OVERALL SUMMARY
India, the world's largest democracy and soon-to-be most populous country, has shown a sustained decline in malaria cases over the past decade. However, malaria remains an enormous public health problem, and India faces several challenges in its elimination drive. Infections in India can be caused by all four species of human malaria parasite and transmitted by at least six different Anopheles vectors. Several important barriers to elimination have recently come to light, including persistent malaria parasite transmission in areas of intense elimination efforts, inadequacy of PfHRP2-based RDTs, and cryptic reservoirs of transmission. “Hidden Plasmodium infections: reservoirs, impact, and biomarker discovery”, is the main theme of the CSCM in this application. The overall goals of the Center are to develop the knowledge, tools, and evidence-based strategies needed to support Indian intervention and control programs, and to build research capacity in India. The CSCMi research proposed in this application comprises two projects: Project 1: Monitoring the changing epidemiology of malaria in Odisha, India, will comprise of a four-year community-based cohort in three districts of differing endemicity to investigate factors supporting persistent malaria transmission. This will include the analysis of malaria parasite diagnostic failure, complemented by a passive surveillance of patients with febrile illnesses presenting at district healthcare centers, the assessment of Pfhrp2/Pfhrp3 gene deletions, the monitoring of historically low prevalence parasite species, as well as the assessment of Anopheles vector species composition, density, and resistance to insecticide. Project 2: Developing new diagnostic tools for the detection of Plasmodium infection will leverage a prospective cohort sub-study nested within Project 1 to the focus on the characterization of local malaria parasite transmission patterns through sero-epidemiology and the detection of anti-Plasmodium antibodies, as well evaluating new circulating host- and parasite-derived biomarkers of infection. The CSCMi projects will be supported by an Administrative Core and Data Management and Biostatistics Core, and advised by a team of other significant contributors and a Scientific Advisory Group.