546 THE TETANUS BACILLUS 



of serum required to neutralize a given volume of toxin of known strength. 

 The immunizing property of a serum does not increase pari passu with the 

 antitoxic strength. 



Properties of tetanus antitoxin. In vitro the serum of immunized animals 

 mixed with tetanus toxin neutralizes the latter instantly. The volume of 

 serum required to neutralize a given volume of toxin varies with the anti- 

 toxic content of the former. Antitoxic serums can be obtained of which 

 0*000,01 c.c. neutralizes 100 fatal doses of toxin (Pasteur Institute, Paris). 



It may be again mentioned that in a toxin- antitoxin mixture, the toxin is not 

 destroyed (p. 224) ; the toxin has merely entered into unstable combination with 

 the antitoxin and its toxic properties are easily brought into evidence again. Thus, 

 for example, if a guinea-pig already inoculated with a culture of M. prodigiosus or 

 B. coli be inoculated with a toxin- antitoxin mixture which is harmless for a normal 

 animal the inoculated animal soon shows symptoms of tetanus intoxication. 



The inoculation into the peritoneum of a guinea-pig of a dose of serum 

 (active in 10 OO Q QQQ) equivalent to the three hundred and forty-fifth part 

 of the weight of the animal, rapidly leads to the manifestation of distinct 

 antitoxic properties in its blood. The blood of a rabbit inoculated with 

 T i(yth part of its weight of serum is antitoxic and has marked immunizing 

 properties. 



The sub-cutaneous inoculation of 1 c.c. of antitoxic serum administered 

 10-40 minutes before the inoculation of 0*0066 c.c. of toxin (a dose fatal to the 

 control animals in 48 hours) protects guinea-pigs against tetanus. But in 

 animals inoculated with the toxin less than 40 minutes after the inoculation 

 of serum the protection is not complete. Symptoms of tetanus result the 

 severity of which is inversely proportional to the length of time elapsing 

 between the inoculation of serum and toxin ; the longer the interval the 

 less severe the symptoms. But the animals always recover. 



It is a much more difficult matter to prevent the onset of tetanus if serum 

 be given only after the inoculation of toxin, during, that is to say, the period 

 of incubation. Similarly, it is less easy to prevent the affection resulting 

 from the multiplication of the bacillus in the tissues. 



Immunity is developed in half an hour or so after the inoculation of serum, 

 but it does not last long, rarely exceeding a fortnight or a month in the case 

 of laboratory animals and a week in the case of the human subject. 



Roux and Vaillard summarize their investigations on the prevention of tetanus 

 as follows : 



" 1. Anti- toxic serum even in extremely small doses will certainly protect against 

 tetanus if inoculated before the toxin. The immunity conferred by the serum is 

 transitory. It begins to dimmish after about a fortnight and disappears altogether 

 in about 6 or 7 weeks. 



" 2. When serum and toxin are inoculated at the same time a local tetanus always 

 results however large the dose of serum. 



" 3. When the serum is inoculated after the toxin but before the appearance of 

 any symptom of tetanus a local tetanus is always observed. The longer the admini- 

 stration of serum is delayed the larger must be the quantity administered. After 

 the lapse of a certain length of time varying in different animals prevention is 

 impossible even though very large quantities of serum be used. 



" 4. Tetanus develops more or less rapidly and is therefore more or less easy to 

 prevent according to the site of inoculation of the toxin. (Animals inoculated in 

 the paw are more resistant than those inoculated beneath the skin of the thorax 

 or abdomen.) 



" These conclusions refer to moderate doses of toxin. 



"5. When infection is due to the bacilli multiplying in the tissues, prevention 

 again depends upon the amount of serum inoculated and on the time elapsing between 

 the moment of infection and the administration of the serum. When animals are 



