TETANUS.
Synonyms. Definition: infectious disease, due to bacillus, and shown by tonic spasms of groups of voluntary muscles. Animals susceptible: warm-blooded animals—dogs and chickens least: ⅔ds solipeds, ⅐th cattle. Pathology and Causes: Bacillus tetani: 4 to 5µ by 0.2 to 0.3µ, often enlarged by spore at one end; anærobic, liquefying, tardily motile, until spore forms, grows in ordinary, alkaline media under hydrogen, death point 60° to 65° C. (140° to 149° F.), for spores 80° C. (176° F.), for an hour, dried it lives for years, in putrid matter 2½ months, stains easily, saprophytic in garden mould, in ingesta of man and horse, abundant in tropics; infection local, killed by oxygen in blood, toxins tetanize: tetanin, spasmotoxin, toxalbumin, diastase; spasms first local near wound, then abruptly general, intravenously causes general spasms first, theory of fermentation in blood; changes in nerve cells, neuroglia, ependyma, peripheral nerves: muscles soft, pallid, red, ruptured fibres, ecchymosis; rigor mortis early, marked: sarco-lactic acid. Accessory causes: traumas and their causes, parturition, umbilical infection, alimentary. General symptoms: incubation 3 to 15 days, minimum 6 hours; tonic contraction of muscle groups of locomotor system beginning near infection wound,—trismus, orthrotonos, opisthotonos, emprosthotonos, pleurosthotonos, ocular muscles; costive, difficult urination, hyperæsthesia, irritability, perspiration, hyperthermia, mastication, deglutition, sucking. Symptoms in horse: neck raised concave above, nose elevated, nostrils wide, eyes sunken, haw protruded, ears rigid, pricked, facial muscles rigid, prominent, mouth drawn back, muscles of back hard, tail elevated, trembles, limbs extended outward, stiff, stilty, jaws clenched or open slightly, stands. Symptoms in cattle; sheep and goat; swine; dogs; birds: Course: violent cases with short incubation are rapid and fatal; mild ones with prolonged incubation hopeful; cattle slow, sheep, goats and dogs acute. Mortality: sheep and pigs 100 per cent.; horses 75 to 85; cows 70 to 80; lambs very fatal. Death from asphyxia, hyperpyrexia, or exhaustion. Lesions: trauma, often healed; congested nerves, gray horns of myelon, increase of cells and granules in nervous matter of cord, corpus striatum, cerebellum; blood extravasations at torn muscle fibres, intestinal and cystic congestion. Diagnosis: from strychnia poisoning by slow advance, and persistence of spasm; from rabies by absence of bite, the continuous masseteric spasms, by absence of resentment, mischief, hallucinations or depraved appetite; from rheumatism by the persistent trismus, hyperæsthesia and excitability; from meningitis by the trismus, perfect mentality, absence of clonic spasm; from tetany by shorter and less perfect remissions, failure to develop under nerve pressure, or improve under thyroid extract; from laminitis by the absence of high early hyperthermia, heat and tenderness of the feet, and advance of hind legs under the body. Treatment: best in slight cases, after long incubation, with slow progress; antispasmodics; rest, darkness, absolute quiet, no litter, nor visitors, slings, sloppy food, gruels, milk, green food, at level of manger; clothing to favor perspiration; excision or antisepsis of wound, carbolic acid, bleeding, opium, prussic acid, potassium cyanide, bromides, physostigma, eserine, chloroform, sulphonal, trional, tartar emetic, tobacco, apomorphia, lobelia, phenacetin, acetanilid, cocaine, chloral, phenic acid, iodine terchloride, iodide of potassium, orrotherapy, antitoxin; best as a preventive, value decreases with development of disease; cerebral injections; brain emulsion; use up toxins in blood; no use if nerve centres are already in combination with toxins, only to ward off fresh toxin. Toxins produce leucocytosis. Prevention: disinfection of all dirty wounds, injections of phenic acid, or iodine; remove foreign bodies, use muriatic and carbolic acids; antisepsis of navel; disinfection of stables, feet, careful shoeing; immunization.
Synonyms. Lockjaw. Trismus.
Definition. An infectious disease of animals and man, characterized by tonic spasms of the voluntary muscles in a given region or more generally, with exacerbations, and dependent on the bacillus tetani.
Animals susceptible. Immunity cannot be claimed for any class of warm blooded animal. Experimentally the dog and chicken prove among the most refractory, in keeping with the comparative insusceptibility of the last named animal to strychnia, but neither can be held to be in any sense immune. Inoculated frogs become tetanic if the temperature is maintained above the normal standard. In 208 cases in domestic animals recorded by Cadiot and Hoffmann, 140 were in horses, 10 in mules, 5 in asses, (solipeds, 155), 28 in cattle, 9 in sheep, 5 in goats, 5 in pigs, and 6 in dogs. Such statistics are liable to prove misleading when we have no means of comparing them with the members of the different genera from which the cases were drawn and the relative exposure of each genus to traumatic lesions (infection atria). Solipeds lead with practically ⅔ds of the entire number of cases, but these were presumably the most numerous of the domestic animals, and preëminently the work animals and therefore the most liable to traumatism. Cattle follow with ⅐th of all cases but here again the large numbers to be drawn upon, and the proportion of work oxen and wounds, are to be considered. The omnivora and carnivora are comparatively little susceptible and among these the chicken may be included. The omnivorous rat is quite susceptible.
Tetanus occurs in 1 per 1000 sick horses in the Prussian army (Friedberger and Fröhner), and in 1 per 3000 sick in that of Wurtenburg (Hering). It is so prevalent in San Domingo that a gelding costs twice as much as a stallion (Wagenfeld). Heat and filth favor its preservation.
In man tetanus is most frequent as the result of wounds (in feet and hands) which are most likely to come in contact with the soil, and it has visibly decreased in connection with the general adoption of antiseptic surgery.
