566 DISEASES OF UNKNOWN ETIOLOGY 



which usually first becomes manifest in the limbs and arms ; it ascends 

 gradually and death occurs when the higher centres are reached. 



The disease occurs in every country except England, and possibly 

 Australia. The elimination of rabies from England dates from the 

 law of 1889 which required all dogs to be muzzled and all imported 

 animals to be quarantined for several months. The law was allowed 

 to lapse for a time, the disease reappeared, but a new and rigid enforce- 

 ment of the muzzling and quarantine laws has completely eliminated 

 rabies from the British Isles. No cases have been reported since 1903. 



The first definite lesions characteristic of rabies were described 

 by Negri, 1 who found characteristic cell inclusion bodies in the ganglion 

 cells, in the cells of Purkinje, and other large nerve cells. These minute 

 granular pleiomorphic bodies are now recognized as specific, or nearly 

 so, for hydrophobia, but there is discussion of their nature. Williams 2 

 regards them as protozoa and conferred upon them the name Neuror- 

 rhyctes hydrophobise ; in collaboration with Lowden 3 she has made a 

 careful study of the occurrence of Negri bodies and considers them the 

 true etiological agent of rabies. Remlinger, 4 Poor and Steinhardt, 5 

 and others have found that the virus is filterable, and Noguchi 6 has 

 cultivated an organism from "street" virus and from the central 

 nervous system of animals infected with "street" virus, "fixed" 

 virus and with "passage" virus, which resemble Negri bodies observed 

 in lesions in many particulars. The smallest of these bodies are just 

 visible with the highest magnifications obtainable; larger nucleated 

 or oval bodies occasionally appear in older cultures. Inoculation of 

 dogs, rabbits and guinea-pigs with cultures containing the granular 

 pleiomorphic or nucleated bodies was followed by typical symptoms 

 of rabies. The relation of the organisms grown by Noguchi to Negri 

 bodies is not definitely determined as yet, but the organism has been 

 kept alive for over three months in artificial cultures and found to 

 be virulent after the twenty-first transfer in artificial media. This 

 would suggest strongly that Noguchi's organism was the etiological 

 agent of rabies. The possibility that a filterable virus was growing 

 in these cultures cannot be overlooked, as Noguchi has pointed out, 

 but there is no evidence that such is the case. 



The most important rapid laboratory method for the diagnosis of 



1 Ztschr. f. Hyg., 1903, xliii, 507; 1909, Ixiii, 421. 



2 Proc. New York Path. Soc., 1906, vi, 77. 



3 Williams and Lowden, Jour. Inf. Dis., 1906, iii, 452. 

 Ann. Inst. Past., 1903, xvii, 834: 1904, xviii, 150. 



5 Jour. Inf. Dis., 1913, xii, 202. 6 Jour. Exp. Med., 1913, xviii, 314. 



