Part 44

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.