(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
Amato, Roberto; Pearson, Richard D; Almagro-Garcia, Jacob et al. (2018) Origins of the current outbreak of multidrug-resistant malaria in southeast Asia: a retrospective genetic study. Lancet Infect Dis 18:337-345
Bopp, Selina; Magistrado, Pamela; Wong, Wesley et al. (2018) Plasmepsin II-III copy number accounts for bimodal piperaquine resistance among Cambodian Plasmodium falciparum. Nat Commun 9:1769
Mukherjee, Angana; Bopp, Selina; Magistrado, Pamela et al. (2017) Artemisinin resistance without pfkelch13 mutations in Plasmodium falciparum isolates from Cambodia. Malar J 16:195
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
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
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
St Laurent, Brandyce; Oy, Kolthida; Miller, Becky et al. (2016) Cow-baited tents are highly effective in sampling diverse Anopheles malaria vectors in Cambodia. Malar J 15:440
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

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