Sensitivity To Dihydrofolate Reductase Inhibitors And Molecular Karyotypes In Some Plasmodium Falciparum Isolates In Kenya

Abstract

Ten Kenyan isolates of Plasmodium [alcip arum were characterized by their molecular karyotype and antimalarial drug sensitivity. For chromosomal analysis pulse field gradient gel electrophoresis was used. Plasmodium jalciparum isolates from malarious areas in Nyanza. Rift Valley and Coast provinces were cultivated ill vitro and used for the karyotype study. The sensitivities of cultured isolates to three antifolate malarial drugs (pyrimethamine, cycloguanil and chlorcycloguanil) and sulphadoxine which is a sulphonamide were examined by the ill vitro radioisotopic methods of Desjardins et al. (1979) with minor modifications. Considerable variation was found in the antimalarial drug response of the 10 parasite isolates. Among the four antimalarial drugs examined, chlorcycloguanil and cycloguanil had similar potencies. They were more potent than pyrimethamine and sulphadoxine. Sulphadoxine and pyrimethamine had similar potencies. Cycloguanil and chlorcycloguanil, which are closely related biguanides were highly correlated in their antimalarial activities. There was no correlation between the activity of the three antifolates and sulphadoxine. The isolates from the Rift Valley province showed significantly lower susceptibility to the four antimalarial drugs tested than those from the Coast and Nyanza provinces. The isolates from Coast province showed the highest susceptibility. The chromosomal bands were found to range- in number from 14 to 16 and in size from 600 to 4300 kilobase pairs, and there was extensive variation in chromosome size. Two isolates had more than the constant number of chromosomes, suggesting a mixed population of parasite strains in natural malarial infections.There were inter and intraregional differences in the sizes of the chromosomes. However. there was no correlation between band size and drug sensitivity. The degree of polymorphism shown by the

chromosomes was such that each isolate could be individually characterised by its chromosomal pattern.