8. Summary of findings table: Mass drug administration in areas of high endemicity (≥40%).

Mass drug administration in areas of high endemicity
Patient or population: People living in malaria endemic areas Settings: Areas with high malaria endemicity (≥ 40%) Intervention: Mass drug administration (any regimen) Comparison: No intervention (or baseline data in before‐and‐after studies)
Timepoint post MDA	Outcomes	Study design	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	No of studies	Quality of the evidence (GRADE)
			Assumed risk	Corresponding risk
			Control	MDA
< 1 month	Parasitaemia prevalence	Cluster‐randomized	500 per 1000	410 per 1000 (335 to 505)	RR 0.82 (0.67 to 1.01)	1 study	⊕⊕⊝⊝ low1,2,3
		Non‐randomized	500 per 1000	85 per 1000 (50 to 140)	RR 0.17 (0.10 to 0.28)	3 studies	⊕⊕⊕⊝ moderate4,5,6,7
		Before‐and‐after	500 per 1000	185 per 1000 (140 to 245)	RR 0.37 (0.28 to 0.49)	4 studies	⊕⊕⊝⊝ low8,9,10
	Parasitaemia incidence	Cluster‐randomized	60 per 1000	25 per 1000 (14 to 44)	RR 0.41 (0.23 to 0.73)	1 study	⊕⊕⊕⊝ moderate1,2,11
	Gametocytaemia prevalence	Non‐randomized	100 per 1000	16 per 1000 (8 to 30)	RR 0.16 (0.08 to 0.30)	3 studies	⊕⊕⊕⊝ moderate4,5,6,7
		Before‐and‐after	100 per 1000	38 per 1000 (13 to 108)	RR 0.38 (0.13 to 1.08)	3 studies	⊕⊕⊝⊝ low8,12
4‐6 months	Parasitaemia prevalence	Cluster‐randomized	500 per 1000	580 per 1000 (465 to 720)	RR 1.16 (0.93 to 1.44)	1 study	⊕⊕⊕⊝ moderate1,2,13
		Non‐randomized	‐	‐	‐	0 studies	‐
		Before‐and‐after	500 per 1000	205 per 1000 (120 to 360)	RR 0.41 (0.24 to 0.72)	3 studies	⊕⊕⊝⊝ low8,14
	Parasitaemia incidence	Cluster‐randomized	60 per 1000	67 per 1000 (52 to 85)	RR 1.11 (0.87 to 1.41)	1 study	⊕⊕⊕⊝ moderate1,2,13
	Gametocytaemia prevalence	Cluster‐randomized	100 per 1000	107 per 1000 (62 to 185)	RR 1.07 (0.62 to 1.85)	1 study	⊕⊕⊝⊝ low1,2,3
		Non‐randomized	‐	‐	‐	0 studies	‐
		Before‐and‐after	100 per 1000	35 per 1000 (10 to 128)	RR 0.35 (0.10 to 1.28)	2 studies	⊕⊝⊝⊝ very low8,15
The assumed risk for parasitaemia prevalence has been set at 50%. Gametocytaemia prevalence was generally lower in the included studies and the assumed risk has therefore been set at 10%. The assumed risk for parasitaemia incidence is taken from the control group of the single trial. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.

¹ No serious risk of bias: This cluster‐randomized trial was at low risk of bias.
 ² Downgraded by 1 for serious indirectness: This single study from the Gambia in 1999 administered MDA as AS+SP. The findings may not be easily generalized to other settings, or to alternative MDA regimens. The first time point measured post‐MDA was 1‐3 months.
 ³ Downgraded by 1 for serious imprecision: The result was not statistically significant but the 95% CI is wide and includes important effects.
 ⁴ No serious risk of bias: Although there was some evidence of baseline imbalance between the intervention and control areas, these were generally of smaller magnitude than the effects seen.
 ⁵ No serious indirectness: The data presented here were measured during ongoing multiple‐round MDA programmes, not at one month post‐intervention. The studies were conducted in Burkina Faso in 1961 (CQ or AQ plus PQ every two to four weeks), and Nigeria in 1975 (SP given every two weeks or every 10 weeks). Although these studies are old, similar effects might be expected today with effective anti‐malarials.
 ⁶ No serious inconsistency: The observed effects were consistently large in all three trials.
 ⁷ Upgraded by 1 for the large effect size: Large effects seen in all trials.
 ⁸ No serious risk of bias: These studies are uncontrolled, and so are at very high risk of confounding. However, as the GRADE approach automatically downgrades non‐randomized controlled studies by two levels for risk of bias we did not further downgrade.
 ⁹ No serious indirectness: These four studies were conducted in Palestine in 1930 (plasmoquine plus quinine every three weeks for three rounds), Burkina Faso in 1959 (pyrimethamine every two weeks), in Malaysia in 1985 (SP + PQ once only), and Cambodia in 2006 (AS + piperaquine once only plus PQ every 10 days).
 ¹⁰ No serious inconsistency: Three studies observed large effects, while one small study found no effect.
 ¹¹ No serious imprecision: The result is statistically significant.
 ¹² No serious indirectness: Two large studies found large effects in Burkina Faso in the 1950s (pyrimethamine every 2 weeks for 8 rounds), and Palestine in the 1930s (plasmoquine plus quinine every three weeks for three rounds). One small study from Malaysia in the 1980s found no effect.
 ¹³ No serious imprecision: The 95% CI excludes clinically important reductions at this time point.
 ¹⁴ No serious inconsistency: The two large studies from Palestine and Cambodia still demonstrated a large reduction at 4‐6 months while the small study from Malaysia found no difference
 ¹⁵ Downgraded by 1 for serious indirectness: Benefits beyond three months have only been demonstrated in this single study from Cambodia. MDA was administered as artesunate plus piperaquine once only followed by primaquine every 10 days for six months.