Pathology and Etiology. Sir James Simpson suggested in 1854 that puerperal and surgical tetanus was due to the absorption of a poison produced in the wound (Woodhead). Spinola charged it on infection in wounds in horses. Carle and Rattone in 1884 successfully inoculated 11 out of 12 rabbits with the products from the wound of a man suffering from tetanus. A year later Nicolaier produced tetanus in animals by inoculating them subcutem with garden mould or street dust, and found in the suppurating wounds in connection with various other microbes a minute bacillus longer but thinner than that of mouse septicæmia to which he attributed the tetanizing action. In 1886 Rosenbach inoculated two Guinea pigs with the pus of a tetanic man, and found in the sores of the tetanic pigs the bacillus of Nicolaier in company with another larger spore-forming bacillus. In 1889 Kitasato succeeded in making pure cultures of the bacillus tetani, and successfully inoculated the disease on mice, rabbits, and Guinea pigs producing typical tetanic symptoms and death. This was promptly corroborated by Tizzoni and Cattani and later by a great variety of observers.
Bacillus Tetani. This organism is a minute rod 4 to 5μ in length by 0.2 to 0.3μ in thickness, with slightly rounded ends. In many mature forms the one end is enlarged by the formation of a spherical, refrangent spore which gives the bacillus the appearance of a pin or a “drum-stick.”
The bacillus is anærobic, liquefying, tardily motile, and sporogenous. When spores form the bacillus loses its motility. It grows at room temperatures, in ordinary culture media which have a feebly alkaline reaction, and in an atmosphere of hydrogen, but more actively at a temperature of 36° to 38° C. Below 14° C. growth ceases and the bacillus is killed at 60° to 65° C. The spores, however, can resist a temperature of 80° C., in water for an hour, and 100° C. for four minutes. It was this unusual resistance of the spore to heat that enabled Kitasato to kill off the contaminating organisms and obtain pure cultures from the surviving spores. The spores will survive desiccation for years, retaining their virulence, and may live 2½ months in putrefying material. The addition to the culture medium of 1½ to 2 per cent. of glucose makes the growth much more rapid and abundant, and causes opacity in the medium. The upper portion clears up in 6 or 7 days by the precipitation of the bacilli as a grayish mass. In a glucose culture medium growth is not prevented by the presence of oxygen at the surface. The colonies formed in gelatine plate cultures show an opaque centre with fine divergent rays, and a similar radiating growth is shown in deep stick cultures. At the end of the second week the gelatine begins to liquefy and form a little gas, and finally the whole mass becomes soft and sticky. The bacillus does not liquefy blood serum. Cultures have a disagreeable aromatic odor.
The bacilli stain readily in aniline colors and by Gram’s method. The spores may be stained by Ziehl’s method. To 10 parts of a 10 per cent. alcoholic solution of basic fuchsin, add 100 parts of a watery solution of carbolic acid. Float the cover glass upon this, heating gently for three to five minutes until steam begins to rise, wash well in water, and decolorize in nitric or sulphuric acid, 25 per cent. solution, then in 60 per cent. alcohol to remove color from albuminous background. Wash in water and mount. By placing the specimen for two minutes in a watery solution of methylene blue a contrast is obtained, the bacillus blue and the spore red.
Outside the animal body the bacillus has a saprophytic life in rich garden mould, street dust, stables, yards and drains, and the cracks of floors. Nicolaier failed to obtain it in soil from forests and from the deeper layers of garden earth. Marchesi found it to a depth of two metres but no more. Again it is much more abundant in tropical countries than in temperate and cold ones, and appears to be to a great extent limited to particular localities. It has been found in the intestinal contents of man and horse (Babes, Sormani), and in horse manure, and this mingling with the surface soil and generating an abundance of ammonia determines the anærobic conditions which favor the growth of the microbe. This serves to explain the remarkable prevalence of the disease among those living or working about stables, gardeners, agricultural laborers, soldiers on campaign, and children and others walking with bare feet. The contact with rich infected soil greatly favors inoculation in any accidental wound.
An important feature in the pathology of tetanus is that the bacillus is confined to the seat of the inoculation wound. The many attempts to transmit the infection by blood, nervous matter, and by one or other of the tissues have uniformly failed, though the pus of the infected wound has proved virulent. Similarly, the attempts of Kitasato and others to obtain cultures from the animal liquids or tissues apart from the wound have been futile.
By inoculating the toxins remaining in the pus of the infection wound, however, or in virulent cultures from which the bacilli have been removed by filtration or in which they have been destroyed by heat, all the symptoms of tetanus can be produced (Kitasato, Kund Faber, etc.) In such cases too, the symptoms appear at once, as soon as the toxin is absorbed, and not after a definite period of incubation as in inoculation of the unaltered virus. Kitasato, Vaillard and Vincent reached this conclusion by another channel. They inoculated mice at the root of the tail with virulent tetanus cultures, and at definite intervals after, namely, half an hour, one hour, and one and a half hour, they made a circular incision round the wound and thoroughly cauterized the whole, thus destroying all the inoculated bacilli. They found that tetanus was prevented in those animals only which were operated on at the first half hour. Again, Kitasato injected mice with 0.2 to 0.3cc. of the blood from the heart of a fresh tetanus cadaver, and thereby produced typical tetanic symptoms and death in 1 to 3 days.
Various poisons have been separated from cultures of bacillus tetani. Brieger isolated three substances—tetanin, tetano-toxin and spasmotoxin—which in large doses caused tetanic symptoms and even death. Brieger and Fränkel later isolated a toxalbumin which proved of incomparably greater potency. Again, Brieger, Kitasato and Wehl separated what appeared to be an enzyme or diastase which proved 500 times more potent than atropia. This was in the form of yellow, transparent flakes, soluble in water, but which was not destroyed by drying, nor in the dry state by absolute alcohol, chloroform nor anhydrous ether, but which, like the virulent cultures of tetanus, was easily destroyed by acids, alkalies, hydrogen sulphide, or heat. Like the natural virulent product this may be kept unchanged for months on ice, apart from the light, or with the addition of 0.5 per cent. of carbolic acid, or its own bulk of glycerine. It kills the Guinea-pig in a dose of 0.000025 gramme, and the mouse in a dose of 0.00000025 gramme.
While the propagation of the bacillus in the animal body appears to be local, and the general tetanic symptoms are caused by the absorption of the poison, it remains to be seen on what organ this directly operates, and what accessory conditions favor its efficiency.
