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A new WWARN study, published in BMC Medicine, supports a World Health Organization (WHO) recommendation that a single primaquine target dose of 0.25 mg/kg is generally safe and well tolerated when given together with an ACT to treat malaria.

Woman carrying a child, in a limited-resource settlement in Kenya © Peter Kapuscinski, World Bank

Primaquine has been available for more than 70 years and millions of doses have been administered over the years, but safety outcomes have not been well documented.

The WHO changed its guidelines to lower the dosage of primaquine in 2012, to accelerate malaria elimination efforts and avoid the spread of artemisinin resistance. However, uptake of the recommendation has been slow due to safety concerns among those with G6PD deficiency. G6PD deficiency is an inherited enzyme deficiency that is particularly common in some malaria endemic areas that makes red blood cells more likely to break down.

Researchers performed a systematic review and an individual patient data (IPD) meta-analysis of single dose (SD) primaquine studies for Plasmodium falciparum malaria with the aim of establishing the safety of SD primaquine, improving uptake and potentially setting guidelines for the implementation of weight or age-based dosing bands. The data included 20 studies of 6,406 participants, of which over 80% had received a single target dose of primaquine ranging between 0.0625 and 0.75 mg/kg. There was no effect of primaquine on haemoglobin concentrations (a measure for anaemia) in G6PD normal participants, and only a small effect on haemoglobin among the 194 G6PD-deficient African participants given a 0.25 mg/kg primaquine target dose.

The authors said the results could now reassure national malaria control programmes that were considering the use of SD primaquine to advance malaria elimination or reduce the spread of artemisinin resistance.

The full story is available on the WWARN website.

Read the full paper 'Safety of single dose primaquine as a Plasmodium falciparum gametocytocide: a systematic review and meta-analysis of individual patient data' on the BMC Medicine website