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The Activity of a Repository Form of 4,6-Diamino-1-(p-Chlorophenyl)-1,2-Dihydro-2,2-Dimethyl-s-Triazine against Infections with Plasmodium Cynomolgi^*

L. H. Schmidt, Richard N. Rossan AND Kathleen F. Fisher

This report deals with the activities of a pamoate salt of the triazine metabolite of chlorguanide (CGT·P) against experimental infections with Plasmodium cynomolgi, with special emphasis on sporozoite-induced disease. The major objectives of the study were: (1) to determine the duration of protection afforded by a single dose of CGT·P against repeated challenge with massive doses of sporozoites; (2) to ascertain whether resistance of the plasmodia to chlorguanide triazine (CGT) develops during the protective period, especially in its terminal phases; (3) to determine whether CGT·P acts in effect as a "prophylactic" or merely as a long-term suppressive; and (4) to compare the rapidity of clearance of established parasitemias in recipients of CGT·P with the rates of parasite clearance achieved by the water-soluble hydrochloride salts of CGT and chlorguanide (CG).

The results of these explorations have led to the following conclusions: (1) A single 50 mg per kg dose of CGT·P confers protection against repeated sporozoite challenges for at least 6 months and in isolated cases for 11 to 15. (2) When breakthroughs do occur, the parasites which appear exhibit no evidence of resistance to CGT. (3) CGT·P administered in an appropriate doseacts as an effective "prophylactic" against challenge with a massive dose of sporozoites. (4) Parasite clearance in established infections is as rapid in recipients of a single 50 mg per kg dose of CGT·P as it is when conventional daily doses of the hydrochlorides of CGT and CG are administered.

The significance of the above findings for control of human malarias is discussed as are some of the problems which must be dealt with before the full potential of CGT·P can be realized.

^* This investigation was supported in part by grants from the National Institute of Allergy and Infectious Diseases, Public Health Service, (AI-02372) and the Research Laboratories, Parke, Davis and Company, Ann Arbor, Michigan.

Present address: National Primate Center, University of California, Davis, Davis, California.

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