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TETANUS ( Lock jaw ) Compared with the major plagues of man, lockjaw has always been a rare disease. It is on account of the characteristic and fatal spasms that it early attracted attention. The student will be well repaid by a atudy of the historical development of the theories that have been ad raced since the time of Hippocrates to explain the cause of tetanus. These theories mirror the prevailing thought upon the nature of dis ease as it developed from that of evil spirits, through the humoral theory, the realm of miasms and noxious effluvia, to the germ theory. Tetanus could not escape the rheumatism theory which has been such an alluring catchall for symptoms and diseases difficult of explanation. "Taking cold" was assigned its usual role here as elsewhere. When no assignable cause seemed at hand, the disease was given the learned title —idiopathic tetanus.

Etiology. Carle and Rattini,'" in 1884, first clearly demonstrated the infectious nature of tetanus by inoculating rabbits subcutaneously with pus from a human case of the disease. In the same year, Nico laier 17 inoculated laboratory animals subcutaneously and saw the tetanus bacillus at the site of injection. In 1889, Kitasato 18 for the first time grew the organism in pure culture, and by successful inoculation ex periments proved that this bacillus was the real cause of tetanus. Kita sato further showed that the tetanus bacillus is not found in the heart's blood of mice dead of tetanus, and therefore concluded that we are deal ing with an intoxication, and not bacteremia. We now regard tetanus as a type of the true toxemias; that is, the virus remains localized in the wound, and the soluble toxin does the damage. This work of Kita sato's was one of great importance, and led to the epochmaking dis covery of Behring and Kitasato 119 in the following year (1890) upon tetanus and diphtheria toxins and antitoxins, laying the foundation of serum therapy.

Tetanus may be regarded almost solely as a wound complication. All wounds are not equally liable to this complication, even though tetanus spores are present. Punctured, lacerated, and contused wounds are much more susceptible to tetanus than clean-cut or open wounds. The size of the wound is of much less consequence than its character and content. Fatal tetanus may develop from trivial wounds, such as pin scratches, small splinters, insect bites, vaccinations, etc. Necrotic tissue, foreign bodies and other irritants favor the development of tetanus.

Symbiosis is an important factor in tetanus. Wounds infected with the gas bacillus, vibrion septique, pyogenic organisms and other bacteria favor anaerobic conditions and permit the tetanus spores to germinate, and seem to encourage the growth of the bacillus and the development of Tetanus spores washed free of toxin and placed in healthy tissues do no harm, but add a trace of gas gangrene toxin, or a chemical irritant as saponin, or a physical irritant such as a foreign body, and tetanus develops.

Weinberg has shown the multiplicity of anaerobic wound infec tions, and has also shown how they influence each other. The gas bacil lus (B. perfringens, also known as B. Weickii) plays an auxiliary part in the causation of tetanus. The bacillus of malignant edema (vi brion septique) is also an ally of tetanus. Antitoxins against both these spore-bearing anaerobes have been produced. These antitoxic sera, as in the case of tetanus, have prophylactic value, but feeble curative prop erties. The experience in the war soon taught the usefulness of em ploying, for the prevention of tetanus, a serum containing three anti bodies: (1) against tetanus, (2) against the gas bacillus, and (3) against vibrion septique. These are the commonest but not the only in fective agents that play a part in stimulating the growth of the tetanus bacillus in wounds. Tulloch on the basis of agglutination tests has separated tetanus cultures into four types. Fortunately, any one of the four antitoxins will neutralize any or all of the four toxins.

The normal habitat of tetanus is in the intestinal tract of herbiv orous animals. Sanchez, Toledo, and Veillon 123 found tetanus in the feces of 4 out of 6 horses and in the feces of 1 of 2 cows. Park found tetanus bacilli in the intestines of about 15 per cent. of horses and calves living in the vicinity of New York City. They are present to a variable extent in the intestines of man; from 5 per cent. up to 20 per cent. in ostlers and dairymen.

