New research supports co-administration of primaquine with artemisinin-based combination therapies for P. vivax malaria

An individual patient data meta-analysis of 2,017 patients from 19 studies has found a high risk of recurrence following treatment of P. vivax malaria with artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) unless they are co-administered with primaquine. The research, published in PLOS Medicine supports recommendations that these artemisinin-based combination therapies (ACT) should be combined with primaquine.

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Resistance of Plasmodium vivax malaria parasites to chloroquine – the most commonly used antimalarial drug – is increasing around the world, threatening malaria control and elimination efforts. In response to this, some countries have changed their national antimalarial guidelines to recommend artemisinin-based combination therapies for treatment of both vivax and falciparum malaria. However, the optimal ACT for treatment of vivax malaria remains unclear and there is the potential that drug-drug interactions may reduce the efficacy of primaquine when combined with some ACTs.

In the largest study of its kind to date conducted with the support of the WWARN data platform, researchers compared the efficacy of AL and DP, with and without primaquine to treat P. vivax malaria in order to help inform decisions about optimal treatment policies in regions with increasing resistance to chloroquine. It was found that treatment with DP led to a lower risk of recurrence 42 days after treatment compared with AL, however, by day 63 the risk of recurrence was high following either ACT. First author on the study Dr Rob Commons says: "The study suggests that delaying the time to recurrence allows patients to improve their haemoglobin prior to the next episode of clinical malaria, and may reduce the risk of anaemia in patients undergoing multiple malaria recurrences."

Combining primaquine with both treatments led to the greatest reduction in risk of recurrence – 80% by day 42 following AL and over 90% by day 63 following DP. This suggests that primaquine is effective when combined with either of these ACTs, and supports the recommendation that ACTs should be combined with PQ to prevent recurrences.  

Read the research: Commons et al. The efficacy of dihydroartemisinin-piperaquine and artemether-lumefantrine with and without primaquine on Plasmodium vivax recurrence: A systematic review and individual patient data meta-analysis. PLOS Medicine. Published: October 4, 2019.

This work was done as part of the WWARN Vivax Recurrence Study Group.