Comparison 1. Dihydroartemisinin‐piperaquine versus Artesunate plus mefloquine.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Total failure (P. falciparum) Day 28 PCR‐unadjusted	8		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
1.1 Asia	8	3487	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.28, 3.72]
2 Total failure (P. falciparum) Day 28 PCR‐adjusted	8		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
2.1 Asia	8	3482	Risk Ratio (M‐H, Fixed, 95% CI)	0.41 [0.21, 0.80]
3 Total failure (P. falciparum) Day 42 PCR‐unadjusted	7		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
3.1 Asia	7	3421	Risk Ratio (M‐H, Random, 95% CI)	0.90 [0.54, 1.50]
4 Total failure (P. falciparum) Day 42 PCR‐adjusted	6		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
4.1 Asia	6	2901	Risk Ratio (M‐H, Fixed, 95% CI)	0.48 [0.26, 0.88]
5 Total failure (P. falciparum) Day 63 PCR‐unadjusted	6		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
5.1 Asia	5	2715	Risk Ratio (M‐H, Fixed, 95% CI)	0.84 [0.69, 1.03]
5.2 South America	1	445	Risk Ratio (M‐H, Fixed, 95% CI)	6.19 [1.40, 27.35]
6 Total failure (P. falciparum) Day 63 PCR‐adjusted	6		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
6.1 Asia	5	2500	Risk Ratio (M‐H, Fixed, 95% CI)	0.50 [0.30, 0.84]
6.2 South America	1	435	Risk Ratio (M‐H, Fixed, 95% CI)	9.55 [0.52, 176.35]
7 Gametocyte carriage	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
7.1 Gametocyte carriage day 0	3	2322	Risk Ratio (M‐H, Random, 95% CI)	1.07 [0.66, 1.73]
7.2 Gametocyte carriage day 7	3	2270	Risk Ratio (M‐H, Random, 95% CI)	1.99 [1.57, 2.51]
7.3 Gametocyte carriage day 14	3	2249	Risk Ratio (M‐H, Random, 95% CI)	5.11 [3.26, 7.99]
7.4 Gametocyte carriage day 21	3	2218	Risk Ratio (M‐H, Random, 95% CI)	9.44 [0.80, 110.80]
7.5 Gametocyte carriage day 28	3	2199	Risk Ratio (M‐H, Random, 95% CI)	9.55 [1.80, 50.61]
8 Gametocyte development (in those negative at baseline)	3	1234	Risk Ratio (M‐H, Fixed, 95% CI)	3.06 [1.13, 8.33]
9 Serious adverse events (including deaths)	8	3522	Risk Ratio (M‐H, Fixed, 95% CI)	1.20 [0.59, 2.42]
10 Other adverse events: Gastrointestinal	10		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
10.1 Early vomiting	9	4114	Risk Ratio (M‐H, Fixed, 95% CI)	0.91 [0.71, 1.15]
10.2 Nausea	9	4531	Risk Ratio (M‐H, Fixed, 95% CI)	0.68 [0.60, 0.78]
10.3 Vomiting	5	2744	Risk Ratio (M‐H, Fixed, 95% CI)	0.59 [0.47, 0.75]
10.4 Anorexia	6	3497	Risk Ratio (M‐H, Fixed, 95% CI)	0.86 [0.73, 1.02]
10.5 Diarrhoea	5	2217	Risk Ratio (M‐H, Fixed, 95% CI)	1.46 [1.05, 2.04]
10.6 Abdominal pain	7	3887	Risk Ratio (M‐H, Fixed, 95% CI)	0.99 [0.82, 1.20]
11 Other adverse events: Neuro‐psychiatric	9		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
11.1 Headache	4	2039	Risk Ratio (M‐H, Fixed, 95% CI)	0.80 [0.64, 1.00]
11.2 Dizziness	9	4531	Risk Ratio (M‐H, Fixed, 95% CI)	0.72 [0.66, 0.78]
