442 Tetanus. 



will produce the disease wlien fine sand, coal dust, foreign bac- 

 teria (Bac. prodigiosus), or negatively chemotactic fluids (as lac- 

 tic acid) are added. 



In animals which are infected subcutaneously or intramus- 

 cularly tetanus always begins with local symptoms. After such 

 an infection into the thigh the muscle spasm appears first in 

 the posterior extremity of the same, then on the opposite side 

 and later spreads to the anterior extremities, until it becomes 

 general. After intravenous injection of toxins there is general- 

 ized tetanus from the beginning, while after intracerebral inocu- 

 lation there follow excitement, intermittent spasms and disturb- 

 ances of motility (tetanus cerebralis) (Eoux & Borrel) ; after 

 injection into the spinal cord severe attacks of pain occur with 

 subsequent . tetanic symptoms (tetanus dolorosus) (Meyer & 

 Ransom, Tiberti). 



The horse possesses the greatest susceptibility for the 

 virulent living cultures as well as for the toxins, and is followed 

 by the guinea pig, goat, sheep, mouse, rabbit; cattle are very 

 slightly susceptible, dogs and cats still less so, while chickens 

 are infected with difficulty with very large doses. Man is very 

 susceptible to both infection and toxins. 



The toxic products of the tetanus bacillus were first studied by 

 Brieger who grew mixed cultures on beef broth and obtained four 

 substances (tetanin, hydrotetanin, tetanotoxin and spasmotoxin) which 

 caused muscular spasms after subcutaneous injection into experiment 

 animals. As these substances acted at once and in comparatively large 

 doses they could not be considered as true toxins. Later, after pure 

 cultures of tetanus bacilli were grown Kitasato, Behring & Knorr, 

 Tizzoni & Cattani, Eoux & Vaillard studied the toxic culture filtrates 

 carefully without, thus far, succeeding in establishing the nature of 

 the toxic substances. It is probable that they represent specific secre- 

 tions of the bacilli and do not develop as the result of decomposition 

 of albumin-containing nutritive media as they are formed also on albumin- 

 free asparagin (Buchner). The toxin is soluble in water, insoluble 

 in alcohol, chloroform and ether; otherwise in certain characteristics 

 it resembles very much diastases (is not very stable, is precipitated by 

 alcohol, dializes, etc.). 



The tetanus toxin is an extremely powerful poison. 1.0 ec. of the 

 filtrate of a highly virulent culture kills a horse 500 kg. in weight; 

 0.001 cc. kills a guinea pig of 300 gram, while other species of animals 

 require proportionally larger doses of toxin. If for 1 gram body 

 weight of horse the lethal dose is 1, guinea pigs require 2, goats 4, 

 mice 13, rabbits 2,000, chickens 200,000 doses per gram of body weight 

 (Knorr) . 



The toxic value of toxins is usually designated by the smallest 

 amount of virus necessary to kill an animal of a certain weight. If 

 therefore 0.0000001 cc. toxin kills a 15 gram mouse, 1.0 cc. will kill 

 10 millions of mice of 15 gram body weight each, equivalent to 150 

 millions grams weight of mice (Behring). 



The action of the toxin follows only upon subcutaneous, intra- 

 muscular, intraperitoneal, intravenous or intracerebral injection, while 

 large doses of toxin when given by mouth or intestine are entirely 



