filter, the filtrate in such cases being capable of acting as a
rabic virus. In the more chronic cases and in the later stages of
the disease the Negri bodies may attain a considerable size and
may be easily seen under the microscope. They are from 0·5μ
to 20μ in diameter—the longer the course of the disease the larger
the bodies, these larger forms seldom if ever being met with in
specially susceptible animals, which soon succumb to the disease.
The Negri bodies may be constricted in the middle, or, if somewhat
elongated, there may be two or three constrictions which
give it the appearance of a string of sausages. They may be met
with in almost all the nerve cells of the central nervous system
in well-developed cases of hydrophobia, but they are most numerous
and are found most readily in the cells of the cornu ammonis,
and then in the Purkinje cells of the cerebellum.
Although there are several methods of preparing these organisms for microscopical examination, the following is perhaps the simplest. A fragment of the grey substance, say from the cornu ammonis, is taken from a section made at right angles to the surface and placed on a slide about one inch from the end. A coverslip is now “pressed upon it until it is spread out in a moderately thin layer; then the coverslip is moved slowly and evenly over the slide,” leaving the first three-quarters of an inch of the slide clear. In making the smear only slight pressure is used, the pressure beginning on the edge of the coverslip away from the end of the slide towards which the coverslip is travelling, thus driving more of the nerve tissues along the smear “and producing more well-spread nerve cells.” The smears are then air-dried, placed in methyl-alcohol for one minute, and then in a freshly-prepared mixture of 10 c.c. of distilled water, three drops of a saturated alcoholic solution of rose anilin violet, and six drops of Loeffler's alkaline methylene blue, which is warmed until steam rises; the stain is then poured from the specimen, which after being rinsed in water is allowed to dry and is then mounted in Canada balsam.}}
The nature of the disease produced by the inoculation of saliva from a rabid animal appears to depend upon (1) the quantity of the rabic virus introduced; (2) the point of its introduction; (3) the activity of the virus. Thus by diluting the poison with distilled water or saline solution and injecting small quantities, the period of incubation may be prolonged. Slight wounds of the skin, of the limbs and of the back are followed by a long incubation period; but when the inoculation takes place in the tips of the fingers or in the skin of the face, where nerves are numerous, and especially where the wound is lacerated or deep, the incubation period is much shorter and the attack usually more severe. This, as in tetanus, is accounted for by the fact that the lymphatics of the nerves are much more directly continuous with the central nervous system than are any other set of lymphatics. The poison appears to act directly upon the cells of the central nervous system.
Arising out of recent researches on hydrophobia, two methods of treatment—one of which, at any rate, has been attended by conspicuous success—have been put into practice. The first of these, Pasteur's, is based upon the fact that rabic virus may be intensified or attenuated at will. Pasteur found that although the virus taken from the cerebrospinal fluid of the dog always produces death in the same period when inoculated into the same animal, virus taken from other animals has not the same activity. If passed through a succession of monkeys it may become so attenuated that it is no longer lethal. If either the “monkey virus,” which is not fatal to the rabbit, or the “dog virus,” which kills in twelve to fourteen days, be passed through a series of rabbits, the virulence may be so exalted that it may kill in about six days: its activity cannot be increased beyond this point by any means at present at our disposal. This intensified virus was therefore named virus fixe by Pasteur, and it forms a standard from which to work. He found, too, that under certain conditions of temperature the virus may be readily attenuated, one hour at 50° or half an hour at 60° C. completely destroying it. A 5% solution of carbolic acid acting for half an hour, or a 1 per 1000 solution of bichloride of mercury or acetic acid or permanganate of potash, brings about the same result, as do also exposure to air and sunlight. The poison contained in the spinal cord of the rabbit exposed to dry air and not allowed to undergo putrefactive changes gradually loses its activity, and at the end of fourteen to fifteen days is incapable of setting up rabic symptoms. A series of cords from rabbits inoculated with the virus fixe are cut into short segments, which, held in series by the dura mater, are suspended in sterile glass flasks plugged with cotton-wool and containing a quantity of potassium hydrate—a powerful absorbent of water. At the end of twenty-four hours the activity of the virus is found to have fallen but slightly; at the end of forty-eight hours there is a still further falling off, until on the fourteenth or fifteenth day the virus is no longer lethal. With material so prepared Pasteur treated patients who had been bitten by mad dogs. On the first day of treatment small quantities of an emulsion of the cord exposed for thirteen or fourteen days in saline solution are injected subcutaneously, and the treatment is continued for from fifteen to twenty-one days, according to the severity of the bite, a stronger emulsion—i.e. an emulsion made of a cord that has been desiccated for a shorter period—being used for each succeeding injection, until at last the patient is injected with an emulsion which has been exposed to the air for only three days. In the human subject the period of incubation of the disease is comparatively prolonged, owing to the insusceptibility of the tissues to the action of this poison; there is therefore some chance of obtaining a complete protection or acclimatization of the tissues before the incubation period is completed. The virus introduced at the bite has then no more chance of affecting the nerve centres than has the strong virus injected in the late stages of the protective inoculation: the nerve centres, having become gradually acclimatized to the poisons of the rabic virus, are able to carry on their proper functions in its presence, until in time, as in the case of microbial poisons, the virus is gradually neutralized and eliminated from the body. Various modifications and improvements of this method have from time to time been devised, but all are based on, and are merely extensions of, Pasteur's original work and method. As soon as it was found that antitoxins were formed in the tissues in the case of an attack of tetanus, attention was drawn to the necessity of determining whether something similar might not be done in the production of an antirabic serum for the treatment of rabies. Babes and Lepp, and then Tizzoni and his colleagues Schwarz and Centanni, starting from virus fixe, obtained a series of weaker inoculating materials by submitting it for different periods to the action of gastric juice. Beginning with a weak virus so prepared, and from time to time injecting successively stronger emulsions (seventeen injections in twenty days) into a sheep, they succeeded in obtaining a serum of such antirabic power that if injected in the proportion of 1 to 25,000 of body-weight, an animal is protected against a lethal dose of virus fixe. The activity of this serum is still further reinforced if a fresh series of injections is made at intervals varying from two to five months, according to the condition of the animal, each series occupying twelve days. This antirabic substance stored in the blood has not only the power of anticipating (neutralizing?) the action of the poison, but also of acting as a direct curative agent; as a prophylactic agent, readily kept in stock and easily and rapidly exhibited, it possesses very great advantages over the inoculation method. It must be borne in mind that the longer the period after the infection the greater must be the amount of serum used to obtain a successful result.
As regards the necessity for any treatment it may be pointed out that although the saliva of a rabid dog may be infective three days before the manifestation of any symptoms of the disease death takes place almost invariably within six days of the first symptom. If therefore the animal remains alive for ten days after the patient is bitten, there is no necessity for the antirabic treatment to be applied and the patient need fear no evil results from the bite.
There can be little doubt that hydrophobia is a specific disease due to a multiplication of some virus in the nervous system, in the elements of which it is ultimately fixed; that it passes from the wound to the central nervous system by the lymphatics; and that, as in tetanus, the muscular spasms are the result of the action of some special poison on the central nervous system.
Scarlet Fever.—In scarlet fever recent observations have been comparatively few and unimportant. Crooke, and later Klein,
