Table 2.
Efficacy Outcomes and Treatment Success Rates.*
| Variable | Artemether- Lumefantrine (N = 880) |
Amodiaquine- Artesunate (N = 842) |
Dihydroartemisinin- Piperaquine (N = 853) |
Mefloquine- Artesunate (N = 848) |
| Efficacy outcome — no. (%)† | ||||
| Early treatment failure | 0 | 2 (0.2) | 1 (0.1) | 0 |
| Development of danger signs or severe malaria |
0 | 0 | 1 (0.1) | 0 |
| Rescue treatment on any of days 0–3 | 0 | 1 (0.1) | 0 | 0 |
| Parasitemia on day 3 ≥ day 0 | 0 | 1 (0.1) | 0 | 0 |
| Late clinical failure | 26 (3.0) | 13 (1.5) | 6 (0.7) | 28 (3.3) |
| Recrudescence | 4 (0.5) | 2 (0.2) | 1 (0.1) | 8 (0.9) |
| New infection | 21 (2.4) | 10 (1.2) | 5 (0.6) | 18 (2.1) |
| Indeterminate or sample unavailable | 1 (0.1) | 1 (0.1) | 0 | 2 (0.2) |
| Late parasitologic failure | 362 (41.1) | 123 (14.6) | 91 (10.7) | 176 (20.8) |
| Recrudescence | 37 (4.2) | 9 (1.1) | 5 (0.6) | 17 (2.0) |
| New infection | 303 (34.4) | 100 (11.9) | 71 (8.3) | 144 (17.0) |
| Indeterminate or sample unavailable | 22 (2.5) | 14 (1.7) | 15 (1.8) | 15 (1.8) |
| Adequate clinical and parasitologic response | 436 (49.5) | 642 (76.2) | 653 (76.6) | 557 (65.7) |
| Response could not be determined | 56 (6.4) | 62 (7.4) | 102 (12.0) | 87 (10.3) |
| Received rescue treatment but had no infection |
6 (0.7) | 11 (1.3) | 8 (0.9) | 9 (1.1) |
| Died‡ | 0 | 0 | 0 | 1 (0.1) |
| Lost to follow-up or withdrew | 50 (5.7) | 51 (6.1) | 94 (11.0) | 77 (9.1) |
| Treatment success§ | ||||
| Per-protocol analysis | ||||
| PCR-adjusted | ||||
| No. of patients | 789 | 729 | 707 | 716 |
| Rate — % (95% CI) | 94.8 (93.0–96.1) | 98.5 (97.3–99.2) | 99.2 (98.2–99.6) | 96.8 (95.2–97.9) |
| PCR-unadjusted | ||||
| No. of patients | 810 | 742 | 720 | 728 |
| Rate — % (95% CI) | 52.5 (49.0–55.9) | 82.3 (79.4–84.9) | 86.9 (84.3–89.2) | 73.8 (70.4–76.8) |
| Intention-to-treat analysis | ||||
| PCR-adjusted | ||||
| No. of patients | 807 | 776 | 744 | 753 |
| Rate — % (95% CI) | 94.2 (92.3–954.6) | 96.9 (95.4–97.9) | 98.0 (96.7–98.8) | 95.5 (93.8–96.8) |
| PCR-unadjusted | ||||
| No. of patients | 830 | 791 | 759 | 770 |
| Rate — % (95% CI) | 52.5 (49.1–55.9) | 81.2 (78.3–83.7) | 86.0 (83.4–88.3) | 72.3 (69.1–73.4) |
CI denotes confidence interval.
Early treatment failure was defined as one of the following: the development of danger signs or severe malaria or worsening of clinical conditions on day 0, 1, 2, or 3 in the presence of parasitemia; parasitemia on day 3 that was the same as or greater than the count on day 0; or parasitemia on day 3 and fever (axillary temperature, −37.5°C). Late clinical failure was defined as the either the development of danger signs or severe malaria or worsening of clinical conditions on any day after day 3 in the presence of parasitemia, without the patient having previously met any of the criteria for early treatment failure, or the presence of parasitemia and fever on any day after day 3, without the patient having previously met the criteria for early treatment failure. Late parasitologic failure was defined as the presence of parasitemia after day 3 and an axillary temperature of less than 37.5°C, without the patient having previously met any of the criteria of early treatment failure or late clinical failure. An adequate clinical and parasitologic response was defined as the absence of parasitemia at the end of the follow-up period (day 63), regardless of the axillary temperature, without the patient having previously met any of the criteria of early treatment failure or late clinical or parasitologic failure. In the polymerase-chain-reaction (PCR)-adjusted estimates, patients with late asexual-parasite reappearance (with or without fever) were considered to have had an adequate clinical and parasitologic response if the PCR analysis showed a new infection rather than a recrudescence.
The one death that occurred during the trial was not considered by the investigators to be related to malaria or to treatment (probably due to meningitis).
In the estimation of the PCR-adjusted cure rate, only recurrent infections that were shown to be the same as those before treatment were considered to be treatment failures. Conversely, for the estimation of the PCR-unadjusted cure rate, all recurrent infections were considered to be treatment failures. If the difference in the true (PCR-adjusted) cure rates was less than 5 percentage points, the treatments were considered to be therapeutically equivalent. Treatment success rates according to country are provided in Tables S7 (per-protocol analysis) and S8 (intention-to-treat analysis) in the Supplementary Appendix.