibers. The primary symptoms are caused by tetanospasmin, a neurotoxin produced by the Gram-positive, rod-shaped, obligate anaerobic bacterium Clostridium tetani. […] Tetanospasmin is an A-B toxin. The B subunit binds to the receptors on motor neurons, while the A subunit induces endocytosis to enter the neuron. […] Tetanus affects skeletal muscle, a type of striated muscle used in voluntary movement. […] Because C. tetani is an anaerobic bacterium, it and its endospores survive well in an environment that lacks oxygen. […] Unlike many infectious diseases, recovery from naturally acquired tetanus does not usually result in immunity to tetanus. This is due to the extreme potency of the tetanospasmin toxin; even a lethal dose of tetanospasmin is insufficient to provoke an immune response. […] To combat the effects of the toxin, tetanus immune globulin (TIG) antitoxin can be given to the patient. These antibodies are able to neutralize the tetanospasmin if they are not already bound to motor neurons, and can confer passive immunity.

• #19 Tetanus: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/229594-overview

  When the proper anaerobic conditions are present, the spores germinate and produce the following 2 toxins: Tetanolysin This substance is a hemolysin with no recognized pathologic activity […] Tetanospasmin This toxin is responsible for the clinical manifestations of tetanus; by weight, it is one of the most potent toxins known, with an estimated minimum lethal dose of 2.5 ng/kg body weight. […] Tetanospasmin is synthesized as a 150-kd protein consisting of a 100-kd heavy chain and a 50-kd light chain joined by a disulfide bond. The heavy chain mediates binding of tetanospasmin to the presynaptic motor neuron and also creates a pore for the entry of the light chain into the cytosol. The light chain is a zinc-dependent protease that cleaves synaptobrevin. […] After the light chain enters the motor neuron, it travels by retrograde axonal transport from the contaminated site to the spinal cord in 2-14 days. When the toxin reaches the spinal cord, it enters central inhibitory neurons. The light chain cleaves the protein synaptobrevin, which is integral to the binding of neurotransmitter containing vesicles to the cell membrane.

• #20 Tetanus toxin – Wikipedia

  https://en.wikipedia.org/wiki/Tetanus_toxin

  Tetanus toxin (TeNT) is an extremely potent neurotoxin produced by the vegetative cell of Clostridium tetani in anaerobic conditions, causing tetanus. […] The mechanism of TeNT action can be broken down and discussed in these different steps: […] The first three steps outline the travel of tetanus toxin from the peripheral nervous system to where it is taken up to the CNS and has its final effect. The last three steps document the changes necessary for the final mechanism of the neurotoxin. […] Transport to the CNS inhibitory interneurons begins with the B-chain mediating the neurospecific binding of TeNT to the nerve terminal membrane. […] Once the toxin has been translocated into the cytosol, chemical reduction of the disulfide bond to separate thiols occurs, mainly by the enzyme NADPH-thioredoxin reductase-thioredoxin.

• #21 Tetanus: Pathophysiology, Treatment, and the Possibility of Using Botulinum Toxin against Tetanus-Induced Rigidity and Spasms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3564069/

  However, unlike botulinum toxin, tetanus toxin undergoes extensive retrograde transport in the axons of lower motor neurons and thus reaches the spinal cord or brainstem. Here, the toxin is transported across synapses and taken up by nerve endings of inhibitory GABAergic and/or glycinergic neurons that control the activity of the lower motor neurons. Once inside inhibitory nerve terminals, tetanus toxin cleaves VAMP, thereby inhibiting the release of GABA and glycine. The result is a partial, functional denervation of the lower motor neurons, which leads to their hyperactivity and to increased muscle activity in the form of rigidity and spasms. […] The action of tetanus toxin is not confined to the motor system. Autonomic dysfunction with episodes of tachycardia, hypertension, and sweating, sometimes rapidly alternating with bradycardia and hypotension are common, especially in generalized tetanus. Such symptoms are paralleled by dramatic increases in circulating adrenaline and noradrenaline, which may cause myocardial necrosis.

• #22 Structure and mechanism of action of botulinum and tetanus neurotoxins: A review – Skryabina – Epidemiology and Infectious Diseases

  https://rjeid.com/1560-9529/article/view/321328

  The different transport pathways of tetanus and botulinum neurotoxin within neurons are not mutually exclusive, as tetanus neurotoxin can cause local peripheral paralysis and botulinum neurotoxin can migrate retrogradely within neurons and be released into the CNS at different levels. […] The binding of tetanus and botulinum neurotoxins to polysialogangliosides allows the toxins to diffuse across the lipid presynaptic membrane, which greatly increases the probability of their binding to a second receptor. […] Both tetanus and botulinum neurotoxins target the peripheral motor nerve terminals into which they enter, but the important difference between them is that the L-chain of botulinum neurotoxin is released into the cytosol of motor neurons, whereas tetanus neurotoxins are preferentially transported retrograde along the axon of the motor neuron to the soma.

