Table 1.
Association between candidate molecular markers (mutations and copy number variation (CNV)) previously associated with piperaquine resistance and in vitro piperaquine survival assay (PSA) phenotypes of 32 culture-adapted isolates collected from patients treated with 3-day courses of dihydroartemisinin-piperaquine in 2012
| Gene polymorphism | Piperaquine survival assay (PSA) | ||||||
|---|---|---|---|---|---|---|---|
| n | Survival rate (median, IQR) | P value* | PSA <10 % n = 8 | PSA ≥10 % n = 21 | P value ** | ||
| P. falciparum chloroquine resistant transporter gene - Pfcrt (PF3D7_0709000) | |||||||
| Alleles | 74I/75E/76 T/220S/271E/326S/343L/356 T/371I | 7 | 61.5 (53.6–69.2) | 0.005 | 0 (0 %) | 7 (33 %) | 0.03*** |
| 74I/75E/76 T/220S/271E/326S/356T/371I (Dd2 allele) | 16 | 12.8 (0.6–43.7) | 8 (100 %) | 8 (38 %) | |||
| 74I/75E/76 T/220S/271E/326S/353V/356 T/371I | 2 | 49.2 (37–61.5) | 0 (0 %) | 2 (9.5 %) | |||
| 74I/75E/76 T/97Y/220S/271E/326S/356T/371I | 4 | 47.1 (40.9–61.2) | 0 (0 %) | 4 (19 %) | |||
| P. falciparum multidrug resistance 1 gene - Pfmdr-1 (PF3D7_0523000) | |||||||
| Alleles | 643D | 1 | 70.6 | 0.16 | 0 (0 %) | 1 (5 %) | 0.27 |
| 184 F | 16 | 51.8 (3.5–61.5) | 5 (63 %) | 11 (52 %) | |||
| 184 F/293D | 3 | 19.3 (9.3–35.4) | 1 (12 %) | 2 (9.5 %) | |||
| 184 F/1087 L | 6 | 44 (40.1–49.6) | 0 (0 %) | 6 (29 %) | |||
| wild-type | 3 | 0.8 (0.5–27.9) | 2 (25 %) | 1 (5 %) | |||
| CNV (957885 to 962144) | single copy | 24 | 48.1 (38.2–60.1) | 0.001 | 3 (38 %) | 21 (100 %) | 10−3*** |
| multi-copy (184 F, n = 2 and wild-type, n = 3) | 5 | 0.6 (0.4–2.1) | 5 (62 %) | 0 (0 %) | |||
| P. falciparum multidrug resistance-associated protein 1 - Pfmrp-1 (PF3D7_0112200) | |||||||
| Alleles | 191Y/437A/785 N/876 V/1007 M | 3 | 0.8 (0.5–83.1) | 0.15 | 2 (25 %) | 1 (5 %) | 0.02*** |
| 191Y/437A/876 V | 1 | 37 | 0 (0 %) | 1 (5 %) | |||
| 191Y/437A/876 V/1390 T | 16 | 50.5 (39.7–60.1) | 1 (13 %) | 15 (72 %) | |||
| 191Y/437A/876 V/1390 T/1669D | 1 | 0.6 | 1 (12 %) | 0 (0 %) | |||
| 191Y/325S/437A | 8 | 22.9 (0.6–47.1) | 4 (50 %) | 4 (19 %) | |||
| P. falciparum multidrug resistance-associated protein 2 - Pfmrp-2 (PF3D7_1229100) | |||||||
| Alleles | 199 V/295R/593D/714I/1527 T/1531I | 1 | 0.7 | 0.07 | 1 (12.5 %) | 0 (0 %) | 0.003*** |
| 199 V/622D/646D/714I/1188 N/1527 T/1531I | 2 | 3.5 (0.6–6.4) | 2 (25 %) | 0 (0 %) | |||
| 199 V/646D/714I/1176 N/1188 N/1527 T/1531I | 1 | 0.8 | 1 (12.5 %) | 0 (0 %) | |||
| 199 V/646D/714I/1188 N/1527 T/1531I | 10 | 58.7 (29.0–62.1) | 2 (25 %) | 8 (35 %) | |||
| 199 V/646D/714I/1527 T/1531I | 16 | 41.7 (38.2–51.6) | 1 (12.5 %) | 15 (65 %) | |||
| 199 V/646D/714I/964D/970 N/1527 T/1531I | 1 | 0.3 | 1 (12.5 %) | 0 (0 %) | |||
| MAL10:688956 (Chr10) | |||||||
| Alleles | 3D7 allele type (T) | 10 | 22.9 (0.6–51.8) | 0.20 | 5 (62.5 %) | 5 (24 %) | 0.08 |
| V1/S mutant-type (A) | 19 | 46.7 (31–58.2) | 3 (37.5 %) | 16 (76 %) | |||
| MAL13:1718319 (Chr13) | |||||||
| Alleles | 3D7 allele type (A) | 1 | 0.3 | – | 1 (12.5 %) | 0 (0 %) | 0.27 |
| V1/S mutant-type (T) | 28 | 41.6 (12.8–57.7) | 7 (87.5 %) | 21 (100 %) | |||
| PFE1010w (Chr5, 831614 to 834340) | |||||||
| CNV | single copy | 29 | – | – | 8 (100 %) | 21 (100 %) | – |
| multi-copy | 0 | – | 0 (0 %) | 0 (0 %) | – | ||
| PFE1085w (Chr5, 882373 to 884898) | |||||||
| CNV | single copy | 29 | – | – | 8 (100 %) | 21 (100 %) | – |
| multi-copy | 0 | – | 0 (0 %) | 0 (0 %) | – | ||
Pfcrt Dd2, MAL10:688956 and MAL13:1718319 allele types are defined based on sequences available at plasmoDB.org
*Calculated by the Mann-Whitney U or Kruskal-Wallis (H-test) tests
**Calculated by the Fisher exact or χ2 tests
***Significant P values are shown in bold font