In cases due to inoculation the spasms are at first local in the vicinity of the inoculation wound and later become general. Kund Faber shows that there is no gradual transition from the local manifestations to the general, but the latter appear abruptly and in force as a new and independent phenomenon. When we consider further that in inoculation with pure cultures (uncontamininated by pus or saprophytic microbes) the wound often heals promptly, without any sign of remaining local irritation, we may conclude that simple nervous irritation in the sore cannot be invoked as a cause of the early local spasm. It is more likely due to the local diffusion of the poison into the peripheral nerves while the little that has been absorbed is as yet too much diluted in lymph and blood to seriously derange the nerve centres.
When general spasms set in it must be assumed that the poison has reached the nerve centres in toxic quantities, either through the circulation or as is alleged by Babes and others through the nerve trunks. When the poison is injected intravenously the general spasms are the first to appear. Again the section of the nerves of a limb before inoculation prevents spasms in its peripheral muscles when all the body beside has become tetanic (Tizzoni and Vaillard). The removal of the brain from a tetanized frog had no effect, while the removal of a portion of the spinal cord abolished the spasms in the muscles corresponding to that part. Moreover Gumbrecht cut the whole of the sensory nerves of a limb but the spasms occurred in its muscles notwithstanding. It must be admitted, therefore, that the general tetanic spasms are induced by disorder caused by the poison in the spinal nervous centres.
Gumprecht and Goldscheider claim that the poison reaches the spinal centres by way of the nerve trunks basing the conclusion on the observation that the spasms sometimes remain for a time more marked on that side of the body on which the wound or inoculation was made. Absorption through the circulation also is conceded.
Courmont and Doyon claim that the product of the bacillus tetani only operates as a ferment, which produces in the blood the real tetanizing agent, basing the conclusion on an apparent delay in its action, in man, as compared with strychnia, and on the prompt action of the injected blood of a tetanic animal in which this poison is presumably preformed. It should be noted, however, that the disease in man is only seen after accidental inoculation of the bacillus, and that time must be allowed for the increase of the microbe.
Vaillard and Vincent have shown that the promptitude and certainty of the result depend on the age of the culture employed. A culture of 5 days in bouillon at 20° to 22° C. will not harm a Guinea pig in a hypodermic dose of 0.25cc. to 0.5cc. A culture of 20 days old is deadly.
The action on the nerve cell of the spinal cord has been investigated by Goldscheider and Flatau, who found degeneration of the chromatin granules within a short time after inoculation. (Centr. für Allg. Path. Anat. 1897). W. K. Hunter found that the ganglion cell stained more diffusely than normal cells. There were also some capillary dilatation and punctiform hæmorrhages in certain cases (Brit. Med. Jour. 1897).
Péchoutre examined the lumbar enlargement of tetanic rabbits, by Nissl’s method and found the following lesions in the motor cells of the anterior horns: 1st. A partial or total disappearance of the distinct outer marginal line; enlargement of the cell and pericellular space; diffuse coloration of the achromatic substance; a disappearance of the regular concentric disposition of the granules of Nissl which were in part reduced to a fine powder; 2d. Encrease of nucleus and nucleolus.
Others have observed encrease of the cerebro-spinal fluid, thickening of the ependyma, nuclear proliferation in the neuroglia, and softening of the cord, but in many cases no appreciable lesions in the nerve centres have been found, and none can be affirmed as constant. Neuritis in the region of the wound is sometimes found especially if the lesion is a contused or painful one.
The muscles often show lesions the result of the violent contractions. There may be points of ecchymosis and partial rupture of individual fibres, they may be of a deep red, or again pale, soft and as if parboiled. There may be hyperæmia or œdema of the lungs, congestion of the larynx, ecchymosis on the pericardium and other serous and mucous membranes, and congestion of the liver, spleen and kidneys. Rigor mortis sets in rapidly and is usually very persistent. The muscles contain an excess of lactic acid.
Accessory Causes. Whatever contributes to traumas must be classed in this list. Solipeds, work oxen, and dogs are especially exposed in this sense. In all animals castration wounds; in horses and lambs amputation of the tail; in solipeds pricks, bruises and fistulæ of the feet; all kinds of surgical wounds; in females the parturient condition; and in the new born the umbilical sore form infection atria. The tendency to infection in wounds of the feet in animals, and of the hands and feet in man, is easily explained by contact with the virulent earth or dust. Children running barefoot, or injuring their bare knees and soldiers sleeping on the ground are similarly exposed. The contamination of the clothes is the main condition. It has been held that infection never takes place from the gastro-intestinal canal, but the facts that the bacillus is frequently present in the prima viæ and that the mucosa is often perforated by blood-sucking parasites, suggest that some cases (idiopathic) are probably due to intestinal infection. The gland ducts also and the follicles of Peyers’ patches and of the solitary glands offer available fields for the colonization of the bacillus and for infection atria.
General Symptoms in Animals. In experimental cases, in which there has been a large intravenous injection of the blood of a victim of tetanus the symptoms may set in speedily and violently. In casual cases, however, there is usually an incubation period varying on an average from three to fifteen days in the horse while it may be as short as two days in cow and sheep. Hoffmann quotes one incubation in the horse as but six hours after a wound in the neck, and another as twenty-five days, following a castration. The last is rather unreliable as infection may have taken place long after the operation. He quotes cases in the pig and goat, after castration as eight to fourteen days, and one in the dog almost immediately after a bite on the loins.
Following the incubation the marked phenomena are tonic contractions of groups of muscles beginning usually with those near to the seat of the infected wound and extending with varying rapidity to the locomotor muscles generally (limbs, croup, back, loins, neck, tail, abdomen) and those of mastication (jaw) and the eye. The muscles of respiration are only involved at a late date, causing stertorous breathing and it may be asphyxia. Peristalsis is impaired so that there is some costiveness and tardiness in digestion. Urination becomes difficult and infrequent on account of the difficulty of assuming the normal position for the act, and spasm of the sphincter vesicæ and dangerous distension of the bladder may follow. The urine is often albuminous and has a high density and color. Priapism is not infrequent in the male.
The predominance of the spasm in special groups of muscles has been the occasion of giving different names to individual cases.
Trismus or lockjaw is that condition in which the muscles of the jaws are violently contracted so that the incisors can only be separated slightly or not at all.
Orthrotonos is that condition in which the muscles in tonic spasms keep the neck, back and loins rigid, straight and unbending, in one horizontal line.
Opisthotonos is when the muscles of the spine are in rigid spasm, so that the back and loins are slightly depressed, the tail elevated and trembling, the neck drawn upward with a concave superior border (“ewed”), the head extended and the nose elevated.
