RABIES 647 



afflicted animal, subdurally, through a trephined opening in the skull, 

 but may also be accomplished by injection into the peripheral nerves, 

 the spinal canal, or the anterior chamber of the eye. Intravenous and 

 intramuscular injections are also successful, though less regularly so. 



The time of incubation after inoculation varies with the nature of the 

 virus used, the location of the injection, and the quantity injected. In 

 accidental infections of man and animals the incubation is shortest and 

 the disease most severe when the wounds are about the head, neck, and 

 upper extremities and are deeply lacerated. This is explained by the 

 fact that the poison is conveyed to the central nervous system chiefly 

 by the path of the nerve trunks. This has been experimentally shown 

 by di Vestea and Zagari ' who inoculated animals by injection into 

 peripheral nerves, and showed that the nerve tissue near the point of 

 inoculation becomes infectious more quickly than the parts higher up ; 

 thus the lumbar cord of an animal inoculated in the sciatic nerve is in- 

 fectious several days before virus can be demonstrated in the medulla. 



In man, infected witli "street virus," that is, with the virus of a dog 

 or other animal not experimentally inoculated, the incubation period 

 varies from about forty to sixty days. Isolated cases have been reported 

 in which this period was prolonged for several months beyond this. 



The virulence of rabic virus may be markedly increased or diminished 

 by a number of methods. By repeated passage of the virus through 

 rabbits, Pasteur ^ was able to increase its virulence to a more or less 

 constant maximum. Such virus which had been brought to the 

 highest obtainable virulence, he designated as "virus fixe." Inocu- 

 lation of rabbits, dogs, guinea-pigs, rats, and mice with such virus 

 usually results in symptoms within six to eight days. The same animals 

 inoculated with street virus may remain apparently healthy for two to 

 three weeks! 



In dogs and guinea-pigs inoculation usually results first in a stage 

 of increased excitability, restlessness, and sometimes viciousness. This 

 is followed by depression, torpor, loss of appetite, inability to swallow, 

 and finally paralysis. In rabbits the disease usually takes the form of 

 what is known as "dumb rabies," the animals gradually growing more 

 somnolent and weak, with tremors and gradual paralysis beginning in 

 the hind legs. 



In experimentally infected birds the disease is slow in appearing and 



' di Vestea and Zagari, Ann. de I'inst. Pasteur, iii. 



' Pasteur's work on rabies. Compt. rend, de I'acad. des sciences, 1881, 1882, 1884, 

 1885, 1886, and Ann. de I'inst. Pasteur, 1887 and 1888. 



