Because the serum exerts no regenerative nor bactericidal action, two facts stand out, which are advanced by the opponents of serum therapy as proof of its uselessness: (1) it sometimes happens that the pseudomembrane spreads for twenty-four hours after the injection, even involving intact mucous membrane. In spite of the antitoxin there may also develop albuminuria, heart-weakness and postdipht her itic paralysis; these are symptoms which the judicious could not impute to the antitoxin, but which are to be credited to the general intoxica tion existing before the injection. (2) No action is observed on the diph theria bacilli which remain much more active and virulent and are often found for months after the injection on the mucous membrane in which restitution has occurred (in one case after eighty-two days, Trumpp). It is easy to understand this, for the serum, derived by the use of the toxin, is able to call forth only a (transitory) artificial toxin immunity and not, in the strict sense, an infection-immunity.
Following the conditions under which the healing action of the anti toxin is possihl2, an almost certain success may be expected in mildly toxic cases, the most marked success being seen in progressive diph theria with moderate toxemia. While it was customary in preantitoxin days to see in such cases a rapid advance of the fibrinous exudate to the bronchial tree, now the local process halts at the bifurcation of the trachea. In progressive diphtheria with great intoxication, many eases still succumb to bronchopneumonia. and rapidly advancing heart failure, in spite of the antitoxin treatment. The success of the antitoxin in malignant diphtheria is much less; as in the other forms it depends on the time of injection; frequently its action is only to prolong the dura tion of the disease.
The value of the antitoxin treatment stands out clear and sharp in statistics. Even if we except the fact that the mortality of diphtheria has fallen in the last decade to one-third, which may rightly be in part* attributed to a mildness in the type of the disease, there nevertheless remain the significant results of the antitoxin treatment in progressive and malignant cases. While two-thirds of the croup cases died in pre antitoxin days, now two-thirds recover. Of the malignant cases formerly SO per cent. to 90 per cent. died, now about 40 per cent. to 50 per cent. (see Fig. SO, p. 357).
In such a state of affairs it is the duty of the physician to use the antitoxin in treating diphtheria. It is furthermore his duty to give the injection at the earliest moment, because of the fact that recovery is so much surer the earlier the antitoxin is given (see Fig. 95); further, because of the fact that in every case of diphtheria there may suddenly occur a life-threatening extension to the respiratory tract or an equally sudden development of grave general toxannia; finally, because of the fact that experience has shown that mixed infections are usually sec ondary to the diphtheria-infection.
These reasons will therefore impel the thoughtful physician not to wait in doubtful eases for the result of the bacteriologic examination, especially if the patient is very young or reduced by another disease, such as measles or tuberculosis.
In older children, with membrane of slight extent and absence of general poisoning, the injection of antitoxin may be deferred if there are other reasons for doing so, but only in such cases as may be inspected several times a clay.
Much smaller doses are needed for prophylactic injections, because it is much easier to protect the organism against the diphtheria toxins than to combat an already-existing intoxication. 200 units are suffi cient (see page 40S). [In this country the average dose for prophylactic injections is at least 500 units. Doses of 1000 units are frequently used for this purpose and cases are at times reported where the disease develops in a mild form three days to two weeks after the injection of 1500 units. The U. S. Pharmacopoeia gives 500 units as the average close for prophylactic purposes.] Because the passive immunity furnished by the injection lasts scarcely three weeks, the injection should be repeated if circumstances demand it. The value of this regulation of safety has been settled beyond peradventure by many thousands of eases.
Serum Disease.—The opponents of serum therapy assert not only that the antitoxin is useless but that it is to be blamed for the more fre quent occurrence of albuminuria, paralysis and diphtheritic marasmus. This charge is just only in so far as such severe toxic cases are kept alive by the antitoxin long enough to develop the sequels of general tomemia, while those patients would have died in the early clays of the disease if the antitoxin had not been given. It cannot, however, be denied that the serum may still produce certain symptoms of disease, which cannot be ascribed to its content, in antitoxin, nor to the small amount of preserving substance (0.5 per cent. phenol, chloroform, etc.) but to the horse-serum, as such. In the human system this acts like a kind of foreign substance. in a toxic way. On this account it is desira ble to use a serum of the highest possible strength, in order to make the volume of the injection as small as possible. This disease is caused by simple horse-serum as well as that containing antitoxin. Its manifesta tions appear after a symptomless incubation-period of from seven to fourteen days and last for a few days, if only small doses have been used, as is usual. They consist of urticaria followed by an eruption which may resemble measles, rbtheln or scarlet fever, in the course of which fever develops, with swelling olthe regional lymph-nodes; (edema corresponding in location to that of nephritis; at times, albuminuria; occasionally violent joint pains of brief duration with no objective symptoms in the joints; leukopenia. This disease, which has been studied by von Pirquet and Schick very carefully, depends on an individual pre disposition and the volume of the serum injected. If, after an interval of from sixteen to forty-two days—or during the time when the specific products of the reaction set. up by the first injection are still in the body —a second injection is given, the reaction appears immediately and is shown by an intense oedema around the site of injection, with fever and a general exanthem rarely present. If the reinjection is given after all the reactive products have been eliminated, the system then shows only a certain susceptibility to the horse-serum, the reaction is hastened, occurring after an incubation period of five to seven days (without symptoms), and is over in a few hours.