Emprosthotonos is caused by spasms of the muscles of the ventral aspect of the body, with arching of the back and tucking up of the abdomen.
Pleurosthotonos is when the trunk is spasmodically bent to one side, right or left.
Spasms of the muscles of the eyeball, cause sinking and apparent diminution of that organ, with the protrusion of the membrana nictitans over one-third, one-half or even more of its front surface. This is often referred to by owners as “hooks”.
More striking and pathognomonic than the above is the extreme hyperæsthesia and irritability which rouse into activity or aggravate the symptoms under the slightest cause of disturbance. The effort required to feed from the ground, the stretching of himself to urinate or defecate, the rustling of straw litter under his feet, loud talking, or other sudden noise, banging of doors or windows, hammering in the vicinity, a current of cold air, a flash of light, moving the patient in the stall, attempts at mastication, simple handling, administering medicine, or sudden jerking of the head upward promptly brings on a paroxysm of spasm. Pushing the head suddenly upward or jerking on the halter, is often resorted to as a means of diagnosis, the sudden resulting rigidity of the muscles generally, the rolling of the eye, its retraction toward the depth of the orbit and the protrusion of the membrana nictitans over one-half, one-third or more of the cornea, bringing out the diagnostic symptoms in a striking manner. In very severe cases the head may be drawn upward and backward almost to above the loins (Henry), or one or more of the dorsal or lumbar vertebræ may be broken or crushed (Zundel). A sudden loud noise will sometimes cause the exhausted animal to drop to the ground.
Perspiration is not uncommon. Breathing is usually accelerated, the encrease being in ratio with the violence of the spasms. Pulse and temperature are usually normal at first and may be in slight cases throughout. Even in severe cases the pulse does not rise so much as the respiration. In violent and fatal cases the temperature often rises excessively before death (104° to 110° F.).
When the jaws are not absolutely closed, the tongue is often wounded by the teeth, and, in any case is covered by a tenacious mucus, which may hang in strings from the lips. If the jaws are still movable, mastication is still carried on, but slowly, painfully and imperfectly, and deglutition is more or less difficult. Young animals are unable to suck.
Symptoms in the horse. When the symptoms are fully developed, they are very characteristic. The neck is raised, often concave along its upper border, the nose raised and protruded more or less, the nostrils widely expanded, the eyes sunken, fixed and anxious, with diluted pupils and protrusion of the haw outward and upward from the inner canthus, the ears are pricked, rigid, and drawn toward each other at their tips, the facial muscles may stand out visibly and are firm, the angle of the mouth is drawn back, the veins of the head are full and prominent, saliva froths or drivels from the lips, the tail is elevated and during paroxysms will tremble, and the muscles of the back and limbs are projecting and hard. The limbs are extended outward to give a wider base of support. If moved, the general stiffness is at once seen. The patient cannot be turned round in his stall, he may not even be able to turn the neck to one side, and if backed he resists, or accomplishes the movement only with the greatest difficulty. In walking, the limbs are used as stilts with little or no bending of the joints, and if turned, the body is not bent but moved around with difficulty as if one rigid mass. The pulse is small and hard, the breathing slightly hastened, and the mucosæ congested and reddened. The jaws may be firmly closed, or they may still part for a time half to one inch. In all severe cases the patient obstinately stands, and if he should drop, or lie down, the breathing and spasms are usually encreased and, in the efforts to rise, the respiratory muscles may become spastic with promptly fatal results.
In cattle the same general symptoms prevail. The stiffness of neck and back, the habitual elevation of nose and tail, the stiffness of the legs, propped outward for support, and moved like unbending posts when made to walk, the hardness of the muscles, standing out under the skin, the rigidity of the lips, firmly closed or slightly opened, the general fixity of the erect, retracted ears, and the sunken appearance of the eyes with marked protrusion of the haw, are largely as in the horse. The muzzle is usually dry and hot, the jaws clenched, the tongue firmly compressed against the palate and covered with thick, tenacious mucus, and the flanks are often flattened by the contraction of the oblique muscles, so that they descend almost vertically from the lumbar transverse processes. There is great difficulty in turning and the trunk moves in rather a rigid mass without bending laterally, and the limbs are stiff and stilted. Tympany of the rumen sets in early with oppressed breathing and arrest of defecation and urination, which had been already difficult. The reflex excitability to noises, or other causes of disturbance is often less than in the horse. In cases following metritis, this may be due in part to the depressing poisons absorbed.
Sheep and Goat. Show the same general rigidity of trunk and limbs, the drawing of the head and neck upward and backward, the elevation of nose and tail and the firm closure of the jaws. As the disease advances they may lie on the side with legs straitened and rigid and head and tail raised toward the back. The occlusion of the eye by the haw is the same as in the horse.
In swine the spasms begin with the jaws and face, and extend to the neck, back and limbs with the same general symptoms as in other animals. Champing of the jaws and profuse frothing at the mouth have been noted and the protrusion of the haw is characteristic. As in sheep, the animal may lie on its side with head and limbs rigid and an early death may be looked for. Convulsions are easily distinguished by their transient character.
In dogs tetanus is rare. Möller had two cases in 50,000 sick dogs, Friedberger and Fröhner but one out of 70,000. Cadiot saw two cases in ten years of the Alfort clinic. Labat had several cases in sheep dogs. A slight transient trismus has been noticed as common in puppies. When generalized there is stiffness of the trunk and limbs, abduction of the members. The spine may be straight and rigid or drawn upward and backward, and the loins depressed. The haw covers the eye more or less, the lips are rigid, the jaws clenched, and the skin of the forehead wrinkled. The ears are stiff and drawn toward each other, or backward. The reflex excitability is as great as in the horse, the slightest touch or sudden noise producing violent paroxysms. Inability to bark is a marked feature. Temperature may be normal or up to 107° F.
In birds it is very rare, in keeping with the insusceptibility to strychnia, ergot and other tetanizing agents. Dreymann gives one case in a turkey, and Babes’ experimental cases in pigeons and chickens from a specially virulent bacillus obtained from the horse. The pigeons suffered much more certainly and severely than the chickens, in which there was a marked power of resistance. Dreymann’s turkey moved with stiff limbs and body, had the wings clinging firmly to the body, the head and neck extended and the bill firmly closed. The haw protruded over the eye, and there was hurried and oppressed breathing.