• #23 Tetanus: Pathophysiology, Treatment, and the Possibility of Using Botulinum Toxin against Tetanus-Induced Rigidity and Spasms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3564069/

  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. 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. […] Botulinum toxins enter nerve terminals of lower motor neurons. The toxins are zinc metalloproteinases that attack synaptic vesicle proteins, but they do so differentially: botulinum toxin A cleaves synaptosomal-associated protein (SNAP-25), botulinum toxins B, D, F, and G cleave synaptobrevin (which is also attacked by tetanus toxin); botulinum toxin C cleaves SNAP-25 and syntaxin. Compared to tetanus toxin, the botulinum toxins undergo less axonal and trans-synaptic transport, although some transport does seem to occur. 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.

• #24 Tetanus: Pathophysiology, Treatment, and the Possibility of Using Botulinum Toxin against Tetanus-Induced Rigidity and Spasms

  https://www.mdpi.com/2072-6651/5/1/73

  However, unlike botulinum toxin, tetanus toxin undergoes extensive retrograde transport in the axons of lower motor neurons and thus reaches the spinal cord or brainstem. Here, the toxin is transported across synapses and taken up by nerve endings of inhibitory GABAergic and/or glycinergic neurons that control the activity of the lower motor neurons. […] Once inside inhibitory nerve terminals, tetanus toxin cleaves VAMP, thereby inhibiting the release of GABA and glycine. The result is a partial, functional denervation of the lower motor neurons, which leads to their hyperactivity and to increased muscle activity in the form of rigidity and spasms. […] The action of tetanus toxin is not confined to the motor system. Autonomic dysfunction with episodes of tachycardia, hypertension, and sweating, sometimes rapidly alternating with bradycardia and hypotension are common, especially in generalized tetanus.

• #25 Tetanus: Pathophysiology, Treatment, and the Possibility of Using Botulinum Toxin against Tetanus-Induced Rigidity and Spasms

  https://www.mdpi.com/2072-6651/5/1/73

  However, unlike botulinum toxin, tetanus toxin undergoes extensive retrograde transport in the axons of lower motor neurons and thus reaches the spinal cord or brainstem. Here, the toxin is transported across synapses and taken up by nerve endings of inhibitory GABAergic and/or glycinergic neurons that control the activity of the lower motor neurons. […] Once inside inhibitory nerve terminals, tetanus toxin cleaves VAMP, thereby inhibiting the release of GABA and glycine. The result is a partial, functional denervation of the lower motor neurons, which leads to their hyperactivity and to increased muscle activity in the form of rigidity and spasms. […] The action of tetanus toxin is not confined to the motor system. Autonomic dysfunction with episodes of tachycardia, hypertension, and sweating, sometimes rapidly alternating with bradycardia and hypotension are common, especially in generalized tetanus.

• #26 Tetanus: Pathophysiology, Treatment, and the Possibility of Using Botulinum Toxin against Tetanus-Induced Rigidity and Spasms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3564069/

  Tetanus toxin, the product of Clostridium tetani, is the cause of tetanus symptoms. Tetanus toxin is taken up into terminals of lower motor neurons and transported axonally to the spinal cord and/or brainstem. Here the toxin moves trans-synaptically into inhibitory nerve terminals, where vesicular release of inhibitory neurotransmitters becomes blocked, leading to disinhibition of lower motor neurons. Muscle rigidity and spasms ensue, often manifesting as trismus/lockjaw, dysphagia, opistotonus, or rigidity and spasms of respiratory, laryngeal, and abdominal muscles, which may cause respiratory failure. […] 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. Tetanus toxin is a zinc-dependent metalloproteinase that targets a protein (synaptobrevin/vesicle-associated membrane proteinVAMP) that is necessary for the release of neurotransmitter from nerve endings through fusion of synaptic vesicles with the neuronal plasma membrane.

• #27 Tetanus toxin – Wikipedia

  https://en.wikipedia.org/wiki/Tetanus_toxin

  The final target of TeNT is the cleavage of synaptobrevin and, even in low doses, has the effect of interfering with exocytosis of neurotransmitters from inhibitory interneurons. […] The action of the A-chain also stops the affected neurons from releasing excitatory transmitters, by degrading the protein synaptobrevin 2. […] The combined consequence is dangerous overactivity in the muscles from the smallest sensory stimuli, as the damping of motor reflexes is inhibited, leading to generalized contractions of the agonist and antagonist musculature, termed a „tetanic spasm”.

• #28 Tetanus – UpToDate

  https://www.uptodate.com/contents/tetanus/print

  Tetanus occurs when spores of C. tetani, an obligate anaerobe normally present in the gut of mammals and widely found in soil, gains access to damaged human tissue. […] After inoculation, C. tetani transforms into a vegetative rod-shaped bacterium and produces the metalloprotease tetanus toxin (also known as tetanospasmin). […] After reaching the spinal cord and brainstem via retrograde axonal transport within the motor neuron, tetanus toxin is secreted and enters adjacent inhibitory interneurons, where it blocks neurotransmission by its cleaving action on the membrane proteins involved in neuroexocytosis. […] The net effect is inactivation of inhibitory neurotransmission that normally modulates anterior horn cells and muscle contraction. […] This loss of inhibition (ie, disinhibition) of anterior horn cells and autonomic neurons results in increased muscle tone, painful spasms, and widespread autonomic instability.

