This project aims to assess specific P. falciparum genetic markers for resistance to artemisinin-based combinations (ACT), and to develop innovative, rapid and simple diagnostics for malaria and these markers. Specific objectives are: • To develop and evaluate in disease endemic countries accurate low-tech molecular diagnostic tests. • To identify alleles of candidate resistance genes associated with increased transmission success of P. falciparum after ACT treatment in completed clinical trials (endpoints at gametocyte or infected mosquito level). • To conduct ACT treatment trials with transmission endpoints, and measure impact of resistance-associated alleles on gametocyte emergence, and on the infectiousness of gametocyte-positive or randomly-selected treated individuals to Anopheles mosquitoes. • To measure ACT efficacy using in vivo treatment trials, and in vitro drug sensitivity testing of natural parasite isolates. The impact of candidate resistance markers will be measured in patients with treatment failure, and in parasites with reduced in vitro sensitivity. • To develop new low-tech diagnostic tools able to demonstrate the presence of mutations conferring drug resistance in the Plasmodium population, particularly those markers validated by the project. • To investigate commercial value aspects of developed tests. The project will move our knowledge of ACT resistance forward in 2 complementary ways: 1) In order to identify and validate genetic markers for ACT resistance, we will use our unprecedented access to parasites isolated both from ACT-treated individuals and from mosquitoes fed on blood from ACT-treated individuals. 2) we will develop and validate simple tests in new formats for detection of these and other markers of relevance, and for rapid detection of persisting parasites in treated patients. The work is a balanced mix of clinical field work, laboratory research and (commercial) test development and linked to EU initiative EDCTP.