Tetanus
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'''Tetanus''' ({{etymology|grc|{{wikt-lang|grc|τέτανος}}|tension', 'stretched', 'rigid}}), also known as '''lockjaw''', is a [[bacterial infection]] caused by ''[[Clostridium tetani]]'' and characterized by [[muscle spasm]]s. In the most common type, the spasms begin in the jaw and then progress to the rest of the body. Each spasm usually lasts for a few minutes. Spasms occur frequently for three to four weeks.<ref name="CDC2012Pink" /><ref>{{Cite journal |last1=Sudarshan |first1=Raghav |last2=Sayo |first2=Ana Ria |last3=Renner |first3=David Roman |last4=Saram |first4=Sophia de |last5=Godbole |first5=Gauri |last6=Warrell |first6=Clare |last7=Duong |first7=Ha Thi Hai |last8=Thwaites |first8=C. Louise |last9=Mehta |first9=Arpan R. |last10=Coughlan |first10=Charles |date=2025-06-18 |title=Tetanus: recognition and management |journal=The Lancet Infectious Diseases |issue=11 |pages=e645–e657 |language=English |volume=25 |doi=10.1016/S1473-3099(25)00292-0 |pmid=40543524 |issn=1473-3099|pmc=7617864}}</ref> Some spasms may be severe enough to [[bone fracture|fracture bones]].<ref name="CDC2013S">{{cite web |date=January 9, 2013 |title=Tetanus Symptoms and Complications |url=https://www.cdc.gov/tetanus/about/symptoms-complications.html |url-status=live |archive-url=https://web.archive.org/web/20150212225108/http://www.cdc.gov/tetanus/about/symptoms-complications.html |archive-date=12 February 2015 |access-date=12 February 2015 |publisher=Centers for Disease Control and Prevention}}</ref> Other symptoms of tetanus may include [[fever]], [[sweating]], [[headache]], [[dysphagia|trouble swallowing]], [[hypertension|high blood pressure]], and a [[tachycardia|fast heart rate]]. The onset of symptoms is typically 3 to 21 days following infection. Recovery may take months; about 10% of cases prove to be [[death|fatal]].<ref name=CDC2012Pink>{{cite book|last1=Atkinson|first1=William|title=Tetanus Epidemiology and Prevention of Vaccine-Preventable Diseases|date=May 2012|publisher=Public Health Foundation|isbn=978-0-9832631-3-5|pages=291–300|edition=12|url=https://www.cdc.gov/vaccines/pubs/pinkbook/tetanus.html|access-date=12 February 2015|url-status=live|archive-url=https://web.archive.org/web/20150213010501/http://www.cdc.gov/vaccines/pubs/pinkbook/tetanus.html|archive-date=February 13, 2015}} {{CDC}}</ref> '''Tetanus''' ({{etymology|grc|{{wikt-lang|grc|τέτανος}}|tension', 'stretched', 'rigid}}), also known as '''lockjaw''', is a [[bacterial infection]] caused by ''[[Clostridium tetani]]'' and characterized by [[muscle spasm]]s. In the most common type, the spasms begin in the jaw and then progress to the rest of the body. Each spasm usually lasts for a few minutes. Spasms occur frequently for three to four weeks.<ref name="CDC2012Pink" /><ref name="Sudarshan"/> Some spasms may be severe enough to [[bone fracture|fracture bones]].<ref name="CDC2013S">{{cite web |date=January 9, 2013 |title=Tetanus Symptoms and Complications |url=https://www.cdc.gov/tetanus/about/symptoms-complications.html |url-status=live |archive-url=https://web.archive.org/web/20150212225108/http://www.cdc.gov/tetanus/about/symptoms-complications.html |archive-date=12 February 2015 |access-date=12 February 2015 |publisher=Centers for Disease Control and Prevention}}</ref> Other symptoms of tetanus may include [[fever]], [[sweating]], [[headache]], [[dysphagia|trouble swallowing]], [[hypertension|high blood pressure]], and a [[tachycardia|fast heart rate]]. The onset of symptoms is typically 3 to 21 days following infection. Recovery may take months; about 10% of cases prove to be [[death|fatal]].