492 THE SPIROCHETES 



zilian strains of L. interrogans showed symptoms and lesions identical with those of 

 human yellow fever.' 



The interrogans is decidedly more destructive for the liver and kidneys than the 

 icterohaemorrhagiae, as shown by comparison of the pathological changes in the ex- 

 perimental infections. The difference is an expression of an elective afhnity of the 

 interrogans for the liver and kidney, rather than of greater virulence. The ictero- 

 haemorrhagiae is invariably more virulent than the interrogans for guinea pigs and 

 dogs, attacking these animals when they are fully grown, while the interrogans is 

 only slightly pathogenic for these animals, even when they are very young. 



Repeated successive passages through guinea pigs for a long time alters the patho- 

 genic properties of the interrogans. A strain passed through the guinea pig for many 

 passages no longer produces the original picture of yellow fever but kills the animals, 

 after an incubation period of two to three days, with an acute leptospiremia. At the 

 time of death, which occurs on the fourth or fifth day of illness, the blood is swarming 

 with leptospiras, and the liver and kidneys are less characteristically affected than 

 in animals inoculated with newly isolated strains. There is no question but that the 

 biological and pathogenic properties of the micro-organism undergo a profound modi- 

 fication through continued animal passage. Under normal conditions Leptospira in- 

 terrogans never passes from man to man but passes alternate generations in the in- 

 sect-carrier Aedes aegypti, retaining its predilection for the liver and kidney as well 

 as its ability to pass on to the mosquito body. 



L. interrogans is specifically influenced by the serum of yellow fever convalescents, 

 the relationship being analogous to that existing between L. icterohaemorrhagiae and 

 the serum of convalescents from infectious jaundice. This statement applies to 

 strains which have been recently isolated and have not been subjected to repeated 

 animal passages. Serological tests carried out by means of the Pfeiffer reactions and 

 also by cross-protection experiments with freshly isolated cultures yielded clear-cut 

 specific results. The contradictory findings of some investigators^ who have recently 

 carried out Pfeiffer reactions and cross-protection tests with old passage strains for 

 the purpose of differentiating Leptospira interrogans from L. icterohaemorrhagiae may 

 have been due to the masking of specificity by a group reaction. The question of 

 strain specificity and group relations is a complex one, and, as observed by Park and 

 Williams,^ there is theoretically no reason to believe that apparently complete mutual 

 cross-protection might not occur with two closely related but not identical strains. 



The negative Pfeiffer reactions obtained with the sera of yellow fever convales- 

 cents in West Africa may be due either to the use of old strains, which have been 

 modified serologically by continued passages in guinea pigs or on artificial medium, 

 or to a difference between the strain causing West African yellow fever and those iso- 

 lated from cases in Central and South America. The difficulty of cultivation and of 

 animal transmission of the African strain seems to be even greater than in the case 



' Noguchi, H., Muller, H. R., Torres, O., Silva, F., Martins, H., Ribeiro dos Santos, A., Vianna, 

 G., and Biac, M.: Rockefeller Inst, for Med. Research, Mono. 20. 1924. , 



^'Theiler, M., and Sellards, A. W.: Am. J. Trop. Med., 6, 383. 1926; Sellards, A. W.: ibid., 7, 

 71. 1927; Schuffner, W.: Cetilralbl. f. Baktcriol., loj, 40$. 1927. 



3 Park, W. H., Williams, A. W., and Krumwiede, C: Pathogenic Microorganisms (8th ed.), 

 p. 235. 1924. 



