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The Effect of a Repository Preparation of the Dihydrotriazine Metabolite of Chlorguanide, CI-501, Against the Chesson Strain of Plasmodium Vivax in Man

A repository preparation of the dihydrotriazine metabolite of chlorguanide, CI-501, was tested in 28 volunteers for its efficacy as an antimalarial drug. A single intramuscular injection at a dose of 5 mg (base)/kg body weight was given to each volunteer.

The medicated volunteers were exposed to infection with the Chesson strain of Plasmodium vivax either by bites of heavily infected mosquitoes or by the intravenous inoculation of parasitized homologous blood. The number of challenges (exposures to infection) ranged from one to ten. The intervals of time between exposures were variable. Twenty-three volunteers were used as controls to prove mosquito infectivity.

To date (24 January 1963), CI-501 continues to protect 20 out of 24 volunteers exposed to vivax malaria by the bites of infected mosquitoes. The duration of protection ranges from 267 to 367 days (9 to 12 months). The four volunteers who developed patent parasitemias were protected for 169, 264, 341 and 426 days.

Four volunteers challenged with parasitized homologous blood at 49 to 146 days after medication were completely protected.

Four infected control volunteers were treated therapeutically with this repository preparation. The response was equal to that following administration of a single 600 mg (base) dose of chloroquine. There has been no evidence of relapse through 181 to 246 days.

These results indicate that the repository preparation known as CI-501 has the capacity to exert long-term protection and is therapeutically effective against human vivax malaria. The importance of such a preparation in a program of world-wide malaria eradication is obvious.

^* Present address: The Boston City Hospital, 818 Harrison Avenue, Boston 18, Massachusetts.

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