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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

From: Plasmodium falciparum dihydroartemisinin-piperaquine failures in Cambodia are associated with mutant K13 parasites presenting high survival rates in novel piperaquine in vitro assays: retrospective and prospective investigations

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 %)
  1. Pfcrt Dd2, MAL10:688956 and MAL13:1718319 allele types are defined based on sequences available at plasmoDB.org
  2. *Calculated by the Mann-Whitney U or Kruskal-Wallis (H-test) tests
  3. **Calculated by the Fisher exact or χ2 tests
  4. ***Significant P values are shown in bold font