Course. Duration. The course of tetanus varies with the genus affected, with the individual susceptibility and above all with the length of the incubation, and severity of the attack. Cases that set in with great violence after an incubation of two or three days or less are likely to advance to an early death. An early generalization of the spasms, with high temperature (104° F), hurried breathing, congestion of the mucosæ and extreme excitability may end fatally in twenty-four hours or within a week.
If on the other hand the incubation appears to have extended over one, two or three weeks; if the disease is at first equivocal, with some stiffness and firmness of the muscles, but with little or no trismus; if the patient can open the jaws an inch or more and masticate even slowly for a number of days after the onset of the first symptoms; if the haw projects only slightly over the eyeball and the excitability is not extreme the prospect for recovery is much better. Such tardy cases may seem to stand still for a week and then have a slight aggravation and this may be repeated, or a slow improvement may set in and go on gradually to complete convalescence. Improvement may be manifested by a softer or more relaxed condition of the muscles, by a slightly freer movement of the limbs and jaws, by a greater ease in swallowing, by encreasing movements of the ears and eyes, by the lessened projection of the haw, by the freer breathing and circulation and by the permanent lowering of temperature to the normal standard. Convalescence is always slow, but especially slow in severe cases in which time must be allowed for repair not only of the central nervous lesions but also of the ruptures and trophic changes in the muscles.
In cattle the disease is usually slow in its progress and improvement may not set in till the close of the third week. In sheep, goats and dogs on the other hand it is habitually acute, and death may supervene from the third to the eighth day. In the horse all forms are met with and the result will vary according to the severity of the attack.
Mortality. Friedberger and Fröhner sets the mortality in sheep and pigs at nearly 100 per cent.: in horses at 75 to 85 per cent.: and in cows at 70 to 80 per cent. In tetanus neonatorum in lambs, the deaths reach about 100 per cent. In this case the disease usually sets in within forty-eight hours after birth, and with a very high temperature difficult deglutition becomes a marked feature, so that if the patient is not speedily killed by dyspnœa, it soon perishes from starvation and exhaustion.
The cause of death is usually asphyxia, hyperpyrexia, or exhaustion.
Lesions. There are no constant or pathognomonic structural changes in tetanus. Those that are found are inconstant and as a rule secondary. A wound (entrance channel) can usually be made out, often in the region of the foot, or in connection with castration. In the new born there is the unhealed navel, and in parturient cows the catarrhal, septic or injured womb. In the seat of such wound may be found the foreign body (nail, splinter, etc.), and some pus or simple congestion or even necrosis. The nerve trunks leading from such infected wound may be hyperæmic. The presence of the bacillus in the wound may be determined by microscopic examination or inoculation on a small animal.
The changes in the nerve centres may be congestion of the horns of gray matter, and there may be slight hæmorrhage, exudation, especially shown in the encrease of the cerebro-spinal fluid, softening, cell proliferation, and granular invasion of the nervous tissue. In separate cases the myelon, the corpus striatum and the cerebellum have shown lesions. The meninges are occasionally hyperæmic. Spinal lesions have been noted especially in the bulbo-cervical and lumbar regions. Exceptionally in the horse there are blood extravasations from fractures or dislocations of the vertebræ.
In subjects dying of asphyxia the lungs and right heart are congested, and the blood may be black, only loosely coagulable and with free hæmoglobin. There is congestion of the intestinal as of the respiratory mucosa, and also of the liver, spleen and kidneys. The congested bladder usually contains urine contrary to what is the case in rabies.
Diagnosis. From strychnia poisoning tetanus is distinguished by the gradual and progressive approach of the spasms and by the absence of the intervals of complete relaxation which separate the rapidly recurring and violent spasms of strychnia. In tetanus the spasms may be modified but never completely intermitted, and more or less stiffness, trismus and protrusion of the haw constantly persist. In strychnia too, the paroxysm is far more intense than in the early stages of tetanus. The spasms of strychnia are general, while those of tetanus are often most intense in particular groups of muscles often at first in the vicinity of the inoculation wound.
From rabies, tetanus is easily distinguished by the absence of any history of a bite; by the persistence of the tonic spasms especially of the masseters and abdominal muscles during the intervals between the more violent paroxysms (in rabies there is temporary complete relaxation); by the absence of clonic spasms which alone occur in rabies; by the absence of the paralysis which characterizes advanced rabies; by the mental clearness and the absence of hallucinations or mischievous disposition which are marked features of rabies; by the absence of the depraved appetite of rabies; and by the fact that the brain does not contain the infecting germ as is the case in rabies.
From rheumatism of the neck (torticollis) tetanus is easily distinguished by the permanent trismus which is not shown in rheumatism, and by the fact that spasms are easily roused by any artificial excitement, indicating an extraordinary hyperæsthesia and excitability which are nearly absent in rheumatism. The steady unmistakable progress of tetanus is in itself diagnostic.
From meningitis tetanus is to be diagnosed by the presence of trismus without impairment of the mental faculties or fever. In meningitis the spasms are usually confined to particular groups of muscles and do not become generalized under active excitement as in tetanus. Even if the spasms of meningitis affect the jaws and pharynx they are rarely paroxysmal or roused by excitement as in tetanus. They may even be clonic.
Tetany is more commonly localized in particular groups of muscles, and shows longer and more irregular intervals between paroxysms than does tetanus. It is improved by thyroid extract, and may be roused at will to contraction by pressing on the nerve going to the affected muscles.
Laminitis in its most violent form and early stages, may be confounded at first glance with tetanus, but the high fever, the standing on the heels, the advance of the hind legs under the body, the great heat and tenderness of the feet, the impossibility of standing on one fore foot when the other is lifted and the strong pulsation of the digital arteries, are sufficiently distinctive.
Treatment. For fully developed tetanus no known resort of therapeutics can be relied on. In slight cases that have shown a long incubation and a slow increase and extension of spasm and in those having trismus only, a recovery may be expected. Treatment has been conducted largely on theoretic lines and may be divided into antispasmodic, eliminating and antidotal or antiseptic.