It is rather a curious paradox that the horse, which is the most sus ceptible of all animals to tetanus toxin, is one of the principal hosts of the tetanus bacillus. The intestinal canals of certain animals are per fect anaerobic incubators for the growth of tetanus bacilli; such animals may be regarded as "tetanus carriers." Ocennence. The spores taken in the food are not affected by gastric digestion, and in the intestines find ideal anaerobic conditions, food supply and temperature for growth and development. Here they multi ply and pass in the dejecta to pollute the soil. The soil, therefore, in all regions inhabited by man and animals is more or less con taminated with tetanus. The bacilli, however, do not multiply in the soiL While the soil acts only as a vehicle, it is the immediate source of the large proportion of tetanus in man. The presence of tetanus spores in soil, street dust, fresh vegetables and on clothing and the skin may be traced to fecal contamination.

On account of the great resistance of the spores, they are blown about in dust and are spread everywhere by dirt and manure. Tetanus has been found in hay dust, on horses' hair, in the dust of houses, barracks, and hospitals, in the mortar of old masonry, in street dust, on food, in gelatin, on the skin, and in the greatest variety of places.

One of the agencies in the distribution of tetanus spores over limited areas is undoubtedly the common house fly. The poisoned arrowheads of certain savages in the New Hebrides contain tetanus spores obtained by smearing the arrowheads with dirt from crab holes in the swamps Dantic).

Tetanus bacilli are not equally numerous in all localities. The in fection is much more prevalent in warm than in cold countries. It is especially severe in the tropics, yet Iceland at one time suffered severely from tetanus neonatorum. In the United States, tetanus occurs es pecially in the Atlantic States, and in some parts of Long Island, New Jersey, and the Hudson Valley, which have become noticeable for the lumber of cases of tetanus complicating small wounds. The soil of Flanders and France has through long cultivation become saturated with the spores of tetanus and other anaerobes. One grain of it from the trenches injected into a laboratory animal invariably produced tetanus. Tetanus spores are widely disseminated in India. Goodrich states that in Bombay alone there were 1,955 cases of tetanus in five years. These do not include the puerperal cases.

Tetanus occurs either sporadically or in epidemic form. Formerly epidemics in hospitals (especially in lying-in hospitals), and in wars were rather common. The conditions of trench warfare in the World War favored wound complications, and included a frightful amount of tetanus until antitoxin was used as a routine prophylactic in all wounds. Before the days of asepsis the infection was often spread through sur gical instruments, fingers. bandages, etc.

The wounds produced by blank cartridges are especially liable to develop tetanus. The source of the tetanus spore in these cases is not entirely clear. Wells examined 200 cartridges from five firms without finding the tetanus bacillus. It is probable that the spore is upon the skin and is carried along with the paper and powder from the blank cartridge. The peculiar character of the wound favors the development of tetanus.

The great decrease in the number of cases of tetanus following Fourth of July wounds is due to the vigorous campaign carried on by the American Medical Association. In 1903 there were 406 deaths from tetanus; in 1904, 91; 1905, 87; 1906, 75; 1907, 73; 1908, 76; in 1911 only 18 cases and 10 deaths and so on until 1916 when no deaths occurred from this cause. Eighty per cent. of these followed blank cartridge wounds. The good results are attributed to the more thorough and careful treatment of the wounds and especially the use of tetanus antitoxin as a prophylactic—and more recently to safer and saner methods of celebration.

Tetanus spores or toxin may contaminate bacterial vaccines, anti toxic sera, vaccine virus, and other biologic products used in human therapy. The possible association of tetanus with bacterial vaccines was demonstrated in the unfortunate outbreak at Mulkowal, India, in One hundred and seven persons were inoculated with Haff kine's plague prophylactic. Of these 19 were affected with symptoms of tetanus and died. In this case the tetanus probably grew as a con tamination in the plague culture, for it is now well known that the anaerobic conditions produced in B. diphtheriae, B. pestis, B. subtilis, and other organisms in liquid culture media favor the growth of tetanus and the development of its toxin.

