(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
Ataide, Ricardo; Ashley, Elizabeth A; Powell, Rosanna et al. (2017) Host immunity to Plasmodium falciparum and the assessment of emerging artemisinin resistance in a multinational cohort. Proc Natl Acad Sci U S A 114:3515-3520
Amato, Roberto; Lim, Pharath; Miotto, Olivo et al. (2017) Genetic markers associated with dihydroartemisinin-piperaquine failure in Plasmodium falciparum malaria in Cambodia: a genotype-phenotype association study. Lancet Infect Dis 17:164-173
Mukherjee, Angana; Bopp, Selina; Magistrado, Pamela et al. (2017) Artemisinin resistance without pfkelch13 mutations in Plasmodium falciparum isolates from Cambodia. Malar J 16:195
Fairhurst, Rick M; Dondorp, Arjen M (2016) Artemisinin-Resistant Plasmodium falciparum Malaria. Microbiol Spectr 4:
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
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
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
Rasmussen, Charlotte; Ariey, Frédéric; Fairhurst, Rick M et al. (2016) Role of K13 Mutations in Artemisinin-Based Combination Therapy. Clin Infect Dis 63:1680-1681
Hostetler, Jessica B; Lo, Eugenia; Kanjee, Usheer et al. (2016) Independent Origin and Global Distribution of Distinct Plasmodium vivax Duffy Binding Protein Gene Duplications. PLoS Negl Trop Dis 10:e0005091
Srimuang, Krongkan; Miotto, Olivo; Lim, Pharath et al. (2016) Analysis of anti-malarial resistance markers in pfmdr1 and pfcrt across Southeast Asia in the Tracking Resistance to Artemisinin Collaboration. Malar J 15:541

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