Table 4.
Association between piperaquine (PPQ) resistance mutations (SNPs as well as copy number variation (CNV)) with in vitro PPQ IC50s of Kenyan field isolates collected between 2008 and 2021
| In vitro SYBR Green I assay | |||||
|---|---|---|---|---|---|
| Gene Polymorphisms/Assay | N | Proportions (%) |
PPQ median IC50 (IQR) nM | P value | |
|
P. falciparum multidrug resistance 1 gene, Pfmdr1 SNPs |
N86 | 34 | 75.6 | 23.5 (12.7–44.4) | 0.26 |
| 86N/Y | 6 | 13.3 | 34.9 (22.0–80.5) | ||
| 86Y | 5 | 11.1 | 29.9 (26.5–288.5) | ||
| Y184 | 22 | 47.8 | 29.5 (21.1–39.0) | 0.55 | |
| 184Y/F | 6 | 13.0 | 26.9 (9.2–80.7) | ||
| 184F | 18 | 39.1 | 23.9 (11.4–45.0) | ||
| A1034 | 34 | 85.0 | 29.7 (21.1–39.0) | 0.81 | |
| 1034T | 6 | 15.0 | 30.3 (10.3–279.4) | ||
|
P. falciparum chloroquine resistance transporter 1 gene, Pfcrt SNPs |
K76 | 25 | 65.8 | 18.9 (10.1–31.9) | 0.0026** |
| 76K/T | 5 | 13.2 | 36.6 (26.1–249.9) | ||
| 76T | 8 | 21.0 | 33.8 (22.2–73.2) | ||
| T356 | 9 | 37.5 | 18.9 (7.7–42.6) | 0.73 | |
| 356C | 15 | 62.5 | 15.7 (6.5–29.5) | ||
| G371 | 10 | 64.3 | 16.6 (8.0–30.3) | 0.96 | |
| 371T | 18 | 35.7 | 20.2 (9.2–31.2) | ||
|
P. falciparum dihydrofolate reductase gene, Pfdhfr SNPs |
C59 | 4 | 11.8 | 18.3 (7.8–69.1) | 0.98 |
| 59R | 30 | 88.2 | 22.4 (1.7–33.4) | ||
| I164 | 30 | 92.3 | 23.2 (10.8–33.4) | 0.58 | |
|
P. falciparum dihydropteroate synthetase gene, Pfdhps SNPs |
164L | 2 | 7.7 | 30.3 (18.3–42.2) | |
| S436 | 16 | 84.2 | 22.4 (11.8–34.7) | 0.88 | |
| 436F | 3 | 15.8 | 18.9(2.2–416.1) | ||
| A437 | 19 | 73.1 | 20.2 (8.8–32.7) | 0.33 | |
| 437G | 7 | 26.9 | 31.4 (22.4–36.6) | ||
|
P. falciparum multidrug resistance 1 gene, Pfmdr1 CNV |
Single copy | 271 | 96.8 | 29.9 (14.4–47.4) | 0.48 |
| Multiple copies | 9 | 3.2 | 46.1 (12.1–99.9) | ||
|
P. falciparum plasmepsin 2 gene, Pfpm2 CNV |
Single copy | 280 | 97.9 | 29.9 (14.4–47.2) | 0.63 |
| Multiple copies | 6 | 2.1 | 44.6 (18.3 –71.0) | ||
|
P. falciparum plasmepsin 3 gene, Pfpm3 CNV |
Single copy | 276 | 92.9 | 30.0 (14.5–47.6) | 0.72 |
| Multiple copies | 20 | 7.1 | 31.3 (19.6–48.2) | ||
** Show P < 0.05 consistent with statistically significant differences in frequency over time using Kruskal-Wallis (H) tests for three groups and Mann-Whitney (U) test for two groups