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

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

WHO designations		This paper
Codon	Status	Codon	N total isolates	# sites	N mutant	% Prevalence: Median (Range)¹	xPC_1/2 (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	Validated	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	Candidate	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)

¹Prevalence is calculated per study site, combining data from all studies in that location, restricted to range of years when the mutation was observed
²Increase in PC_1/2 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]
*With study ID 8, study site ID 23 (Tra Lang) removed
**20 P527H, one P527L, analyzed together, two P527H not analyzed since clearance data did not meet criteria
***With study ID 13, study site ID 15 (Pyin Oo Lwin) removed
****6 P667T, 1 P667R not analyzed since clearance data did not meet criteria

ISSN: 1741-7015