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A Study of the Prophylactic, Curative and Suppressive Activity of SN-11,437 (Metachloridine¹ in Standardized Infections of Vivax Malaria^,2

Introduction SN-11,437, a metanilamide (Fig. 1), was chosen for study of its pharmocological and antimalarial properties in Plasmodium vivax infections in man, because it is an effective prophylactic agent in Plasmodium gallinaceum infection in the chick, at one-fifteenth the dose needed to achieve prophylaxis with sulfadiazine, and because it has high activity in other avian malarias (1, 2). The unique efficacy of a few sulfonamides, notably sulfadiazine, in gallinaceum infections, which is characterized by an abundance of exo-erythrocytic parasites (3), has created special interest in related compounds since these forms of the parasite are refractory to quinacrine and quinine. Considerable indirect evidence also suggests that the persistence of pre-erythrocytic or tissue stages is responsible for relapses in vivax malaria. The marked qualitative superiority of SN-11,437 over sulfadiazine in avian infections led to the consideration that it might prove effective in vivax malaria, where sulfadiazine has only slight, if any, effect as a suppressive agent (4, 5) and does not lead to radical cure (5, 6).

¹ Metachloridine is the proprietary name for N¹-(5-chloro-2-pyrimidyl) metanilamide, one of a number of metanilamides prepared in the laboratories of the Calco Chemical Division of the American Cyanamide Company.

² This investigation was carried out under contract, recommended by the Committee on Medical Research, between the Office of Scientific Research and Development and the University of Chicago. The studies were planned in cooperation with the Panel on Clinical Testing of Antimalarials of the Board for the Coordination of Malarial Studies. This work was further aided by the participation of Army Medical Officers assigned to the project by The Surgeon General, U. S. Army.

Through a cooperative arrangement between Professor Clay G. Huff and Dr. Frederick Coulston, Department of Bacteriology and Parasitology, and the Malarial Research, Unit, Department of Medicine, the former group bred Anopheles quadrimaculatus mosquitoes, supervised their infection and the inoculation of volunteers, and determined the intensity of infection in the salivary glands of the mosquitoes. The latter group assumed the responsibility for clinical care of patients studied by both groups.

³ Captain, M.C., A.U.S.