754 TOXINS, TOXOIDS, AND ANTITOXINS 



ature is normal. On resuming injections a lower percentage of increase usually must be 

 given. These early reactors rarely produce a high antitoxic value; about 50 percent of the 

 horses after a month's immunization will test five hundred or more units to each mil. From 

 the economic view, those horses that do not have more than three hundred units to each mil 

 after five weeks of immunization are not injected further. Experience has proved that those 

 .that are three hundred units or under rarely go to a higher value even though much greater 

 amounts of toxin than the scheduled dose be given. Regular full bleedings of about 8 liters 

 of blood have been tried on these refractory horses on the assumption that during the process 

 of the stimulation of blood formation an indirect stimulation of antitoxin production would 

 occur. The results do not warrant the trouble. 



Horses with above three hundred units are listed for the regular full bleedings. The 

 blood is drawn from the jugular vein by means of a suitable-sized canula. An injection of 

 toxin is given the next day after bleeding. Usually two or three daily injections are given 

 between bleedings. Six days after the last injection they are bled again, averaging three 

 bleedings a month. These horses, as a rule, even though full bleedings be taken, respond to 

 the further injections and go to a higher unit content. This increase in unit value may con- 

 tinue for three, four, or more bleedings. They may then remain stationary in unit content for 

 six to twelve or more bleedings and then slowly or rapidly drop in value with each successive 

 bleeding. 



A horse may give, after a month's immunization, a test bleeding containing a thousand 

 units to the mil, and on its first full bleeding about two weeks later, test only six hundred 

 units. Because of these occasional instances the practice is to take a regular full bleeding 

 after about twenty-eight days of immunization. If horses are not bled for the full bleedings 

 and the injections continued with the hope of increasing the unit content, the high-unit period 

 may be missed. All horses after seven to eight weeks of intensive immunization with toxin 

 will drop in antitoxic value if full bleedings have not been taken. 



There is no doubt that the full bleedings act as a stimulation in most horses and tend to 

 lead to a higher antitoxic content. This holds true only with those horses which respond 

 favorably to the first four or five weeks' immunization. Those which respond poorly may 

 hold their low unit level but usually drop lower with each successive bleeding. 



Ramon recommends the use of anatoxin (toxoid) for the immunization of horses. 

 He also advocates the addition to the anatoxin of finely powdered tapioca (i gm. to 

 each liter) to delay the absorption of the toxoid, the idea being that a more prolonged 

 stimulus will result in a greater antitoxin response. Madsen injected intravenously 

 lo-mil amounts of a 10 per cent manganese chloride solution to augment the stimu- 

 lation of antitoxic productions. None of these methods have been more successful in 

 our laboratories than the regular methods of toxin injections. 



Tetanus antitoxin. — In immunizing horses against tetanus toxin the daily injec- 

 tion method of increased doses cannot be given as with diphtheria toxin. Diphtheria 

 toxin acts on the local tissues, causing in a short time local disturbances and a rise in 

 temperature. These are warnings of a too toxic dose, thereby indicating the amount 

 of toxin for the next injection. With the injection of tetanus toxin there are none of 

 these early danger signals. During the early injections, muscular rigidity may de- 

 velop. When this occurs it is due to cumulative toxic action and may be followed by 

 exhaustion and death, even though large amounts of tetanus antitoxin be injected 

 into the spinal canal and by the intravenous route. The early immunity response to 

 injections of tetanus toxin is extremely slow. In order to aid the animal to withstand 



