In vitro susceptibility studies of Plasmodium falciparum isolates and clones against type II antifolate drugs

Six clones were derived from each Plasmodium falciparum isolate obtained from Malaysia, Africa and Thailand and were characterized against type II antifolate drugs, cycloguanil and pyrimethamine using the modified in vitro microtechnique. Results showed that these isolates were of a heterogeneous population, with 50% inhibitory concentrations of Gombak A clones at 0.0151-0.1450 and 0.0068-0.1158 mu M, Gambian clones at 0.0056-0.1792 and 0.0004-0.0068 mu M and TGR clones at 0.0103-0.0703 and 0.0776-0.3205 mu M against cycloguanil and pyrimethamine, respectively. All clones displayed similar susceptibilities as their parent isolates except A/D3, A/D5, A/G4 and A/H7 clones which were sensitive to cycloguanil at 0.0735, 0.0151, 0.0540 and 0.0254 mu M but Gm/B2 clone was resistant at 0.1797 mu M, respectively. However, A/D3, TGR/B4, TGR/B7, TGR/C4, TGR/C7 and TGR/H2 clones were resistant to pyrimethamine at 0.1158, 0.1070, 0.1632, 0.1580, 0.2409 and 0.3205 mu M respectively. Further results indicated that they were pure clones compared to their parent isolates as their drug susceptibility studies were statistically different (p < 0.05).