In St. Louis (1901) diphtheria antitoxin was taken from a horse during the period of incubation of tetanus and used in amounts from 5 to 10 c. c. upon 7 children, all of whom died of tetanus. Bolton, Fisch, and Walden 125 found that the serum was sterile, but contained tetanus toxin in considerable amount. If the serum had first been tested upon animals, its poisonous properties would have been discovered. This test is now required by the United States law of July 1, 1902, for all serums and vaccines sold in interstate traffic. As a further precaution against this complication horses undergoing treatment for the production of im mune sera are given prophylactic doses of tetanus antitoxin from time to time. Tetanus sometimes occurs as a complication of vaccination. See page 22.

It io, of course, not the rust on a nail that is dangerous, so far as tetanus is concerned, but the spore-bearing dirt it carries into the deep, contused wound that causes the trouble. Gelatin may contain tetanus spores, and the subcutaneous injection of imperfectly sterilized gelatin as a hemostatic has sometimes resulted in accidents.

Tetanus is harmless when taken by the mouth. Susceptible animals mai: be given enormous doses of tetanus toxin by the mouth without producing the disease. The bacillus and its spore may be regarded as a saprophyte in the intestinal tract. There is, however, a suspicion that tetanus spores sometimes invade the organism through small wounds in the digestive or respiratory tract. Perhaps some of the cases following surgical operations may be accounted for in this way rather than by in fection of the catgut used for ligatures.

Tetanus sometimes occurs where no wound can be found. This is the so-called "idiopathic tetanus." One explanation of these cases is to be found in the fact that the spores are numerous in street dust and may enter the respiratory tract. They cannot do harm so long as the mucous membrane is healthy, but may enter through inflamed mem branes or through small wounds in the nose.

Tetanus bacilli have been found in the bronchial mucus of idiopathic cases. Tetanus spores have occasionally been found in the lymph glands, liver, and other parts of the body, upsetting our previous view that they are always strictly confined to the site of the wound. The spores may remain latent or dormant in scar tissue or the sequestrum of bone and may be released and start an attack months or years afterwards, thus giving another plausible explanation of some cases of idiopathic tet anus.

Puerperal tetanus was formerly a frequent and serious complication following childbirth, but has been conquered by asepsis.

Thum Neonatorum, or tetanus of the newborn, is still a common and very fatal infection, especially in the tropics. Before the days of asepsis the infection was permitted to enter through the umbilical wound. In certain of the West Indian islands more than one-half of the mortality among the negro children has been due to this cause. In Venezuela, trismus neonatorum is one of the chief causes of deaths, and goes by the name of mocezuelo.

