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Table 7 List of new pfk13 mutant alleles strongly associated with slow parasite clearance

From: Association of mutations in the Plasmodium falciparum Kelch13 gene (Pf3D7_1343700) with parasite clearance rates after artemisinin-based treatmentsa WWARN individual patient data meta-analysis

WHO designations This paper
Codon Status Codon N total isolates # sites N mutant % Prevalence: Median (Range)1 xPC1/2 (95% CI)2
pfk13 mutant alleles associated with slow parasite clearance
 N458Y Validated N458Y 1118 2 38 3 (2–4) 2.5 (2.2–2.9)
 Y493H Validated Y493H 638 8 41 4 (2–19) 2.7 (2.3–3.1)
 R539T Validated R539T 767 10 80 7 (2–53) 2.1 (1.9–2.4)
 I543T Validated I543T 323 4 94 13 (4–81) 2.1 (1.8–2.4)
I543T* 240 3 27 10 (4–16) 2.8 (2.3–3.5)
 R561H Validated R561H 1083 4 42 4 (3–6) 2.2 (1.9–2.6)
 C580Y Validated C580Y 2343 14 536 21 (2–75) 2.3 (2.1–2.4)
pfk13 mutant alleles newly associated with slow clearance phenotype
 E252Q Not assoc E252Q 1236 2 124 13 (10–16) 1.5 (1.4–1.6)
 P441L Candidate P441L 1248 3 67 8 (5–10) 2.2 (2.0–2.4)
 F446I Candidate F446I 764 7 98 31 (1–67) 1.5(1.4–1.7)
 G449A Candidate G449A 88 3 7 15 (3–25) 1.9 (1.3–2.7)
M476I Low prev M476I 886 3 10 3 (1–3) 2.0 (1.5–2.5)
A481V Low prev A481V 852 3 10 8 (1–9) 1.6 (1.2–2.2)
 R515K Low prev R515K 573 1 6 1 (1–1) 2.0 (1.5–2.7)
 P527H Low prev P527H/L** 711 1 23 3 (3–3) 1.7 (1.5–2.0)
 N537I/D Low prev N537I 656 2 10 3 (1–4) 1.8 (1.4–2.4)
 G538V Candidate G538V 1163 2 27 2 (2–2) 1.9 (1.6–2.2)
 P553L Candidate P553L 1112 4 18 6 (1–12) 2.2 (1.8–2.8)
 V568G Candidate V568G 195 2 6 3 (2–4) 2.7 (1.8–4.1)
 P574L Candidate P574L 1203 8 48 6 (2–50) 2.0 (1.7–2.2)
P574L*** 1177 7 35 5 (2–17) 1.8 (1.6–2.1)
 P667T Low prev P667T 346 1 7 2 (2–2) 2.1 (1.6–2.9)****
 A675V Candidate A675V 1114 1 53 5 (5–5) 2.2 (2.0–2.4)
  1. 1Prevalence is calculated per study site, combining data from all studies in that location, restricted to range of years when the mutation was observed
  2. 2Increase in PC1/2 compared to wild type; all p values for comparison with WT < 0.001. All have a half-life between 1.5 and 2.7 fold greater than the wild type. WHO designations can be found in [57]
  3. *With study ID 8, study site ID 23 (Tra Lang) removed
  4. **20 P527H, one P527L, analyzed together, two P527H not analyzed since clearance data did not meet criteria
  5. ***With study ID 13, study site ID 15 (Pyin Oo Lwin) removed
  6. ****6 P667T, 1 P667R not analyzed since clearance data did not meet criteria