PLOS Medicine publishes paper recommending review of DP antimalarial dosing

4 December 2013

A WWARN Research Study Group recently completed a large pooled analysis of the artemisinin combination drug known as dihydroartemisinin-piperaquine (DP) to investigate how well it cures patients suffering from malaria, and to share research results which might help to support continued drug performance.

There are a number of highly effective drugs deployed to treat malaria worldwide. However, widespread use of suboptimal drug treatment is known to lead to the emergence of resistant malaria parasites, particularly in Southeast Asia where it has been confirmed in the last few years. It remains critical therefore that all antimalarial drugs should be monitored to ensure that the dosing regimens remain as effective as possible, for as long as possible.

Dihydroartemisinin plus piperaquine, is a widely administered combination ACT prescribed for patients with malaria caused by the parasite Plasmodium falciparum. This treatment was the focus of a recent WWARN DP Dosing Impact Study Group who worked together to produce a paper published in PLOS Medicine this week. 

The paper highlights the importance of tablet dosing recommendations for artemisinin combination therapies (ACTs), and concludes that public health policy-makers may need to review current dosing recommendations for dihydroartemisinin-piperaquine, particularly for young children.

To prepare these results, the WorldWide Antimalarial Resistance Network worked with 76 researchers to coordinate the compilation of individual patient data from 26 clinical study sites in Asia, Africa and South America. These data then formed part of a series of dosing impact pooled analyses that assess how well different ACTs are currently performing, and whether these results can support decision-makers to review current dosing strategies.

The Study Group analysis includes more than 7,000 patients, constituting almost 70% of all available published data on dihydroartemisinin-piperaquine. The scale of the data provides, for the first time, the power to identify groups of patients in whom treatment does not appear to be optimised.

Although dihydroartemisinin-piperaquine is still a highly efficacious drug, curing more than 97% of all patients, this recent study highlights that children under the age of 5 years are at a greater risk of treatment failure. The explanation for this appears to be that a third of these young children received a dose of piperaquine below the level recommended by the World Health Organisation.

The study results suggests that patients who receive a lower than adequate antimalarial dose are slower to respond to treatment, less likely to kill all the parasites they have in their bodies, and more likely to have malaria again a few weeks later.

Professor Umberto D’Alessandro, one of the co-authors of this paper,highlights “Despite considerable efforts, the burden of malaria remains unacceptability high, with more than half a million deaths each year, and could be reduced by ensuring effective treatment to all patients in need.”

The WWARN team has spent more than 5 years working to develop the methods and partnerships that enable the data from different clinical studies to be stored, pooled and analysed.

Professor Ric Price, one of the lead investigators working with WWARN, concludes, “This first paper highlights that researchers from around the world can come together and pool their data to benefit the whole malaria research community.  The power of such a collaborative research approach will help to support the optimisation of current antimalarial treatments, reduce the likely spread of antimalarial drug resistance and ultimately save more lives.”

Read a review on the paper "Artemisinin Combination Therapy: A Good Antimalarial, but is the dose right?" by Paul Garner and download the paper from PLOS Medicine

The WorldWide Antimalarial Resistance Network (WWARN) DP Study Group (2013) The Effect of Dosing Regimens on the Antimalarial Efficacy of Dihydroartemisinin-Piperaquine: A Pooled Analysis of Individual Patient Data. PLOS Med 10(12): e1001564. doi:10.1371/journal.pmed.1001564

You can also view the perspective article written by Paul Garner, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.

Discover the background to the WWARN DP Dosing Impact Study Group and our other Study Groups. Visit our website in early 2014 to find out more about our new Study Groups.

Additional information:

For further media information please contact Andrea Stewart, WWARN Communications on email: andrea [dot] stewart [at] wwarn [dot] org or telephone: +44 (0) 7528 132 489.

Lead investigator:

Prof Ric Price, Head of WWARN Clinical Group and Senior Principal Research Fellow, Menzies School of Health Research, Darwin, Australia. See full bio.

Co-author:

Prof Umberto D’Alessandro, Theme Leader: Disease Control & Elimination, Medical Research Council, The Gambia Unit. See full bio.

Funding: WWARN is funded by the Bill & Melinda Gates Foundation.

No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the PLOS Medicine paper.