The last man standing is the most resistant: eliminating artemisinin-resistant malaria in Cambodia.

Richard J Maude,Ricardo Aguas,Wirichada Pontavornpinyo,Shunmay Yeung,Sompob Saralamba,Lisa J White,Arjen M Dondorp,Nicholas J White,Nicholas Pj Day

doi:10.1186/1475-2875-8-31

Abstract

BackgroundArtemisinin combination therapy (ACT) is now the recommended first-line treatment for falciparum malaria throughout the world. Initiatives to eliminate malaria are critically dependent on its efficacy. There is recent worrying evidence that artemisinin resistance has arisen on the Thai-Cambodian border. Urgent containment interventions are planned and about to be executed. Mathematical modeling approaches to intervention design are now integrated into the field of malaria epidemiology and control. The use of such an approach to investigate the likely effectiveness of different containment measures with the ultimate aim of eliminating artemisinin-resistant malaria is described.MethodsA population dynamic mathematical modeling framework was developed to explore the relative effectiveness of a variety of containment interventions in eliminating artemisinin-resistant malaria in western Cambodia.ResultsThe most effective intervention to eliminate artemisinin-resistant malaria was a switch of treatment from artemisinin monotherapy to ACT (mean time to elimination 3.42 years (95% CI 3.32–3.60 years). However, with this approach it is predicted that elimination of artemisinin-resistant malaria using ACT can be achieved only by elimination of all malaria. This is because the various forms of ACT are more effective against infections with artemisinin-sensitive parasites, leaving the more resistant infections as an increasing proportion of the dwindling parasite population.ConclusionContainment of artemisinin-resistant malaria can be achieved by elimination of malaria from western Cambodia using ACT. The "last man standing" is the most resistant and thus this strategy must be sustained until elimination is truly achieved.

Highlights

Artemisinin combination therapy (ACT) is the recommended first-line treatment for falciparum malaria throughout the world
Which anti-malarial should be used in different situations? Under consideration are atovaquone plus proguanil (AP) and/or dihydroartemisinin and piperaquine, both given for three days, plus one "gametocytocidal" dose of primaquine (APP)
Continuing availability of artesunate monotherapy The model predicts that if there is no intervention, and use of artemisinin monotherapies continues, there will be an exponential rise in the proportion of resistant infections and a slowly increasing prevalence of infection

Summary

Introduction

Artemisinin combination therapy (ACT) is the recommended first-line treatment for falciparum malaria throughout the world. Cure rates with ACT have been worse in this area than anywhere else This was attributed initially to resistance to the partner drugs (mefloquine [8] and lumefantrine [9]), but recent detailed studies show that parasite clearance times following standard doses of artesunate in uncomplicated falciparum malaria are significantly longer than elsewhere in the world [5-7]. If reduced in-vivo parasitological efficacy is the first sign of artemisinin resistance immediate action should be taken to prevent the spread of these parasites elsewhere [11] Loss of these drugs would be a disaster for global malaria control and elimination prospects as there are no obvious replacements emerging from the development pipeline in the near future [12]. Several different interventions to contain and ideally eliminate the threat of artemisinin resistance are

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