<ref name=CDC2012Pink>{{cite book|last1=Atkinson|first1=William|title=Tetanus Epidemiology and Prevention of Vaccine-Preventable Diseases|date=May 2012|publisher=Public Health Foundation|isbn=978-0-9832631-3-5|pages=291–300|edition=12|url=https://www.cdc.gov/vaccines/pubs/pinkbook/tetanus.html|access-date=12 February 2015|url-status=live|archive-url=https://web.archive.org/web/20150213010501/http://www.cdc.gov/vaccines/pubs/pinkbook/tetanus.html|archive-date=February 13, 2015}} {{CDC}}</ref>
''C. tetani'' is commonly found in soil, saliva, dust, and manure. The bacteria generally enter through a break in the skin, such as a cut or puncture wound caused by a contaminated object.<ref name="CDC2012Pink" /><ref name="CDC2013C">{{cite web |date=January 9, 2013 |title=Tetanus Causes and Transmission |url=https://www.cdc.gov/tetanus/about/causes-transmission.html |url-status=live |archive-url=https://web.archive.org/web/20150212223308/http://www.cdc.gov/tetanus/about/causes-transmission.html |archive-date=12 February 2015 |access-date=12 February 2015 |publisher=Centers for Disease Control and Prevention}}</ref> They produce [[toxin]]s that interfere with normal muscle contractions.<ref name=CDC2013Doc>{{cite web|title=Tetanus For Clinicians|url=https://www.cdc.gov/tetanus/clinicians.html|publisher=Centers for Disease Control and Prevention|access-date=12 February 2015|date=January 9, 2013|url-status=live|archive-url=https://web.archive.org/web/20150212224705/http://www.cdc.gov/tetanus/clinicians.html|archive-date=12 February 2015}}</ref> Diagnosis is based on the presenting signs and symptoms. The disease does not spread between people.<ref name=CDC2012Pink/> ''C. tetani'' is commonly found in soil, saliva, dust, and manure. The bacteria generally enter through a break in the skin, such as a cut or puncture wound caused by a contaminated object.<ref name="CDC2012Pink" /><ref name="CDC2013C">{{cite web |date=January 9, 2013 |title=Tetanus Causes and Transmission |url=https://www.cdc.gov/tetanus/about/causes-transmission.html |url-status=live |archive-url=https://web.archive.org/web/20150212223308/http://www.cdc.gov/tetanus/about/causes-transmission.html |archive-date=12 February 2015 |access-date=12 February 2015 |publisher=Centers for Disease Control and Prevention}}</ref> They produce [[toxin]]s that interfere with normal muscle contractions.<ref name=CDC2013Doc>{{cite web|title=Tetanus For Clinicians|url=https://www.cdc.gov/tetanus/clinicians.html|publisher=Centers for Disease Control and Prevention|access-date=12 February 2015|date=January 9, 2013|url-status=live|archive-url=https://web.archive.org/web/20150212224705/http://www.cdc.gov/tetanus/clinicians.html|archive-date=12 February 2015}}</ref> Diagnosis is based on the presenting signs and symptoms. The disease does not spread between people.<ref name=CDC2012Pink/> Line 68: Line 68: == Pathophysiology == == Pathophysiology == [[File:Neurotransmitter vesicle before and after exposure to Tetanus Toxin.jpg|thumb|upright=1.4|A neurotransmitter-filled vesicle before and after exposure to the tetanus toxin. The cleavage of the VAMP protein by the toxin inhibits vesicle fusion and neurotransmitter release into the synapse.]] [[File:Neurotransmitter vesicle before and after exposure to Tetanus Toxin.jpg|thumb|upright=1.4|A neurotransmitter-filled vesicle before and after exposure to the tetanus toxin. The cleavage of the VAMP protein by the toxin inhibits vesicle fusion and neurotransmitter release into the synapse.]] 