THE RATE OF ACTION OF SULFADIAZINE AND QUININE ON THE MALARIAL PARASITE, PLASMODIUM GALLINACEUM

¹ From the Research Laboratories of the American Cyanamid Company, Stamford, Connecticut

1. a. The erythrocytic stages of the malarial parasite, Plasmodium gallinaceum, were treated continuously with large amounts of either sulfadiazine or quinine and observed at frequent intervals to determine the rate of action of these drugs.

b. Quinine completely inhibited growth and development of the parasites almost immediately in four out of five birds and in the fifth bird did not permit development beyond the four-nucleate stage.

c. With sulfadiazine the first detectable retardation of growth occurred by 24 but not by 12 hours. Development of the first treated generation proceeded to segmentation, but the average number of merozoites produced per segmenter was only 12.7 as compared to 20.3 for the untreated controls. These merozoites invaded erythrocytes but did not develop beyond the four-nucleate stage before complete inhibition occurred.

d. With quinine the parasites never increased in number and by the second day had dropped below the initial count. With sulfadiazine there was a four-fold increase in parasitemia in the first two days, compared to fifteen-fold in the controls. The parasitemia declined to the initial level by the third or fourth day and dropped below it on the fifth day.

2. The compound, 2-sulfanilamido-5-bromopyrimidine, also acts slowly

3. Sulfanilamides may also act slowly in sporozoite-induced infections since more than two days of treatment were required for maximum effects.

4. It is suggested that the length of time required for effective inhibition by sulfanilamides and other slowly acting compounds increases as the growth rate of the organism decreases. This may have practical implications in chemotherapeutics trials.