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Proceedings of the Royal Society of Edinburgh. [Sess. 
M. melitensis is pathogenic for these animals whether injected intra- 
cerebrally, intravenously, intraperitoneally, or subcutaneously. Speaking 
generally, the period that elapses between infection and death is shorter 
when the intracerebral and the intravenous methods of inoculation are 
practised, and longer when the intraperitoneal or the subcutaneous is chosen, 
though the course of the infection may, under different conditions, be acute 
or chronic after any form of injection, and I therefore propose to consider 
my experiments under these two headings. 
A. Intracerebral Inoculation . — Infection after this method of inocula- 
tion falls under the headings of (1) Acute and (2) Chronic, according to 
whether death is caused in a few hours or days, or is delayed for from one 
week to two or three months. 
1. Acute Infection . — An animal dying within a few days of inoculation 
with a moderate dose of a highly virulent cultivation, or a large dose of a 
less virulent one introduced into the brain substance in accordance with the 
technique I have previously described {Med. Fever Reports, part ii. p. 71), 
supplies the type for this form of M. melitensis infection. 
A short incubation period, varying in duration from two or three to 
twenty-four hours, follows the inoculation ; and during this time the animal 
appears to be in normal health and eats well, although the progressive loss 
of weight which is the marked characteristic of the infection begins within 
a few hours of inoculation. A stage of irritation follows the incubation 
period, and lasts for about twenty-four hours : it is marked by convulsions, 
at first localised and produced in response to direct stimuli, and not 
necessarily bearing any relationship to the area of cortex injured by the 
inoculating needle ; afterwards becoming generalised, tonic in character, 
and occurring at frequent and irregular intervals. Progressive muscular 
weakness is a marked feature of this stage, throughout which the animal 
is obviously ill and stupid, and refuses food. The stage of irritation passes 
gradually into one of coma, with paresis or even paralysis affecting first the 
hind legs, afterwards involving the fore limbs also. Handling or even 
touching will at first rouse the animal and provoke general convulsions ; 
later, the guinea-pig falls on its side, becomes insensible, and in fact appears 
moribund. In this condition, however, the animal may remain for twenty- 
four or even thirty-six hours, and during the latter part of this period no 
rectal temperature can be recorded by the ordinary clinical thermometer, 
for 30° C. is hardly ever exceeded. Death is sometimes preceded by con- 
vulsions, but usually no such warning is given. To illustrate the train of 
symptoms and post-mortem findings in these acute infections I cannot do 
better than cite in full the clinical history of one of my experimental 
