New: AS-MQ Dose Impact Study Group

Optimising the dose of malaria treatments is critical if patients are to have the best chance of being cured. Children are a special challenge. They might be over-dosed because of weight and age-based banding, or sub-optimally dosed when antimalarials are given as tablets, or fractions of tablets, rather than in specific paediatric formulations.

Mefloquine is a commonly-used partner drug in artemisinin combination therapies (ACTs) especially in Asia. The standard regimen for uncomplicated malaria is a three day regimen, with a total of 12mg/kg artesunate and 25mg/kg of mefloquine. In order to improve the tolerability of mefloquine, the mefloquine is usually divided into two doses (15 and 10 mg/kg), or prescribed as a fixed dose combination of three (8mg/kg/day).

WWARN is initiating a new artesunate-mefloquine (AS-MQ) Dose Impact Study Group, pooling individual patient data from across the world on the efficacy of AS-MQ dose regimens. In this meta-analysis the two formulations of AS-MQ will be compared with regard to tolerability, efficacy and practicality of dose banding.

The group will look at the effects of mefloquine and artesunate mg/kg dosing on early and late clinical outcomes. It will also investigate the tolerability of AS-MQ across different study sites, populations and age groups.

“Resistance is one of the factors affecting antimalarial efficacy, but not the only one,” says Prof Philippe Guérin, Director of WWARN. “WWARN is working with partners in other study groups to assess all the factors challenging the efficacy of ACTs. Many of these challenges are detectable only after drug registration when large numbers of patients have been treated and relevant information can be assembled to provide sufficient evidence.”

“It is critical that the dose regimens of all antimalarial drugs are optimised so that our best treatments are highly effective in vulnerable populations and continue to work in the future,” adds Prof Francois Nosten, Director of the Shoklo Malaria Research Unit. “This analysis will help determine whether differences in current dosing strategies affect the efficacy of artesunate-mefloquine, particularly in vulnerable groups such as children.”

This is WWARN’s fourth dose impact study group. Results released in April 2015 from the artemether-lumefantrine (AL) Dose Impact Study Group and the artesunate-amodiaquine (AS-AQ) Dose Impact Study Group confirm that the current recommended doses for both antimalarials are still working very well in most patients. However, the data analyses suggest that a higher dose of AL could potentially further improve treatment results for young children in Asia and underweight children in Africa. The efficacy of the AS-AQ can also vary due to changes in the formulation of the two parts of the ACT.

The dihydroartemisinin-piperaquine (DP) Dose Impact Study Group found that small children who receive lower doses of DP are slower to respond to treatment. The study concluded that policy makers and health workers should consider reviewing current dosing recommendations for DP, particularly for vulnerable groups such as young children. This information has now been incorporated into the latest ‘Guidelines for the Treatment of Malaria’ published by the World Health Organization.

Find out more about the analysis and governance proposal and how to join this group. For further information, email clinical@wwarn.org.

Now available: We’ve made some of our study group presentations available to the wider malaria community. Take a look and see if any of the slides could be beneficial to your research or teaching.

• AL Dose Impact Study Group presentation
• AS-AQ Dose Impact Study Group presentation
• DP Dose Impact Study Group presentation