(1) We are completing a final analysis of our 3-year longitudinal cohort study of Cambodian children and adults to determine whether hemoglobin E, alpha-thalassemia, G6PD deficiency, and ABO blood group polymorphisms protect our study population against P. vivax and P. falciparum malaria. (2) We have completed our final analysis and drafted a preliminary manuscript of our 4-year case-control study of severe malaria in Pursat, western Cambodia. (3) We have completed and published our study of parasite clearance rates in response to artesunate in patients with uncomplicated malaria in Pursat, western Cambodia. In this study we have identified candidate host and parasite genetic factors that contribute the artemisinin resistance phenotype of slow parasite clearance in vivo. (4) We have completed and drafted a preliminary manuscript of our study of parasite clearance rates in response to artesunate in patients with uncomplicated malaria in Ratanakiri, eastern Cambodia. In this study we have identified age-associated acceleration of parasite clearance rates and have explored the role of specific acquired antibody responses, such as IgG reactivity to the surface of parasitized erythrocyte, growth-inhibitory activity of plasma IgG, and IgG titers to four merozoite antigens. (5) We have completed a 2-year study of parasite clearance rates in Pursat, Preah Vihear and Ratanakiri, Cambodia, as part of the Southeast Asia Tracking Resistance to Artemisinin Collaboration. This consortium, which Dr. Fairhurst presently co-chairs with Dr. Arjen Dondorp (Mahidol-Oxford Research Unit), involves our three sites in Cambodia, as well as additional sites in Cambodia, Thailand, Burma, Laos, Vietnam, India, Bangladesh, Nigeria and Kenya. The purpose of TRAC and our own studies is to (i) map the artemisinin resistance phenotype across Southeast Asia and (ii) to improve our understanding of parasite clearance in response to artesunate. Specifically, we are interested in how hemoglobin E (HbE), naturally-acquired immunity, pharmacokinetics, and intrinsic parasite susceptibility to artemisinins influence the parasite clearance curve.
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