Drug-resistance in <i>Plasmodium gallinaceum</i>, and the persistence of paludrine-resistance after mosquito transmission

Abstract

1. Attempts, made over a period of more than 6 months, to produce a strain of Plasmodium gallinaceum resistant to mepacrine failed. 2. A strain of P. gallinaceum resistant to daily doses of 0·08 mg./20 g. of pamaquin was obtained after approximately 8 months' treatment with the drug. 3. A strain of P. gallinaceum resistant to the maximum dose of paludrine which the chicks would tolerate (1·0 mg./20 g. twice daily) was obtained after 4½ months' treatment with gradually increasing doses of the drug. 4. The exo-erythrocytic parasites of P. gallinaceum formed in chicks infected with a paludrine-resistant strain are themselves resistant to the drug. It is not, however, considered probable that the development of resistance is due to the action of the drugs upon the exo-erythrocytic parasites, as the technique used was one which reduced their number to a minimum. 5. A strain of P. gallinaceum resistant to paludrine showed a normal sensitivity to mepacrine and pamaquin, but was resistant to 4430, the methyl homologue of paludrine. 6. Chicks carrying a latent infection of the normal strain of P. gallinaceum were immune to infection with the paludrine-resistant strain; and conversely chicks carrying a latent infection of the paludrine-resistant strain were immune to infection with the normal parasite. 7. A paludrine-resistant strain of P. gallinaceum retained its resistance to this drug after five cyclical passages through mosquitoes without intervening drug treatment.