Chapter XIII: Front Matter (13)

In cases in which premonitory symptoms are lacking, violent spasms of the throat and chest are commonly roused by an attempt to drink and this is so painful that the patient cannot again be induced to try. After this any suggestion of drinking, the offer of drink, the noise of trickling water, the sight of water, the sight of a vessel in which the water was contained, or even of a clear shining surface of glass or metal is likely to bring on a paroxysm. This hydrophobia is peculiar to man being rarely seen in rabid animals. During a paroxysm dyspnœa is extreme, respiration is gasping or sighing, and in the attempt to dislodge the tenacious mucus which is present in the throat, hoarse or shrill inarticulate sounds are emitted which have been supposed to resemble the bark of the dog. There is a sense of closure of the throat and of rising of the stomach, and retching or even vomiting may ensue. Hyperæsthesia, reflex irritability, and exaltation of the special senses, now become extreme, so that a paroxysm may be brought on by the slightest disturbance, a current of air, a bright light, the rustling of a dress, the noise of a footfall, the noise even of talking, or a slight touch. The “tendon reflex” and skin reflex are often much encreased. During a paroxysm there are muscular trembling and clonic spasms,—sometimes opisthotonos. The intervals of complete relaxation, however, serve to distinguish from tetanus. The face is red and drawn, the eyes congested and sometimes squinting, the pupils dilated and the expression one of suffering, apprehension and horror. Mental disorder appears sooner or later, the speech is disconnected, with indication of delusions from which the patient may at first be recalled by the attendant. There is, however, a constant disposition to be reticent, morose and above all, suspicious, as shown by the absence of a direct look, and the frequency of side glances as though in expectation of a hidden danger. This may even rise to mania, the patient charges those about him with having caused his sufferings, or with conspiracy to injure him, and he may seek to defend himself with hands, feet, teeth or any available object. The necessary restraint aggravates and prolongs the attack. On its subsidence the patient collects his scattered senses, regrets, apologizes, and warns against future occurrences of the same kind which he realizes to be beyond his control. Sometimes the delusions continue during the remission as well. Sexual excitement is common in man as in animals.

The convulsive paroxysms may last ½ to 1 hour, and they tend to encrease in duration and force. A violent paroxysm may cause sudden death from asphyxia or apoplexy.

Sooner or later exhaustion and paresis appear. The convulsions become gradually weaker, the reflex irritability and hyperæsthesia abate, and the patient may become once more able to swallow, but an ascending paralysis, beginning in the limbs spreads over the body and death occurs in from one to eighteen hours. In the paralytic stage there may still be slight jerking of the muscles, or tremors, but violent convulsion no longer occurs, and there is extreme prostration, with hurried, rattling breathing, small, weak, irregular pulse and finally, stupor and coma.

_Diagnosis in man._ The only additional point, to those already stated for animals, is in regard to _lyssophobia_. This false form of hydrophobia is usually fortified by the fact of a bite, but as a rule it lacks the exaltation of common sensation and of the special senses which characterizes genuine hydrophobia. Very often also there is a flaw in the history, the dog that inflicted the bite is unknown and may still be alive, in which case no medicine is so good as to bring the healthy dog into the presence of the patient. The dog may have been killed by an excited community without any identification of his symptoms as those of rabies or any post mortem examination to throw light on his case. The attack may have come on after a conversation on the subject of the bite, or of rabies, and perhaps, as in the case of the Montpellier cadet, long after and when the patient had for the first time heard that the dog that bit him had been mad. It may be that rabies does not exist in the district and that no other victim in man nor beast can be adduced. It may be that the patient has a nervous organization or is subject to hysteria, and therefore specially predisposed to any disease of the imagination. Such cases cannot be accepted as rabies until a successful inoculation has been made on one or more animals.

RABIES AND HYDROPHOBIA. LESIONS. TREATMENT AND PREVENTION.

