HYDROPHOBIA (LYSSA; RABIES).

The exciting agent of hydrophobia is not yet known. Nevertheless, the specific treatment of this disease has been successful, owing to the genius of Pasteur.

The susceptibility for hydrophobia exists among all warm-blooded animals. Human beings are infected through the bites, in the first place, of rabid dogs, then of cats, wolves, foxes, jackals, and other animals, and, in rare cases, of human beings suffering from hydrophobia. The saliva must thus contain the virus of the disease, and as a matter of fact this had already been demonstrated experimentally at the beginning of the last century by inoculation of dogs from human beings. The parotid is the gland most concerned, while the remaining salivary glands, though virulent, are not so constantly so as the parotid. The saliva of dogs contains the virus of rabies as early as two days before the appearance of the first symptoms of the disease. The lacrimal glands, the adrenal glands, the pancreas, and the mammary glands of rabid animals are further infectious; the milk, at times is so; the blood, never. Besides, the central nervous system is virulent—the brain and the spinal cord and, in a conspicuous and constant manner, the medulla oblongata.

Experiments on Animals.-The saliva is not used for inoculation-experiments because, in addition to the virus of rabies, it always contains a number of pyogenic microorganisms that act as a disturbing factor. The medulla oblongata of animals or individuals that have died of rabies is used exclusively for inoculation-purposes. A watery emulsion is made from a small portion of the medulla oblongata, and a few drops thereof are injected beneath the dura mater or into the anterior chamber of the eye in dogs, rabbits, etc. After a period of incubation of from twelve to fifteen days the animals develop, with almost absolute certainty, the symptoms of rabies. Subcutaneous injection is not quite so trustworthy. In order to obtain positive results the injection must be made deeply, and preferably into the exposed and divided. muscle-bundle. Direct injection of the virus into a peripheral nerve is likewise attended with success. Healthy mucous membranes (as of the nose and the conjunctiva) also absorb the virus. The possibility of intrauterine

transmission of rabies has been established experimentally in a small number of instances.

If

Infection takes place by way of the nervous system. the spinal cord of a dog is divided transversely, and the virus of rabies is injected into a nerve of the hind-paw, only the cord below the point of division proves virulent after the death of the animal. The reverse conditions prevail after inoculation of a fore-paw. Having reached the central nervous system from the periphery (site of inoculation or of bite) through the intermediation of the nerves, the virus descends into the peripheral nerves of the opposite side. For this reason, if the disease has developed slowly, the nerves of the uninjured side are also found poisonous in experiments on animals.

The as yet unknown excitant of rabies appears to exert its influence through its metabolic products. At least, according to Italian observers, the filtrate through porcelain of an emulsion of the spinal cord from animals suffering from rabies induces paralytic manifestations in dogs. Rabies may, therefore, as suggested by Romberg, be designated a toxoneurosis.

The dissemination of the virus of rabies in the course of the nerve-paths explains why in human pathology the prognosis of the disease varies so widely in accordance with the number, the seat, and the depth of the bite-wounds. Everything depends upon whether the virus gains entrance into a nerve or not. Deep wounds are, therefore, much more dangerous than superficial ones; injuries in regions with an abundant nerve-supply (as, for instance, the finger-pulp) more so than in other parts of the body. The greatest danger is involved in wounds of the head and the face. From these the virus of rabies quickly reaches the medulla oblongata, the main seat of the disease. The morbidity and the mortality of rabies (the developed disease is incurable) are, according to the most reliable statistics, about 16 per cent. of those bitten.

Incubation. The duration of the period of incubation depends upon the same factors that have been mentioned as significant in prognosis. The period is the shorter the nearer to the head the portal of infection is situated. The usual duration of the incubation-period is from twenty to sixty days. The trustworthy minimum observed has been fourteen days; the maximum, eighteen months.

Resistance of the Virus of Rabies (Medulla Oblongata of Dogs Dead of Rabies).-The virus is destroyed by exposure for an hour to a temperature of 50° C. (122° F.); further, to 5 per cent. carbolic acid for fifty minutes; to mercuric chlorid, 1 : 1000; to acetic acid; to potassium permanganate. The spinal cord of (Paris) rabbits dead of rabies, kept in dry air and protected from putrefaction, loses its toxicity only after fourteen or fifteen days. The smaller the animal, the thinner the spinal cord, the more rapidly does the loss in virulence take place.

