There Is No Agreement Among Clinician as to the Amount of Antitoxin That Should Be Administered
Unnecessarily. In a severe case of diphtheria, the prognosis depends largely upon how early in the course of the disease an adequate amount of anti-toxin can be administered. There is no agreement among clinician as to the amount of antitoxin that should be administered. A conservative scheme calls for 10,000 to 20,000 units for mild cases and 50,000 to 100,000 units for severe cases. These figures are for aver-age adults, but in actual practice, age and weight are not often taken into account except among the very young. The total dose required should be administered at one time if possible.
The route of administration may be intramuscular or intravenous. The latter route has the advantage of speedier absorption but in theory, gives a greater risk of an overwhelming anaphylactic reaction. In general, the intramuscular route is preferred for doses up to 20,000 units, and the intravenous route for amounts above this. The subcutaneous route should not be used, because absorption is relatively slow. As diphtheria antitoxin is a foreign protein (horse serum), precautions should be observed against the occurrence of hypersensitivity reactions, i.e., anaphylaxis. These are,
(1) inquiry of the patient or his family concerning a history of sensitivity to horses (or equine products such as dander, etc.) or of previous exposure to horse serum, and,
(2) performance of ophthalmic Clinician and intradermal sensitivity tests. In both tests, a 1:10 dilution of antitoxin in saline is used.
In the first method, one drop of this dilution is dropped into the conjunctival sac, and the eye is observed for the development of redness during the next 30 minutes. In the second method, 0.1 ml. of the 1:10 dilution is injected intracutaneously in the fore-arm, and the area is observed for the development of erythema, wheals, and similar reactions for the next half hour. If a positive reaction is obtained by either method, it is prima facie evidence of sensitivity to the horse serum, and hence anti-toxin should be administered with great caution. Desensitization is carried out by giving small doses of highly diluted antitoxin subcutaneously at first and then gradually working up to intramuscular and intravenous administration until the full dose has been given.
Desensitization may be a tedious and nerve-racking task, but as anti-toxin is the only specific therapeutic Clinician weapon available, it is a process that must be carried out in cases in which sensitivity exists. Epinephrine must be at hand before antitoxin is administered by any route. Since it has been shown that the administration of certain antimicrobial drugs (notably penicillin, tetracycline, and erythromycin) helps to eliminate the causative organisms from the nasopharynx and the cutaneous lesions, there has been an understandable tendency toward the routine use of one or more of these drugs in the treatment of all cases of diphtheria. Although diphtheria bacilli are susceptible to the action of these drugs in vitro, the drugs have no neutralizing effect. upon the toxin; thus. they cannot be substituted for antitoxin.
They find their greatest usefulness in the prevention of secondary infections and the treatment of chronic carriers. The real danger in the routine use of these antimicrobial drugs lies in their masking effect; the elimination or reduction of the infecting organisms may render a laboratory diagnosis impossible and hence may prevent the physician from administering the life-saving antitoxin. General Management. Complete bed rest is the first requirement. The period over which this should be maintained depends upon the degree of toxicity and the presence or absence of cardiac complications. In any event, the return to activity should be gradual and guided by the careful observations of the physician.
Local therapy Clinician of the throat is rarely needed in the absence of secondary infection, although hot saline irrigations may be comforting. Dehydration should be treated with parenteral fluids containing dextrose. The careful watch must be kept for signs of developing cardiac or neurologic complications. With these complications, adequate rest is also the main feature of therapy. Digitalis appears to be without benefit in the treatment of cardiac complications.
The patient should be kept isolated until two successive daily pharyngeal and nasal cultures are negative for the presence of virulent diphtheria bacilli. Prevention. Active. immunization represents the basic and practical means at hand with which to control the occurrence of clinical diphtheria. Of the various preparations available, fluid toxoid and adsorbed (aluminum phosphate, aluminum potassium sulfate, etc.) toxoid are the most widely used in the United States. Both preparations consist of a filtrate of a broth culture of diphtheria bacilli, i.e., diphtheria toxin, which has been treated with 0.3 to 0.5 percent formalin at a temperature of 37° C. until toxicity has dis-appeared.
The resulting fluid toxoid Clinician is given in a primary course, consisting of three injections (0.5 ml., 1.0 ml., 1.0 ml.) at weekly intervals. If suitable amounts of alum are added to the fluid toxoid, a precipitate forms. This alum-precipitated toxoid may be resuspended, giving a relatively purified immunizing preparation with a slightly superior antigenic potency because of a local stimulating effect of the alum on the tissues. A primary course consists of two 1 ml. injections spaced a month apart. Against the obvious advantage of the alum-precipitated toxoid must be weighed the fact that the greater sensitizing ability of this preparation may lead to unpleasant reactions upon subsequent reinjection.
Also, a sterile abscess occasionally develops at the inoculation site as a result of the irritating action of the alum. Both fluid Clinician and aluminum-adsorbed toxoid are excellent immunizing agents; at least 85 percent of persons receiving a primary course may be expected to become Schick-negative. The primary course of active immunization should be administered within the first year of life, preferably at about the third month. It may be combined with immunizations against tetanus, pertussis, and poliomyelitis. One stimulating dose