432 THE DIPHTHERIA BACILLUS GROUP 
toxin), the same process is repeated, using this L+ dose of toxin mixed 
with gradually diminishing amounts of the antitoxin to be stan- 
dardized. That dilution of antitoxin of unknown potency which will 
neutralize all except sufficient toxin to kill a 250-gm. guinea-pig in 
four days contains 100 antitoxin units in the example cited. Knowing 
the dilution of the antitoxin, it is a simple problem to determine 
the number of units in 1 cc. A good antitoxic serum should contain 
from 200 to 700 units per cc. of the unconcentrated product. 
Curative Valve of Diphtheria Arititoa^in.—D'iphther'm antitoxin 
should be used as early as possible in order to obtain the maximum 
curative effect. This is clearly set forth in the following table. ^ 
Day of Cures, 
illness. Treated. Cured. Died. per cent. 
1 7 7 100 
2 71 69 2 97 
3 30 26 4 87 
4 .39 30 9 77 
5 25 15 10 60 
6 17 9 8 47 
7 to 14 41 21 20 51 
Indefinite 3 2 1 
Total 233 179 54 77 
According to Donitz and others, the initial dose of antitoxin should 
be large; it is believed that with large doses of antitoxin even some 
of the toxin attached to the tissue cells can be neutralized. For this 
purpose 4000 units is a minimal initial dose, and severe or desperate 
cases are given 10,000 to 100,000 units. The antitoxin should be 
repeated the following day if necessary. It is better to administer 
too much than too little antitoxin. Antitoxin given subcutaneously 
is least dangerous so far as danger from anaphylaxis is concerned 
but the absorption is slow\ Intramuscular injections, particularly 
in the gluteal region, are said to be more efficient curatively. In des- 
perate cases intravenous injections of antitoxin (without carbolic 
acid as a preservative if possible) are indicated. 
Active Immiinizaiio7i with Toxin-a7ititoxin J/i.r/?//-^'^. — Following a 
suggestion of Theobald Smith, ^ Von Behring^ and others have attempted 
to create active immunity to diphtheria in man by subcutaneous injec- 
tions of toxin-antitoxin mixtures which are neutral or but slightly toxic 
for guinea-pigs. Park'* has practiced toxin-antitoxin injection in a 
large series of children giving a positive Schick reaction, and finds 
that over 90 per cent of the cases reexamined retained sufficient 
immunity to give a negative Schick test after two years. In a few 
instances abscesses developed as the direct result of inoculation. From 
various sources 5 deaths have been reported due to an excess of toxin 
' Quoted from Citron (Immunity). 
2 Jour. Med. Res., 1907, 16, 359. 
3 Deutsch. med. Wchnschr., 1913, 39, 873. 
* New York State Med. Jour., 1923, 23, 141. 
