25 Michel R. Popoff Tetanus is a neurologic disease characterized by spastic paralysis. It is caused by a toxin, tetanus toxin (TeNT), which is produced by an environmental and sporulating anaerobic bacterium, Clostridium tetani. See Chapters 2, 3, and 7 for a description of the agent and the toxin. Tetanus is the result of wound contamination with C. tetani spores acquired from the environment. Deep wounds with a little exposure to air and the presence of necrotic tissue, both ensuring anaerobic conditions, favor spore germination. C. tetani spores germinate at low oxidation–reduction potential (Eh 10 mV or less) at neutral pH. In traumatized tissues with acidic pH due to local ischemia and anoxia, germination and C. tetani growth can occur at higher oxidation–reduction potential (until Eh 85 mV at pH 6.5). C. tetani is not an invasive pathogen but rather the presence of necrotic cells provides nutrients for the growth of C. tetani. Experimentally, C. tetani infection has been reproduced by intramuscular injection of spores with a necrotizing reagent such as calcium chloride. In in vitro cultures, C. tetani spores can germinate in a wide range of Eh from −100 mV to +580 mV, but subsequent vegetative growth cannot be obtained with Eh above +300 mV. Details of local colonization by C. tetani are not yet fully characterized. In addition to TeNT, C. tetani produces tetanolysin, a hemolysin from the cholesterol-dependent cytolysin family, the prototype of which is the perfringolysin of C. perfringens. Tetanolysin may facilitate local tissue colonization and resistance to macrophages of C. tetani during the early steps of wound tetanus, since tetanolysin is able to form pores and to induce membrane damage in macrophages. Tetanus occurs after contamination of a wound, and this can sometimes be small and difficult to find. Tetanus may even develop after healing of the wound. Wounds in parts of the body in contact with the soil are most at risk of producing tetanus. Examples include accidental wounds or punctures with prickly plants of the end of the limbs, the lower side of the trunk, and the abdomen. The umbilicus is a common source of tetanus in newborns, notably in lambs and foals. Surgical and other wounds can be contaminated with C. tetani spores: these include castration (Figures 25.1 and 25.2), tail docking, ear surgery, injections such as vaccinations, or wounds incurred during shearing. Puerperal tetanus occurs after contamination of the vaginal mucosa and uterus during difficult delivery. Although all animal species are susceptible to tetanus, there is considerable variability in susceptibility among species. The most susceptible species are horses, guinea pigs, monkeys, sheep, mice, goats, and humans, whereas carnivores such as cats and dogs are less vulnerable, and birds are resistant (Table 25.1). Unlike other ruminants, cattle are quite resistant. Interestingly, poikilothermic animals such as frogs are resistant to tetanus intoxication when maintained at low temperature (below 18 °C) despite large amounts of TeNT in the circulating body fluids, but are susceptible when exposed to higher temperatures (27 °C and above). The protective effects of cooling have been attributed to a retardation of binding rate of TeNT on target neurons and the inhibition of its action. Table 25.1 Sensitivity of animal species to tetanus toxin. Relative minimum lethal doses compared to guinea pig lethal dose for various animal species
Tetanus
Introduction
Epidemiology
Clinical signs
Species
Minimum lethal dose
Guinea pig
Horse
Monkey
Sheep
Mouse
Goat
Rabbit
Dog
Cat
Goose
Pigeon
Hen
Human
1
0.5
2–4
2
2–6
12
4–900
300–480
960–1200
6000
6000–24,000
180,000
10