BACILLUS TETAM 517 
before or iiiiinediately following the injection of toxin. Donitz' has 
shown that as many as 12 fatal doses of toxin may be nentrahzed b\- 
1 cc. of a 0.001 to 0.002 (hhition of antitoxin, provided the toxin and 
antitoxin are mixed l)efore injection. Four minutes after injection of 
1 cc. of toxin, 1 cc. of 1 to ()0() dilution of antitoxin is reciuired for neu- 
tralization; eight minutes after injection of the same amount of toxin, 
1 cc. of 1 to 200 dilution of antitoxin is required to protect the animal, 
and fifteen minutes after the injection of 1 cc. of toxin, 1 cc. of 1 to 100 
dilution of antitoxin is rec|uired. These experiments illustrate clearly 
the necessity of administering tetanus antitoxin at the earliest possible 
moment to obtain favorable results. 
Inasmuch as the toxin appears to reach the central nervous system 
by way of the nerves, while the antitoxin circulates in the blood stream, 
it is not surprising, as Welch- has pointed out, that tetanus antitoxin 
has been disappointing as a curative agent. Used prophylactically it is 
very much more satisfactory. Flooding the nerves near the site of 
inoculation with antitoxin, or the intracerebral injection of antitoxin 
in desperate cases is sometimes successful.^ Tetanus antitoxin has also 
been administered intraneurally and subdurally in desperate cases. 
Subcutaneous injection is comparatively ineffective. The subcu- 
taneous injection of 200 or more units at the site of infection, or, 
better, after exposure of the regional nerves, is said to be very efficient 
in preventing the development of tetanus. 
Bruce has studied the effects of the introduction of tetanus antitoxin 
in a series of 1000 cases, and has published the following figures. The 
average mortality in 960 cases was 38.8 per cent. 
Cases 
Mode of injection. treated. Mortality. 
Subcutaneous, only 223 50.7 
Intramuscular, only 73 16.4 
Intravenous only 30 40.0 
Intrathecal only 43 48.8 
Intrathecal, together with other methods .... 545 37.4 
No intrathecal, but combination of other methods . 413 41 . 1 
Intravenous, together with other methods .... 189 38 . 6 
No intravenous, but combination of other methods 770 39 . 
He has de\'ised a system of administration which combines the 
advantage of immediate effect through the intrathecal injection 
together with the prolonged flooding of the body by intramuscular and 
subcutaneous injections. 
Subcutaneous Intramuscular Intrathecal 
units. units. units. 
First day 8,000 16,000 
Second day 8,000 16,000 
Third day . . . .- 4,000 8,000 
Fourth day 4,000 8,000 
Fifth day 2,000 
Seventh day 2,000 
Ninth day 2,000 
1 Deutsch. med. Wchnschr., 1897, 23, 428. 
2 Bull. Johns Hopkins Hosp., 1895, 6, 97. 
' Roux and Borrel: Ann. Inst. Pasteur, 1898, 12, 225. Chauffard and Quenu: La 
presse med., 1S9S, No. 5. 