Rest, darkness and absolute quiet are the first and main considerations. A dark stall, with no straw litter, the rustling of which often excites the patient, but rather a little chaff, saw dust or even earth to prevent noise from the feet, and the exclusion of all visitors are essential. As a rule slings should be put under the patient so that he cannot lie, nor drop down, and this becomes more imperative as the disease advances. The aggravation of the spasms when down, and the danger of their extension to the respiratory muscles are far more to be dreaded than the temporary excitement caused by the application of slings. Food should be sloppy mashes, of bran, middlings, oat meal, linseed meal, gruels or milk, or green food may be allowed in moderate amount if the jaws are still movable. It must not be forgotten that digestion is impaired and food that is indigestible, especially fermentescible, or in excess, may arouse fatal colics and bloating, yet in a protracted exhausting disease like tetanus, the strength must be sustained by all means in our power. Pure water should always be accessible. Food and water should be furnished in buckets at a level which will not necessitate either raising or dropping the head to get to them (about 4 feet). The food must be given often, in small quantity to avoid fermentation and spoiling. If noise cannot be wholly excluded it may be an advantage to put cotton wool in the ears. I have seen a mare recover when completely covered with cotton wool under blanket and hoods.
Local antiseptic treatment. Theoretically this is of great value since the microbe is confined to the inoculation wound and by the time the first symptoms appear, the spores have developed into bacilli and are in a condition to be easily destroyed by disinfectants. We can, therefore, by caustics or active disinfectants destroy the infecting microbian colony, and prevent the further entrance of any toxins into the circulation and nerve centres. The principle has been shown experimentally successful in cases of inoculation in the tails of cats and Guinea pigs, and the amputation of these members as soon as tetanic symptoms appear (Kitasato, Babes). Unfortunately in too many cases, when first seen, too much of the marvelously potent toxin has already reached the nerve centres, and these have already undergone such changes, that the disease is likely to go on to a fatal issue in spite of the cutting off of future supplies of toxin. Yet the principle is sound and proves helpful in proportion as it is applied nearer to the time of infection. The most thorough method is the amputation of the infected member, if like the tail or ear it can be excised without ruining the animal. In 1875, Barbillon had success in again amputating the tail, in a case of tetanus after docking. Next to this comes the excision of the wounded tissues, but this can too seldom be effectually and certainly accomplished, and we must fall back on caustics and antiseptics. The actual cautery if thoroughly applied may be trusted to destroy the bacillus along with the tissues, but most of the chemical escharotics unite with the albumen to form an impermeable film, which protects the tissues in the deeper part of the wound against the antiseptic action. Of the different antiseptic applications carbolic acid should be especially recommended as being not only antiseptic, but also an antidote to the toxins as shown below. It has the further advantage of acting as a local anæsthetic, and of not coagulating albumen. Creosote, creolin, lysol or other antiseptic may be used instead and should be applied thoroughly to all parts of the depth of the wound on a pledget of surgeon’s cotton or through a tube. When agents so little destructive are employed they may be continuously applied to the sores for a length of time.
Recoveries have taken place after neurectomy, and after stretching the nerve going to the wounded part, the theory being to check the afferent (sensory) nervous current, and arrest the reflex spasms. The new irritation, however, caused by the surgical wound is to be dealt with, and may itself turn the balance against recovery.
Nervous derivation appears to have been beneficial in some advanced, or partially convalescent cases. One horse after 14 days illness (Taffanel) and another after 21 days (Prud’homme), were castrated, bled freely and slowly recovered. Tisserand gives another case without mentioning the stage of the disease. A horse with advanced tetanus was taken to the seashore and shot. He fell into deep water, swam ashore and made a recovery. But whatever virtue may be in elimination of the toxins by bleeding, in nervous derivation or in the shocking of an unbalanced nervous system, these can hardly be recommended as regular methods of treatment. Yet the older veterinary records contain many instances of alleged benefit from bleeding.
Internal treatment. The whole list of antispasmodics have been tried, with no very satisfactory result. Opium has been extensively employed in spite of its tendency to encrease constipation, and morphia given hypodermically has checked spasm and induced sleep. Hydrocyanic acid and potassium cyanide have shown a decided reducing action on the spasms with the same drawback of favoring constipation. Potassium and other bromides are useful in mild and chronic cases, and may be given in full doses in combination with chloral hydrate. Calabar bean and eserine have been given for their physiological action on the nerve centres, and recoveries have followed their use, but they have little effect on the spasms until the system has been saturated to the point of threatening collapse. Chloroform has the advantage that it can be easily given by inhalation, but while it may be pushed to the extent of temporarily checking the spasms, yet these return at once when the action of the drug is exhausted. Chloroform is always dangerous to a weak or exhausted heart and cannot be given for any great length of time continuously. It is, therefore, very unsatisfactory. Sulphonal and trional have similarly checked the spasms. Gelsemium has given good results in certain mild cases, but it must be pushed to the extent of coming just short of poisonous doses, and the fear of an overdose, together with its failure in severe cases, have prevented its general acceptance. The same end has been sought by the use of nauseating antispasmodic agents, as tartar emetic, tobacco, apomorphia, and lobelia, but though useful in individual cases, these are on the whole no more successful than other agents. Phenacetin, antipyrin, acetanilid and cocaine have respectively received credit for some recoveries.
Chloral hydrate commends itself as being at once a most potent antispasmodic and hypnotic, and an antiseptic. It can, moreover, be conveniently given as a rectal injection, thus avoiding the irritation and excitement of administration by the mouth. Given in this way too, it tends to relaxation of the bowels, instead of constipation. Carbolic acid which can be conveniently given by enemata has an anæsthetic action.
Antiseptic and Antidotal or Antitoxin treatment is more promising, yet it has failed to come up to the full measure of expectation, mainly because the nervous changes have already reached a stage which cannot be undone speedily or at all. Under this heading would come phenic acid (½ oz.) and probably chloral hydrate (1 oz.), already referred to, and the various compounds of iodine which may be here noted.
Iodine Terchloride. Iodine. Behring and Kitasato secured immunity of two months duration, by injecting the animal with a filtrate of a culture of tetanus bacillus, and then injecting at the same point 3cc. daily, for five days, of a 1 per cent solution of iodine terchloride. Roux and Chamberland had similar results by using iodine instead of the iodine terchloride, and maintained the full measure of immunity by repeating the inoculation every fortnight. Here it is evident that the action of the iodine is directly antitoxic or antidotal, when introduced along with the toxins and before they can reach the nerve centres.
