MIXED INFECTIONS 249 



which commenced as a papule, became a vesicle, then a true pustule and finally an 

 ulcer : the diphtheria bacillus was found in the vesicles and was traced on many 

 occasions into the milk. Klein observed a similar eruption on two cows which 

 succumbed to the inoculation of a very virulent culture. [Other observers have 

 failed to confirm these experiments.] 



(/) Birds. 



Pigeons and fowls rapidly succumb to the inoculation of a broth culture 

 of the diphtheria bacillus injected sub-cutaneously or into the pectoral 

 muscles in doses of 1 c.c. : death takes place in less than 60 hours. 

 With doses of less than O2 c.c. the animal usually recovers ; sometimes 

 paralysis is observed. Post mortem a thin greyish film and a gelatinous 

 oedema is found around the site of inoculation. When the culture has been 

 inoculated into the muscle the latter is swollen and its fibres have an ochre 

 tint : the internal organs are intensely congested. 



Following inoculation of the bacillus into the larynx these animals suffer 

 from croup as do rabbits. 



Small birds (sparrows, chaffinches, etc.) are highly susceptible and rapidly 

 succumb to sub-cutaneous inoculation. 



(g) Rats and mice are immune to diphtheria. 



To sum up, it is characteristic of the diphtheria bacillus that it cannot pene- 

 trate the tissues of susceptible animals ; it remains localized at the site of inocula- 

 tion and even in this situation its development is quickly arrested, so that passage 

 through a series of animals rapidly becomes impossible. 



2. Influence of other organisms on the clinical course 

 of the disease. 



Roux and Yersin have shown that certain other organisms may be associated 

 with the diphtheria bacillus and at times play an important part in the clinical 

 manifestations of the disease. The diphtheria bacillus is rarely found in 

 pure culture in the false membranes : occasionally the organisms associated 

 with it are few in number and of no clinical importance, but it often happens 

 that a considerable number of other bacteria are present many of which play 

 an important role in the clinical course of the disease and to some extent 

 determine its severity. 



Martin has pointed out that the mere presence of a few other organisms with the 

 diphtheria bacillus in cultures sown with the material from a case of diphtheria 

 is not sufficient evidence upon which to base a diagnosis of secondary infection ; 

 such an infection can only be diagnosed when the number of other organisms is very 

 considerable. And it is in this connexion that a preliminary microscopical examina- 

 tion of the material from the throat is of great importance, because it can then be 

 determined whether any associated bacillus has multiplied therein and whether it is 

 or is not the predominant organism present : whereas when the material is sown on 

 culture media one species of organism (perhaps sparsely represented originally) may 

 outgrow all others, and moreover the presence of anaerobic organisms may pass 

 entirely unnoticed. It must be remembered that the surface of the membrane 

 may be contaminated by the different organisms of the mouth, and must therefore 

 be cleansed before material is removed for investigation. 



The following are the most important of the organisms which may be 

 found in association with the diphtheria bacillus : 



(i) Brisou's coccus. Roux and Yersin and also Martin drew attention to 

 a small coccus which they frequently found associated with the diphtheria 

 bacillus ; they called it the Brisou coccus after the name of the child from 

 whom they first isolated it. The organism occurs either in the form of single 

 cocci or as diplococci or in clusters. It is gram-positive. On coagulated 