Lesions: blood fluid or clot diffluent. Fauces, pharynx and larynx
congested, exceptionally ulcerated. In dog, mouth cyanotic, with
tenacious mucus, sublingual petechiæ and erosions, stomach contains
many foreign bodies, but no food, small intestines and cæcum empty,
and like stomach congested: petechiæ on skin and elsewhere, cutaneous
and cardiac veins gorged, hyperæmic liver, kidneys and bladder: brain
congested, capillaries dilated or blocked, hæmorrhagic, leucocytic
collections in lymph spaces, nerve cells swell up with hyaline bodies
near nuclei, and neuroglia has hyperplasia, especially near the
respiratory centre. Congestion of nerves. Leucocytosis. Therapeutic
treatment: Orrotherapy: of little avail. Nerve sedatives; darkness,
quiet, nutritive enemata, chloroform, chloral, etc. Prevention:
eradicate the virus; muzzle all dogs absolutely, under heavy penalty,
for one year; Gower’s view; examples of muzzling; collar with name and
owner, shoot all unmuzzled dogs, cage for 6 months bitten dogs and
cats, also all imported dogs, shut up in cage for 10 days all dogs
that have bitten; treatment of bites, tourniquet, cup, suck through
tube, wring wound, cauterize—hot skewer, cautery, mineral solid
caustic, mineral acids on pledget or through a tube; Pasteur method:
emulsion of spinal cord (of rabid rabbit) after aseptic æration in
vitro for 3 to 14 days, injected in graduated doses for 21 days, table
of doses, table of mortality; Orrotherapy: by blood serum of immune
animal: advantages, disadvantages—technique: Use of sterilized brain
matter from rabid animal: experiments; protection by snake venom.

_Pathological Anatomy._ The blood is fluid or the clot diffluent. Congestion of the fauces, pharynx and larynx is patent during life but may have disappeared after death. Yet I have seen extensive ulceration of the vocal cords in a rabid cow. The congestion may extend to the trachea bronchia and lungs. In _dogs_ the buccal mucosa is often cyanotic, covered with a thick mucus, and may present sublingual ecchymoses and erosions, and wounds of various kinds made by objects bitten or swallowed. The stomach in the same animal is usually almost pathognomonic, being filled with foreign bodies of all kinds—straw, hay, hair, wood, coal, pebbles, pieces of metal, cord, leather, cloth, earth, sand, etc.—the result of the depraved appetite. There is an absence of normal food principles in stomach and small intestines and the cæcum and colon are usually empty. The gastric mucosa is congested, and may be wounded and its contents mixed with blood. Such a condition of the stomach in a dog, that has been bitten, and which after a customary incubation period has shown symptoms like those of rabies, is virtually diagnostic.

The following lesions are common to man and animals: Marked emaciation, cyanosis or petechiæ in skins that are naturally white, early sepsis, cutaneous veins and heart gorged with dark inspissated blood, hyperæmic liver and kidneys, and slightly congested, petechiated empty bladder.

The most important lesions, however are those of the central nervous system. In seven cases out of nine, Gowers found these very distinct. There were vascular disturbance, capillary dilatation, capillary clots, minute hæmorrhages, and accumulations around the affected capillaries of leucocytes occupying the lymph spaces. Benedikt and Babes attach much importance to the formation of hyaline patches in the thickened walls of the vessels and around them, compressing the vessels in some cases to virtual obliteration. The nerve cells swell up, and show small hyaline bodies in the vicinity of the nuclei, and these latter finally disappear. Germano and Capobianco found in addition marked hyperplasia of the neuroglia. Babes, who looks on these changes as pathognomonic, takes a small portion of spinal cord, hardens it in alcohol for 24 hours, stains it with aniline red and examines for the characteristic hyaline nodes.

These brain lesions have been found mainly in the medulla near the floor of the fourth ventricle and the respiratory center, but they are also to be found in other parts of the encephalon and spinal cord. The greater constancy of the medullary lesions serves to explain the characteristic symptoms.

Congestions of the peripheral nerves have also been found. Lüttkemüller found in rabies a moderate increase of the white blood corpuscles and a great number of microcytes.

_Therapeutic Treatment._ It was long thought that rabies was necessarily fatal, as indeed nearly all developed cases are to the present day. For this reason and much more on account of the risk of preservation and propagation of the deadly germ, the attempts at curative treatment in the lower animals have been looked on as utterly unwarranted or absolutely criminal. Yet it is now known that very exceptionally a recovery takes place, and in that case immunity for the future may be counted on. Yet the frightful danger attendant on the preservation and treatment of a rabid animal, may well forbid the keeping of any of the lower animals affected by rabies unless it be in the safest seclusion and for the production of immunizing or curative products.