• #29 Tetanus – Wikipedia

  https://en.wikipedia.org/wiki/Tetanus

  Tetanus is caused by the tetanus bacterium, Clostridium tetani. The disease occurs almost exclusively in people who are inadequately immunized. […] Tetanus neurotoxin (TeNT) binds to the presynaptic membrane of the neuromuscular junction, is internalized, and is transported back through the axon until it reaches the central nervous system. […] Tetanus toxin specifically blocks the release of the neurotransmitters GABA and glycine from inhibitory neurons. […] The light chain of the tetanus toxin is zinc-dependent protease. […] The light chain binds to VAMP, and cleaves it between Gln76 and Phe77. Without VAMP, vesicles holding the neurotransmitters needed for motor neuron regulation (GABA and glycine) cannot be released, causing the above-mentioned deregulation of motor neurons and muscle tension.

• #30 Tetanus: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/229594-overview

  As a result, gamma-aminobutyric acid (GABA)-containing and glycine-containing vesicles are not released, and there is a loss of inhibitory action on motor and autonomic neurons. With this loss of central inhibition, there is autonomic hyperactivity as well as uncontrolled muscle contractions (spasms) in response to normal stimuli such as noises or lights. […] Once the toxin becomes fixed to neurons, it cannot be neutralized with antitoxin. Recovery of nerve function from tetanus toxins requires sprouting of new nerve terminals and formation of new synapses. […] Localized tetanus develops when only the nerves supplying the affected muscle are involved. Generalized tetanus develops when the toxin released at the wound spreads through the lymphatics and blood to multiple nerve terminals. The blood-brain barrier prevents direct entry of toxin to the CNS.

• #31 Tetanus (Clostridium tetani Infection) – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK482484/

  Clostridium tetani is an anaerobic, spore-forming bacillus that produces muscle rigidity and hypersympathetic activity leading to tetanus. […] Tetanus toxin inhibits neurotransmitter release in the brain stem and spinal cord. […] Inoculation of wounds with C tetani spores facilitates germination of bacilli. These bacteria produce 2 toxins: tetanospasmin (tetanus toxin) and tetanolysin. Tetanospasmin circulates through lymphatics and the bloodstream, binding to receptors in the peripheral nervous system at neuromuscular junctions. Subsequently, it is endocytosed and retrogradely transported in the peripheral nerve axons to inhibitory interneurons within the central nervous system (CNS). Within the CNS, tetanospasmin blocks the release of the neurotransmitters gamma amino butyric acid (GABA) and glycine from inhibitory interneurons within the spinal cord and brain stem. In addition, it blocks the release of the inhibitory neurotransmitters within the sympathetic nervous system. The absence of inhibitory signals allows excitatory neurotransmitters to act unchecked, resulting in muscle spasms and hypersympathetic activity. […] Toxin binding at the neuromuscular junction is irreversible.

• #32 Tetanus – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/anaerobic-bacteria/tetanus

  Tetanus is acute poisoning resulting from a neurotoxin produced by Clostridium tetani. […] Manifestations of tetanus are caused by an exotoxin (tetanospasmin) produced when bacteria lyse. The toxin enters peripheral nerve endings, binds there irreversibly, then travels retrograde along the axons and synapses, and ultimately enters the central nervous system (CNS). As a result, release of inhibitory transmitters from nerve terminals is blocked, thereby causing unopposed muscle stimulation by acetylcholine and generalized tonic spasticity, usually with superimposed intermittent tonic seizures. Disinhibition of autonomic neurons and loss of control of adrenal catecholamine release cause autonomic instability and a hypersympathetic state. Once bound, the toxin cannot be neutralized. […] Tetanus toxin binds irreversibly to nerve terminals, and once bound, it cannot be neutralized.

• #33 Tetanus – almostadoctor

  https://almostadoctor.co.uk/encyclopedia/tetanus

  Spores germinate in anaerobic conditions at wound site and produce neurotoxin (tetanus toxin). The toxin enters peripheral nerves namely motor neurons, and then travels up peripheral nerves and the spinal cord and brainstem. It the proximal end of the nerve it cleaves the protein that allows fusion of the synaptic vesicle with the membrane prevents neurotransmitter release particularly of inhibitory neurons. This causes muscle spasm and over activation. […] Primarily affects inhibitory glycine or GABA. […] Leads to less inhibition (relaxation), increased firing, contraction skeletal muscle. […] The binding of tetanus toxin at the synapse is permanent. New synapses can grow, but this process typically takes 6-8 weeks. As such, the duration of symptoms is usually around 6-8 weeks.

• #34 Tetanus – UpToDate

  https://www.uptodate.com/contents/tetanus/print

  Tetanus occurs when spores of C. tetani, an obligate anaerobe normally present in the gut of mammals and widely found in soil, gains access to damaged human tissue. […] After inoculation, C. tetani transforms into a vegetative rod-shaped bacterium and produces the metalloprotease tetanus toxin (also known as tetanospasmin). […] After reaching the spinal cord and brainstem via retrograde axonal transport within the motor neuron, tetanus toxin is secreted and enters adjacent inhibitory interneurons, where it blocks neurotransmission by its cleaving action on the membrane proteins involved in neuroexocytosis. […] The net effect is inactivation of inhibitory neurotransmission that normally modulates anterior horn cells and muscle contraction. […] This loss of inhibition (ie, disinhibition) of anterior horn cells and autonomic neurons results in increased muscle tone, painful spasms, and widespread autonomic instability.