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]].<ref name=":0">{{cite journal |vauthors=Pellizzari R, Rossetto O, Schiavo G, Montecucco C |title=Tetanus and botulinum neurotoxins: mechanism of action and therapeutic uses |journal=Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences |volume=354 |issue=1381 |pages=259–68 |date=February 1999 |pmid=10212474 |pmc=1692495 |doi=10.1098/rstb.1999.0377 |veditors=Clementi F, Fesce R}}</ref><ref>{{Cite journal |last1=Sudarshan |first1=Raghav |last2=Sayo |first2=Ana Ria |last3=Renner |first3=David Roman |last4=Saram |first4=Sophia de |last5=Godbole |first5=Gauri |last6=Warrell |first6=Clare |last7=Duong |first7=Ha Thi Hai |last8=Thwaites |first8=C. Louise |last9=Mehta |first9=Arpan R. |last10=Coughlan |first10=Charles |date=2025-06-18 |title=Tetanus: recognition and management |journal=The Lancet Infectious Diseases |issue=11 |pages=e645–e657 |language=English |volume=25 |doi=10.1016/S1473-3099(25)00292-0 |pmid=40543524 |issn=1473-3099|pmc=7617864}}</ref> Here, it selectively binds to and is transported into inhibitory neurons via [[endocytosis]].<ref name=":1">{{cite journal |vauthors=Montecucco C, Schiavo G, Meldolesi J, Valtorta F |title=Mechanism of action of tetanus and botulinum neurotoxins |journal=Molecular Microbiology |volume=13 |issue=1 |pages=1–8 |date=July 1994 |pmid=7527117 |doi=10.1111/j.1365-2958.1994.tb00396.x |s2cid=45069991 |doi-access=free}}</ref> It then leaves the vesicle for the neuron cytosol, where it cleaves [[Vesicle-associated membrane protein|vesicle associated membrane protein]] (VAMP) [[synaptobrevin]], which is necessary for membrane fusion of small synaptic vesicles (SSV's).<ref name=":0" /> SSV's carry [[neurotransmitter]] to the membrane for release, so inhibition of this process blocks neurotransmitter release.<ref>{{Cite journal |last=Jung |first=Jae Hoon |date=2019-05-31 |title=Synaptic Vesicles Having Large Contact Areas with the Presynaptic Membrane are Preferentially Hemifused at Active Zones of Frog Neuromuscular Junctions Fixed during Synaptic Activity |journal=International Journal of Molecular Sciences |volume=20 |issue=11 |page=2692 |doi=10.3390/ijms20112692 |doi-access=free |issn=1422-0067 |pmc=6600287 |pmid=31159267}}</ref> 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]].<ref name=":0">{{cite journal |vauthors=Pellizzari R, Rossetto O, Schiavo G, Montecucco C |title=Tetanus and botulinum neurotoxins: mechanism of action and therapeutic uses |journal=Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences |volume=354 |issue=1381 |pages=259–68 |date=February 1999 |pmid=10212474 |pmc=1692495 |doi=10.1098/rstb.1999.0377 |veditors=Clementi F, Fesce R}}</ref><ref name="Sudarshan"/> Here, it selectively binds to and is transported into inhibitory neurons via [[endocytosis]].<ref name=":1">{{cite journal |vauthors=Montecucco C, Schiavo G, Meldolesi J, Valtorta F |title=Mechanism of action of tetanus and botulinum neurotoxins |journal=Molecular Microbiology |volume=13 |issue=1 |pages=1–8 |date=July 1994 |pmid=7527117 |doi=10.1111/j.1365-2958.1994.tb00396.x |s2cid=45069991 |doi-access=free}}</ref> It then leaves the vesicle for the neuron cytosol, where it cleaves [[Vesicle-associated membrane protein|vesicle associated membrane protein]] (VAMP) [[synaptobrevin]], which is necessary for membrane fusion of small synaptic vesicles (SSV's).<ref name=":0" /> SSV's carry [[neurotransmitter]] to the membrane for release, so inhibition of this process blocks neurotransmitter release.<ref>{{Cite journal |last=Jung |first=Jae Hoon |date=2019-05-31 |title=Synaptic Vesicles Having Large Contact Areas with the Presynaptic Membrane are Preferentially Hemifused at Active Zones of Frog Neuromuscular Junctions Fixed during Synaptic Activity |journal=International Journal of Molecular Sciences |volume=20 |issue=11 |page=2692 |doi=10.3390/ijms20112692 |doi-access=free |issn=1422-0067 |pmc=6600287 |pmid=31159267}}</ref>
