(1) We have completed an analysis of our 4-year case-control study of severe malaria in Pursat province, Cambodia, and have found that increasing age (but not hemoglobin E) confers protection against severe disease. (2) We have measured parasite clearance rates in response to artesunate in patients with uncomplicated and severe malaria in Pursat, and have found that artemisinin resistance is a highly-prevalent, parasite-heritable trait in this province. (3) We have completed an analysis of our study of parasite clearance rates in response to artesunate in patients with uncomplicated malaria in Ratanakiri province, and have found that artemisinin resistance is extremely rare in this area of eastern Cambodia. (4) We have completed a preliminary analysis of our 2-year study of parasite clearance rates in Pursat, Preah Vihear and Ratanakiri provinces, Cambodia, as part of the Tracking Resistance to Artemisinin Collaboration, which aims to map the distribution and spread of artemisinin resistance in Southeast Asia. (5) Through whole-genome sequence analysis, we have identified subpopulations of artemisinin-resistant P. falciparum parasites in Pursat and Preah Vihear provinces, Cambodia, and have produced a list of mutations that may be involved in artemisinin resistance. (6) We have developed and validated an ex vivo assay to detect artemisinin-resistant parasites in the field and an in vitro assay to investigate the molecular mechanism of artemisinin resistance in the laboratory. (7) We have completed a study of the efficacy of chloroquine in the treatment of P. vivax malaria in Pursat, Cambodia. (8) We have initiated a study of the efficacy of dihydroartemisinin-piperaquine in the treatment of uncomplicated P. falciparum malaria in Pursat, Preah Vihear and Ratanakiri provinces in Cambodia.

Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2013
Total Cost
$472,502
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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