Volume 21, Number 10—October 2015
Research
Induction of Multidrug Tolerance in Plasmodium falciparum by Extended Artemisinin Pressure
Table 3
Recrudescence parameters of Plasmodium falciparum F32-ART5 and F32-TEM lineages exposed to 10 antimalarial drugs*
| Drug | Drug dose | No. experiments† | Median (range) recrudescence time, d‡ |
Mean ± SEM difference of recrudescence time, d¶ | p value‡ | |
|---|---|---|---|---|---|---|
| F32-ART5 | F32-TEM§ | |||||
| Artemisinin |
11 µmol/L | 7 | 8 (6–11) | 22 (15–>28) | 11.5 ± 1.5 | <0.001 |
| 18 µmol/L |
3 |
7 (6–9) |
19 (17–20) |
11.3 ± 1.3 |
0.024 |
|
| Artesunate |
1.3 µmol/L | 3 | 8 (7–10) | 16 (15–18) | 8 ± 1.5 | 0.024 |
| 2.6 µmol/L |
3 |
8 (7–10) |
16 (15–18) |
8 ± 1.5 |
0.024 |
|
| Artemisone |
1.2 µmol/L | 3 | 8 (7–10) | 20 (18–20) | 11 ± 1.5 | 0.024 |
| 2.5 µmol/L |
3 |
8 (7–11) |
21 (20–28) |
14.3 ± 1.4 |
0.025 |
|
| Artemether |
1.7 µmol/L | 2 | 7.5 (7–8) | 15 (15–15) | 7.5 ± 0.5 | 0.089 |
| 3.4 µmol/L |
2 |
7.5 (7–8) |
16 (16–16) |
8.5 ± 0.5 |
0.089 |
|
| Chloroquine |
78 nmol/L |
4 |
10 (7–11) |
13 (11–20) |
4.8 ± 1.5 |
0.028 |
| Quinine |
43 µmol/L |
5 |
10 (8–14) |
13 (10–>20) |
2.7 ± 0.9 |
0.086 |
| Amodiaquine |
62 nmol/L |
4 |
7.5 (7–9) |
14.5 (12–16) |
6 ± 0.6 |
0.006 |
| Mefloquine |
241 nmol/L |
5 |
8 (6–12) |
11 (10–>20) |
3 ± 1.1 |
0.044 |
| Pyrimethamine |
4 µmol/L |
5 |
5 (5–7) |
9 (7–10) |
3 ± 0.5 |
0.008 |
| Atovaquone | 3 µmol/L | 5 | 13 (3–27) | 12 (3–21) | −1.4 ± 1.3 | 0.730 |
| 7 µmol/L | 4 | 14.5 (11–18) | 13 (11–19) | −0.5 ± 0.6 | 0.848 | |
*Recrudescence capacity of F32-TEM and F32-ART5, synchronized at ring-form cultures (0–12-h-old parasites), was evaluated after 48 h of drug treatment. After cultures were washed, parasitemia was monitored daily to determine the recrudescence time, defined as the time to reach day 0 parasitemia.
†Each experiment was performed for F32-ART and F32-TEM cultivated in parallel in the same conditions (adjusted to the same initial parasitemia and cultivated with the same lot of erythrocytes and same batch of human serum) to generate paired results. The same number of experiments was performed for each parasite lineage and statistically analyzed.
‡A log-rank (Mantel-Cox) test was used for statistical analysis of recrudescence time in days.
§If no parasites were observed at the end of the experiment, the culture was classified as showing no recrudescence, and the recrudescence day was noted as >d. Parasite counts were monitored microscopically daily until day 28 except when the batch of blood needed to be changed (in this instance, the experiment was stopped earlier).
¶Differences in recrudescence time as Gaussian data.
1Current affiliation: Universitas Gadjah Mada, Yogyakarta, Indonesia.
2Current affiliation: Institut Pasteur, Phnom Penh, Cambodia.