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A New Criterion for the Selection of Compounds for Curative Activity in Plasmodium Vivax Malaria

Levon A. Terzian, P. A. Ward AND N. Stahler^*,,

It appears, therefore, that there is a specific relation between the toxic activity of a compound to the sporozoites of P. gallinaceum and its curative activity against the forms that produce relapse in P. vivax malaria since only those compounds which have a curative action in P. vivax malaria equal to or greater than pamaquine are specifically toxic to the sporozoites of P. gallinaceum, whereas those compounds with no curative action, or a curative activity below that of pamaquine, have no discernible effect on the sporozoites of this parasite. It seems not unlikely, therefore, that there may be a physiological similarity, at least in drug reaction, between the sporozoites of P. gallinaceum and the forms responsible for relapse in P. vivax.

Thus, this relation should provide a reliable method for the evaluation of compounds for possible therapeutic or curative activity in P. vivax malaria, eliminating thereby the most serious defect, already noted, inherent in testing methods utilizing the vertebrate cycle of experimental animal malarias. Furthermore, both A. aegypti and P. gallinaceum are comparatively easy and inexpensive to maintain in the laboratory, only very small samples of drug are required, and as a consequence, this technic would make possible an extensive and accelerated drug testing program at very little cost.

^* The Naval Medical Research Institute, Bethesda 14, Maryland.

The authors wish to thank Dr. Joseph Greenberg and Dr. E. S. Josephson of the Laboratory of Tropical Diseases, National Institutes of Health, who supplied the drugs used in this study, and in some cases, converted compounds into their soluble salts, and Dr. E. Jerome for the statistical analyses of the data.

The opinions or assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the Navy Department or the Naval Service at large.