The development of resistance to metachloridine inPlasmodium gallinaceumin Chicks

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Abstract
1. An increase in resistance to metachloridine of more than 100-fold was obtained within a few weeks in a strain ofPlasmodium gallinaceumtreated with gradually increasing doses of the drug and maintained in young chicks by blood-inoculation at intervals of 2–3 days.2. There was no evidence that the rapid development of resistance arose by the selection of highly resistant individuals present in the normal population.3. Two strains ofP. gallinaceumpassaged through chicks treated with 0·025 mg. doses of the drug gradually became resistant to greater concentrations than that to which they had been exposed, though their growth rate decreased when they were inoculated into birds receiving higher doses of the drug.4. In both strains maintained in birds treated with 0·025 mg. doses of the drug, resistance reached a maximum beyond which it did not increase.5. Cross-resistance tests failed to show any relationship in mode of action between meta-chloridine and pamaquin, mepacrine, quinine or chloroquine. A strain ofP. gallinaceum, highly resistant to metachloridine, showed slight resistance to sulphadiazine, sulphapyridine and sulphathiazole, but none to sulphanilamide or proguanil.We are indebted to the Cyanamid Products Ltd., London, for the gift of the Folvite used in these experiments.