Susceptibility studies of Plasmodium falciparum isolates and clones against cycloguanil and pyrimethamine using the modified in vitro microtechnique

Six clones were derived from each Malaysian Plasmodium falciparum isolate and characterized for their susceptibilities against type II antifolate drugs, cycloguanil and pyrimethamine. Re suits showed that these isolates were of a heterogeneous population, with average IC50 values of Gombak C clones at 0.012-0.084 mu M and 0.027-0.066 mu M, ST 9 clones at 0.019-0.258 mu M and 0.027-0.241 mu M, ST 12 clones at 0.015-0.342 mu M and 0.012-0.107 mu M, ST 85 clones at 0.022-0.087 mu M and 0.024-0.426 mu M, and ST 148 clones at 0.027-0312 mu M and 0.029-0.690 mu M against cycloguanil and pyrimethamine, respectively. Generally, most of these clones displayed susceptibility patterns similar to their parent isolates except ST 9/A4, ST 9/A7, ST 9/B5, ST 9/D9, ST 9/D10, ST 148/A4, ST 148/A5, ST 148/A7, ST 148/F7, ST 148/F8 clones, which were sensitive at 0.027 mu M, 0.019 mu M, 0.022 mu M, 0.063 mu M, 0.037 mu M, 0.031 mu M, 0.042, mu M, 0.042 mu M, 0.062 mu M, and 0.027 mu M, whereas, ST 12/D7 clone was resistant at 0.342 mu M, against cycloguanil respectively. However, ST 9/A4, ST 9/D8, ST 12/D5, ST 85/A5, ST 85/B3, ST 85/B4, ST 85/D3, ST 85/D7, ST 148/A6, and ST 148/A7 clones were resistant to pyrimethamine at 0.158 mu M, 0.241 mu M, 0.107 mu M, 0.223 mu M, 0.393 mu M, 0.402 mu M, 0.426 mu M, 0.115 mu M, 0.690 mu M, and 0.520 mu M, respectively.