Tetanus toxin specifically blocks the release of the neurotransmitters [[Gamma-Aminobutyric acid|GABA]] and [[glycine]] from inhibitory neurons. These neurotransmitters stop overactive motor neurons from firing and also play a role in muscle relaxation after contraction. When inhibitory neurons are unable to release their neurotransmitters, motor neurons fire out of control, and muscles have difficulty relaxing. This causes the muscle spasms and [[Spasticity|spastic paralysis]] seen in tetanus infection.<ref name=":0" /> Tetanus toxin specifically blocks the release of the neurotransmitters [[Gamma-Aminobutyric acid|GABA]] and [[glycine]] from inhibitory neurons. These neurotransmitters stop overactive motor neurons from firing and also play a role in muscle relaxation after contraction. When inhibitory neurons are unable to release their neurotransmitters, motor neurons fire out of control, and muscles have difficulty relaxing. This causes the muscle spasms and [[Spasticity|spastic paralysis]] seen in tetanus infection.<ref name=":0" /> Line 128: Line 128: ==Treatment== ==Treatment== [[File:Tetanus world map-Deaths per million persons-WHO2012.svg|thumb|upright=1.3|Tetanus deaths per million persons in 2012{{Div col|small=yes|colwidth=10em}}{{legend|#ffff20|0–1}}{{legend|#ffa020|1–2}}{{legend|#ff9a20|2–3}}{{legend|#f08015|4–8}}{{legend|#e06815|9–13}}{{legend|#d85010|14–28}}{{legend|#d02010|29–151}}{{div col end}} [[File:Tetanus world map-Deaths per million persons-WHO2012.svg|thumb|upright=1.3|Tetanus deaths per million persons in 2012{{Div col|small=yes|colwidth=10em}}{{legend|#ffff20|0–1}}{{legend|#ffa020|1–2}}{{legend|#ff9a20|2–3}}{{legend|#f08015|4–8}}{{legend|#e06815|9–13}}{{legend|#d85010|14–28}}{{legend|#d02010|29–151}}{{div col end}} ]]Treatment of adult tetanus was covered in a state-of-the-art review in 2025.<ref>{{Cite journal |last1=Sudarshan |first1=Raghav |last2=Sayo |first2=Ana Ria |last3=Renner |first3=David Roman |last4=Saram |first4=Sophia de |last5=Godbole |first5=Gauri |last6=Warrell |first6=Clare |last7=Duong |first7=Ha Thi Hai |last8=Thwaites |first8=C. Louise |last9=Mehta |first9=Arpan R. |last10=Coughlan |first10=Charles |date=2025-06-18 |title=Tetanus: recognition and management |journal=The Lancet Infectious Diseases |issue=11 |pages=e645–e657 |language=English |volume=25 |doi=10.1016/S1473-3099(25)00292-0 |pmid=40543524 |issn=1473-3099|pmc=7617864}}</ref> ]]Treatment of adult tetanus was covered in a state-of-the-art review in 2025.<ref name="Sudarshan">{{Cite journal |last1=Sudarshan |first1=Raghav |last2=Sayo |first2=Ana Ria |last3=Renner |first3=David Roman |last4=Saram |first4=Sophia de |last5=Godbole |first5=Gauri |last6=Warrell |first6=Clare |last7=Duong |first7=Ha Thi Hai |last8=Thwaites |first8=C. Louise |last9=Mehta |first9=Arpan R. |last10=Coughlan |first10=Charles |date=2025-06-18 |title=Tetanus: recognition and management |journal=The Lancet Infectious Diseases |issue=11 |pages=e645–e657 |language=English |volume=25 |doi=10.1016/S1473-3099(25)00292-0 |pmid=40543524 |issn=1473-3099|pmc=7617864}}</ref>
