New Primaquine Dosing Recommendation for Non-complicated P. falciparum Malaria

UptoDate: Treatment of uncomplicated falciparum malaria in nonpregnant adults and children

[Updated at 31 July 2019]

Gametocytes may persist in the blood after successful treatment of infection; they are not harmful to the patient but serve as a source of ongoing transmission. Artemether-lumefantrine has been shown to be superior to non-artemisinin antimalarial drugs in reducing gametocytemia. Primaquine has activity against mature gametocytes but no effect on blood-stage parasites.

To further reduce transmissibility of treated P. falciparum infection in endemic areas with low transmission, we are in agreement with the WHO which favors administration of primaquine (0.25 mg/kg single dose) on the first day of malaria treatment to nonpregnant adults and children ≥6 months. This approach is supported by a systematic review including 24 randomized trials in which a single low dose of primaquine added to ACT therapy reduced infectiousness of humans to mosquitoes on day 3 or 4 (from 14 to 2 percent) and was as effective as higher doses of primaquine. Data on the impact on community transmission levels and hemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficiency are needed. Primaquine should be avoided in pregnant women and infants <6 months of age given the particular vulnerability of these patient groups.

Primaquine can cause hemolysis in individuals with G6PD deficiency; however, G6PD testing is not required for patients receiving primaquine for reducing transmissibility given the relatively low dose for this indication. In one study including 274 Senegalese patients with mild malaria randomized to ACT plus primaquine (0.25 mg/kg, single dose) versus ACT alone, the mean reduction in hemoglobin at day 7 was equivalent. Among 54 patients with G6PD deficiency, the drop in hemoglobin was 0.63 g/dL greater in those who received primaquine than in those who received an ACT alone.

World Health Organisation: Guidelines for the Treatment of Malaria (3^rd Edition, 2015)

In low-transmission areas, give a single dose of 0.25 mg/kg bw primaquine with ACT to patients with P. falciparum malaria (except pregnant women, infants aged < 6 months and women breastfeeding infants aged < 6 months) to reduce transmission. Testing for glucose-6-phosphate dehydrogenase (G6PD) deficiency is NOT required. 

(Strong recommendation, low quality evidence)