Article Figures & Data
Figures
- FIG. 1.
In vitro activities of the amino alcohols quinine (QN), mefloquine (MFQ), and halofantrine (HLF). Values on the y axis represent drug concentrations that inhibit 50% of parasite growth (IC50s), in nanomoles. Median IC50s for each drug are also represented.
- FIG. 2.
Diagram of pfnhe-1 gene (A) and ms4760 microsatellite sequence profiles (B). (A) Asterisks indicate polymorphic codons (894, 950, and 1437). (B) ms4760 profiles. Profiles 1 to 18 were previously described (10, 13), and we identified 4 new profiles, 20 to 23.
- FIG. 3.
Association between the number of DNNND repeats in pfnhe and the quinine concentration that inhibits 50% (A) or 90% (B) of parasite growth. Isolate numbers are in brackets. (A) Our current data from Kilifi. (B) Data from Ferdig et al. (10) (from Table 1). In both graphs, differences between 1 and 2 and between 2 and 3 repeats were significant (P < 0.0 5), while those between 1 and 3 repeats were not (P > 0.05). In the work of Fergid et al. (10), 1 isolate had 4 copies (IC90 = 582 nM) and was not included.
- FIG. 4.
Relationship between drug concentrations that inhibit 50% of parasite growth (IC50s) and the genotype combination of DNNND repeat number and pfmdr1-86 (A) or pfcrt-76 (B). On a backdrop of 2 repeats of DNNND, the pfcrt-76 genotype did not affect QN activity, while a 3-fold increase in the IC50 was observed for the pfmdr1-86 mutants.
Tables
- TABLE 1.
IC50s of quinine and pfnhe polymorphisms in P. falciparum
Isolate IC50 (nM) Codon polymorphisms Microsatellite polymorphisms 894 950 1437 No. of SDNN repeats msR1 ms3580 ms4760 3D7 27.1 AAT GTG TAT 4 Absent NIH ms4760-2 AK127 569.5 AAT GGG TAT 4 TCDNNMPNNNMSNNN NIH ms4760-1 AK182 549.2 AAT GGG TTT 2 TCDNNMPNNNMSNNN NIH ms4760-1 AK227 495.3 AAT GGG TAT 4 TCDNNMPNNNMSNNN NIH ms4760-1 CDA-1553 333.3 AAT GGG TTT 4 TCDNNMPNNNMSNNN NIH ms4760-1 AK150 D-0 296.6 AAT GGG TAT 3 Absent NIH ms4760-1 AK249 270.4 AAT GTG TAT 3 Absent NIH ms4760-1 AK121 270.2 AAT GGG TAT 4 TCDNNMPNNNMSNNN NIH ms4760-21 AK158 234.0 AAT GGG TAT 2 TCDNNMPNNNMSNNN NIH ms4760-1 AK167 227.0 AAT GGG TAT 4 TCDNNMPNNNMSNNN NIH ms4760-1 AK222 210.5 AAT GGG TAT 2 TCDNNMPNNNMSNNN NIH ms4760-1 AK152 D-56 207.7 AAA GTG TAT 2 Absent NIH ms4760-6 AK062 181.5 AAT GTG TAT 4 TCDNNMPNNNMSNNN NIH ms4760-1 AK144 145.8 AAT GTG TTT 4 Absent NIH ms4760-23 AK018 141.1 AAT GGG TTT 2 Absent NIH ms4760-20 AK150 D-42 91.6 AAT GGG TAT 2 Absent NIH ms4760-1 9067 80.1 AAT GTG TAT 4 TCDNNMPNNNMSNNN NIH ms4760-3 8885 78.2 AAT GGG TAT 3 Absent NIH ms4760-22 AK183 73.9 AAT GGG TTT 4 TCDNNMPNNNMSNNN Absent ms4760-20 6816 73.3 AAT GGG TAT 1 TCDNNMPNNNMSNNN NIH ms4760-18 8966 55.8 AAT GTG TAT 4 TCDNNMPNNNMSNNN Absent ms4760-1 AK033 D-49 54.1 AAT GGG TAT 3 TCDNNMPNNNMSNNN NIH ms4760-7 AK022D-0 42.4 AAT GGG TAT 4 TCDNNMPNNNMSNNN NIH ms4760-22 9070 41.5 AAT GGG TAT 4 TCDNNMPNNNMSNNN NIH ms4760-22 8977 35.9 AAT GGG TTT 3 Absent NIH ms4760-7 AK033 D-0 32.8 AAT GGG TAT 4 Absent NIH ms4760-1 8968 30.6 AAA GGG TAT 4 Absent NIH ms4760-2 8948 27.8 AAA GGG TAT 4 Absent NIH ms4760-7 AK022 D-28 22.0 AAT GGG TAT 4 TCDNNMPNNNMSNNN NIH ms4760-1 8973 20.0 AAT GGG TAT 4 TCDNNMPNNNMSNNN NIH ms4760-7