=== Mild tetanus === === Mild tetanus ===
'''Tetanus''' ({{etymology|grc|{{wikt-lang|grc|τέτανος}}|tension', 'stretched', 'rigid}}), also known as '''lockjaw''', is a [[bacterial infection]] caused by ''[[Clostridium tetani]]'' and characterized by [[muscle spasm]]s. In the most common type, the spasms begin in the jaw and then progress to the rest of the body. Each spasm usually lasts for a few minutes. Spasms occur frequently for three to four weeks.<ref name="CDC2012Pink" /><ref>{{Cite journal |last1=Sudarshan |first1=Raghav |last2=Sayo |first2=Ana Ria |last3=Renner |first3=David Roman |last4=Saram |first4=Sophia de |last5=Godbole |first5=Gauri |last6=Warrell |first6=Clare |last7=Duong |first7=Ha Thi Hai |last8=Thwaites |first8=C. Louise |last9=Mehta |first9=Arpan R. |last10=Coughlan |first10=Charles |date=2025-06-18 |title=Tetanus: recognition and management |journal=The Lancet Infectious Diseases |issue=11 |pages=e645–e657 |language=English |volume=25 |doi=10.1016/S1473-3099(25)00292-0 |pmid=40543524 |issn=1473-3099|pmc=7617864}}</ref> Some spasms may be severe enough to [[bone fracture|fracture bones]].<ref name="CDC2013S">{{cite web |date=January 9, 2013 |title=Tetanus Symptoms and Complications |url=https://www.cdc.gov/tetanus/about/symptoms-complications.html |url-status=live |archive-url=https://web.archive.org/web/20150212225108/http://www.cdc.gov/tetanus/about/symptoms-complications.html |archive-date=12 February 2015 |access-date=12 February 2015 |publisher=Centers for Disease Control and Prevention}}</ref> Other symptoms of tetanus may include [[fever]], [[sweating]], [[headache]], [[dysphagia|trouble swallowing]], [[hypertension|high blood pressure]], and a [[tachycardia|fast heart rate]]. The onset of symptoms is typically 3 to 21 days following infection. Recovery may take months; about 10% of cases prove to be [[death|fatal]].<ref name=CDC2012Pink>{{cite book|last1=Atkinson|first1=William|title=Tetanus Epidemiology and Prevention of Vaccine-Preventable Diseases|date=May 2012|publisher=Public Health Foundation|isbn=978-0-9832631-3-5|pages=291–300|edition=12|url=https://www.cdc.gov/vaccines/pubs/pinkbook/tetanus.html|access-date=12 February 2015|url-status=live|archive-url=https://web.archive.org/web/20150213010501/http://www.cdc.gov/vaccines/pubs/pinkbook/tetanus.html|archive-date=February 13, 2015}} {{CDC}}</ref> '''Tetanus''' ({{etymology|grc|{{wikt-lang|grc|τέτανος}}|tension', 'stretched', 'rigid}}), also known as '''lockjaw''', is a [[bacterial infection]] caused by ''[[Clostridium tetani]]'' and characterized by [[muscle spasm]]s. In the most common type, the spasms begin in the jaw and then progress to the rest of the body. Each spasm usually lasts for a few minutes. Spasms occur frequently for three to four weeks.<ref name="CDC2012Pink" /><ref name="Sudarshan"/> Some spasms may be severe enough to [[bone fracture|fracture bones]].<ref name="CDC2013S">{{cite web |date=January 9, 2013 |title=Tetanus Symptoms and Complications |url=https://www.cdc.gov/tetanus/about/symptoms-complications.html |url-status=live |archive-url=https://web.archive.org/web/20150212225108/http://www.cdc.gov/tetanus/about/symptoms-complications.html |archive-date=12 February 2015 |access-date=12 February 2015 |publisher=Centers for Disease Control and Prevention}}</ref> Other symptoms of tetanus may include [[fever]], [[sweating]], [[headache]], [[dysphagia|trouble swallowing]], [[hypertension|high blood pressure]], and a [[tachycardia|fast heart rate]]. The onset of symptoms is typically 3 to 21 days following infection. Recovery may take months; about 10% of cases prove to be [[death|fatal]].