COMPARISON OF CHLOROQUINE, QUINACRINE (ATABRINE), AND QUININE IN THE TREATMENT OF ACUTE ATTACKS OF SPOROZOITE-INDUCED VIV AX MALARIA (CHESSON STRAIN) 1

Abstract

C h I o r o q u i n e, 7-chloro-4-(4-diethylamino-l-methyl-butylamino)-quinoline, a synthetic anti-malarial agent developed during the war, has proved superior to atabrine and quinine (1). The following investigations were designed to supplement other observations in induced malaria and field observations by a study of the relative effectiveness of chloroquine, quinacrine, and quinine in the treatment of acute attacks of standardized sporozoite-induced vivax infections. PROCEDURES AND METHODS General Details of the general procedure and the plan of investigation are reported elsewhere (2). Thirty-nine healthy Caucasian volunteers at Stateville Penitentiary were infected with South Pacific zAvax malaria (Chesson strain) by the bites of ten infected Anopheles quadri-maculatus mosquitoes or by injection of their infected salivary glands.8 The Chesson strain (3) was chosen of because it is characterized by a high relapse rate, short latent interval between relapses, and almost complete absence of delayed primary attacks (4, 5, 6). Evaluation of results could be made with a small number of subjects because the complete history of each infection was known; and because the effect of immunity on relapse rate was minimized by utilizing presumably susceptible individuals living in a non-endemic area, and by limiting therapeutic trials to primary attacks and early relapses. In addition, treatment was initiated early in most of the attacks.4 Drug administration Chloroquine. A total of 2 grams of base (equivalent to 3.2 grams of the diphosphate) was administered over a period of one week. After an initial dose of 0.4 gram of base, followed by two doses of 0.2 gram at four-hour intervals, the daily maintenance was 0.2 gram. Quinacrine. After an initial dose of 0.4 gram of quina-crine dihydrochloride (approximately 80 per cent base) followed by three of 0.2 gram at four-hour intervals, the daily maintenance dose was 0.4 gram. The total amount of, quinacrine for seven days was 3.4 grams of the salt. Quinine. Two groups of subjects received quinine; one for seven days and one for 14 days. In the first group, a total of 11-12 grams of base (approximately equivalent to 13-15 grams of the hydrochloride or sul-fate) was administered over seven days. In the second group, a total of 21-23 grams of base was administered over a 14-day period. Analysis of drugs in plasma Whole blood was centrifuged for 15 minutes at 2,000 r.p.m.; the plasma was separated and recentrifuged for the Department of Bacteriology and Parasitology. They supervised infection of mosquitoes, inoculation of volunteers and determined the intensity of infection in the salivary glands of the mosquitoes. 4The investigations reported in this paper would not have been possible except for the enthusiastic cooperation of the inmates and the administrative staff of Stateville Penitentiary. 46