Partner study description

In field-based studies, Rick Fairhurst and colleagues investigated patient responses to artemisinin combination therapies (ACTs), in three Cambodian provinces, where artemisinin resistance is entrenched (Pursat), emerging (Preah Vihear), or uncommon (Ratanakiri). They provided samples from this study with the aim to identify genetic markers of antimalarial drug resistance, use them in real time to define frontline treatments at the provincial level, and eliminate multidrug-resistant malaria in the Greater Mekong Subregion. All three sites provided Plasmodium falciparum samples, with Pursat additionally providing samples from patients presenting with Plasmodium vivax. In related laboratory-based studies, researchers aimed to elucidate the molecular mechanisms of P. falciparum artemisinin and partner-drug resistance, to develop point-of care diagnostics to identify drug-resistant parasites, and discover new compounds to treat drug-resistant malaria episodes. For P. vivax, they investigated whether red blood cell polymorphisms protected against P. vivax malaria, P. vivax-infected erythrocyte binding to monocytes, reticulocyte invasion, immune responses to candidate vaccine antigens, and efficacy of chloroquine against P. vivax malaria.

Publications

• Genetic markers associated with dihydroartemisinin–piperaquine failure in Plasmodium falciparum malaria in Cambodia: a genotype–phenotype association study
  Amato, Lim, et al.
  The Lancet Infectious Diseases, 2016;
  10.1016/S1473-3099(16)30409-1
• Independent origin and global distribution of distinct Plasmodium vivax Duffy Binding Protein gene duplications
  Hostetler et al.
  PLoS Neglected Tropical Diseases, 2016; 10(10) e0005091
  10.1371/journal.pntd.0005091
• Genomic analysis of local variation and recent evolution in Plasmodium vivax
  Pearson et al
  Nature Genetics, 2016; 48 959-964
  10.1038/ng.3599
• Genomic epidemiology of artemisinin resistant malaria
  MalariaGEN P. falciparum Community Project
  eLife, 2016; 5 e08714
  10.7554/eLife.08714
• Genetic architecture of artemisinin-resistant Plasmodium falciparum
  Miotto et al
  Nature Genetics, 2015; 47(3) 226-34
  10.1038/ng.3189
• Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia
  Miotto et al
  Nature Genetics, 2013; 45(6) 648-55
  10.1038/ng.2624
• Population genetic analysis of Plasmodium falciparum parasites using a customized Illumina GoldenGate genotyping assay
  Campino S et al.
  PLoS One, 2011; 6(6) e20251
  10.1371/journal.pone.0020251