<ref name=CDC2012Pink>{{cite book|last1=Atkinson|first1=William|title=Tetanus Epidemiology and Prevention of Vaccine-Preventable Diseases|date=May 2012|publisher=Public Health Foundation|isbn=978-0-9832631-3-5|pages=291–300|edition=12|url=https://www.cdc.gov/vaccines/pubs/pinkbook/tetanus.html|access-date=12 February 2015|url-status=live|archive-url=https://web.archive.org/web/20150213010501/http://www.cdc.gov/vaccines/pubs/pinkbook/tetanus.html|archive-date=February 13, 2015}} {{CDC}}</ref>
''C. tetani'' is commonly found in soil, saliva, dust, and manure. The bacteria generally enter through a break in the skin, such as a cut or puncture wound caused by a contaminated object.<ref name="CDC2012Pink" /><ref name="CDC2013C">{{cite web |date=January 9, 2013 |title=Tetanus Causes and Transmission |url=https://www.cdc.gov/tetanus/about/causes-transmission.html |url-status=live |archive-url=https://web.archive.org/web/20150212223308/http://www.cdc.gov/tetanus/about/causes-transmission.html |archive-date=12 February 2015 |access-date=12 February 2015 |publisher=Centers for Disease Control and Prevention}}</ref> They produce [[toxin]]s that interfere with normal muscle contractions.<ref name=CDC2013Doc>{{cite web|title=Tetanus For Clinicians|url=https://www.cdc.gov/tetanus/clinicians.html|publisher=Centers for Disease Control and Prevention|access-date=12 February 2015|date=January 9, 2013|url-status=live|archive-url=https://web.archive.org/web/20150212224705/http://www.cdc.gov/tetanus/clinicians.html|archive-date=12 February 2015}}</ref> Diagnosis is based on the presenting signs and symptoms. The disease does not spread between people.<ref name=CDC2012Pink/> ''C. tetani'' is commonly found in soil, saliva, dust, and manure. The bacteria generally enter through a break in the skin, such as a cut or puncture wound caused by a contaminated object.<ref name="CDC2012Pink" /><ref name="CDC2013C">{{cite web |date=January 9, 2013 |title=Tetanus Causes and Transmission |url=https://www.cdc.gov/tetanus/about/causes-transmission.html |url-status=live |archive-url=https://web.archive.org/web/20150212223308/http://www.cdc.gov/tetanus/about/causes-transmission.html |archive-date=12 February 2015 |access-date=12 February 2015 |publisher=Centers for Disease Control and Prevention}}</ref> They produce [[toxin]]s that interfere with normal muscle contractions.<ref name=CDC2013Doc>{{cite web|title=Tetanus For Clinicians|url=https://www.cdc.gov/tetanus/clinicians.html|publisher=Centers for Disease Control and Prevention|access-date=12 February 2015|date=January 9, 2013|url-status=live|archive-url=https://web.archive.org/web/20150212224705/http://www.cdc.gov/tetanus/clinicians.html|archive-date=12 February 2015}}</ref> Diagnosis is based on the presenting signs and symptoms. The disease does not spread between people.<ref name=CDC2012Pink/> Line 68: Line 68: == Pathophysiology == == Pathophysiology == [[File:Neurotransmitter vesicle before and after exposure to Tetanus Toxin.jpg|thumb|upright=1.4|A neurotransmitter-filled vesicle before and after exposure to the tetanus toxin. The cleavage of the VAMP protein by the toxin inhibits vesicle fusion and neurotransmitter release into the synapse.]] [[File:Neurotransmitter vesicle before and after exposure to Tetanus Toxin.jpg|thumb|upright=1.4|A neurotransmitter-filled vesicle before and after exposure to the tetanus toxin. The cleavage of the VAMP protein by the toxin inhibits vesicle fusion and neurotransmitter release into the synapse.]] 