SERUM THERAPY 471 



The vaccine has no toxic properties and gives rise to no symptoms in mice and 

 guinea-pigs. Inoculated mice are immune in 48 hours and the immunity has been 

 shown to last for five months and a hah . 



For man the dose is the amount of emulsion corresponding to 5 mg. 

 of dead bacilli. The vaccine has been used in clinical practice in Peru and 

 Mexico. 



5. Serum therapy. 



The serum of persons who have recovered from plague has slight prophy- 

 lactic and curative properties (Metin). 



Similarly, the serum of rabbits immunized against the bacillus also shows 

 therapeutic and prophylactic properties. A rabbit, for instance, can be pro- 

 tected against an experimental infection with a virulent virus by the inocula- 

 tion of 3 c.c. of such serum sub-cutaneously, and in a rabbit which has already 

 been infected the disease can be arrested and the animal cured by the admini- 

 stration of the same dose of serum provided that the latter be treated 

 within 12 hours of the infecting inoculation. 



Yersin's serum. The serum of horses immunized by Roux's method (vide 

 ante) and collected 3 weeks after the last inoculation exhibits immunizing, 

 therapeutic and antitoxic properties. 



(a) Preparation of the serum. Method adopted at the Pasteur Institute in 

 Paris. The bacillus used is a fully virulent bacillus of human origin kept virulent 

 by frequent passage through guinea-pigs and rats. The bacillus is sown on agar 

 in Roux bottles and incubated for 3 days, the growth is then scraped off, made into 

 an emulsion with normal saline solution and filtered through absorbent wool. The 

 homogeneous filtrate is heated at 65 C. for 1 hour. 



The first inoculation consisting of a small quantity of heated emulsion (about 

 T/^th of a bottle culture or |th of a tube culture) is given into the jugular vein of 

 the horse. The horse reacts sharply and has a marked rise of temperature during 

 the next 48 hours. Sometimes the inoculation is followed immediately by severe 

 syncopal attacks from which the animal may die. 



A second inoculation is given a fortnight later and after that the inoculations are 

 repeated at intervals of a week, the amount of material inoculated being pro- 

 gressively increased until a whole bottle culture is administered at one inoculation. 

 When the serum exhibits immunizing properties heated cultures are superseded by 

 living hyper- virulent bacilli, the initial dose being about ^jth of a bottle culture. 

 The animals lose a good deal of weight during immunization and the inoculations 

 must not be pressed unduly. Immunization occupies some 6-8 months and the 

 horse is not bled until 10 days or a fortnight after the last inoculation. The immunity 

 is maintained by administering in the intervals between bleeding two inoculations 

 of one- half and a whole bottle of culture respectively at an interval of a week. 

 Before leaving the Institute the serum is heated on three separate occasions at 54 C. 

 to diminish its toxic properties. 



(6) Properties of the serum. Yersin's antiplague serum exhibits immunizing and 

 therapeutic properties. If injected previously to an experimental inoculation the 

 development of the disease in susceptible animals is prevented. If given after an 

 infecting inoculation the course of the disease is interrupted : the longer the time 

 which is allowed to elapse between infection and the administration of serum, the 

 larger must be the dose of serum and the smaller are the chances of recovery. In 

 guinea-pigs infected through a shaved area of skin the serum has no therapeutic 

 properties even though administered one hour after the infection. The Pasteur 

 Institute serum cures mice infected by the bite of an insect if inoculated in doses 

 of O'l c.c. sixteen hours after infection. The immunity following the inoculation of 

 serum lasts but a very short time, some ten days or so. 



(c) Human serum therapy. The efficacy of antiplague serum in the treatment 

 of plague in the human subject is shown by the experience of Yersin, Calmette and 

 Salimbeni, Metin and others. 



(i) Prophylaxis. The inoculation of 10 c.c. of the serum prepared at the Pasteur 

 Institute affords immunity to the disease at once, but the immunity only lasts about 



