In 2012, the World Health Organization recommended adding a single low dose of 0.25 mg/kg primaquine (PQ) to Plasmodium falciparum treatment schedules. This review aims to assess effectiveness of this approach, and at this dose, for reducing transmission.
We searched the literature to 21 July 2017 for trials which added PQ alongside treatment for P. falciparum. Outcomes sought were transmission (community incidence), infectiousness (people infectious and mosquitoes infected), and potential infectiousness (gametocyte measures) for analysis using RevMAN software.
We included 25 trials with 43 arms, of which seven used low dose PQ and five tested infectiousness. No cluster trials evaluating community effects on malaria transmission met the inclusion criteria. With artemisinin treatment and low dose PQ, infectiousness was reduced at day 3 or 4 (risk ratio (RR) 0.12, 95% CI 0.02 to 0.88,) and day 8 (RR 0.34, 95% CI 0.07 to 1.58); low certainty evidence for both time points. This translates to absolute reduction in percentage of gametocyte carriers infectious from 14% to 2% on day 3 to 4, and from 4% to 1% on day 8. There was no effect of PQ on gametocytes at day 3 or 4 (RR 1.02, 95% CI 0.87 to 1.21; moderate certainty evidence) but reduction at day 8 (RR 0.52, 95% CI 0.41 to 0.65; high certainty evidence). Results were similar at higher PQ doses up to 0.75 mg/kg and with non-artemisinin partner drugs.
A single low dose of PQ reduces infectiousness to mosquitoes and appears as effective as higher doses. The absolute effect is greater at day 3 or 4, and smaller at day 8, in part because of the lower infectiousness in the control group. PQ does reduce the infectiousness of gametocytes, but this may not translate into reduced community transmission.