Clinical Investigation of In-vivo Susceptibility of P.Falciparum to Artesunate in Western Cambodia

Primary objective:

To assess the level of resistance to artemisinin derivatives in Western Cambodia.

Secondary objective:

To assess the level of resistance to other antimalarial drugs in Western Cambodia

1. Background; There are worrying signs from Western Cambodia that parasitological responses to artesunate and artemether containing treatment regimens for uncomplicated falciparum malaria are slower than elsewhere in the world [1-4]. Both delayed parasite clearance and unusually high failure rates with artesunate-mefloquine and artemether-lumefantrine have been reported [1,2]. Although occasional poor responses to artesunate have been described previously [5] the current reports suggest a consistent problem. As the rate of parasite clearance is a good pharmacodynamic measure of efficacy of the artemisinin related compounds [6,7], this could indicate the emergence of significant resistance[8]. These antimalarials are central to current treatment strategies[9], and so spread of significant resistance outside this area would be a disaster. Radical containment measures might be needed. In this context there is an urgent need to proceed quickly to investigate the level of resistance to artemisinin derivatives in Western Cambodia to provide a definitive assessment so that if necessary containment plans can be developed in 2007. A group of malaria investigators from Cambodia and Thailand have joined together to address this urgent question as quickly and effectively as possible.