460 FAMILY: TRYPANOSOMID^ 



single injection a dose sufficiently large to kill all the parasites and yet not 

 to kill the host. Accordingly, in treating trypanosomiasis it is necessary 

 to continue the treatment with small doses over long periods in the hope 

 of ultimately killing all the trypanosomes or assisting the body to do so. 

 There is a danger in prolonged treatment that drug-fast strains may 

 be created. It was noted that after treatment by a single dose of a drug 

 trypanosomes reappeared after varying intervals. Further treatment 

 caused them to disappear again. Eventually, after several relapses, the 

 drug frequently became incapable of causing the organisms to disappear 

 from the blood. This phenomenon was studied by Ehrlich and his co- 

 workers. It was discovered that there was a real resistance on the part 

 of the trypanosomes, for it persisted even when the trypanosomes had been 

 subjected to many passages through animals which had had no previous 

 injections of drugs. Strains resistant to various arsenic and antimony 

 compounds were obtained. It was further demonstrated that certain 

 arsenic-free substances, as, for instance, pyronine and acridine, were able 

 to produce strains resistant to atoxyl. In some cases arsenic resistant 

 strains could be made resistant to tartar emetic by injecting other arsenic 

 compounds. These facts are of great importance from the point of view 

 of treatment of trypanosome diseases. It may be that in this process a 

 kind of natural selection occurs, the more resistant survivors always 

 producing larger numbers of resistant forms after the susceptible ones 

 have been killed by the drug. Mesnil and Brimont (19086) have showni, 

 however, that a race which had become resistant to atoxyl, and had main- 

 tained this resistance when passed through mice, lost it when transferred 

 to the rat, only to regain it w^hen again passed into the mouse. It is 

 evident that the tissues of the host play a part in the therapeutic process. 



A curious action of certain drugs, such as pyronine and others of the 

 oxazin series, on trypanosomes was noticed first by Werbitzki (1910). If 

 animals infected with T. hrucei are treated with these drugs, it will be 

 found that an increasing number of the trypanosomes lose the parabasal 

 body in the kinetoplast. In some cases the strain becomes normal again 

 after several passages through animals, but occasionally all the trypano- 

 somes present show this peculiarity, which persists through many passages. 

 The exact meaning of this alteration is not understood, but it is interesting 

 to note that in T. equinum of horses of South America the parabasal is 

 normally absent. 



Voegtlin et al. (1920) have studied the action of various arsenic and anti- 

 mony compounds on trypanosome infections. They note that the trivalent 

 arsenic and antimony are markedly toxic for animals and also for trypano- 

 somes, which disappear very rapidly after intravenous injections. The 

 substances have a marked trypanocidal action in vitro. On the other 



