its former strength. Again, if it be passed through a succession
of dogs it becomes intensified up to a maximum of strength
which is called the virus fixe. Pasteur further discovered that
the strength can be modified by temperature and by keeping
the dried tissues of a rabid animal containing the virus. Thus,
if the spinal cord of a rabid dog be preserved in a dry state, the
virus loses strength day by day. The system of treatment
consists in making an emulsion of the cord and graduating the
strength of the dose by using a succession of cords, which have
been kept for a progressively diminishing length of time. Those
which have been kept for fourteen days are used as a starting-point,
yielding virus of a minimum strength. They are followed
by preparations of diminishing age and increasing strength,
day by day, up to the maximum, which is three days old. These
are successively injected into the circulatory system. The
principle is the artificial acquisition by the patient of resistance
to the rabic virus, which is presumed to be already in the system
but has not yet become active, by accustoming him gradually
to its toxic effect, beginning with a weak form and progressively
increasing the dose. It is not exactly treatment of the disease,
because it is useless or nearly so when the disease has commenced,
nor is it exactly preventive, for the patient has already been
bitten. It must be regarded as a kind of anticipatory cure.
The cords are cut into sections and preserved dry in sterilized
flasks plugged with cotton-wool. Another method of preparing
the inoculatory virus, which has been devised by Guido Tizzoni
and Eugenio Centanni, consists in subjecting the virus fixe to
peptic digestion by diluted gastric juice for varying periods of
time.
The first patient was treated by Pasteur’s system in July 1885. He was successively inoculated with emulsions made from cords that had been kept fourteen and ten days, then eleven and eight days, then eight, seven, six days, and so on. Two forms of treatment are now used—(1) the “simple,” in which the course from weak to strong virus is extended over nine days; (2) the “intensive,” in which the maximum is reached in seven days. The latter is used in cases of very bad bites and those of some standing, in which it is desirable to lose no time. Two days are compressed into one at the commencement by making injections morning and evening instead of once a day, so that the fifth-day cord is reached in four days instead of six, as in the “simple” treatment. When the maximum—the third-day cord—is reached the injections are continued with fifth-, fourth-, and third-day cords. The whole course is fifteen days in the simple treatment and twenty-one in the intensive. The doses injected range from 1 to 3 cubic centimetres. Injections are made alternately into the right and left flanks. The following table shows the number treated from 1886 to 1905, with the mortality.
| Year. | Patients Treated. | Deaths. | Mortality per cent. |
| 1886 | 2671 | 25 | .94 |
| 1887 | 1770 | 14 | .79 |
| 1888 | 1622 | 9 | .55 |
| 1889 | 1830 | 7 | .38 |
| 1890 | 1540 | 5 | .32 |
| 1891 | 1559 | 4 | .25 |
| 1892 | 1790 | 4 | .22 |
| 1893 | 1648 | 6 | .36 |
| 1894 | 1387 | 7 | .50 |
| 1895 | 1520 | 5 | .33 |
| 1896 | 1308 | 4 | .30 |
| 1897 | 1521 | 6 | .39 |
| 1898 | 1465 | 3 | .20 |
| 1899 | 1614 | 4 | .25 |
| 1900 | 1419 | 10 | .70 |
| 1901 | 1318 | 5 | .37 |
| 1902 | 1105 | 2 | .18 |
| 1903 | 630 | 4 | .65 |
| 1904 | 757 | 5 | .66 |
| 1905 | 727 | 4 | .54 |
These figures do not include cases which develop hydrophobia during treatment or within fifteen days after treatment is completed, for it is held that persons who die within that period have their nervous centres invaded by virus before the cure has time to act. The true mortality should therefore be considerably higher. For instance, in 1898 three deaths came within this category, which just doubles the mortality; and in 1899 the additional deaths were six, bringing the mortality up to two-and-a-half times that indicated in the table. When, however, the additional deaths are included the results remain sufficiently striking, if two assumptions are granted—(1) that all the persons treated have been bitten by rabid animals; (2) that a large proportion of persons so bitten usually have hydrophobia. Unfortunately, both these assumptions lack proof, and therefore the evidence of the efficacy of the treatment cannot be said to satisfy a strictly scientific standard. With regard to the first point, the patients are divided into three categories—(1) those bitten by an animal the rabidity of which is proved by the development of rabies in other animals bitten by it or inoculated from its spinal cord; (2) those bitten by an animal pronounced rabid on a veterinary examination; (3) those bitten by an animal suspected of being rabid. The number of patients in each category in 1898 was (1) 141, (2) 855, (3) 469; and in 1899 it was (1) 152, (2) 1099, (3) 363. As might be expected, the vast majority came under the second and third heads, in which the evidence of rabidity is doubtful or altogether lacking. With regard to the second point, the proportion of persons bitten by rabid animals who ordinarily develop hydrophobia has only been “estimated” from very inadequate data. Otto Bollinger from a series of collected statistics states that before the introduction of the Pasteur treatment, of patients bitten by dogs undoubtedly rabid 47% died, the rate being 33% in those whose wounds had been cauterized and 83% when there had been no local treatment. If the number of rabid dogs be compared with the deaths from hydrophobia in any year or series of years, it can hardly be very high. For instance, in 1895, 668 dogs, besides other animals, were killed and certified to be rabid in England, and the deaths from hydrophobia were twenty. Of course this proves nothing, as the number of persons bitten is not known, but the difference between the amount of rabies and of hydrophobia is suggestively great in view of the marked propensity of rabid dogs to bite, nor is it accounted for by the fact that some of the persons bitten were treated at the Institut Pasteur. A comparison of the annual mortality from hydrophobia in France before and after the introduction of the treatment would afford decisive evidence as to its efficacy; but unfortunately no such comparison can be made for lack of vital statistics in that country. The experience of the Paris hospitals, however, points to a decided diminution of mortality. On the whole it must be said, in the absence of further data, that the Pasteur treatment certainly diminishes the danger of hydrophobia from the bites of rabid animals.
More recently treatment with an anti-rabic serum has been suggested (see Parasitic Diseases). Victor Babes and Lepp and later Guido Tizzoni and Eugenio Centanni have worked out a method of serum treatment curative and protective. In this method not the rabic poison itself, as in the Pasteur treatment, but the protective substance formed is injected into the tissues. The serum of a vaccinated animal is capable of neutralizing the power of the virus of rabies not only when mixed with the virus before injection but even when injected simultaneously or within twenty-four hours after the introduction of the virus. These authors showed that the serum of a rabbit protects a rabbit better than does the serum of a dog, and vice versa. At the end of twenty days’ injections they found they could obtain such a large quantity of anti-rabic substance in the serum of an animal, that even 1 part of serum to 25,000 of the body weight would protect an animal. This process differs from that of Pasteur in so far as that in place of promoting the formation of the antidote within the body of the patient, by a process of vaccination with progressively stronger and stronger virus, this part of the process is carried on in an animal, Babes using the dog and Centanni the sheep, the blood serum of which is injected. This method of vaccination is useful as a protective to those in charge of kennels.
