Summary As the Asia-Pacific aim to eliminate malaria from the entire region by 2030, a number of key challenges related to increasing strong variations in malaria transmission, the presence of a large reservoir of infected but asymptomatic individual and the development of resistance to frontline antimalarial treatment need to be confronted. In addition, the predominance of P. vivax infections in the region results in the particular challenge of dealing with P. vivax hypnozoites and the relapsing infections the cause. The Asia-Pacific ICEMR project is proposing to conduct coordinated set of field and in-depth biological studies in 3 sites in Cambodia, Papua New Guinea and Thailand that span the range of transmission intensities currently found in the Asia-Pacific regions. In the Epidemiology Project spatio-temporal patterns of risk of malaria infection and disease will be investigate through a combination of large cross-sectional and longitudinal cohort studies that combine excellent epidemiological study designs with state-of-the-art molecular detection and genotyping of Plasmodium spp. infections and an assessment of host immune responses and their link to exposure and clinical protection. The information thus gained will be used to evaluate improved surveillance strategies through an innovative combination of computer simulations and field application. The Transmission Project will use direct membrane feeding assay as a xenodiagnostic tool to determine the infective reservoir as each site and investigate host, parasite and host factors that contribute to sustaining endemic transmission at each site. In addition, we will study patterns of human-vector contact in low transmission settings by investigating human antibodies to anopheline salivary protein as marker exposure to mosquito bites. A key question in both studies is how artemisinin and partner drug resistance affects parasite fitness both in chronic asymptomatic infections and transmissibility. Finally, the P. vivax Relapse Project will specifically address the role of relapsing infections from long-lasting liver stages in the increased resilience of P. vivax against control and elimination. The conduct of these studies will use spatially explicit malaria transmission models, next- generation sequencing (NGS)-based high-throughput genotyping methods and a range of high-throughput and functional assay of humoral immune responses that will be developed in 3 resource cores. These interconnected, multi-disciplinary studies thus aim to identify and characterize critical steps in malaria transmission cycle and thereby gain a better understanding of parasite, host and vector factors that contribute to continued transmission in the context of intensive national malaria control and elimination programs. This knowledge will assist in the development of novel approaches to target residual transmission pockets.

Narrative Eliminating malaria from the Asia-Pacific will be made much easier if countries have a good understanding not only where people with malaria infections and disease are living but also where they may have acquired infections and who could infect new mosquito and thus pass the infection on to other people. With a coordinated of epidemiological and vector studies in Thailand, Cambodia, and Papua New Guinea, that span the different levels of malaria transmission in the Asia-Pacific, we will now determine the key reasons where and when people acquire infection and how likely they are to pass it on to other people. This information will help design better ways to identify village and population groups at the highest risk of malaria