**6. Choice of drug for malaria elimination: is the pipeline empty?**

The current malaria elimination program along the Thai-Myanmar border is using artemetherlumefantrine (AL) for treating the clinical cases at the village malaria posts or by malaria workers [114], whereas dihydroartemisinin-piperaquine (DP) is deployed in MDA activities [117]. In this area, the third ACT, mefloquine-artesunate combination, is already failing [25], and the prospect of elimination program is highly dependent on the therapeutic efficacy of AL and DP. Recent emergence of piperaquine resistance following the artemisinin resistance has depleted the available ACTs to be deployed in malaria elimination programs. High failure rates of AL in Laos PDR and DP in Vietnam and Cambodia have cast doubts on the optimism of malaria elimination [10, 26, 87, 118].

There are very few new compounds in the development pipeline. The front runners are OZ439, a synthetic endoperoxide, structurally related to artemisinin, and KAF156 belonging to a new class of antimalarial (imidazolopiperazines) and the spiroindolone cipargamin (formerly KAE609). However, these short-acting drugs will have to be deployed in combination therapies and their full development will take many years.

As a stopgap measure, two triple ACTs (mefloquine plus DP and amodiaquine plus AL) are under multicentre trial, using the inverse correlation between susceptibility to amodiaquine and lumefantrine as well as between piperaquine and mefloquine. The trial has completed the patient recruitment and the results are promising with high cure rates. However, recent increasing prevalence of parasite isolates with potential resistance to both mefloquine and piperaquine has questioned the longevity of the triple ACT [20].
