Table 2.
Overall ex vivo sensitivity for each drug according to the species tested
| Drug | Indicated values for each group of isolates |
|||||
|---|---|---|---|---|---|---|
| Median IC50 (nM) in each P. falciparum lab linea |
P. falciparum clinical field isolates |
P. vivax clinical field isolates |
||||
| FC27 (CQs) | K1 (CQr) | n (%)c | Median IC50 (range) in nM and P valueb | n (%)c | Median IC50 (range) in nM and P valueb | |
| Chloroquine | 39.9 | 168.7 | 23 (100) | 91.4 (37.3–147.7) | 18 (100)d | 48.3 (12.9–143.4) |
| Amodiaquine | 36.2 | 21.7 | 23 (100) | 11.8 (5.6–22.8) | 18 (100) | 15.9 (7.1–25.8) |
| Piperaquine | 64.2 | 50.2 | 23 (100) | 16.4 (4.0–43.6) | 18 (100) | 14.6 (4.0–28.9) |
| Artesunate | 15.4 | 10.3 | 22 (96)e | 4.5 (0.3–9.8) | 15 (83)e | 4.0 (1.6–6.3) |
| DHA | 10.0 | 9.6 | 22 (96)f | 6.4 (2.2–11.1), P = 0.013 | 16 (89)e | 4.9 (2.8–11.5), P = 0.013 |
| OZ277 | 10.9 | 20.0 | 23 (100) | 3.6 (0.1–18.3), P = 0.884 | 16 (89)e | 4.6 (1.7–16.3), P = 0.088 |
| OZ439 | 11.1 | 18.6 | 23 (100) | 2.1 (0.4–10.5), P = 0.012 | 16 (89)e | 4.5 (1.3–10.3), P = 0.306 |
| Artemisone | 1.9 | 2.0 | 22 (96)e | 1.9 (0.1–5.7), P < 0.001 | 15 (83)e | 0.7 (0.3–4.1), P < 0.001 |
| Artemiside | 4.0 | 4.3 | 22 (96)e | 2.5 (0.2–15.0), P = 0.592 | 15 (83)e | 3.0 (0.5–14.4), P = 0.460 |
Mean IC50s (derived from 2 independent experiments) were assessed by in vitro schizont maturation quantified by microscopy. CQs, chloroquine-sensitive laboratory strain; CQr, chloroquine-resistant laboratory strain.
P values are from a comparison with values for artesunate (Wilcoxon signed-rank test).
Total number of assays with acceptable IC50s (percentage of samples which fulfilled the criteria for a successful culture).
One P. vivax isolate was excluded from analysis (harvested at <30 h).
Insufficient BMM mixture to test all compounds in 3 P. vivax isolates and 1 P. falciparum isolate.
No IC50 estimate of DHA for 1 P. falciparum isolate (highly sensitive, model not possible).