Tetanus affects skeletal muscle, a type of striated muscle used in voluntary movement. The other type of striated muscle, cardiac, or heart muscle, cannot be tetanized because of its intrinsic electrical properties.The tetanus toxin initially binds to peripheral nerve terminals. It is transported within the axon and across synaptic junctions until it reaches the central nervous system. There it becomes rapidly fixed to gangliosides at the presynaptic inhibitory motor nerve endings, and is taken up into the axon by endocytosis. The effect of the toxin is to block the release of inhibitory neurotransmitters glycine and gamma-aminobutyric acid (GABA) across the synaptic cleft, which is required to check the nervous impulse. If nervous impulses cannot be checked by normal inhibitory mechanisms, the generalized muscular spasms characteristic of tetanus are produced. The toxin appears to act by selective cleavage of a protein component of synaptic vesicles, synaptobrevin II, and this prevents the release of neurotransmitters by the cells Passive immunization with human tetanus immune globulin (TIG) shortens the course of tetanus and may lessen its severity.
A dose of 500 U may be as effective as larger doses. Therapeutic TIG (3,000-6,000 units as 1 dose) has also been recommended for generalized tetanus. Other treatment measures include ventilatory support, high-calorie nutritional support, and pharmacologic agents that treat reflex muscle spasms, rigidity, tetanic seizures and infections.
We present a prospective, double blinded, clinical trial comparing two groups of patients with oral anticoagulants: one group was administered tetanus-diphtheria vaccine by intramuscular injection, while the other was administered the same vaccine by subcutaneous injection. Allocation to each group was randomized and the duration of the study was six years. Study population: all patients treated with oral anticoagulants, who had been administered with at least one dose of vaccine, at 15 Health Centres in Vigo (Spain), and who agreed to participate in the study.
The sample size was 115 patients in each group. The main variables for the safety analysis were the measurement of the brachial diameter, the appearance of basic injuries at the vaccine administration site, the appearance of pain and systemic reactions. The variable used for the efficacy analysis was a significant increase in the titres of anti-tetanus toxoid antibodies. An Intention-to-treat analysis will be performed. Details will be classified according to the administration route, while within each group a 3-tiered stratification will be defined by the administered number of doses. As a measure of association, relative risk will be estimated; the reduction of relative risk will also measure. For safety and to control the confounder effect, a logistic regression analysis will be carried out. As a measure of impact the reduction of absolute risk in relation to the total number of patients to be treated and the Number Needed to Treat will be estimated.