HIDEYO NOGUCHI 493 



of the American strains, but the symptomatology and the pathological features of 

 South American and West African yellow fever are essentially alike. That there 

 may exist more than one serological race among the interrogans is made highly prob- 

 able by the fact that other leptospiras have shown this characteristic. Two or more 

 varieties of L. icterohaemorrhagiae and L. hcbdomadis have been described.' It is also 

 possible that there is a disease known as yellow fever which is not caused by Leptospira 

 interrogans. 



So far as the writer is aware, there are no other two diseases which resemble each 

 other as closely as do yellow fever and infectious jaundice. The fundamental differ- 

 ence between them is epidemiological: one being transmitted by a certain species of 

 insect, the other by infected rodents. This difference may be due to the climatic 

 conditions under which each disease prevails. Tropical temperature and humidity 

 and abundant diptera would favor the adaptation of the micro-organism to an insect, 

 while in cold climates, where severe winters destroy the insects annually, the parasite 

 must be disseminated in some other way. Numerous trypanosomes are carried by 

 flies in the tropics, but in cold climates only those species exist which are harbored 

 and transmitted by wingless arthropods parasitic on warm-blooded animals. 



L. interrogans has been shown experimentally to be conveyed in a tropical country 

 (Ecuador) from man to animal and animal to animal by Aedes aegypti.^ Mosquito- 

 transmission experiments made in a colder climate yielded negative results.^ 



Once isolated, L. interrogans is readily maintained on artificial culture media, but 

 the primary cultivation of a strain from human materials has proved extremely diffi- 

 cult. A highly developed human parasitism must account for the resistance of the 

 interrogans to artificial cultivation and transmission to animals. The interrogans is 

 not an unusual organism in this respect, however, since there are many human 

 pathogens which cannot be readily grown or transmitted to animals. Failure to iso- 

 late the interrogans in a given case of yellow fever is certainly not proof that it is 

 not present. 



For studies of pathogenic as well as of immunological relations it is important to 

 employ recently isolated strains. Apparently the same biological factors which oper- 

 ate to convert a non-pathogenic water leptospira with unrelated serological proper- 

 ties into a new strain indistinguishable from L. icterohaemorrhagiae in every respect 

 come into play to modify the characteristics of a pathogenic leptospira. Indeed, it 

 is highly probable that if various species of leptospiras are subjected to prolonged 

 successive passages in guinea pigs until they become highly virulent for this animal 

 they will all acquire a new set of common biological properties. It would be desirable 

 to determine this point by experiment; but it has not been possible so far, owing to 

 the low virulence of most leptospiras for the guinea pig. L. interrogans, once rendered 

 virulent, can be carried on for many generations; but L. hcbdomadis cannot be main- 

 tained through successive generations, and most water leptospiras fail to infect guinea 

 pigs at all. 



Leptospira asthenalgiae. — The assertion is often made that yellow fever and den- 

 gue are allied infections, owing no doubt to their common intermediate insect host, 



' Koshina, M., Shiozawa, S., and Kitayema, K.: loc. cit. 



^ Noguchi, H.: /. Exper. Med., 30,401. 1919. J Mochtar, A.: loc. cit. 



