PROJECT 1 SUMMARY Despite the recent global reduction in malaria morbidity and mortality, malaria in the Greater Mekong Subregion (GMS) of Southeast Asia remains one of the most important public health problems. While nations in this region are moving towards malaria elimination, they face a daunting array of challenges, including continuous transmission of malaria along the international borders, introduction and spread of multidrug resistant malaria parasites by human migrants from neighboring countries, and the persistent Plasmodium vivax malaria. Accordingly, we strategically select study sites at the international borders of China, Thailand and Myanmar, which vary significantly in malaria endemicity, to address these problems. The overarching objective of this project is to gain critical epidemiological information about factors contributing to the persistence of border malaria in the GMS so that more effective malaria control strategies can be developed. In this project, we aim to (1) conduct malaria surveillance and use highly sensitive molecular diagnostic tools to identify transmission hotspots and risk factors for malaria infection; (2) determine and monitor the impact of control programs and parasite introduction in the border regions on changes in parasite population diversity in space and time using population genomic and landscape genetic tools; and 3) evaluate the effectiveness of the chloroquine-primaquine treatment regimen as a radical cure of vivax malaria in border areas with high prevalence of glucose-6-phosphate dehydrogenase deficiency. This project lays important foundations for other projects of the ICEMR program, and will provide critical knowledge for developing and evaluating integrated malaria management strategies.