_Orrotherapy_ with the blood serum of an immunized animal is of little value, and attended by risk from the rabid animal, but will be noticed below as a prophylactic.

In man when the disease is manifested, palliation has been obtained and very exceptionally recovery, under darkness, quiet, nutritious enemata and antispasmodics or soporifics. Among such antispasmodics and nerve sedatives may be named chloroform, chloral, curare (3 alleged recoveries), eserine (1 recovery), pilocarpin (1 recovery), morphia, datura, atropia, and bromide of potassium. Others have recovered without any medicinal treatment, so that the mildness of the attack must be duly considered in every case.

_Prophylaxis._ The most effective way of preventing rabies is to eradicate the virus from the country. All immunizing measures resorted to after the infecting bite has been sustained, are of little value as compared with this, they may save the bitten individual, but they do nothing to prevent others from being bitten in the future, and indirectly they contribute to the maintenance of the disease by drawing attention from such radical measures as would rid the country forever of the scourge. In his great work on Diseases of the Nervous System, Gowers puts this not a whit too strongly when he says: “The enforced muzzling of dogs for a period of one year would almost certainly stamp out the disease. That such a measure is not adopted is a national disgrace, which is accentuated by the fact that the Government derives part of its revenue from a tax upon dogs. The opposition to the use of the muzzle is one of the strangest developments of morbid sentiment. There are apparently thousands of well-meaning people who would prefer that hundreds of dogs should perish every year of a painful disease, that many human lives should be annually lost, and scores of persons should be subjected for months to acute mental agony—rather than that dogs should be made to wear an apparatus which causes them a trifling annoyance. This perverted sentiment ought to be met with universal abhorrence as a disgrace to humanity.” Such a statute, backed by a penalty in some degree commensurate to the homicidal criminality of the person who would leave his dog free to inflict this horrible disease on humanity would doubtless be effectual, but some nations have such laws on their statute books, and yet allow them to become dead letters. Others have enforced them to good purpose. Berlin in 1853 had many cases of rabies and muzzling was enforced. In three years the disease was completely eradicated and the city enjoyed nine years of immunity or so long as the law was enforced. Similar successes were met with in Holland, new cases occurring only on the borders or in imported dogs. London in 1889 had 123 cases and muzzling was enjoined. In 1892 the cases were reduced to 3, and the muzzling law was suspended, and a steady yearly encrease resulted, until the 1st three months of 1896 furnished as many as 72 cases.

In the absence of this radical measure muzzling should be enforced for a year in any locality where a case of rabies has occurred, and every dog should wear a collar with the name and residence of his owner inscribed on it. All stray dogs and all unmuzzled ones should be summarily shot. Dogs and cats that have been bitten by rabid animals should be destroyed or shut up in cages for six months under veterinary supervision. Imported dogs should be similarly secluded. Dogs that have bitten animals or men should be shut up for ten days under supervision, when, if rabid, the animal will develop unequivocal symptoms.

_Treatment of bites._ Absorption from a wound in a limb may be prevented by applying a tourniquet. Wounds on the body may be cupped, or sucked through a tube. Or the wound may be wrung to encrease the flow of blood. As soon as possible it should be thoroughly cauterized. A hot skewer, a Paquelin cautery, a stick of silver nitrate or zinc chloride or caustic potash or a crystal of cupric sulphate will meet this end. If liquid caustics are to be employed they can be applied to all parts of the wound by means of a pipette, a glass tube, or swab.

With thorough cauterization shortly after the bite there is practically nothing to fear, and even if it has not been applied for hours after, it is still valuable in destroying the poison left in the wound from which a continuous infection of the brain, by the transmission of the unknown germ and its toxins, would otherwise take place. It has besides in the human being a good moral effect against lyssophobia by giving the bitten person a certain sense of protection.

