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 | 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) |
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 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]
*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