• #35 Tetanus – UpToDate

  https://www.uptodate.com/contents/tetanus

  Tetanus occurs when spores of C. tetani, an obligate anaerobe normally present in the gut of mammals and widely found in soil, gains access to damaged human tissue. […] After reaching the spinal cord and brainstem via retrograde axonal transport within the motor neuron, tetanus toxin is secreted and enters adjacent inhibitory interneurons, where it blocks neurotransmission by its cleaving action on the membrane proteins involved in neuroexocytosis. […] The net effect is inactivation of inhibitory neurotransmission that normally modulates anterior horn cells and muscle contraction. […] This loss of inhibition (ie, disinhibition) of anterior horn cells and autonomic neurons results in increased muscle tone, painful spasms, and widespread autonomic instability. […] Muscular rigidity in tetanus occurs though a complex mechanism that involves an increase in the resting firing rate of disinhibited motor neurons and lack of inhibition of reflex motor responses to afferent sensory stimuli.

• #36 Tetanus and Tetanus Vaccination | Doctor

  https://patient.info/doctor/tetanus-and-tetanus-vaccination

  Tetanus bacteria spores are found in virtually all soil, particularly soil rich in manure, but also in house dust and animal and human faeces. Spores can enter even the smallest wound; in the presence of anaerobic conditions found in necrotic tissue, active infection, or a foreign body, the bacteria produce a powerful exotoxin called tetanospasmin (also known as tetanus toxin (TeNT) or tetanus neurotoxin). This spreads via lymph and blood to the neuromuscular junction, where it binds to the presynaptic membrane and is transported up motor neurones to the spinal cord and/or brainstem. Here, the toxin blocks inhibitory neurotransmission that would normally suppress the activity of these motor neurones. This disinhibition of lower motor neurones results in muscle hyperactivity, such as the characteristic muscle spasms (severe enough to tear muscles, cause long-bone fractures or spinal compression fractures) and rigidity seen clinically.

• #37 Tetanus: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/229594-overview

  As a result, gamma-aminobutyric acid (GABA)-containing and glycine-containing vesicles are not released, and there is a loss of inhibitory action on motor and autonomic neurons. With this loss of central inhibition, there is autonomic hyperactivity as well as uncontrolled muscle contractions (spasms) in response to normal stimuli such as noises or lights. […] Once the toxin becomes fixed to neurons, it cannot be neutralized with antitoxin. Recovery of nerve function from tetanus toxins requires sprouting of new nerve terminals and formation of new synapses. […] Localized tetanus develops when only the nerves supplying the affected muscle are involved. Generalized tetanus develops when the toxin released at the wound spreads through the lymphatics and blood to multiple nerve terminals. The blood-brain barrier prevents direct entry of toxin to the CNS.

• #38 Tetanus: Pathophysiology, Treatment, and the Possibility of Using Botulinum Toxin against Tetanus-Induced Rigidity and Spasms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3564069/

  However, unlike botulinum toxin, tetanus toxin undergoes extensive retrograde transport in the axons of lower motor neurons and thus reaches the spinal cord or brainstem. Here, the toxin is transported across synapses and taken up by nerve endings of inhibitory GABAergic and/or glycinergic neurons that control the activity of the lower motor neurons. Once inside inhibitory nerve terminals, tetanus toxin cleaves VAMP, thereby inhibiting the release of GABA and glycine. The result is a partial, functional denervation of the lower motor neurons, which leads to their hyperactivity and to increased muscle activity in the form of rigidity and spasms. […] The action of tetanus toxin is not confined to the motor system. Autonomic dysfunction with episodes of tachycardia, hypertension, and sweating, sometimes rapidly alternating with bradycardia and hypotension are common, especially in generalized tetanus. Such symptoms are paralleled by dramatic increases in circulating adrenaline and noradrenaline, which may cause myocardial necrosis.

• #39 Autonomic instability in severe tetanus: a case report

  https://www.e-acn.org/journal/view.php?number=607

  Although autonomic dysfunction pathogenesis is unclear, the tetanus toxin prevents the synaptic vesicles from fusing with the cell membrane by cleaving synaptobrevin. This inhibits inhibitory interneuron discharge release, causing sympathetic hyperactivity and the excessive secretion of catecholamines. Motor neuron overexcitation also causes excessive acetylcholine secretion, which leads to parasympathetic overactivity. Autonomic dysfunction can therefore present with both sympathetic and parasympathetic overactivity. […] Severe autonomic dysfunction associated with tetanus can be life-threatening, and so adequate immunization at an early stage of trauma is crucial. This case underlines the importance of managing cardiovascular instability, and its associated challenges.

