Given the emergence of Plasmodium falciparum (Pf) artemisinin resistance Médecins sans Frontières launched in May 2014 a research programme in Chey Saen district (Cambodia), aimed at preventing its spread. The activities of passive case detection (PCD) of Pf infections started in May 2014. In 2015, the project focused on ensuring that the different subgroups of infected people being sources of malaria transmission (both symptomatic and asymptomatic), could be identified early and managed by a MSF-supported network of test providers, along with strengthened prevention activities. Prevalence survey had been implemented in September 2014 with PCR, which was also introduced in PCD to complement RDT in October 2015. It was used by Village Malaria Workers, Health Centers and Registered Private Providers, in order to increase the detection capability of the above mentioned network. In addition, the strategy aimed at identifying symptomatic and asymptomatic Pf cases through different activities by including reactive case detection for people co-exposed with the Pf index case (household, co-workers and co-exposed), as well as pro-active case detection for high risk people (forest goers or people spending one night in a plantation), through periodic active screening rounds in the villages. These activities were accompanied by follow up of cases (check in Day 28 and D63) treated by DHA-PPQ and ASMQ as of February 2016, and systematic analysis of molecular markers of resistance. Pre-elimination levels were reached during the season 2016-2017 in Chey Saen. As infections occurred in Chey Saen forest, expansion of activities started in October 2017 to include villages of three neighbouring districts (Chaeb, Rovieng and Thala Barivat in Stung Treng province) as a belt to protect the forest from re-introduction/re-infestation phenomena. In 2017 cases bounced back in all these districts up to mid 2018. Genetic analysis of parasite populations should help us understanding the origin and mechanism of this dramatic increase.