266 
MALARIA 
tried in malarial infections. Methylene 
blue, inorganic and organic arsenicals, 
acridin dyes, bismuth preparations, anti¬ 
mony compounds have all been used with 
some degree of success. However, none of 
them approaches in efficacy and safety the 
performance of the specific antimalarials 
previously discussed,- and interest in them 
today is only historic. 
The situation is different with chemo¬ 
therapeutic agents belonging to the so- 
called organic, sulfur compounds. This 
group, of which prontosil was the first rep¬ 
resentative, consist now of thousands of 
synthetic compounds, among which sulf- 
apyridine, sulfanilamide, and sulfathiazole 
are the best known. Some of its members 
have been tried in the therapy and prophy¬ 
laxis of malaria, but no definite conclusions 
as to their usefulness in this field have as 
yet been reached. While none of the com¬ 
pounds so far investigated compared favor¬ 
ably with quinine, plasmochin or atabrine, 
the number of those which have undergone 
sufficient trials is still very limited. Cer¬ 
tain experimental and clinical findings seem 
to justify a systematic investigation of this 
group, particularly for its value in chemo¬ 
prophylaxis. Not only have favorable clini¬ 
cal results been reported following the use 
of sulfonamide compounds in tertian, quar¬ 
tan and P. falciparum malaria (de Leon 
1937; Hill and Goodwin 1937; van der 
Wielen 1937, Chopra, Hayter and Sen 
1939; Chopra, Das Gupta, Sen and Hayter 
1939; Farinaud and Ragiot 1939), but it 
has been shown that sulfapyridine destroys 
the sexual as well as the asexual forms of 
P. vivax and that no relapses of the patients 
occur after treatment with large doses of 
this drug. In simian malaria sulfanilamide 
(Coggeshall 1938c), soluseptazine (Chopra 
and Das Gupta 1938) ^nd sulfapyridine 
(Chopra and Das Gupta'1939) were found 
to possess not only curative but also pro¬ 
phylactic value. For Soluseptazine the 
latter property has also been reported in 
man (Sinton, Hutton and Shute 193a). 
However, since in these experiments the 
prophylactic dose was rather large and the 
duration of the protection did not exceed 
32 hours, these findings have no practical 
significance and are important only from 
a theoretical viewpoint because they repre¬ 
sent the first instance of a chemoprophy- 
lactic effect in man with a non-toxic dose 
of an antimalarial. Although successful 
experiments along similar lines have been 
reported with plasmochin (James 1937), 
the doses required were distinctly in the 
toxic range. 
In view of the fact that effective prophy¬ 
laxis is the goal of all malarial control and 
that chemoprophylaxis is bound to play one 
of the most important parts in this work, 
the future efforts of research workers will 
probably be directed towards the finding of 
new compounds with prophylactic proper¬ 
ties, rather than towards further modifica¬ 
tions of quinine, plasmochin or atabrine 
which, although therapeutically highly 
effective, possess no chemoprophylactic 
properties. This work will necessitate not 
only the most careful investigation of pos¬ 
sible damages produced by very prolonged 
administration, but also the development 
of a dependable and practical method 
for the testing of prophylactic properties. 
Whether organic synthesis will provide us 
with the new agents or whether they will 
be isolated from one of the many plants 
used in the native tropical medicine, such 
as Oelipea jasminiflora (Peckolt 1899a), 
Tachia guanensis (Peckolt 1899b), Heli- 
anthus (Danzel 1929), etc., only future 
research will show. Up to this time only 
the synthetic compounds belonging to the 
sulfanilamide group have offered some 
promise, but it must be remembered that 
the great majority of tropical plants has 
not yet been investigated except in a super¬ 
ficial and incomplete manner. Existing 
reports are usually many years old and 
based on questionable statements collected 
from natives by explorers who themselves 
were laymen in the fields of pharmacology 
and medicine. Pharmacological analyses 
have been carried out either with inade¬ 
quate methods or under conditions which 
do not exclude the possibility of missing 