Iodide of Potassium. In an experimental case of general tetanus in the dog, Babes had a recovery in ten days, by injecting subcutem 5cc. of Lugol’s solution and thereafter for eight days 10 to 30cc. daily. This suggests the use of this agent along with phenic acid, or as an alternate, in any case in which phenol appears to be losing its effect by use. It may be used hypodermically, or in the drinking water or by rectal injection. It has an advantage over phenic acid in being actively diuretic and eliminating, while phenic acid has the recommendation that it tends to lower nervous excitability and moderate the reflex spasm. Theoretically the combination of the two agents, which do not mutually decompose each other, should give the best results.
These experiments have been often repeated showing clearly the antidotal action of the iodine compounds when mixed with the virus before inoculation, or injected with the virus into the seat of the wound. When employed later when the symptoms have developed, everything depends on the changes already accomplished in the nerve centres, and the severity and generalization of the spasms.
Serum Antitoxin Orrotherapy. Babes appears to have been the first (1889) to use the serum of animals (rat) recovered from tetanus in mitigating and curing tetanus in experimental cases. An attempt on a well developed case in man failed. His method of preparing the serum is as follows: A horse of 900 lbs. (461 kgm.), is inoculated with a mixture composed of 0.5cc. toxin (of which 0.001 mgm. kills a mouse) and 0.5cc. iodo-potassium iodide, and then at intervals of four or five days of 2.5cc., 4, 5 and 10cc. of the iodine mixture. Then stronger mixtures are used: first 2 parts of toxin to 1 part of the iodine mixture; dose 10cc.; then 3:1 dose 10cc.; then 4:1 dose 5cc.; then 15:1 dose 10cc.; then 30:1 dose 25cc.; and finally virulent cultures in progressively encreasing doses 10, 20, 30 and 50cc. One week after the last injection 1cc. of the blood serum will antidote 50cc. of toxin. Injection of toxin is however continued and the dose is gradually raised to 200cc. Eight or fourteen days after the last injection the blood serum may be taken for protective purposes. He has prepared antitoxin from cows in the same way, and Brieger and Ehrlich have prepared it from the goat. Chickens being naturally refractory to tetanus toxin can bear large doses and a potent antitoxin is more speedily secured from them. In the case of the cow the milk is rich in antitoxin.
Other methods of preparing an animal for producing the antitoxin have been resorted to as injecting it with a mixture of toxin and antitoxin in increasing doses, or again injecting with a mixture of toxin and thyroid extract in increasing doses. The extract of the normal thyroid contains a natural antitoxin.
It may be fairly inferred that the antitoxin is not formed in the nerve cells alone in their resistance to the toxin, but also in the thyroid, the liver (bile having an antitoxic action), and perhaps in other organs or liquids.
The blood of the immunized animal drawn through the sterilized cannula and aspirating syringe is coagulated in vessels set on ice, and the serum when separated is mixed with 0.5 per cent. carbolic acid and 1 per cent. chloroform, and kept in the dark in well closed bottles. It will usually keep for years.
Early experiments with antitoxins showed that when mixed with the toxin before injection it could be trusted to neutralize it. Ehrlich, Tizzoni and Cattani even claimed success in all experimental subjects if employed as soon as the slightest symptoms of tetanus were shown. They found, however, that it required 1000 to 2000 times the amount of antitoxin in such cases than was required when it was mixed with the toxin prior to injection. They found, moreover, that when the disease is fully developed the dose must be 150 times more than is required when the first symptoms are shown. It should be added that when the disease has developed rapidly, after a short incubation, and is well advanced the antitoxin treatment is usually of little avail. The changes in the nerve centres are already too great to allow hope of recovery. In man the ratio of recoveries are about as follows: After incubation of 10 days or under, 3 to 4.5 per cent. recover. After an incubation of 11 to 15 days 50 per cent. recover (Woodhead). Lambert claims 46 per cent. recoveries in 114 cases, and 38.71 per cent. recoveries in acute cases with an incubation of 8 days and under.
On the whole the ratio of recoveries is greater under the antitoxin treatment than before, though far from sustaining the optimistic views of Behring and other early experimenters. Babes draws attention to the fact that spore laden splinters of wood, in the wound render the antitoxin useless as a continuous succession of fresh spores, bacilli and toxins are thereby supplied. As this is one of the most common forms of casual infection it interferes seriously with the success of antitoxin treatment.
Roux and Borrel found that in animals, intracranial injection of the antitoxin was the most effective method. Recovery also followed its injection into the cerebrum of a tetanic boy. Babes had recoveries in two cases out of three with cerebral or intracranial injections. As the reflex spasms depend on the spinal centres these would seem to be the ideal points of injection.
Babes who has done a large amount of subcutaneous and intraperitoneal injection of antitoxin, employed for man doses of 300 to 500cc., which would represent 8 to 10 ozs. as the dose for an ordinary horse. As the antitoxin is rapidly eliminated from the body, these should be repeated daily or every other day. Nor should this supercede other curative measures. The leading principles may be thus stated: 1st. Antitoxin should be used at the earliest possible moment. 2nd. The infected wound area must be thoroughly disinfected or destroyed by caustics, and that at once. 3rd. The antidotal treatment by phenol and iodine must not be omitted. 4th. Palliative treatment by antispasmodics, narcotics or soporifics must go hand in hand with antitoxic treatment. 5th. Measures should be taken to secure elimination of the toxins present in the blood.
Treatment by brain emulsion. Wassermann and Takaki (Berlin Klin. Woch. Jan. 3d, 1898) have in a number of cases, mixed 1cc. of brain substance of a warm-blooded animal with ten times the lethal dose of tetanus toxin and injected without producing any symptoms of tetanus. They obtained a similar immunity by injecting the brain emulsion 24 hours after the injection of three times, and in other cases of five times the lethal dose of tetanus toxin. Control cases uniformly died of tetanus. The brain matter was obtained from Guinea pigs, pigeons, rabbits, horses, and men. They accordingly advanced the theory that brain matter is a direct antidote to the tetanus toxin, uniting with it chemically and rendering it innocuous. The liver, spleen, kidney, bone marrow and blood serum gave no such protection.
