Co mae isa 1 Ue 
sue * Z 
367 
The failure to demonstrate that the disease can be communicated by 
inoculation with the contents of the vesicles is against the idea that the 
infectious agent is contained in them. This evidence is not absolute and 
moreover a necessary corrollary of such experiments would be the excision 
and study of the area inoculated. It might well be that a slight but 
characteristic lesion may be produced which would not be apparent on 
macroscopic examination and which would not lead to the production 
of an exanthem. If we regaled the production of the entire disease as 
necessary to constitute infection, the infectiousness of smallpox in the 
inoculation of the calf or rabbit would be denied. On the other hand 
the lesions in the disease are so cellular in character and the cellular 
changes in their entirety so characteristic that it is hardly conceivable 
that the process can be produced by anything other than some agent which 
enters into and affects the single epithelial cells. 
That the infectious agent is disseminated by the blood is rendered 
probable by the common occurrence in early lesions, of a process of wider 
distribution in the corium than is found in the epidermis and by the 
occurrence of isolated lesions of blood vessels far from any epidermal 
involvement. It seems reasonably certain that the process in the corium 
antedates that in the epidermis. 
Certain facts brought out in this investigation may be given a practical 
application in the matter of diagnosis. During every epidemic of small- 
pox there occur cases in which there is great difficulty in diagnosis. One 
needs but to scan the literature to acquire a conception of the number 
of these difficult cases. Stelwagon (14) quotes an analysis of thirty- 
eight cases of error in diagnosis of smallpox, of which seventeen turned 
out to be varicella. There has been some dispute in regard to the nature 
of a widespread epidemic reported from Trinidad, whether the cases were 
all varicella or whether some were those of a mild form of smallpox. 
There is no doubt that many cases are passed over without their true 
nature being recognized. One can not depend absolutely on the gross 
appearances of the lesions or on the distribution. 
It seems a matter of considerable importance to be able to distinguish 
from true varicella certain cases of smallpox resembling varicella, which, 
although mild, give rise to severe variola in other individuals. 
Certain methods concerning the diagnosis of smallpox have already 
been suggested. The inoculation of monkeys as recommended by Park 
(11) is not always practicable in that monkeys are expensive and not 
always obtainable. 
Howard (10) suggests in addition to animal inoculation, the study of 
sections of excised skin. he diagnosis is based upon the character of the 
process and the presence of C. variole. 
Thompson (17) has applied a rapid method for embedding the excised 
lesions, by which he is enabled to obtain sections ready for study within 
three hours after excision. ' 
