Variability in schizonticidal drug susceptibility amongst clones and isolates of Plasmodium falciparum.
Plasmodium falciparum isolates from Malaysia, Africa and Thailand were cultured in vitro following the method of Trager and Jensen and subsequently cloned using the limiting dilution method of Rosario. These clones were presently characterized against three schizonticidal drugs, chloroquine, mefloquine and quinine, using the modified in vitro microtechnique. Results showed that all the clones derived from Gombak A isolate were chloroquine-resistant with average IC50 values ranging at 0.1377-1.0420 microM (0.007-0.058 mefloquine activity), sensitive to mefloquine at 0.0032-0.0103 microM and quinine at 0.0025-0.0428 microM (0.075-3.080 mefloquine activity). Similarly, the TGR clone displayed resistance to chloroquine at 0.1715-0.5875 microM (0.002-0.029 mefloquine activity) but were also sensitive to mefloquine at 0.0008-0.0058 microM and quinine at 0.0055-0.0700 microM (0.055-0.202 mefloquine activity). In contrast, four out of six Gambian clones were sensitive to chloroquine at 0.0047-0.0172 microM (0.122-0.617 mefloquine activity) but all were sensitive to mefloquine at 0.0008-0.0029 and 0.0016-0.0102 microM (0.096-1.813 mefloquine activity). In general, most of the clones displayed susceptibility patterns similar to that of their parent isolates against the three schizonticidal drugs except Gm/B2 and Gm/H5 Gambian clones were chloroquine-resistant at 0.3427 microM (0.006 mefloquine activity) and 0.2260 microM (0.004 mefloquine activity), respectively. Further results indicated that they were pure clones compared to their parent isolates as their schizonticidal drug susceptibilities were statistically different (p < 0.05) except Gm/C6 and TGR/B7 clones against mefloquine (p < 0.05).
Ang
H H
HH
School of Pharmaceutical Sciences, University of Science Malaysia, Minden, Penang, Malaysia.
Chan
K L
KL
Mak
J W
JW
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance; D005714:Gambia; D006801:Humans; D008296:Malaysia; D015767:Mefloquine / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects*; D011803:Quinine / Q000494:pharmacology; D013785:Thailand
D000962:Antimalarials; D002738:Chloroquine; D011803:Quinine; D015767:Mefloquine