PQ for reducing P. falciparum transmission with artemisinin-based treatments
Patient or population: People with symptomatic malaria
Settings: Malaria-endemic areas
Intervention: Single dose or short course PQ plus malaria treatment including an artemisinin derivative
Control: Malaria treatment including an artemisinin derivative, without PQ
Outcomes	Illustrative comparative risks* (95% CI)		Relative effect(95% CI)	Number of participants(trials)	Quality of the evidence(GRADE)
	Assumed risk	Corresponding risk
	Control	PQ
Malaria incidence, prevalence or EIR	-	-	-	0 trials	-
People infectious to mosquitoes	-	-	-	0 trials	-
Participants with gametocytes on microscopy or PCR 1 (day 8)	Dose < 0.4 mg/kg		RR 0.67 (0.44 to 1.02)	223 (1 trial)	⊕⊕○○ 2,3,4 low
	34 per 100	23 per 100 (15 to 35)
	Dose 0.4 to 0.6 mg/kg		RR 0.30 (0.16 to 0.56)	219 (1 trial)	⊕⊕⊕○ 2,4,5,6 moderate
	35 per 100	11 per 100 (6 to 20)
	Dose = 0.6 mg/kg		RR 0.29 (0.22 to 0.37)	1380(7 trials)	⊕⊕⊕○ high 7,8,9
	30 per 100	9 per 100 (7 to 11)
Mean percent change in haemoglobin 10	The mean percent drop in Hb from baseline in the control group was15%	The mean percent drop in Hb from baseline in the intervention groups was 3% lower(from 10% lower to 4% higher)	-	101(1 trial)	⊕○○○ very low 10,11
*The basis for the assumed risk (for example, the median control group risk across studies) is provided in footnotes. 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).
PQ: Primaquine; CI: Confidence interval; RR: Risk ratio; AUC: area under curve; G6PD: glucose-6-phosphate dehydrogenase; AS: artesunate; AQ: amodiaquine;DHAP: dihydroxyartemisinin-piperaquine; MQ: mefloquine; AL: artemether-lumefantrine.
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.

¹AUC estimates (log(10)AUC for day 1 to 43) are included as footnotes for each dosing strata.

²No serious risk of bias: includes one trial with no risk of bias detected.

³Downgraded by 2 for very serious imprecision: one small trial with CIs that include 50% reduction and no effect.

⁴There was no log(10)AUC day 1 to 43 % reduction data for this dose.

⁵Downgraded by 1 for serious imprecision. A single trial with few events.

⁶Not downgraded for serious indirectness: however this is a single trial from a single setting.

⁷Includes seven trials, with 11 comparisons: one trial included five separate comparisons with AS-AQ, DHAP, AS-MQ, and AL (Smithuis 2010).

⁸No serious inconsistency: whilst there is marked quantitative heterogeneity, the studies with no demonstrable effect had few events. Not downgraded.

⁹Log(10)AUC day 1 to 43 % reduction: range from 21.1% to 87.5%. We included four trials with 12 comparisons. We excluded one trial as high risk of bias (Vasquez 2009) due to small sample size and large difference in baseline gametocyte count in the two groups.

¹⁰Shekalaghe 2007 reported relative decrease in haemoglobin against baseline in both groups at day 8, 15, 29 and 43 in all participants irrespective of G6PD status. The comparison between those receiving PQ and those not did not demonstrate a difference at any time point. We presented day 43 in this table.

¹¹Downgraded by 2 for very serious indirectness: the percentage of people with large drops in haemoglobin, not the mean change in the population, is the important safety outcome; and the estimates are averages in a small population (N = 99) that includes people with normal G6PD function so unlikely to detect effects in a small subgroup with a relatively uncommon adverse event.