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]].<ref name=":0">{{cite journal |vauthors=Pellizzari R, Rossetto O, Schiavo G, Montecucco C |title=Tetanus and botulinum neurotoxins: mechanism of action and therapeutic uses |journal=Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences |volume=354 |issue=1381 |pages=259–68 |date=February 1999 |pmid=10212474 |pmc=1692495 |doi=10.1098/rstb.1999.0377 |veditors=Clementi F, Fesce R}}</ref><ref>{{Cite journal |last1=Sudarshan |first1=Raghav |last2=Sayo |first2=Ana Ria |last3=Renner |first3=David Roman |last4=Saram |first4=Sophia de |last5=Godbole |first5=Gauri |last6=Warrell |first6=Clare |last7=Duong |first7=Ha Thi Hai |last8=Thwaites |first8=C. Louise |last9=Mehta |first9=Arpan R. |last10=Coughlan |first10=Charles |date=2025-06-18 |title=Tetanus: recognition and management |journal=The Lancet Infectious Diseases |issue=11 |pages=e645–e657 |language=English |volume=25 |doi=10.1016/S1473-3099(25)00292-0 |pmid=40543524 |issn=1473-3099|pmc=7617864}}</ref> Here, it selectively binds to and is transported into inhibitory neurons via [[endocytosis]].<ref name=":1">{{cite journal |vauthors=Montecucco C, Schiavo G, Meldolesi J, Valtorta F |title=Mechanism of action of tetanus and botulinum neurotoxins |journal=Molecular Microbiology |volume=13 |issue=1 |pages=1–8 |date=July 1994 |pmid=7527117 |doi=10.1111/j.1365-2958.1994.tb00396.x |s2cid=45069991 |doi-access=free}}</ref> It then leaves the vesicle for the neuron cytosol, where it cleaves [[Vesicle-associated membrane protein|vesicle associated membrane protein]] (VAMP) [[synaptobrevin]], which is necessary for membrane fusion of small synaptic vesicles (SSV's).<ref name=":0" /> SSV's carry [[neurotransmitter]] to the membrane for release, so inhibition of this process blocks neurotransmitter release.<ref>{{Cite journal |last=Jung |first=Jae Hoon |date=2019-05-31 |title=Synaptic Vesicles Having Large Contact Areas with the Presynaptic Membrane are Preferentially Hemifused at Active Zones of Frog Neuromuscular Junctions Fixed during Synaptic Activity |journal=International Journal of Molecular Sciences |volume=20 |issue=11 |page=2692 |doi=10.3390/ijms20112692 |doi-access=free |issn=1422-0067 |pmc=6600287 |pmid=31159267}}</ref> 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]].<ref name=":0">{{cite journal |vauthors=Pellizzari R, Rossetto O, Schiavo G, Montecucco C |title=Tetanus and botulinum neurotoxins: mechanism of action and therapeutic uses |journal=Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences |volume=354 |issue=1381 |pages=259–68 |date=February 1999 |pmid=10212474 |pmc=1692495 |doi=10.1098/rstb.1999.0377 |veditors=Clementi F, Fesce R}}</ref><ref name="Sudarshan"/> Here, it selectively binds to and is transported into inhibitory neurons via [[endocytosis]].<ref name=":1">{{cite journal |vauthors=Montecucco C, Schiavo G, Meldolesi J, Valtorta F |title=Mechanism of action of tetanus and botulinum neurotoxins |journal=Molecular Microbiology |volume=13 |issue=1 |pages=1–8 |date=July 1994 |pmid=7527117 |doi=10.1111/j.1365-2958.1994.tb00396.x |s2cid=45069991 |doi-access=free}}</ref> It then leaves the vesicle for the neuron cytosol, where it cleaves [[Vesicle-associated membrane protein|vesicle associated membrane protein]] (VAMP) [[synaptobrevin]], which is necessary for membrane fusion of small synaptic vesicles (SSV's).<ref name=":0" /> SSV's carry [[neurotransmitter]] to the membrane for release, so inhibition of this process blocks neurotransmitter release.<ref>{{Cite journal |last=Jung |first=Jae Hoon |date=2019-05-31 |title=Synaptic Vesicles Having Large Contact Areas with the Presynaptic Membrane are Preferentially Hemifused at Active Zones of Frog Neuromuscular Junctions Fixed during Synaptic Activity |journal=International Journal of Molecular Sciences |volume=20 |issue=11 |page=2692 |doi=10.3390/ijms20112692 |doi-access=free |issn=1422-0067 |pmc=6600287 |pmid=31159267}}</ref>
