SIGNIFICANCE OF PHENOMENON 389 



Shope (i()^^). This imesti^ator demonstrated that \\hilst the 

 filtrate of organs of swine infected ^vith inliuenza and, a certain 

 gram-negati\'e l)acillus each separately are iinal^le to produce tlie 

 cHnical syndrome of infhienza, the coml^ination of tlie two re- 

 sults in violent infection. 



By secondary infections one means the imposition of a micro- 

 organism upon a tissue prexioirsly infected xvith an luirelated 

 microorganism. Examples of secondary infections are too nu- 

 merous to re\ iexv and are xvell knoxvn. C^ne may cite the in\ari- 

 able association of mixed pyogenic and anaerobic flora \vith tu- 

 l)erculous infections of the liuigs. According to Fraenkel (cpioted 

 by Seitz) , such secondary infections give rise to a septic intermit- 

 tent fever. In contrast, a contiinious fever does not indicate a 

 secondary infection but apparently is due to an absorption of the 

 tuberculous toxi( materials. Tlie secondary infection brings about 

 exacerbation and dissemination of tuberculous lesions. The Strefj- 

 tococcus heniolyticus bronchopneumonias following tyj^hoid fever 

 and bronchopneumonias following influenza are also well knoxvn. 

 The appearance and role of the secondary infections has been 

 ascribed in the literatiue to a rather vague idea of so-called locus 

 i)i iiw lis resisientiae. 



The experimental demonstration of the synergistic effect of 

 toxic substances derived from unrelated microorganisms and 

 viruses afforded by studies on the phenomenon of local tissue 

 reactivity may serve, then, to explain the above discussed mixed 

 and secondary infections. In this connection the possible rela- 

 tion of bacteria to the occurrence of purpinic smallpox in humans 

 is of interest. Councilman ( 1 904) expressed the view that bacteria 

 probably play a large part in the pathology of smallpox. Ikeda 

 (1927-28) , in reporting a series of 131 cases of purpuric smallpox 

 noted that nearly all the cases had streptococcus bacteremia and 

 that streptococci could be cultured xvith regularity from hemor- 

 rhagic pocks Ijut that the non-hemorrhagic ones xvere always 

 sterile. 



Experimentally, Gratia and Linz (1931^/), and Koplik (1935) 

 were able to transform a mild vaccine infection into a hemor- 

 rhagic one by means of an intravenous injection of a heterologous 

 bacterial filtrate. In one of the rabbits a spontaneous hemorrhage 

 in vaccinia \irus infection coidd be attributed to an incidental 

 B. ivelchii blood stream infection. In direct relation to this topic 

 also stand the observations of Ichikawa (1914-15), who reported 