Marie, in a series of experiments, injected the brain emulsion and tetanus poison at different parts of the body of Guinea pigs and found that fatal tetanus ensued. It would appear, therefore, that the brain emulsion acts by direct contact, and that it is only by its meeting and combining with the toxin before the latter reaches the spinal cord that tetanus can be prevented.
Roux and Borrel (Ann. de l’Instit. Pasteur, 1898) demonstrated this union between the poison and brain matter, by making an emulsion of the two, and putting in a centrifuge, which will separate the brain substance from the clear liquid. The fluid obtained in this way was shown by injection on the living animal to contain almost no toxin. Knorr and Blumenthal reached the same conclusion as to a chemical union with the brain matter which robbed the toxin of its toxicity.
Knorr, and Tizzoni, and Cattani and Morax showed indeed, that if the tetanus toxin is injected subdurally or into the surface layers of the cerebrum, it produces not tetanus, but a characteristic cerebral disease. A dose of ¹⁄₂₀th or ⅒th cc. of tetanus toxin produces in the rabbit, in 10 to 12 hours, restlessness, constant change of place, and signs of great fear like hiding the head, turning rapidly round, attempting to escape, polyuria, grinding the teeth, epileptoid convulsions. The toxin in this case had manifestly united with the brain substance while the cord suffered little.
Metchnikoff (Ann. de l’Inst. Past., April, 1898) holds that the brain matter is only valuable in holding the toxin until it can be destroyed by the leucocytes. He showed that the injection of the tetanus toxin in chickens or Guinea pigs greatly encreased the production of leucocytes. He injected tetanus toxin into the aqueous humor of the rabbit without producing much effect, but when the same agent mixed with cerebral substance was injected, the result was a great accumulation of leucocytes, and hypopion. If the mixture of brain substance and tetanus toxins were injected on the brain, little encrease of leucocytes occurred, but if thrown into the peritoneum, a most remarkable leucocytosis took place. In twenty minutes after the injection the fluid withdrawn from the abdomen showed large numbers of leucocytes filled with brain substance, but no free cerebral matter.
The present status of the treatment by brain substance is therefore somewhat uncertain. The value of that agent in holding the toxin is allowed, but like the antitoxin it must be employed before the toxin has reached the nerve centres and united with the living ganglion cells. Its use would be called for therefore at the earliest possible moment and it should be continued so long as there is reason to suspect the production of fresh toxin in the wound. Its direct action on the toxin would suggest its injection around an infected wound, or even as a dressing for the wound in connection with antiseptics. When tetanus has already set in it cannot be expected to undo the evil already accomplished by the union of the toxin with the cells of the cord, though it might in part arrest and hold new supplies of this poison coming from the wound to the nerve centres.
Prevention. In a disease so deadly as tetanus and so refractory to treatment even by antitoxin when it is once developed, prophylactic measures are of the greatest importance. With the extensive adoption of antiseptic surgery there has already been a material diminution in the number of cases, yet a greater attention is demanded to the prevention of casual cases which result from ordinary wounds. Dirty, grimy wounds filled with the dust of stable yard or garden soil, and such as contain splinters of wood, stones, thorns, straw and the like can only be considered quite safe after thorough disinfection. It has been shown that the toxin is easily neutralized at the time of infection, whereas, after the disease is developed it will require 1,000 or 100,000 times as much antitoxin to produce the same effect. In the case of soiled wounds, therefore, in a valuable animal, a harmless injection of antitoxin or of phenic acid or iodine solution before the development of tetanic symptoms is not an unwise precaution. A succession of such injections might be given to ward off the disease until after a lapse of time exceeding the short and dangerous incubation.
Much more important is the disinfection of the wound itself. All foreign bodies must be removed, but especially those that like splinters of wood and straws are likely to harbor the spores of the bacillus. Then the wound may be thoroughly cauterized thermically or chemically, or it may be irrigated with a strong antiseptic solution and then dressed with some agent that will prove destructive to the spores, and antidotal to the toxin. Strong carbolic acid may be applied to the whole raw surface including the uttermost recesses of the wound, and after a few seconds or half a minute this may be neutralized by filling the wound with dilute acetic acid or alcohol, after which a dressing of Lugol’s solution may be applied. Lambert advises a combination of hydrochloric and carbolic acids.
Weaker antiseptics, like a 5 per cent. solution of carbolic acid, do more harm than good, as they destroy the pus and saprophytic microbes and even the tetanus bacillus in the wound, without affecting the tetanus spores, which finding no other microbes to contest with them the possession of the field may find themselves in a better position than before to develop into bacilli and cause tetanus.
Tetanus neonatorum may be certainly prevented by the application of a disinfectant plaster on the navel at birth. Over 50 years ago in Scotland this desideratum was met by applying on the navel of the new-born child a soft and immaculately clean piece of cotton cloth which had just been flamed over a light. On the island of St. Kilda the former mortality of 67.2 per cent. of new-born infants, was promptly abolished by dressing the navel daily with iodoform. For new-born animals a cheap and convenient application may be made by incorporating 1 oz. powdered iodine and 2 lbs. wood tar, and smearing this on the navel.
Much may be done by disinfection of stables and yards where the victims of tetanus have been. The anærobic germ soon loses its virulence in free air and sunshine, and one has to dread especially, filthy stables, collections of manure, contaminated litter, wood, combs, brushes and buckets. In unpaved yards remove the infected surface soil and replace by fresh disinfected earth, or still better, well burned brick.
For horses which are necessarily exposed to manure or contaminated soil, it is commendable to wash the hoofs and pasterns on returning from work and then sponge with a weak solution (5 per cent.) of phenic acid. Another resort is to smear the hoofs daily with an ointment of tar and lard, equal parts. This cannot protect from infection by splinters of wood containing the spores, but is to a large extent preventive in the case of bacilli that might have been otherwise lodged on the surface and which could have been carried into the wounds inflicted by nails and other noninfected bodies. Careful shoeing is all important, to avoid the bruises, suppurating corns and gravelling which make openings for the ready entrance of the spore.
Roux and Nocard recommend immunization by protective inoculation. This is not only possible, but would be justified economically in the case of valuable animals, or in all animals in a district where the bacillus tetani is universally spread. The method is the same as advised above for the immunization of animals, for the production of antitoxin.
In districts where tetanus is rare, the cost of universal immunization against the disease would very far exceed the losses front casual cases. Under such conditions it would be an economical blunder.