_The Pasteur Method._ This is based on the fact that the spinal cord of the tetanic rabbit when removed aseptically, and kept _in vitro_ in a dry atmosphere, loses in virulence day by day, until on the fourteenth day it is harmless. To render the air more drying, caustic potash is introduced into the flask. The culture of the poison in rabbits intensifies its virulence, until the virus becomes the strongest known and when inoculated subdurally, reduces the incubation to six or seven days.

In Pasteur’s early experiments he began injecting the emulsion of the cord desiccated for 14 days, following with that of the 13th day, and so on to that of the 5th. It was soon found that this was comparatively ineffective when inoculation had been made with a strong virus or in a large dose, and the treatment for such cases was modified to what is now known as the intensive method. The weaker forms of the virus are given at shorter intervals on the first days of treatment, and the stronger forms repeated again and again, and, in place of a 15 days, course of treatment, this is extended to 21 days. The following table illustrates the course:

│ _Number of │
_Day of │ Days that │
Treatment._ │ cord had │_Dose Injected._
│ been │
│desiccated._│
───────┬────────┼────────────┼────────────────
1st day│morning.│ 14 days. │ 3cc.
„ │ „ │ 13 days. │ „
───────┼────────┼────────────┼────────────────
„ │evening.│ 12 „ │ „
„ │ „ │ 11 „ │ „
───────┼────────┼────────────┼────────────────
2d „│morning.│ 10 „ │ 3cc.
„ │ „ │ 9 „ │ „
───────┼────────┼────────────┼────────────────
„ │evening.│ 8 „ │ „
„ │ „ │ 7 „ │ „
───────┼────────┼────────────┼────────────────
3d „│morning.│ 6 „ │ 2cc.
„ │evening.│ 6 „ │ „
───────┼────────┼────────────┼────────────────
4th „│ │ 5 „ │ 2cc.
5th „│ │ 5 „ │ 2cc.
6th „│ │ 4 „ │ 2cc.
7th „│ │ 3 „ │ 1cc.
8th „│ │ 4 „ │ 2cc.
9th „│ │ 3 „ │ 1½cc.
10th „│ │ 5 „ │ 2cc.
11th „│ │ 5 „ │ 2cc.
12th „│ │ 4 „ │ 2cc.
13th „│ │ 4 „ │ 2cc.
14th „│ │ 3 „ │ 2cc.
15th „│ │ 3 „ │ 2cc.
16th „│ │ 5 „ │ 2cc.
17th „│ │ 4 „ │ 2cc.
18th „│ │ 3 „ │ 2cc.
19th „│ │ 5 „ │ 2cc.
20th „│ │ 4 „ │ 2cc.
21st „│ │ 3 „ │ 2cc.

Under this treatment the system becomes educated in the production of antitoxins, and perhaps also in phagocytosis so that when subjected to the lethal doses of three, four, five and six days preservation, it successfully resists them. The most conclusive argument in favor of its efficacy is this undeniable fact that the individual escapes death under injected doses which in any unprotected system would prove fatal.

The results as given by the report of the Pasteur Institute are furnished in the following table, from which are excluded such cases only as developed the disease during the course of treatment, which therefore remained incomplete.

_Years._ _Persons Treated._ _Deaths._ _Mortality per cent._
1886 2671 25 0.94
1887 1770 14 0.79
1888 1622 9 0.55
1889 1830 7 0.38
1890 1540 5 0.32
1891 1559 4 0.25
1892 1790 4 0.22
1893 1648 6 0.36
1894 1387 7 0.50
1895 1520 5 0.33
1896 1308 4 0.30
1897 1521 6 0.39

The following table gives the number of individuals treated who had been bitten by animals which had been proved rabid by successful inoculation of other animals, and of those bitten by reputedly rabid animals, and their respective mortality.

_Died._ _Mort. per ct._
Bitten by animals proved rabid by
inoculation 2,872 20 0.69
Bitten by animals pronounced rabid by
veterinarian 12,547 61 0.48
Bitten by animals suspected of rabies 4,747 15 0.31
————
Average mortality 0.46

The Pasteur treatment by its great success in persons who have already been bitten has in a great measure robbed hydrophobia of its terrors, only it must be resorted to as early as possible in the period of incubation. It has also been advocated as a means of immunizing subjects that have not been bitten but are more or less liable to be so, and on this basis a large number of dogs have been passed through it. This is not likely to be adopted in the case of the human being, the more so that a few, although on the whole a very limited number of persons, have developed rabies long after the taking of the Pasteur treatment. This has been attributed to the retention of latent germs in the system, and argues besides a remaining susceptibility to the poison.

