New systematic review finds that inadequate P. vivax antimalarial treatment more than doubles malaria relapse risk

40% of the world’s population is at risk of Plasmodium vivax malaria, but anti-malarial efficacy studies have usually focussed on the safety and efficacy of anti-malarial drugs – adherence to treatment is often overlooked.

This is a particular issue with vivax malaria, because the P. vivax lifecycle includes stages where it is dormant in the liver, but can reactivate to cause relapses weeks to months after the initial infection. Therefore, treating both the active bloodstream and the dormant liver stages of vivax malaria is important.

Primaquine is a widely used anti-malarial that kills the dormant liver stage of P. vivax. However, it needs to be administered over 7 to 14 days, well after clinical symptoms of malaria have resolved. This means that adherence to the complete course of treatment is often poor.

The WWARN vivax adherence group, led by Dr Parinaz Mehdipour at The University of Melbourne therefore undertook a systematic review of 32 published studies where individual patient data was available, and analysed record from over 6,000 patients to find that poor adherence to primaquine treatment was consistently associated with a greater risk of P. vivax recurrence. When adherence fell below 50%, there was a 2.3-fold increase in the risk of recurrence.

The study assessed adherence through different methods including whether all doses of primaquine were actually taken or whether every dose of primaquine was supervised.

“These results show that it is not just safety and efficacy, but other factors such as treatment adherence and supervision, which need to be taken into account, when making health policy decisions about malaria treatments,” said WWARN researcher Dr Rob Commons, who is based at Menzies School of Health Research in Australia.

Read the full study, published in Malaria Journal.