(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
Amaratunga, Chanaki; Witkowski, Benoit; Dek, Dalin et al. (2014) Plasmodium falciparum Founder Populations in Western Cambodia Have Reduced Artemisinin Sensitivity In Vitro. Antimicrob Agents Chemother 58:4935-7
Amaratunga, Chanaki; Neal, Aaron T; Fairhurst, Rick M (2014) Flow Cytometry-Based Analysis of Artemisinin-Resistant Plasmodium falciparum in the Ring-Stage Survival Assay. Antimicrob Agents Chemother 58:4938-40
Preston, Mark D; Assefa, Samuel A; Ocholla, Harold et al. (2014) PlasmoView: a web-based resource to visualise global Plasmodium falciparum genomic variation. J Infect Dis 209:1808-15
Ocholla, Harold; Preston, Mark D; Mipando, Mwapatsa et al. (2014) Whole-genome scans provide evidence of adaptive evolution in Malawian Plasmodium falciparum isolates. J Infect Dis 210:1991-2000
Ariey, Frederic; Witkowski, Benoit; Amaratunga, Chanaki et al. (2014) A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature 505:50-5
Ashley, Elizabeth A; Dhorda, Mehul; Fairhurst, Rick M et al. (2014) Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 371:411-23
Preston, Mark D; Campino, Susana; Assefa, Samuel A et al. (2014) A barcode of organellar genome polymorphisms identifies the geographic origin of Plasmodium falciparum strains. Nat Commun 5:4052
Amaratunga, Chanaki; Sreng, Sokunthea; Mao, Sivanna et al. (2014) Chloroquine remains effective for treating Plasmodium vivax malaria in Pursat Province, Western Cambodia. Antimicrob Agents Chemother :
Amaratunga, Chanaki; Witkowski, Benoit; Khim, Nimol et al. (2014) Artemisinin resistance in Plasmodium falciparum. Lancet Infect Dis 14:449-50
Amaratunga, Chanaki; Mao, Sivanna; Sreng, Sokunthea et al. (2013) Slow parasite clearance rates in response to artemether in patients with severe malaria. Lancet Infect Dis 13:113-4

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