(1) We analyzed our 4-year case-control study of severe malaria in Pursat, Cambodia, and found that increasing age (but not hemoglobin E) confers protection against severe disease. (2) We measured parasite clearance rates in response to artesunate in patients with uncomplicated malaria in Pursat, Preah Vihear and Ratanakiri and have found that artemisinin resistance is entrenched, emerging and uncommon in these three provinces, respectively. (3) We associated prolonged parasite clearance rates in Cambodia and elsewhere in Southeast Asia with various mutations in K13, a kelch protein expressed by P. falciparum. (4) Through whole-genome sequence analysis, we identified subpopulations of artemisinin-resistant P. falciparum parasites in Pursat and Preah Vihear, Cambodia, and discovered four mutations that constitute a genetic background on which K13 mutations arise and confer artemisinin resistance. (5) Using genetically-edited parasites, we confirmed that K13 mutations are causal for artemsinin resistance in vitro. (6) We 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 completed a study showing that chloroquine remains highly effective for the treatment of P. vivax malaria in Pursat, Cambodia. (8) We completed 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.

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2014
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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
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
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

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