Incubation. The period of incubation in man is usually from 6 to 14 days. The period is directly proportional to the amount of toxin and the severity of the disease. This can readily be demonstrated upon susceptible animals. In a study of 600 serial tests, Rosenau and Ander son found this direct relation between the period of incubation and the severity of symptoms by the subcutaneous injection of varying amounts of toxin into guinea pigs. Thus guinea pigs receiving fairly large doses showed symptoms on the third day and usually died; when the dose is smaller, the period of incubation is longer, the disease milder, and the chances of recovery greater. In man, with a short period of incubation, 6 days or less, the disease is almost invariably fatal. With longer periods the disease is usually milder and recovery frequently takes place without the use of antitoxin or other measures. Tetanus toxin is ab sorbed by the terminal nerve endings, and travels up the axis cy:inders of the nerves to the cord and brain. It is also distributed in the blood. The period of incubation, therefore, depends somewhat upon the point of entrance of the poison and its proximity to abundant motor nerve endings. 127 Resistance. The tetanus bacillus is readily destroyed by the or dinary agencies that kill vegetative bacteria. It is killed almost at once in contact with the free oxygen of the air. On the other hand, few, if any, forms of life have a greater resistance than the tetanus spore. Hours of exposure to 60° or 70° C. do not affect them. They usually survive an exposure of one hour to 80° C., but, as a rule, are killed in streaming steam or boiling water in 60 minutes. Tetanus spores, how ever, vary greatly in the power to resist the boiling temperature. Kits found them to resist 80° C. for one hour, but to be killed in streaming steam in 5 minutes. Vaillard and Vincent 129 found that the spores heated in the presence of moisture in a closed vessel would re sit destruction at 80° C. for 6 hours, at 90° C. for 2 hours, and 100° C. 3 to 4 minutes, that they were not always destroyed in 5 minutes, but never resisted more than 8 minutes at 100° C. Levy and Bruns found that destruction begins at 8% minutes at 100° C.; after 15 minutes few survive, after 30 minutes none. Falcioni 131 studied the subject in view of the dangers of the subcutaneous injection of gelatin. He impregnated gelatin with spores of tetanus bacilli grown in agar or broth for 10 to 12 days, and used Koch's steam sterilizer. He found the spores to resist destruction for but not for 3, hours in stream ing steam.

The experimental results are, therefore, sufficiently varied and con flicting to suggest that races of tetanus bacilli exist, the spores of which vary widely in their resistance to moist heat at 100° C. Theobald Smith 122 found that under certain conditions of cultivation some tet anus spores survive a single boiling or streaming steam regularly for 20 minutes, usually for 40 minutes, and occasionally for 60 minutes; in one case 70 minutes' exposure did not destroy the spores. He also showed the possibility of tetanus spores surviving in culture fluids sterilized by discontinuous boiling or steaming in routine laboratory work for fully 20 minutes on three successive days.

In general, dry spores are more resistant than moist spores; and young spores are often harder to kill than old spores.

Tetanus spores resist the action of 5 per cent. carbolic acid for 10 hours, but are killed in 15 hours. A 5 per cent. solution of carbolic acid, however, to which 0.5 per cent. of hydrochloric acid has been added, destroys them in 2 hours. Bichlorid of .mercury, 1-1,000 kills the spores in 3 hours, and in 30 minutes when 0.5 per cent. of hydrochloric acid is added to the solution. According to Park, silver nitrate solution de stroys the spores of average resistance in 1 minute in 1 per cent. solu tion. and in about 5 minutes in a 1 to 1,000 solution. Tetanus spores are destroyed with certainty when exposed to dry heat at or aIwre C. for one hour, or to steam at 120° C. for 20 minutes. Entire con fidence may be placed upon either of these two methods.

The temperature recorded on the thermometer of the sterilizer may he higher than the actual temperature within the apparatus. Good sterilizing technic is essential and a factor of safety desirable. The time necessary for penetration must be taken into account. Thus, the gov ernment regulations 133 require an exposure of 170° C. for two hours for dry sterilization of glassware intended to contain biologic products. These same regulations require 121° C. (15 pounds) for 30 minutia for steam sterilization of glassware and rubber tubing. Glassware and rub ber tubing must be moistened immediately before steam sterilization and each flask or hollow apparatus should contain one-eighth of its volume of water when put in the autoclave. This is for the purpose of insuring that steam will be in contact with all surfaces. In some cases, rubber goods may be sterilized by boiling for 30 minutes in 3 to 5 per cent, phenol or some similar disinfectant.

Direct sunlight does not kill the spores, but seems to diminish their virulence. Under certain circumstances they may live a very long time; Henrijean reports that, by means of a splinter of wood which once caused tetanus, he was able after 11 years again to cause the disease by inoculating an animal with the infective material.