In spite of its brilliant success and the great boon it has been to humanity, the Pasteur treatment is not an ideal one. Its success does not consist in an entire extinction of rabies, but merely in the reducing of its evil results; its success is indeed based on a preservation and propagation of the germ and a continuous danger of infection of new subjects; finally, the proposition to end the disease by passing the whole canine race through the treatment, is open to the objections that this would require a fabulous outlay, and that even then some rare cases are not found to be fully protected. To continue the disease, when it may be exterminated, and to palliate its results by the treatment of generation after generation of dogs, must be promptly condemned by the political economist, to say nothing of the consideration of probable human infection.

_Orrotherapy._ It is not surprising that essays were made in the line of serum treatment. Babes and Lepp in 1889 had some encouraging results in transferring the blood of an immune animal into a healthy one. But Tizzoni, Schwarz and Centanni have especially worked out this method. These have shown that the blood serum of immunized animals destroyed the virulence of the rabic poison, whether mixed with it before injection, or injected with it, or injected within twenty-four hours afterward. A very small amount of the serum is required and though delayed until the end of the first half of the incubation period, it is only necessary to multiply the amount by six or eight times. In this it has a great advantage over the antitoxin of diphtheria or tetanus, the former of which has to be multiplied 20 to 100 times, and the latter 1000 to 2000 times in the later stages of incubation. Further, it is possible by drying to secure the serum in a permanent form which will remain active for a length of time if secluded from air and light.

This has the decided advantages over the Pasteur treatment, (1) that it employs the antitoxin already formed instead of waiting for its formation in the body of the subject injected with the attenuated virus, and (2) that it does not introduce into the system a virulent germ capable of propagating in a favorable medium, but only an agent which is antidotal to that germ.

It has the disadvantage as compared with Pasteur’s method that its action is purely therapeutic in the sense of acting as an antidote, while it produces no permanent immunity. It does not like the toxins educate the cells to produce an encrease of antitoxin, and it can only protect so long as it remains in the system. Whenever it is eliminated or destroyed, the susceptibility to rabies returns. Hence it is important to continue its administration as long as the microbe remains in the system. As in tetanus and diphtheria antitoxin treatment, it is also important to destroy the microbe and its toxins in the infection wound.

The animal which is to furnish the antitoxin is immunized as in the Pasteur method by a succession of graduated doses of rabic virus. After a treatment of 20 days the rabbit or sheep furnishes a serum which is protective when injected in the proportion of 1 of serum to 25,000 of body weight, even though its use be delayed until 24 hours after the introduction of the virus. The sheep can be immunized in 12 days by doses of 0.25 gramme of emulsion of the infected cord to every kilogramme of body weight. To maintain the serum at its highest standard the treatment must be repeated at intervals of 2 to 5 months, as the animal may be able to bear it without loss of condition.

_Treatment with Sterilized Brain Matter from a Rabid Animal._ In 1886 I sterilized with heat an emulsion of the spinal cord of a man who died of hydrophobia and injected two rabbits with 3 one drachm doses each, and a third with 4 one drachm doses on as many successive days. These rabbits were afterwards inoculated with virulent spinal cord and remained well for nine months, while three control rabbits injected with virulent cord, but which had received no previous treatment died rabid.

Puscarin and Vesesco have shown that the virus is rapidly weakened by heat up to 60° C. at which point the virulence is destroyed. It becomes easy therefore to secure in this way a toxin uncomplicated by any living microbe.

Theoretically the sterilization and use of infecting nervous substance, should share with the Pasteur method the advantage of the selective action of the medullary matter in uniting with the toxins and robbing them to a greater or less extent of their toxicity. It has the additional recommendation that it introduces no living germ, and thus obviates any possible danger of the propagation of disease through the animal operated on.

Fernandez claims an immunity from rabies for dogs that have survived the bite of a viper. Many facts and experiments are adduced in support of this.

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.