EXPERIMENTAL CHEMOTHERAPHY IN MALARIA 
269 
placed in the side-arm of the flask, which is 
then connected with the manometer and 
shaken in a water bath at 37° C. The oxy¬ 
gen uptake is measured for an hour in order 
to be sure that all flasks have the same rate 
of respiration. The drug is then tipped in 
from the sidearm and the respiration mea¬ 
sured for an hour, with two flasks without 
drug as control. The oxygen uptakes are 
calculated per hundred million parasites so 
that all experiments are comparable. The 
difference between the oxygen uptake in the 
control flask and in the drug flask, divided 
by the uptake of the control flask, gives a 
percentage coefficient of inhibition for the 
drug used. 
Results of representative experiments 
are shown in Table I. Here it is seen that 
and sulfadiazine, which also produce 
sterilization of the infection in the host, 
produce no inhibition of respiration in 
vitro. This is to be expected from the 
nature of the two compounds. Sulfadia¬ 
zine is insoluble, only 12 mg per 100 cc 
dissolving at 37° C, and therefore would 
not be expected to show activity in vitro. 
In the monkey it is apparently converted 
into a soluble derivative since the effect is 
just as great as that of sodium sulfathia- 
zole or sulfanilamide. Prontosil is a com¬ 
plex azo dye of which the sulfanilamide 
molecule is a part. In vitro it has no activ¬ 
ity; in vivo it is converted into sulfanila¬ 
mide (Trefouel 1935 et al.; Puller 1937) 
and is fully as effective as this drug. 
Further experiments summarized in 
TABLE I 
Chemotherapeutic Activity of Various Drugs Against P. Tcnowlesi 
Drug 
Concentration 
in flask 
0 2 uptake 
(mm 3 /hr/10 8 parasites) 
Coefficient 
of 
inhibition 
I-II/I 
Therapeutic 
effect 
Control 
flask 
I 
Flask 
with drug 
II 
mg 
molar 
mm * 
mm 3 
Quinine dihydrochloride. 
1.6 
0.001 
15.1 
9.7 
36 
++ 
10.3 
6.7 
35 
Atabrine . 
0;001 
27.2 
9.0 
67 
++ 
15.1 
4.4 
71 
Sodium sulfathiazole . 
10 
0.01 
19.3 
9.8 
49 
+++ 
19.3 
10.9 
44 
11.2 
6.8 
40 
32.0 
18.0 
44 
25.7 
15.3 
41 
Sodium sulfapyridine . 
10 
0.012 
14.2 
7.9 
44 
+++ 
Prontosil . 
10 
0.004 
27.2 
28.0 
0 
+++ 
20 
0.008 
27.2 
26.6 
0 
Sulfadiazine . 
10 
0.010 
23.0 
23.0 
0 
4-H- 
-H-Arrest of acute infection without sterilization. 
+++ Sterilization of acute or chronic infections. 
0.001 M quinine dihydrochloride inhibits 
the respiration of P. knowlesi from 35 to 
36 per cent; 0.001 M atabrine produces 67 
to 71 per cent inhibition. The inhibition 
produced by sodium sulfathiazole (40 to 
49 per cent) is approximately the same as 
that produced by sodium sulfapyridine 
(44 per cent); both these drugs produce 
complete sterilization of the infection in 
the rhesus monkey. However, prontosil 
Table II show the effect of 0.01 M sodium 
sulfathiazole against various plasmodia. It 
is seen that the inhibition of respiration 
produced for P. inui and P. cynomolgi is 
58 and 50 to 51 per cent, respectively, which 
is greater than the inhibition produced for 
P. knowlesi. This is in contrast to the 
activity of the drug against the three infec¬ 
tions in vivo. It sterilizes P. knowlesi 
infections completely, but when given in 
