Malaria diagnosis and infection characterization have definitively moved into the molecular era. Gone are the days of microscopy alone for determining malaria infection. Molecular diagnosis is no longer just a research technique used on a limited number of samples; it has moved to a high-throughput method used for standard detection of the important sub-microscopic malaria infection pool. This proposal completely eschews microscopic diagnosis and instead will require molecular testing of more than 150,000 samples over the course of seven years for detecting malaria infections. In addition to identifying individuals with asexual forms of the malaria parasite in peripheral blood, molecular techniques will be used for to determine which infection characteristics are potentially infectious (Project 2, Transmission Reservoirs) and which characteristics are associated with different levels of disease severity (Project 3, The Pathogenesis Spectrum). For Project 2, the Molecular and Genomics Core will use molecular methods to measure the levels of asexual as well as sexual parasites and also to determine whether male and female gametocytes are present in the same sample (both are required to propagate infection). For Project 3, the Molecular and Genomics Core will be measuring various parasite characteristics, including growth rate and genetic complexity, both of which could influence disease severity. The continued presence of the Molecular and Genomics Core is justified by the volume of the standard molecular assays required, as well as the need for more sophisticated characterization of infections. By supporting each of the three scientific projects with timely and accurate results, the Molecular and Genomics Core will be a vital contributor to the overall scientific success of the proposal.