(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.

Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2012
Total Cost
$390,699
Indirect Cost
City
State
Country
Zip Code
Fairhurst, Rick M; Dondorp, Arjen M (2016) Artemisinin-Resistant Plasmodium falciparum Malaria. Microbiol Spectr 4:
Amaratunga, Chanaki; Lim, Pharath; Suon, Seila et al. (2016) Dihydroartemisinin-piperaquine resistance in Plasmodium falciparum malaria in Cambodia: a multisite prospective cohort study. Lancet Infect Dis 16:357-65
Pearson, Richard D; Amato, Roberto; Auburn, Sarah et al. (2016) Genomic analysis of local variation and recent evolution in Plasmodium vivax. Nat Genet 48:959-64
St Laurent, Brandyce; Miller, Becky; Burton, Timothy A et al. (2016) Corrigendum: Artemisinin-resistant Plasmodium falciparum clinical isolates can infect diverse mosquito vectors of Southeast Asia and Africa. Nat Commun 7:10345
WWARN Parasite Clearance Study Group; Abdulla, Salim; Ashley, Elizabeth A et al. (2015) Baseline data of parasite clearance in patients with falciparum malaria treated with an artemisinin derivative: an individual patient data meta-analysis. Malar J 14:359
Lim, Pharath; Dek, Dalin; Try, Vorleak et al. (2015) Decreasing pfmdr1 copy number suggests that Plasmodium falciparum in Western Cambodia is regaining in vitro susceptibility to mefloquine. Antimicrob Agents Chemother 59:2934-7
St Laurent, Brandyce; Miller, Becky; Burton, Timothy A et al. (2015) Artemisinin-resistant Plasmodium falciparum clinical isolates can infect diverse mosquito vectors of Southeast Asia and Africa. Nat Commun 6:8614
Fogarty, Colin B; Fay, Michael P; Flegg, Jennifer A et al. (2015) Bayesian hierarchical regression on clearance rates in the presence of ""lag"" and ""tail"" phases with an application to malaria parasites. Biometrics 71:751-9
Fairhurst, Rick M (2015) Understanding artemisinin-resistant malaria: what a difference a year makes. Curr Opin Infect Dis 28:417-25
Hostetler, Jessica B; Sharma, Sumana; Bartholdson, S Josefin et al. (2015) A Library of Plasmodium vivax Recombinant Merozoite Proteins Reveals New Vaccine Candidates and Protein-Protein Interactions. PLoS Negl Trop Dis 9:e0004264

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