11.3 Sleeplessness	6	2551	Risk Ratio (M‐H, Fixed, 95% CI)	0.49 [0.40, 0.60]
11.4 Fatigue	2	872	Risk Ratio (M‐H, Fixed, 95% CI)	0.41 [0.23, 0.73]
11.5 Nightmares	1	220	Risk Ratio (M‐H, Fixed, 95% CI)	0.09 [0.01, 0.69]
11.6 Anxiety	1	522	Risk Ratio (M‐H, Fixed, 95% CI)	0.10 [0.03, 0.33]
11.7 Blurred vision	1	464	Risk Ratio (M‐H, Fixed, 95% CI)	0.49 [0.24, 1.02]
11.8 Tinnitus	1	220	Risk Ratio (M‐H, Fixed, 95% CI)	0.4 [0.13, 1.24]
12 Other adverse events: Cardio‐respiratory	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
12.1 Palpitations	3	1175	Risk Ratio (M‐H, Fixed, 95% CI)	0.61 [0.45, 0.82]
12.2 Cough	1	1148	Risk Ratio (M‐H, Fixed, 95% CI)	0.81 [0.54, 1.19]
12.3 Dyspnoea	1	220	Risk Ratio (M‐H, Fixed, 95% CI)	0.3 [0.08, 1.06]
12.4 Prolonged QT interval (reported as adverse events)	1	1148	Risk Ratio (M‐H, Fixed, 95% CI)	1.27 [0.72, 2.24]
12.5 Prolonged QT interval (Bazett's correction)	1	1148	Risk Ratio (M‐H, Fixed, 95% CI)	2.05 [1.20, 3.49]
12.6 Prolonged QT interval (Fridericia's correction)	1	1148	Risk Ratio (M‐H, Fixed, 95% CI)	0.89 [0.52, 1.52]
13 Other adverse events: Musculoskeletal/dermatological	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
13.1 Arthralgia	1	1148	Risk Ratio (M‐H, Fixed, 95% CI)	0.99 [0.60, 1.65]
13.2 Myalgia	1	1148	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.63, 1.70]
13.3 Urticaria	2	719	Risk Ratio (M‐H, Fixed, 95% CI)	0.59 [0.15, 2.35]
13.4 Pruritis	2	872	Risk Ratio (M‐H, Fixed, 95% CI)	0.65 [0.26, 1.60]
13.5 Rash	1	220	Risk Ratio (M‐H, Fixed, 95% CI)	0.33 [0.01, 8.09]
14 Sensitivity analysis: Total failure Day 63 PCR‐unadjusted	4		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
14.1 Total failure (P. falciparum) Day 63 PCR‐unadjusted	4	1627	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.52, 1.70]
14.2 Total failure Day 63 PCR‐unadjusted (losses to follow‐up included as failures)	4	1801	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.65, 1.38]
14.3 Total failure Day 63 PCR‐unadjusted (losses to follow‐up included as successes)	4	1801	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.52, 1.68]
15 Sensitivity analysis: Total failure Day 63 PCR‐adjusted	4		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
15.1 Total failure (P. falciparum) Day 63 PCR‐adjusted	4	1497	Risk Ratio (M‐H, Random, 95% CI)	0.57 [0.17, 1.83]
15.2 Total failure Day 63 PCR‐adjusted (indeterminate PCR included as failures)	4	1508	Risk Ratio (M‐H, Random, 95% CI)	0.67 [0.32, 1.39]
15.3 Total failure Day 63 PCR‐adjusted (new infections included as successes)	4	1627	Risk Ratio (M‐H, Random, 95% CI)	0.67 [0.34, 1.35]
15.4 Total failure Day 63 PCR‐adjusted (losses to follow‐up included as failures)	4	1801	Risk Ratio (M‐H, Random, 95% CI)	0.93 [0.67, 1.30]
15.5 Total failure Day 63 PCR‐adjusted (losses to follow‐up included as successes)	4	1801	Risk Ratio (M‐H, Random, 95% CI)	0.67 [0.34, 1.33]