478 ANAEROBIC BACTERIA 



smaller amounts of toxin are used; symptoms may not appear until 

 two or three days, or even a week after inoculation. Subfatal doses 

 of tetanus toxin administered to experimental animals give rise to 

 local symptoms which are frequently the only signs observed. The 

 incubation period of the natural infection in man is usually about 

 fourteen to sixteen days. It may be stated as a general rule that the 

 shorter the incubation period, the higher the mortality. The "site of 

 inoculation of the tetanus toxin influences the character of the symp- 

 toms and the incubation period quite materially. Subcutaneous 

 injections are usually followed by symptoms (spasms) which affect 

 the muscles nearest the site of inoculation as a rule. Intravenous 

 injections usually cause a generalized spasm. 1 When toxin is intro- 

 duced directly into the central nervous system smaller doses cause 

 death and the symptoms develop much more rapidly. There is great 

 restlessness in these cases before the characteristic spasms occur, and 

 the spasms are epileptiform in character. The toxin is supposed to 

 exert a harmful effect on the central nervous system, which it reaches 

 by way of the nerve trunks. Donitz, 2 and Wassermann and Takaki 3 

 have shown that mixtures of brain tissue (especially the gray substance) 

 and tetanus toxin are practically without effect when they are injected 

 into susceptible animals, indicating that a firm union has taken place 

 between the tissue and the toxin. This union will take place in vitro. 

 The spleen, liver, kidney and other non-nerve-containing tissue have 

 little or no neutralizing power for tetanus toxin. Metchnikoff 4 and 

 Blumenthal 5 have determined experimentally that the brain tissue 

 of pigeons and hens, which are almost refractory to tetanus toxin, 

 possess but little neutralizing power for it. 6 Asakawa 7 has corroborated 

 these results and has also shown that the toxin may circulate for some 



1 Ransom, Deutsch. med. Wchnschr., 1893. Marie and Morax, Ann. Inst. Past. 



1902, xvi, 818. 



2 Deutsch. med. Wchnschr., 1897, 248. 

 s Berl. klin. Wchnschr., 1898, xxxv, 5. 



4 Ann. Inst. Past., 1898, 81. 



5 Deutsch. med. Wchnschr., 1898. 



6 There appears to be some combining power of the brain tissue of non-susceptible 

 animals, as hens and pigeons, for tetanus toxin, however. A possible explanation for 

 this phenomenon is furnished by Landsteiner and Von Eisler (Centralbl. f. Bakt., Orig., 



1903, xxxiv, 567; 1905, xxxix, 315). They found that lipoids would combine with 

 tetanus toxin at least to a limited degree. Levene (Biochem. Ztschr., 1911, xxxiii, 225; 

 xxxiv, 495) has shown that tetanus toxin will unite not only with lipoids but with fats 

 and similar substances. Marie and Tiffeneau (Ann. Inst. Past., 1908, xxii, 289, 644) 

 have discovered that although a small amount of tetanus toxin may be bound by lipoidal 

 substances in the brain in susceptible animals, the greater part of it is bound by albumi- 

 nous substances. They believe .that the essential albuminous substances necessary 

 for this union are absent or inactive in non-susceptible animals. 



7 Centralbl. f. Bakt., 1898, xxiv, 166, 234. 