• #40 Tetanus – UpToDate

  https://www.uptodate.com/contents/tetanus

  Lack of neural control of adrenal release of catecholamines induced by tetanus toxin produces a hypersympathetic state that manifests as sweating, tachycardia, and hypertension. […] Tetanus toxin-induced effects on anterior horns cells, the brainstem, and autonomic neurons are long lasting because recovery requires the growth of new axonal nerve terminals. […] The mechanisms of binding to and inhibition of neural cells are related to specific portions of the tetanus toxin molecule. […] Tetanus toxin is produced initially as an inactive polypeptide chain by actively growing organisms. […] This synthesis is controlled by genes located in an intracellular plasmid. […] After the toxin is released, it is activated by bacterial or tissue proteases into its active form, which contains a heavy chain necessary for binding and entry into neurons and a light chain responsible for its toxic properties.

• #41 Tetanus: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/229594-overview

  As a result, gamma-aminobutyric acid (GABA)-containing and glycine-containing vesicles are not released, and there is a loss of inhibitory action on motor and autonomic neurons. With this loss of central inhibition, there is autonomic hyperactivity as well as uncontrolled muscle contractions (spasms) in response to normal stimuli such as noises or lights. […] Once the toxin becomes fixed to neurons, it cannot be neutralized with antitoxin. Recovery of nerve function from tetanus toxins requires sprouting of new nerve terminals and formation of new synapses. […] Localized tetanus develops when only the nerves supplying the affected muscle are involved. Generalized tetanus develops when the toxin released at the wound spreads through the lymphatics and blood to multiple nerve terminals. The blood-brain barrier prevents direct entry of toxin to the CNS.

• #42 Tetanus: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/229594-overview

  As a result, gamma-aminobutyric acid (GABA)-containing and glycine-containing vesicles are not released, and there is a loss of inhibitory action on motor and autonomic neurons. With this loss of central inhibition, there is autonomic hyperactivity as well as uncontrolled muscle contractions (spasms) in response to normal stimuli such as noises or lights. […] Once the toxin becomes fixed to neurons, it cannot be neutralized with antitoxin. Recovery of nerve function from tetanus toxins requires sprouting of new nerve terminals and formation of new synapses. […] Localized tetanus develops when only the nerves supplying the affected muscle are involved. Generalized tetanus develops when the toxin released at the wound spreads through the lymphatics and blood to multiple nerve terminals. The blood-brain barrier prevents direct entry of toxin to the CNS.

• #43 Tetanus – UpToDate

  https://www.uptodate.com/contents/tetanus

  Tetanus occurs when spores of C. tetani, an obligate anaerobe normally present in the gut of mammals and widely found in soil, gains access to damaged human tissue. […] After reaching the spinal cord and brainstem via retrograde axonal transport within the motor neuron, tetanus toxin is secreted and enters adjacent inhibitory interneurons, where it blocks neurotransmission by its cleaving action on the membrane proteins involved in neuroexocytosis. […] The net effect is inactivation of inhibitory neurotransmission that normally modulates anterior horn cells and muscle contraction. […] This loss of inhibition (ie, disinhibition) of anterior horn cells and autonomic neurons results in increased muscle tone, painful spasms, and widespread autonomic instability. […] Muscular rigidity in tetanus occurs though a complex mechanism that involves an increase in the resting firing rate of disinhibited motor neurons and lack of inhibition of reflex motor responses to afferent sensory stimuli.

• #44 Clinical Overview of Tetanus | Tetanus | CDC

  https://www.cdc.gov/tetanus/hcp/clinical-overview/index.html

  Clostridium tetani bacteria cause tetanus. […] The bacteria produce very potent toxins that the blood stream and lymphatic system can disseminate throughout the body. One of these toxins, tetanospasmin (tetanus toxin), is responsible for the serious effects of tetanus. […] Tetanus toxin causes the typical clinical manifestations of tetanus by interfering with the release of neurotransmitters and blocking inhibitor impulses. This leads to unopposed muscle contraction and spasm.

• #45 Discovery of the mechanism of tetanus toxin that opens up a new approach to treatment | Università di Padova

  https://www.unipd.it/news/discovery-mechanism-tetanus-toxin-opens-new-approach-treatment

  Characterized by muscle spasms, tetanus is a serious disease that has killed millions of people throughout history. Produced by Clostridium tetani, tetanus toxin is an anaerobic bacterium that can infect minor and severe wounds along with the necrotic areas within them. […] In collaboration with a team coordinated by Dr. Ivica Matak of the University of Zagreb, a research group from Padua has discovered that the molecular mechanism responsible for this atypical flaccid paralysis is an unexpected activity of the tetanus toxin at the level of the neuromuscular junction, the synapse that controls muscle contraction. […] The team also observed that the toxin rapidly migrated to the brain stem and inhibited a number of key physiological functions such as breathing and swallowing, thus causing the disease to rapidly turn fatal. […] Published in Journal of Clinical Investigation Insight, the results of the work entitled Facial neuromuscular junctions and brainstem nuclei are the target of tetanus neurotoxin in cephalic tetanus, offer a new therapeutic approach that could considerably reduce the danger of cephalic tetanus.