Immunization and Vaccination.-Pasteur showed that the virus of canine rabies slowly diminishes in intensity when inoculated from dogs upon monkeys in a progressive series. This gradual loss of virulence is distinctly appreciable in the increase in the period of incubation. If the infecting material is reconveyed from monkeys to rabbits, an increase in virulence takes place, which constantly augments on further inoculation into rabbits. The period of incubation becomes shorter; and, finally, after the hundredth passage through the body of the rabbit, the period is not longer than seven days. It was impossible to produce a more active virus. The virus retained its virulence now unchanged, and Pasteur, therefore, designated it virus fixe. Pasteur in this way prepared a series of rabies-viruses that, beginning with the spinal cord of monkeys and progressing to the spinal cord of rabbits that succumbed to the virus fixe, possessed a steadily increasing virulence. On inoculating successively dogs subcutaneously with these spinal cords, of from the lowest to the highest degree of virulence, the animals treated failed to develop rabies, but became immune even to subdural infection with the virus fixe and to the bites of other dogs suffering from ordinary rabies.

A year later, in 1885, Pasteur and his collaborators, Chamberland and Roux, developed a still more practical method of immunization. Proceeding from the fact already mentioned that the medulla of animals suffering from rabies is completely deprived of its virulence in from fourteen to fifteen days by desiccation, they dried the spinal cords of rabbits that had succumbed to the virus fixe for from one to fourteen days with all aseptic precautions in high sterilized glass cylinders. The spinal cord fourteen days old had lost all its virulence; that thirteen days old and that

twelve days old, in part; and the others, successively less and less. Through successive inoculations with these gradations of spinal cords Pasteur established complete immunity in dogs. Upon the basis of these facts Pasteur proceeded to the vaccination of human beings therapeutically against rabies. In view of the long period of incubation of rabies in human beings the attempt was justified and hopeful; for, if it were possible to establish immunity through vaccination immediately after the bite of the rabid animal and before the period of incubation had elapsed, then it could be hoped that the disease would not break out. The results have completely confirmed Pasteur's anticipations. At first, the injections were so made that on the first day the spinal cord of rabbits kept for fourteen days, on the second day that of rabbits kept for thirteen days, and so on for ten days until the cord of rabbits kept for five days was reached, were successively injected subcutaneously into the subject to be treated (methode simple). Pasteur, however, soon recognized that this procedure was not sufficient for the severe cases with deep and numerous wounds.

Vaccination is at present practised in the Pasteur Institute in the following manner (methode intensive): A piece of spinal cord about three millimeters long is rubbed up in sterile bouillon and injected beneath the skin in the hypochondrium, and on the first day in the morning medulla fourteen and ten days old-an injection being made on either side-in the evening medulla twelve and eleven days old; on the second day in the morning medulla ten and nine days old, in the evening medulla eight and seven days old; on the third day two injections of medulla six days old, and from now on an injection every twenty-four hours of the more toxic spinal cords up to that three days old. With the spinal cord three days old a new series is begun, commencing with the medulla five days old. Upon this succeeds a third, and possibly a fourth, series of like character.

Vaccine may be prepared also by dilution with sterile water (Bardach) instead of by desiccation. This fact indicates that also in the dried spinal cord the virus is not actually attenuated, but only diminished in amount. As a matter of fact, Pasteur, after injecting desiccated medulla into a guinea-pig and the animal dying after thirty days, observed the medulla of this animal destroy a second guinea-pig

in exactly seven days; the virus thus remained a virus fixe.

The immunity to rabies appears to persist for a long time -in dogs for two years.

Results of Pasteur's Procedure.-The great utility of the method of vaccination against rabies is no longer seriously doubted by any one. From 1886 to January 1, 1894, 14,430 persons in all were treated in the Pasteur Institute, of whom 72 died. In the year 1891, 394 persons were treated, the diagnosis of rabies in the biting animals being established with all possible certainty; and not a single patient developed the disease. In 1892, 128 persons

were treated, with 1 death. In 1893, 132 bitten persons were treated, of whom none died. In the year 1894, 1387 persons were vaccinated, of whom 7 died, and in the year 1895, 1520 were vaccinated, with 2 deaths.* These statistics require no comment: they speak for themselves.

SMALLPOX (VARIOLA).

Smallpox, like syphilis and rabies, is one of the diseases whose exciting agents are yet unknown.

The virus of smallpox resides in the contents of the variolous pustules, in the desiccating scales of the skin, in the sputum, and in the nasal secretion of those suffering from the disease. It is transported with the linen and the clothing of the sick. Also the air in the neighborhood of the sick must, from clinical experience, be considered a source of infection. Under suitable conditions the contagium may retain its vitality for an exceedingly long time, apparently for years.

The portal of infection for the contagium of smallpox has not yet been definitely determined. According to the common opinion, the disease is generally acquired through direct or indirect contact with the sick, and the skin would thus seem to constitute the portal of infection. In other cases the disease may be attributed to simple inhalation in the neighborhood of smallpox-hospitals, etc. Finally, articles of food (such as milk) and insects are thought to convey the infection, which, under these conditions, would

The figures for 1896 were 1388, with 4 deaths; for 1897, 1521 cases, with 6 deaths.-A. A. E.