Tetanus toxin specifically blocks the release of the neurotransmitters [[Gamma-Aminobutyric acid|GABA]] and [[glycine]] from inhibitory neurons. These neurotransmitters stop overactive motor neurons from firing and also play a role in muscle relaxation after contraction. When inhibitory neurons are unable to release their neurotransmitters, motor neurons fire out of control, and muscles have difficulty relaxing. This causes the muscle spasms and [[Spasticity|spastic paralysis]] seen in tetanus infection.<ref name=":0" /> Tetanus toxin specifically blocks the release of the neurotransmitters [[Gamma-Aminobutyric acid|GABA]] and [[glycine]] from inhibitory neurons. These neurotransmitters stop overactive motor neurons from firing and also play a role in muscle relaxation after contraction. When inhibitory neurons are unable to release their neurotransmitters, motor neurons fire out of control, and muscles have difficulty relaxing. This causes the muscle spasms and [[Spasticity|spastic paralysis]] seen in tetanus infection.<ref name=":0" /> Line 128: Line 128: ==Treatment== ==Treatment== [[File:Tetanus world map-Deaths per million persons-WHO2012.svg|thumb|upright=1.3|Tetanus deaths per million persons in 2012{{Div col|small=yes|colwidth=10em}}{{legend|#ffff20|0–1}}{{legend|#ffa020|1–2}}{{legend|#ff9a20|2–3}}{{legend|#f08015|4–8}}{{legend|#e06815|9–13}}{{legend|#d85010|14–28}}{{legend|#d02010|29–151}}{{div col end}} [[File:Tetanus world map-Deaths per million persons-WHO2012.svg|thumb|upright=1.3|Tetanus deaths per million persons in 2012{{Div col|small=yes|colwidth=10em}}{{legend|#ffff20|0–1}}{{legend|#ffa020|1–2}}{{legend|#ff9a20|2–3}}{{legend|#f08015|4–8}}{{legend|#e06815|9–13}}{{legend|#d85010|14–28}}{{legend|#d02010|29–151}}{{div col end}} ]]Treatment of adult tetanus was covered in a state-of-the-art review in 2025.<ref>{{Cite journal |last1=Sudarshan |first1=Raghav |last2=Sayo |first2=Ana Ria |last3=Renner |first3=David Roman |last4=Saram |first4=Sophia de |last5=Godbole |first5=Gauri |last6=Warrell |first6=Clare |last7=Duong |first7=Ha Thi Hai |last8=Thwaites |first8=C. Louise |last9=Mehta |first9=Arpan R. |last10=Coughlan |first10=Charles |date=2025-06-18 |title=Tetanus: recognition and management |journal=The Lancet Infectious Diseases |issue=11 |pages=e645–e657 |language=English |volume=25 |doi=10.1016/S1473-3099(25)00292-0 |pmid=40543524 |issn=1473-3099|pmc=7617864}}</ref> ]]Treatment of adult tetanus was covered in a state-of-the-art review in 2025.<ref name="Sudarshan">{{Cite journal |last1=Sudarshan |first1=Raghav |last2=Sayo |first2=Ana Ria |last3=Renner |first3=David Roman |last4=Saram |first4=Sophia de |last5=Godbole |first5=Gauri |last6=Warrell |first6=Clare |last7=Duong |first7=Ha Thi Hai |last8=Thwaites |first8=C. Louise |last9=Mehta |first9=Arpan R. |last10=Coughlan |first10=Charles |date=2025-06-18 |title=Tetanus: recognition and management |journal=The Lancet Infectious Diseases |issue=11 |pages=e645–e657 |language=English |volume=25 |doi=10.1016/S1473-3099(25)00292-0 |pmid=40543524 |issn=1473-3099|pmc=7617864}}</ref>
=== Mild tetanus === === Mild tetanus ===