How does tetanus toxin act?

Mellanby, Jane; Green, Jane

doi:10.1016/0306-4522(81)90123-8

Cited by 187 publications

(83 citation statements)

References 120 publications

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“…Centrally, transmission along the inhibitory gamma-amino butyric acid (GABA) and glycinergic neurons is interrupted, and at the level of the spinal cord, inhibitory interneurons are blocked. 2 It is important to recognize that tetanus is not an infection, and therefore patients do not usually experience symptoms of the disease until the toxin is disseminated and reaches the interneurons. 2 Early treatment with immune globulin is critical, because it binds free toxin.…”

Section: Pathophysiologymentioning

confidence: 99%

“…2 It is important to recognize that tetanus is not an infection, and therefore patients do not usually experience symptoms of the disease until the toxin is disseminated and reaches the interneurons. 2 Early treatment with immune globulin is critical, because it binds free toxin. However, it does not treat the effects of toxin protected within the neuron or cell body.…”

Section: Pathophysiologymentioning

confidence: 99%

“…Clinically, the effect of the toxin on the neuron lasts approximately 4-6 weeks and may be irreversible until the re-growth of a new nerve terminal; however, the mechanism of functional recovery is not clear. 2,3 Epidemiology and prevention Adult and neonatal tetanus are still common in many developing countries. Estimates from 2002 suggest that between 213,000 and 293,000 deaths from tetanus occur worldwide each year, including 180,000 infant deaths from neonatal tetanus.…”

Section: Pathophysiologymentioning

confidence: 99%

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Tetanus in developing countries: a case series and review

Gibson

Uwineza

Kiviri

et al. 2009

Can J Anesth/J Can Anesth

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Purpose Few anesthesiologists have expertise in the diagnosis and treatment of tetanus, a disease that remains prevalent in developing countries. We report on a series of four cases of tetanus cases recently encountered in Rwanda. We review the clinical epidemiology, pathophysiology, diagnosis and the treatment of tetanus, and provide implications for anesthesiologists and critical care physicians. Clinical features We report four cases, two involving adults who were inadequately vaccinated and experienced injuries, and two involving neonates, both of whom underwent umbilical cord transection using unsterilized equipment. All patients required tracheal intubation, and were mechanically ventilated when equipment was available. One adult and one neonate succumbed to the disease. These cases highlight the difficulties of diagnosis and management of complicated diseases in the resourcechallenged health care setting of developing countries. Conclusions The differential diagnosis of tetanus may be confusing, and survival depends on the rapidity of treatment with antitoxin, as well as adequate supportive care. High doses of sedatives and muscle relaxants, as well as prolonged mechanical ventilation, are usually necessary. Mortality remains high, usually resulting from late respiratory failure and cardiovascular collapse, associated with autonomic instability. Anesthesiologists and critical care physicians have an important role to play in the management of these patients. Increased involvement in humanitarian health organizations, immigration from developing countries, and emergence of high risk groups in developed countries will likely result in more exposure of anesthesiologists to the complexities of this disease. RésuméObjectif Tre`s peu d'anesthe´siologistes sont experts du diagnostic et du traitement du te´tanos, une pathologie qui demeure pre´valente dans les pays en voie de de´veloppe-ment. Nous rapportons une se´rie de quatre cas de te´tanos survenus re´cemment au Rwanda. Nous passons en revue l'e´pide´miologie clinique, la physiopathologie, le diagnostic et le traitement du te´tanos, et proposons des pistes inte´-ressantes pour les anesthe´siologistes et les me´decins en soins critiques. É léments cliniques Nous rapportons quatre cas dont deux impliquent des adultes mal vaccine´s et qui ont subi des blessures, et deux concernent des nouveaux-ne´s, tous deux ayant subi une coupe transversale du cordon ombilical a`l'aide d'instruments non ste´rilise´s. Tous les patients ont ne´cessite´une intubation trache´ale et ont e´te´venti-le´s me´caniquement lorsque le mate´riel e´tait disponible. Ces cas soulignent les difficulte´s rencontre´es lors du diagnostic et de la prise en charge de pathologies complexes dans le contexte des soins de sante´manquant de ressources des pays en voie de de´veloppement. Conclusions Le diagnostic diffe´rentiel du te´tanos peut porter a`confusion, et la survie de´pend de la rapidite´du traitement avec de l'antitoxine ainsi que de soins d'accompagnement adapte´s. En ge´ne´ral, des...

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Section: Pathophysiologymentioning

confidence: 99%

Section: Pathophysiologymentioning

confidence: 99%

Section: Pathophysiologymentioning

confidence: 99%

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Tetanus in developing countries: a case series and review

Gibson

Uwineza

Kiviri

et al. 2009

Can J Anesth/J Can Anesth

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“…Tetanus toxin (TeTa) and botulinam neurotoxin serotype A (BoTxA) secreted by Clostridium tetani and Clostridium botuliman, respectively, are two of the most toxic proteins known to humankind: only -,,100 pg of pure toxin constitutes one lethal dose [1][2][3]. Although it has been known for many years that these neuroto;~-ins affect synaptic transmission in nervous tissues, their mode of action at the molecular level remains elusive.…”

Section: Introductionmentioning

confidence: 99%

“…Although it has been known for many years that these neuroto;~-ins affect synaptic transmission in nervous tissues, their mode of action at the molecular level remains elusive. TeTx is the agent responsible for the spastieity and convulsions characteristic of human tetanus [1][2][3]o and is more potent in the central nervous system where it blocks the release of the inhibitory neurotransmitters γ-aminobutyric acid and glyeine [3]. BoTxA blocks acetylcholine release in peripheral nervous sys~ tern synapses [1,2] and produces paralysis.…”

Section: Introductionmentioning

confidence: 99%

Identification of an ion channel‐forming motif in the primary structure of tetanus and botulinum neurotoxins

et al. 1992

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Synthetic peptides with amino acid ~eqttences corresponding to predicted transmembran¢ segments of tet~tntts toxin were used as probes to identify a elmnnel-forming motif. A peptide denoted TeTx 1I. with sequence GVVLLLEYIPEITLPVIAALSIA, form.~ cation-selective channels when r~onztltuted in planar lipid bilaycrz. The .~ia~le channel conductance in 0.~ M NaCI or KCI is 28 + 3 ~tnd 24 ± 2 pS. respectively. In contrast, a peptide with sequence NFIGALETTGVVLLLEYIPEIT. denoted as TeTx I. or a peptide with the mine amino acid composition as TeTx II but with a randomized ~eqaence, do not form channels. Conformational enersy calculations show that a baladle of four amphipathic a-helices is a plausible structural motif underlying observable pore properties. The identified functional module may account for the channel-forming activity of both tetanus toxin ~md the hom~losous botulinum to~in A.

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