• #46 Tetanus pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Tetanus_pathophysiology

  The tetanus toxin cleaves the membrane proteins (SNARE proteins) that are responsible for expulsion of inhibitory neurotransmitters at the neuronal synapses. […] The disinhibition of upper motor neurons affects the lower motor neurons responsible for carrying motor cortex excitatory impulses affecting the autonomic neurons and the anterior horn cells. […] The disinhibition involving anterior horn cells leads to an unopposed contraction of the muscles, leading to excessive tone and muscular spasm which can be painful. […] The autonomic nervous system when disinhibited can lead to seizures. […] Neonatal tetanus develops within hours due to the shorter length of the axons.

• #47 Neonatal tetanus

  https://www.pemj.org/journal/view.php?number=121

  Neonatal tetanus, also known as tetanus neonatorum, occurs in young infants of inadequately immunized mothers. It is a kind of generalized tetanus that is exhibited mainly by prevention of the release of the inhibitory neurotransmitters (i.e., disinhibition) and is initiated by tetanospasmin, an exotoxin created by Clostridium tetani. […] Although C. tetani itself does not invade the tissue, this bacterium induces illness through production of tetanospasmin. Toxigenic C. tetani strains encode tetanospasmin on a plasmid, and the toxin is produced by the proliferating C. tetani at the location of infection. The toxin acts in the central nervous system to prevent the discharge of inhibitory neurons, thereby disinhibiting the motor neurons. […] The absorption and transport of tetanospasmin have 2 mechanisms. When a large amount of the toxin is produced, it spreads to the neurons via the circulation and lymphatics, causing spasm at distant sites and initially affecting the muscles with shortest neural path.

• #48 Neonatal tetanus

  https://www.pemj.org/journal/view.php?number=121

  Neonatal tetanus, also known as tetanus neonatorum, occurs in young infants of inadequately immunized mothers. It is a kind of generalized tetanus that is exhibited mainly by prevention of the release of the inhibitory neurotransmitters (i.e., disinhibition) and is initiated by tetanospasmin, an exotoxin created by Clostridium tetani. […] Although C. tetani itself does not invade the tissue, this bacterium induces illness through production of tetanospasmin. Toxigenic C. tetani strains encode tetanospasmin on a plasmid, and the toxin is produced by the proliferating C. tetani at the location of infection. The toxin acts in the central nervous system to prevent the discharge of inhibitory neurons, thereby disinhibiting the motor neurons. […] The absorption and transport of tetanospasmin have 2 mechanisms. When a large amount of the toxin is produced, it spreads to the neurons via the circulation and lymphatics, causing spasm at distant sites and initially affecting the muscles with shortest neural path.

• #49 Pharmacological management of tetanus: an evidence-based review | Critical Care | Full Text

  https://ccforum.biomedcentral.com/articles/10.1186/cc13797

  Tetanus is caused by the obligatory anaerobic Gram-positive bacillus Clostridium tetani. […] The classical presentation of tetanus seen in patients begins with trismus or locked jaw due to spasms of the masseter. Rigidity then spreads down the arms and trunks over the next 1 to 2 days, progressing to generalized muscle rigidity, stiffness, reflex spasms, opisthotonus and dysphagia. […] The principles of treating tetanus are: reducing muscle spasms, rigidity and autonomic instability (with ventilatory support when necessary); neutralization of tetanus toxin with human antitetanus immunoglobulin or equine antitetanus sera; wound debridement; and administration of antibiotics to eradicate locally proliferating bacteria at the wound site. […] Treatment in tetanus is based on several key principles: a) sedation and paralysis to control the progressive spasms and autonomic dysfunction and to avoid exhaustion; b) surgical debridement and antibiotic treatment for the source of infection; c) neutralization of the circulating toxin; and c) supportive care in an ICU.

• #50 Tetanus immune globulin (intramuscular route) – Mayo Clinic

  https://www.mayoclinic.org/drugs-supplements/tetanus-immune-globulin-intramuscular-route/description/drg-20066294

  Tetanus immune globulin is used to prevent tetanus infection (also known as lockjaw). Tetanus is a serious illness that causes convulsions (seizures) and severe muscle spasms that can be strong enough to cause bone fractures of the spine. Tetanus causes death in 30 to 40 percent of cases. […] Tetanus immune globulin works by giving your body the antibodies it needs to protect it against tetanus infection. This is called passive protection. This passive protection lasts long enough to protect your body until your body can produce its own antibodies against tetanus.

• #51 Pharmacological management of tetanus: an evidence-based review | Critical Care | Full Text

  https://ccforum.biomedcentral.com/articles/10.1186/cc13797

  The routine practice in treating patients with tetanus includes heavy sedation and paralysis with neuromuscular blockade by muscle relaxants supported by artificial ventilation. […] Benzodiazepines are the standard therapy for controlling muscle spasms in tetanus and have gained popularity over other agents due to their combined muscle relaxant, anticonvulsant, sedative and anxiolytic effects, which can be quite useful in managing a patient with tetanus. […] Magnesium sulfate is a widely accepted therapy for controlling eclampsia in obstetric practice. It functions as a physiological antagonist of calcium at the cellular level causing vasodilatation, presynaptic neuromuscular blockade and prevention of catecholamine release. […] Baclofen is a GABA-B receptor agonist. Oral baclofen is thought to have poor penetration across the bloodbrain barrier and hence is ineffective in tetanus. However, intrathecal administration is shown to abolish spasms promptly. […] Administration of human antitetanus immunoglobulin (HTIg) or equine antitetanus serum is an established practice in the treatment of tetanus. […] Antibiotics are administered to patients with tetanus on the presumption that it prevents local proliferation of C. tetani at the wound site.