Prophylaxis. Local Treatment of Wounds. Thorough surgical treatment of the wound as soon as possible is the first important meas ure in the prevention of tetanus. Wounds, however insignificant, should be thoroughly cleansed. Punctured or lacerated wounds, in which there is special danger of tetanus, should be freely opened, and every particle of foreign matter carefully removed. Promptness in cleansing the wound surgically is almost as important as thoroughness. Gunttiot wounds and wounds containing garden earth, street dust, or other ma terial liable to contain tetanus spores should receive special considera tion. All necrotic tissue, or tissue likely to die, must be removed. The experience of the war demonstrated that thorough excision of the wound (debridement) is good practice. Germicides are useless—the surgeon's knife is the best antiseptic. The division of the umbilical cord and the treatment of the navel in the newborn must be done under the strictest asepsis. Wounds in which there is suspicion of tetanus should be kept open and freely drained, and otherwise treated so as to discourage anaerobic conditions.

Tetanus spores gain entrance into wounds not only from manure. garden soil, street dust, and similar sources, but also from the hands. instruments, bandages, suture material, or other objects. It is impor tant to remember that the tetanus spore is exceedingly resistant to heat and chemical agents, and that in surgical and obstetrical practice con fidence should not be placed simply upon brief boiling to destroy the spores. Very particular care must he exercised in the disinfection of substances injected into the body, such as gelatin and other organic materials.

Specific Prophylaxis. Tetanus antitoxin is a specific and trust worthy preventive. The great experience of the war adds confirmation to the protective power of this specific and sovereign serum. Its use, however, must be understood to achieve satisfactory results. The anti toxin must be administered before the advent of symptoms, for after the tetanus toxin has combined with the motor nerve cells in the central nervous system it can neither be displaced nor neutralized with anti toxin. In such cases the most that the antitoxin can do is to combine with and neutralize the free toxin and thus prevent further damage.

From 500 to 1500 units of tetanus antitoxin are used as a prophy lactic dose.'" The amount varies with the severity of the wound and the hazard of tetanus. In wounds liable to infection, the injection should be repeated every seven days until the wound is clean, or the danger passed. It is important to remember that the tetanus antitoxin is eliminated or otherwise disposed of in the body in the course of 10 days or 2 weeks. Therefore, in cases in which the wound does not heal well, as a result of mixed infection, or for other reasons, it is desirable to repeat the injection. This may be done at intervals of 7 or 8 days as long as the danger persists. Occasionally tetanus bacilli persist in the pus-infected tissues, and, when the injected antitoxin has been exhausted, there may occur a late development of tetanus. Instances in which 1,500 units of tetanus antitoxin, repeated if necessary, have failed to prevent the development of tetanus are rare. During the latter part of the war, a triple antitoxin, made from the tetanus bacillus, the gas bacillus 'u (B. perfringens), and the bacillus of malignant edema (ribrion septique), was used as a routine prophylactic, and resulted in preventing much suffering and saving many lives.

Gunshot wounds and wounds produced by blank cartridges should always be regarded as suspicious. and should be given careful local treatment, supplemented with a prophylactic injection of antitoxin. Tetanus was a frequent complication of trench foot, and therefore a prophylactic injection of antitoxic serum should be given and repeated at intervals of seven days until the wounds are healed.

The prevention of tetanus complication of vaccine wounds con gigs in: (1) The use of a reliable vaccine which has been biologically tested in accordance with the federal act. (2) Proper methods of vac cination to avoid unnecessary scabs and anaerobic wound conditions. (3) Surgical asepsis of the operation and after-treatment.

Tetanus and 'other wound infections may be avoided, in those ex posed to accidents, by cleanliness of body and clothing. ' A bath before a battle is a reasonable protection said to be adopted in the Japanese Army and Navy. The common experience of mankind teaches that most wounds heal without tetanus, and that tetanus is, in fact, a relatively rare infection. The physician, however, is in no case justified in taking chances, and it is one of the duties of the medical profession to teach the public that it pays to thoroughly cleanse and care for wounds, how ever trivial, at once, and in accordance with modern methods.

spores, wounds, wound, minutes, bacillus, found and toxin