The chemotherapy of Plasmodium berghei. I. Resistance to drugs

Abstract

1. Strains of P. berghei resistant to sulphadiazine, pyrimethamine, and methylene blue were produced by treating acute infections with low doses of drug.2. The strain resistant to methylene blue was sensitive to pamaquin, mepacrine, sulphadiazine, proguanil, pyrimethamine, and 2 : 4-diamino-6 : 7-camphano-pteridine.3. The pyrimethamine-resistant strain was cross-resistant to proguanil and its active metabolite CPT, 2 : 4-diamino-6 : 7-camphanopteridine, 2 : 4-diamino-6 : 7-(l′-ethylindolo)-pteridine, and 2 : 4-diamino-5-p-chlorophenylpyrimidine.4. The sulphadiazine-resistant strain was cross-resistant to pyrimethamine, sulphanilamide, proguanil and its active metabolite CPT, 2 : 4-diamino-6 : 7-dinhexylpteridine, and 2 : 4-diamino-6 : 7-diisopropylpteridine. It was as sensitive as the parent strain to quinine, mepacrine, chloroquin, pamaquin, methylene blue, and M 3349.5. The action of sulphadiazine against the sulphadiazine-resistant strain was inhibited by the same doses of p-aminobenzoic acid and folic acid as were required with the parent strain, although the dose of sulphadiazine was increased 30-fold.