Sulphadiazine-resistance in Plasmodium gallinaceum and its relation to other antimalarial compounds

Abstract

1. A thirty-two-fold increase in resistance to sulphadiazine has been induced in Plasmodium gallinaceum in chicks by treatment with that drug.2. No loss in resistance to sulphadiazine occurred in the resistant strain during cyclical passage through Aëdes aegypti.3. The sulphadiazine-resistant strain was resistant also to sulphathiazole, sulphanilamide and sulphapyridine, but not to mepacrine, quinine or pamaquin. An increase in sensitivity to pamaquin was observed.4. The sulphadiazine-resistant strain was resistant to paludrine and its methyl homologue M 4430.5. In strains maintained in a state of acute infection and treated with sulphadiazine, resistance to paludrine developed more rapidly than resistance to sulphadiazine, and in one strain a high degree of resistance to paludrine was obtained before any increase in resistance to sulphadiazine could be detected.6. Resistance to paludrine as induced by sulphadiazine, develops rapidly and extends at once over the full range of doses which the chick will tolerate, whereas resistance to paludrine as induced by that drug itself, develops more slowly and by stages.7. Whereas resistance to paludrine is induced readily by treatment with sulphadiazine, resistance to sulphadiazine is induced by paludrine only after treatment with high doses of the drug for a prolonged period.8. In latent infections of Plasmodium gallinaceum resistance to paludrine or sulphadiazine was not induced by sulphadiazine during the period of the experiment (49–75 days), though the aggregate dosage of drug used was much greater than that with which resistance was induced in strains maintained in an acute state.9. It is not considered probable that cross-resistance between sulphadiazine and paludrine is due to a similar mode of action of these drugs, as whereas sulphadiazine is antagonized by p-amino-benzoic acid paludrine is not.