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:
| Day of Treatment. | Number of Days that cord had been desiccated. | Dose Injected. | |
|---|---|---|---|
| 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.