• #52 Tetanus toxoid: Canadian Immunization Guide – Canada.ca

  https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-22-tetanus-toxoid.html

  TIg provides immediate passive protection until the exposed person mounts an immune response to the tetanus toxoid. The recommended dose for adults and children 7 years of age and older is 250 units by deep intramuscular injection. […] When used in the treatment of tetanus, TIg should be administered intramuscularly in an effort to neutralize tetanus toxin in body fluids. It has no effect on toxin already fixed to nerve tissue. The optimal therapeutic dose has not been established.

• #53 Pharmacological management of tetanus: an evidence-based review | Critical Care | Full Text

  https://ccforum.biomedcentral.com/articles/10.1186/cc13797

  The routine practice in treating patients with tetanus includes heavy sedation and paralysis with neuromuscular blockade by muscle relaxants supported by artificial ventilation. […] Benzodiazepines are the standard therapy for controlling muscle spasms in tetanus and have gained popularity over other agents due to their combined muscle relaxant, anticonvulsant, sedative and anxiolytic effects, which can be quite useful in managing a patient with tetanus. […] Magnesium sulfate is a widely accepted therapy for controlling eclampsia in obstetric practice. It functions as a physiological antagonist of calcium at the cellular level causing vasodilatation, presynaptic neuromuscular blockade and prevention of catecholamine release. […] Baclofen is a GABA-B receptor agonist. Oral baclofen is thought to have poor penetration across the bloodbrain barrier and hence is ineffective in tetanus. However, intrathecal administration is shown to abolish spasms promptly. […] Administration of human antitetanus immunoglobulin (HTIg) or equine antitetanus serum is an established practice in the treatment of tetanus. […] Antibiotics are administered to patients with tetanus on the presumption that it prevents local proliferation of C. tetani at the wound site.

• #54 Tetanus – Clostridium spp Infections – Bacterial Diseases – Infectious Diseases – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.18.3.2.

  In patients with muscle spasms that are severe or interfere with mechanical ventilation, supportive care and pharmacotherapy (eg, muscle relaxants or paralytic agents) could be used to help control tetanic spasms. […] Having acute tetanus does not confer immunity against subsequent episodes because of the extremely small quantities of toxin in disease pathogenesis.

• #55 Tetanus: Pathophysiology, Treatment, and the Possibility of Using Botulinum Toxin against Tetanus-Induced Rigidity and Spasms

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3564069/

  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. 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. […] Botulinum toxins enter nerve terminals of lower motor neurons. The toxins are zinc metalloproteinases that attack synaptic vesicle proteins, but they do so differentially: botulinum toxin A cleaves synaptosomal-associated protein (SNAP-25), botulinum toxins B, D, F, and G cleave synaptobrevin (which is also attacked by tetanus toxin); botulinum toxin C cleaves SNAP-25 and syntaxin. Compared to tetanus toxin, the botulinum toxins undergo less axonal and trans-synaptic transport, although some transport does seem to occur. 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.

• #56 Tetanus: Pathophysiology, Treatment, and the Possibility of Using Botulinum Toxin against Tetanus-Induced Rigidity and Spasms

  https://www.mdpi.com/2072-6651/5/1/73

  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. […] The use of botulinum toxin against tetanus-induced rigidity and spasms is supported by case reports indicating its effectiveness in controlling muscle rigidity and spasms.

• #57 Tetanus Vaccine – Creative Diagnostics

  https://www.creative-diagnostics.com/tetanus-vaccine.htm

  Tetanus, caused by the bacterium Clostridium tetani, poses a significant threat to individuals worldwide. […] The bacterium produces a powerful neurotoxin called tetanospasmin, which affects the nervous system, leading to muscle stiffness and spasms. […] The tetanus vaccine is a highly effective preventive measure against tetanus infections. It consists of inactivated tetanus toxin, also known as tetanus toxoid. […] When the tetanus toxoid is administered, it stimulates the immune response. This involves the activation of specific cells called TH2 and B cells. These cells produce immunoglobulins, which are antibodies that target the toxoid and provide protection against future tetanus infections. […] The primary objective of tetanus vaccination is to confer immunity against the devastating effects of tetanus infection. The World Health Organization (WHO) recommends the administration of the primary series of tetanus vaccinations during adolescence. This series ensures comprehensive protection against the gram-positive bacillus, Clostridium tetani, and its neurotoxin, tetanospasmin.

