24 STRONG AND TEAGUE. 



All of this work demonstrated that while the course of trypanoso- 

 miasis could be modified and the lives of many of the animals prolonged, 

 with the largest animals, at least, a cure did not result and the disease 

 eventually relapsed. Very severe toxic symptoms and necrosis were 

 frequently produced by the drug. Investigators therefore naturally 

 sought for a less toxic preparation of arsenic and for one which was less 

 likel) r to cause necrosis. 



F. Blumenthal had shown that atoxyl when given to rabbits was forty-five 

 times less toxic than Fowler's solution. Several other observers confirmed these 

 results as to the diminished toxicity of this preparation when compared with 

 arsenious acid. Thomas and Breinl first advanced superior claims for atoxyl as 

 a curative agent in cases of trypanosomiasis after a most searching test on 

 animals. They concluded that it was the only remedy at that time known which 

 gave any promise of a cure. 



Almost immediately, numerous investigators undertook the study of the value 

 of this drug and the first reports regarding its efficacy in trypanosomiasis 

 were usually very favorable. 



R. Koch treated 986 cases of sleeping sickness; out of 35G cases positive 

 results were obtained in 347. The cases were divided into early and advanced. 

 Only the former were affected favorably by the drug. 



Favorable results were also obtained by Manson in 5 cases of this disease. 

 Kopke did not secure good results. Out of 29 treated cases of sleeping sickness, 

 22 died. Only 2 were in good health at the time the report was made. 



Ehrlich then showed that many of the relapses after treatment with atoxyl 

 were due to the fact that the parasites had become more resistant to the drug 

 named; they had grown to be "arsenic or atoxyl fast." Ehrlich found after the 

 use of parafuchsin, trypan red and trypan blue that resistant strains were also 

 developed. Moore's detailed and careful studies in the employment of atoxyl 

 soon demonstrated that the efficacy of this drug in the treatment of trypanoso- 

 miasis was not nearly so great as might have been supposed from the results of 

 the experiments reported earlier. 



In 1909 Moore, Nierenstein and Todd, after extensive experiments with atoxyl 

 on dogs, guinea pigs, mice and donkeys, found this drug entirely unsatisfactory 

 and incapable of saving the animal when employed alone. Brienl also con- 

 cluded that prolonged experience in the treatment of sleeping sickness in man 

 and, to a certain extent in the experimental animals, has proved beyond doubt 

 that atoxyl by itself effects a really permanent cure in comparatively few and 

 only in exceptional cases of sickness in man, even after it has been administered 

 over a prolonged period, and that nearly all the experiments with horses and 

 cattle infected with Trypanosoma gambiense lead necessarily to the conclusion 

 that atoxyl alone is insufficient for a successful issue of the treatment and that 

 it only prolongs life to a certain extent, the animals nearly always eventually 

 succumbing to the disease. 



Hodges also concluded that the treatment of trypanosomiasis, or of sleeping 

 sickness, with atoxyl is far from satisfactory and states that its use alone has 

 practically been discontinued in Uganda. 



More recent experiments in the treatment of trypanosomiasis have 

 been performed with certain derivatives of atoxyl; one of the most im- 

 portant of these is aeetylated atoxyl. 



