606 THE STREPTOCOCCI OF MAN 



increased in virulence by passage through animals. In the laboratory these 

 serums give good results with all streptococci whatever their source provided 

 that the virulence of the latter be first raised by passage. But as Besredka 

 points out, a " passage " streptococcus whose properties have been pro- 

 foundly altered by artificial means differs widely from an organism which 

 has not been subjected to treatment and whose pathogenicity is that natural 

 to it, and herein probably lies the explanation of the discrepancies between 

 laboratory results with these serums and clinical experience. 



[Other observers acting on the theory that there are a number of different 

 streptococci have prepared polyvalent serums. These latter may be regarded 

 as of two types : (1) serums, as for instance that of Tavel, prepared by im- 

 munizing animals with a number of strains from different clinical streptococcal 

 infections but previously " exalted " by passage and (2) Besredka's serum 

 which is also prepared with a number of different strains which however have 

 not been increased in virulence previously to being used for immunization.] 



A. Monovalent serums. 



Marmorek's serum. Marmorek was the first to prepare an antistreptococcal 

 serum for therapeutic purposes. 



Preparation of Marmorek's serum. Marmorek obtains his serum from horses. 

 The animals are immunized in the manner described above and should, in order to 

 yield a potent serum, be inoculated with considerable doses of virulent cultures, 

 each horse receiving at least 2 litres of culture administered in increasing doses 

 over a period of 612 months. An interval of 4 weeks should elapse after the last 

 inoculation before the horse is bled (vide B. diphtheria for the technique of the 

 collection of serum). 



Each inoculation of a living culture into a horse for purposes of immunization is 

 followed by a period of reaction during which the blood is toxic but contains no 

 streptococci. The two following experiments illustrate this. (1) A rabbit was inoculated 

 with 2 c.c. of serum which was collected during a period of febrile reaction from an 

 already highly immunized horse. The rabbit died in a week. (2) Serum taken from a 

 horse in a less advanced stage of immunization and a fortnight after the temperature 

 had become normal was found, when inoculated in doses of O'5-l c.c. into animals 

 weighing 1400 grams, to kill rabbits in 5-10 days. 



The serum ceases to be toxic, and is therapeutic 3 weeks after the last inoculation ; 

 its therapeutic properties are most pronounced at the end of the fourth week (Mar- 

 morek). 



Properties of the serum. Marmorek's serum exhibits curative, prophylactic 

 and antitoxic properties when tested on rabbits. It is not bactericidal in 

 vitro and has very feeble agglutinating properties. 



Bactericidal properties. Streptococci grow in the serum slowly and feebly 

 as they do in normal horse-serum. Growth also takes place in a mixture 

 of the serum and rabbit-serum as in a mixture of normal horse-serum and 

 rabbit-serum and the virulence of the organism is unimpaired (Mironoff : 

 Bordet). 



Agglutination. The property of agglutinating streptococci possessed by 

 Marmorek's serum is very feeble and irregular. To a given volume of culture 

 emulsion at least one-third of that amount of serum must be added (Bordet). 



Antitoxic properties. Using a toxin of which 1 c.c. is fatal to rabbits in 

 3 or 4 days it is found that if 3-5 c.c. of the serum be mixed with the fatal 

 dose the mixture is harmless on inoculation into a rabbit. 



Prophylactic properties. If a rabbit be inoculated under the skin with 2 c.c. 

 of the serum and 24 hours later with 0*000,001 c.c. of a culture which will 

 kill a control animal in a dose of 0-000,000,1 c.c. the animal survives the 

 inoculation. A dose of serum equivalent to r ^ih of the weight of an 

 animal protects it against infection. 