• #58 Tetanus Vaccine – Creative Diagnostics

  https://www.creative-diagnostics.com/tetanus-vaccine.htm

  Tetanus, caused by the bacterium Clostridium tetani, poses a significant threat to individuals worldwide. […] The bacterium produces a powerful neurotoxin called tetanospasmin, which affects the nervous system, leading to muscle stiffness and spasms. […] The tetanus vaccine is a highly effective preventive measure against tetanus infections. It consists of inactivated tetanus toxin, also known as tetanus toxoid. […] When the tetanus toxoid is administered, it stimulates the immune response. This involves the activation of specific cells called TH2 and B cells. These cells produce immunoglobulins, which are antibodies that target the toxoid and provide protection against future tetanus infections. […] The primary objective of tetanus vaccination is to confer immunity against the devastating effects of tetanus infection. The World Health Organization (WHO) recommends the administration of the primary series of tetanus vaccinations during adolescence. This series ensures comprehensive protection against the gram-positive bacillus, Clostridium tetani, and its neurotoxin, tetanospasmin.

• #59 15.20F: Tetanus – Biology LibreTexts

  https://bio.libretexts.org/Bookshelves/Microbiology/Microbiology_(Boundless)/15%3A_Diseases/15.20%3A_Microbial_Diseases_of_the_Nervous_System/15.20F%3A_Tetanus

  Tetanus is a medical condition characterized by a prolonged contraction of skeletal muscle fibers. The primary symptoms are caused by tetanospasmin, a neurotoxin produced by the Gram-positive, rod-shaped, obligate anaerobic bacterium Clostridium tetani. […] Tetanospasmin is an A-B toxin. The B subunit binds to the receptors on motor neurons, while the A subunit induces endocytosis to enter the neuron. […] Tetanus affects skeletal muscle, a type of striated muscle used in voluntary movement. […] Because C. tetani is an anaerobic bacterium, it and its endospores survive well in an environment that lacks oxygen. […] Unlike many infectious diseases, recovery from naturally acquired tetanus does not usually result in immunity to tetanus. This is due to the extreme potency of the tetanospasmin toxin; even a lethal dose of tetanospasmin is insufficient to provoke an immune response. […] To combat the effects of the toxin, tetanus immune globulin (TIG) antitoxin can be given to the patient. These antibodies are able to neutralize the tetanospasmin if they are not already bound to motor neurons, and can confer passive immunity.

• #60 Tetanus toxoid: Canadian Immunization Guide – Canada.ca

  https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-22-tetanus-toxoid.html

  Tetanus (lockjaw) is caused by a neurotoxin produced by the bacterium Clostridium tetani. […] C. tetani spores are usually introduced into the body through a wound that is contaminated with soil, animal/human feces or dust. C. tetani spores will germinate into bacilli in an anaerobic environment, such as necrotic tissue. The bacilli release a potent neurotoxin. The incubation period is generally 3 to 21 days (range, 1 day to several months). Since tetanus is caused by the neurotoxin, it is not transmitted person-to-person. […] Tetanus is characterized by muscle spasms, usually in a descending pattern, beginning in the jaw muscles. As the disease progresses, prolonged frequent spasms may occur, contributing to serious complications and death, unless treatment is provided. […] Because tetanus is caused by the toxins produced by the tetanus bacterium and not by the bacterium itself, recovery from tetanus disease does not confer immunity.

• #61 Pharmacological management of tetanus: an evidence-based review | Critical Care | Full Text

  https://ccforum.biomedcentral.com/articles/10.1186/cc13797

  Tetanus is caused by the obligatory anaerobic Gram-positive bacillus Clostridium tetani. […] The classical presentation of tetanus seen in patients begins with trismus or locked jaw due to spasms of the masseter. Rigidity then spreads down the arms and trunks over the next 1 to 2 days, progressing to generalized muscle rigidity, stiffness, reflex spasms, opisthotonus and dysphagia. […] The principles of treating tetanus are: reducing muscle spasms, rigidity and autonomic instability (with ventilatory support when necessary); neutralization of tetanus toxin with human antitetanus immunoglobulin or equine antitetanus sera; wound debridement; and administration of antibiotics to eradicate locally proliferating bacteria at the wound site. […] Treatment in tetanus is based on several key principles: a) sedation and paralysis to control the progressive spasms and autonomic dysfunction and to avoid exhaustion; b) surgical debridement and antibiotic treatment for the source of infection; c) neutralization of the circulating toxin; and c) supportive care in an ICU.

• #62 Tetanus toxoid: Canadian Immunization Guide – Canada.ca

  https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-22-tetanus-toxoid.html

  Tetanus (lockjaw) is caused by a neurotoxin produced by the bacterium Clostridium tetani. […] C. tetani spores are usually introduced into the body through a wound that is contaminated with soil, animal/human feces or dust. C. tetani spores will germinate into bacilli in an anaerobic environment, such as necrotic tissue. The bacilli release a potent neurotoxin. The incubation period is generally 3 to 21 days (range, 1 day to several months). Since tetanus is caused by the neurotoxin, it is not transmitted person-to-person. […] Tetanus is characterized by muscle spasms, usually in a descending pattern, beginning in the jaw muscles. As the disease progresses, prolonged frequent spasms may occur, contributing to serious complications and death, unless treatment is provided. […] Because tetanus is caused by the toxins produced by the tetanus bacterium and not by the bacterium itself, recovery from tetanus disease does not confer immunity.

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