Pasteur's treatment of rabies by inoculation of emulsions of dried spinal cord is, therefore, a "vaccination" of attenuated virus, resulting in antitoxin formation, to the further protection of the individual against rabies.
One further example of the modern application of the principles of active acquired immunity may be shortly mentioned. We refer to the cholera and plague vaccinations. The vaccination in small-pox is an inoculation of the virus of the disease; the rabies inoculation is a transmission of the vital products of the disease attenuated; the plague and cholera vaccinations are inoculations of pure cultures of living virus from outside the body. Inoculating cholera virus against cholera has been made illegal, as variolation was in 1840. But Haffkine has prepared two vaccines. The weak one is made from pure cultures of Koch's spirillum of Asiatic cholera, attenuated by growth to several generations on agar or broth at 39°C. The strong one is from similar culture the virulence of which has been increased. One cubic centimetre of the first vaccine is injected hypodermically into the flank, and the second vaccine three or four days afterwards. The immunisation is prophylactic, not remedial, and its action takes effect five or six days after the second vaccine has been injected.
INOCULATION TREATMENT FOR PERSONS AFFECTED WITH RABIES
| 1. For those Bitten through Clothes | 2. For those Bitten on Uncovered Skin of Hands, Etc. | 3. For those Bitten on Face or Head. | ||||
| Days of Treatment. | Doses of Emulsion per cc. | Dates of Cord Drying. | Doses of Emulsion per cc. | Dates of Cord Drying. | Doses of Emulsion per cc. | Dates of Cord Drying. |
| 1 at 11 A.M. | 3 | 14 | 3 | 14 | 3 | 14 |
| 1 at"11ii"A | 3 | 13 | 3 | 13 | 3 | 13 |
| 1 at 3 P.M. | .. | .. | .. | .. | 3 | 12 |
| 1 at"11ii"A | .. | .. | .. | .. | 3 | 11 |
| 2 at 11 A.M. | 3 | 12 | 3 | 12 | 3 | 10 |
| 2 at"11ii"A | 3 | 11 | 3 | 11 | 3 | 9 |
| 2 " 3 P.M. | .. | .. | .. | .. | 3 | 8 |
| 2 at"11ii"A | .. | .. | .. | .. | 3 | 7 |
| 3 at 11 A.M. | 3 | 10 | 3 | 10 | 3 | 6 |
| 3 at"11ii"A | 3 | 9 | 3 | 9 | 3 | 6 |
| 4 at 11 A.M. | 3 | 8 | 3 | 8 | 3 | 5 |
| 4 at"11ii"A | 3 | 7 | 3 | 7 | .. | .. |
| 5 at"11ii"A | 3 | 6 | 3 | 6 | 3 | 5 |
| 5 at"11ii"A | 3 | 6 | 3 | 6 | .. | .. |
| 6 at"11ii"A | 3 | 5 | 3 | 5 | 3 | 4 |
| 7 at"11ii"A | 3 | 5 | 3 | 5 | 2 | 3 |
| 8 at"11ii"A | 3 | 4 | 3 | 4 | 3 | 4 |
| 9 at"11ii"A | 2 | 3 | 2 | 3 | 3 | 3 |
| 10 at"11ii"A | 3 | 5 | 3 | 5 | 3 | 5 |
| 11 at"11ii"A | 3 | 5 | 3 | 5 | 3 | 5 |
| 12 at"11ii"A | 3 | 4 | 3 | 4 | 3 | 4 |
| 13 at"11ii"A | 3 | 4 | 3 | 4 | 3 | 4 |
| 14 at"11ii"A | 3 | 3 | 3 | 3 | 3 | 3 |
| 15 at"11ii"A | 3 | 3 | 3 | 3 | 3 | 3 |
| 16 at"11ii"A | ... | .. | 3 | 5 | 3 | 5 |
| 17 at"11ii"A | ... | .. | 3 | 4 | 3 | 4 |
| 18 at"11ii"A | ... | .. | 3 | 3 | 3 | 3 |
| 19 at"11ii"A | .. | .. | .. | .. | 3 | 5 |
| 20 at"11ii"A | .. | .. | .. | .. | 3 | 4 |
| 21 at"11ii"A | .. | .. | .. | .. | 3 | 3 |
In plague the same plan has been followed. Luxurious crops of Kitasato's plague bacillus are grown on ordinary nutritive media plus large quantities of fat. The fat of milk, as clarified butter, is that generally used. Under the globules of fat flakes of culture grow like stalactites, hanging down into the clear broth. These are in time shaken to the bottom, and a second crop grows on the under-surface of the fat. In the course of a month perhaps half a dozen such crops are obtained and shaken down into the fluid, until the latter assumes an opaque milky appearance. This is now, unlike the cholera vaccine, exposed to a temperature of 70° C., by which the microbes are killed. The culture contains all the toxins, and the dose is 3 cc. This preparation has the advantage of being easily prepared, obtainable in large quantities, and requires no animals in its preparation. When inoculated it produces local pain and swelling at the site of inoculation, and general reactive symptoms such as fever. From a careful analysis of the results of this inoculation, it is shown that the efficacy of the prophylactic depends upon the virulence of the bacillus culture from which the vaccine is prepared, and upon its dose and ability to produce a well-marked febrile reaction. It appears to be more effective in the prevention of deaths than of attacks.
The anti-typhoid vaccination is another example of inoculation to secure active immunity. It is needless, perhaps, to point out that all these vaccinations, except rabies, are prophylactic, and not curative.
Passive Immunity; Preparation of Antitoxins. We must now consider the question of passive immunity. This, it will be remembered, may be defined as a protection (against a bacterial disease) produced by inoculation, not of the disease itself, as in small-pox inoculation, nor yet of its weakened toxins, as in rabies, but of the antitoxins produced in the body of an animal suffering from that particular disease. Examples of this treatment are increasing every year, and the term "antitoxin" has now become almost a household word. The chief examples are to be found in diphtheria, tetanus, streptococcus, and pneumococcus.
To be of value, antitoxins must be used as early as possible, before tissue change has occurred and before the toxins have, so to speak, got the upper hand. When the toxins are in the ascendency the patient suffers more and more acutely, and may succumb before there has been time for the formation in his own body of the antitoxins. If he can be tided over the "crisis," theoretically all will be well, because then his own antitoxin will eventually gain the upper hand. But in the meantime, before that condition of affairs, the only way is to inject antitoxins prepared in some animal's tissues whose disease began at an earlier date, and thus add antitoxins to the blood of our patient, early in the disease, and the earlier the better, for, however soon this is done, it is obvious that the toxins begin their work earlier still. It should not be necessary to add that general treatment must also be continued, and indeed local germicidal treatment, e. g., of the throat in diphtheria and the poisoned wound in tetanus. Further, in a mixed infection, as in glandular abscesses with diphtheria, it must be borne in mind that the antitoxin is specific and may therefore probably fail in such mixed cases.