Tetanus

Clostridium tetani is a slender gram-positive rod with a terminal spore. It is an obligate anaerobe, which is a commensal of the human and animal gastrointestinal tract and is widely distributed in the environment, especially in manured soil. Spores are extremely resistant to heat and light; autoclaving at 120°C (248°F), 1.5 bar (21.7 psi) for 15 minutes ensures sterility.[19]Farrar JJ, Yen LM, Cook T, et al. Tetanus. J Neurol Neurosurg Psychiatry. 2000 Sep;69(3):292-301. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1737078/pdf/v069p00292.pdf http://www.ncbi.nlm.nih.gov/pubmed/10945801?tool=bestpractice.com Clinical disease follows inoculation of spores into wounds and most cases occur after an acute injury, including trivial unnoticed injuries and injecting drug use. The incubation period is typically between 3 and 21 days, although it can range from 1 day (cephalic tetanus) to several months, depending on the nature of the wound and its distance from the central nervous system.

When spores of Clostridium tetani are inoculated into a wound, they can germinate under anaerobic conditions into rod-shaped bacteria, which produce tetanospasmin. This single-polypeptide toxin undergoes post-translational cleavage into heavy and light chain fragments.[19]Farrar JJ, Yen LM, Cook T, et al. Tetanus. J Neurol Neurosurg Psychiatry. 2000 Sep;69(3):292-301. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1737078/pdf/v069p00292.pdf http://www.ncbi.nlm.nih.gov/pubmed/10945801?tool=bestpractice.com The heavy chain attaches to gangliosides on peripheral nerves. Subsequently the toxin enters the presynaptic terminal and travels from the peripheral nerve terminals to the central nervous system by retrograde axonal transport and trans-synaptic spread. Free toxin can also enter the bloodstream and lymphatics, disseminating widely to motor neurons at disparate sites. The light chain is a zinc metalloprotease that cleaves synaptobrevin on the membrane of synaptic vesicles.[20]Schiavo G, Benfenati F, Poulain B, et al. Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin. Nature. 1992 Oct 29;359(6398):832-5. http://www.ncbi.nlm.nih.gov/pubmed/1331807?tool=bestpractice.com Synaptobrevin is required for the fusion of synaptic vesicles with the presynaptic membrane. Cleavage of synaptobrevin prevents the synaptic vesicles from releasing the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) into the synaptic cleft. Alpha-motor neurons therefore undergo uninhibited excitatory discharge resulting in muscle spasms. Disinhibition of autonomic neurons causes autonomic instability. Uncontrolled catecholamine release creates a hyper-sympathetic state with sweating, tachycardia, and hypertension.

Tetanospasmin-induced effects on the spinal cord, brain stem, and peripheral and autonomic nerves are long-lasting; growth of new axonal nerve terminals is necessary for recovery, which may take 4 to 6 weeks.