ADDITIONAL SUMMARY OF FINDINGS [Explanation]

PQ for reducing P. falciparum transmission with non-artemisinin-based treatments
Patient or population: people with symptomatic malaria
Settings: malaria-endemic areas
Intervention: Single dose or short course PQ plus malaria treatment which does not include an artemisinin derivative
Control: Malaria treatment not including an artemisinin derivative, without PQ
Outcomes	Illustrative comparative risks* (95% CI)		Relative effect(95% CI)	Number of participants(studies)	Quality of the evidence(GRADE)
	Assumed risk	Corresponding risk
	Control	PQ
Malaria incidence, prevalence or EIR	-	-	-	0 trials	-
People infectious to mosquitoes (day 8)	93 per 100	7 per 100 (1 to 39)	RR 0.07 1 (0.01 to 0.45)	30(2 trials)	⊕⊕⊕○ low 2,3
Participants with gametocytes on microscopy (day 8)	Dose < 0.4 mg/kg		RR 1.76 (0.97 to 3.18)	59(1 trial)	⊕○○○ very low 4,5,6
	33 per 100	58 per 100 (32 to 105)
	Dose 0.4 to 0.6 mg/kg		RR 0.62 (0.50 to 0.76)	283 (2 trials)	⊕⊕⊕⊕ high 7,8
	70 per 100	43 per 100 (35 to 53)
	Dose = 0.6 mg/kg		RR 0.44 (0.27 to 0.70)	206 (3 trials)	⊕⊕⊕⊕ high 9,10
	35 per 100	15 per 100 (9 to 24)
Evidence of haemolysis	-	-		0 trials9,10	-
*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.
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 High category dose PQ used in both studies = 0.6 mg/kg.

² Downgraded by 1 for serious risk of bias: allocation was not concealed; both experiments were performed by the same author team and the methods were not clear.

³ Downgraded by 1 for serious imprecision: the sample size is small (N = 30; downgraded by 2) but the effect is large (upgraded by 1). In the control group, infectivity wanes by day 15.

⁴ Downgraded by 1 for serious risk of bias: trial had methodological deficiencies.

⁵ Downgraded by 1 for serious imprecision: single trial, small sample size, wide CIs.

⁶ Downgraded by 1 for serious indirectness: 7 days of PQ given.

⁷No serious imprecision: although the sample size is limited, the effect is large.

⁸ Log(10)AUC day 1 to 43 % reduction relative decrease: 2 estimates from one trial of 24.3% to 27.1% (N = 219), assessed as moderate quality evidence.

⁹ Data from Khoo 1981 could not be used because it did not distinguish between patients with P. falciparum and P. vivax and their respective treatments. There was a much higher risk of adverse haemolytic events in those who received PQ (OR of 22.27 for both haemolysis and need for blood transfusion), but the participants included those receiving a short course (three days) of PQ with those receiving a 14-day regimen. Only individuals with G6PD deficiency were included.

¹⁰ For the ten included trials, the G6PD status of participants varied: two trials excluded patients with G6PD deficiency trials), one trial included only those with G6PD deficiency, two trials did not screen for G6PD deficiency, and five trials did not report or comment on screening for G6PD status. No trials systematically reported on adverse effects.