title: Genetic diversity of next generation antimalarial targets: A baseline for drug resistance surveillance programmes.
abstract: Drug resistance is a recurrent problem in the fight against malaria. Genetic and epidemiological surveillance of antimalarial resistant parasite alleles is crucial to guide drug therapies and clinical management. New antimalarial compounds are currently at various stages of clinical trials and regulatory evaluation. Using ∼2000 Plasmodium falciparum genome sequences, we investigated the genetic diversity of eleven gene-targets of promising antimalarial compounds and assessed their potential efficiency across malaria endemic regions. We determined if the loci are under selection prior to the introduction of new drugs and established a baseline of genetic variance, including potential resistant alleles, for future surveillance programmes.
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Gomes
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Matt
authors.initials: M
authors.lastname: Ravenhall
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Ernest Diez
authors.initials: ED
authors.lastname: Benavente
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton Cambridge, UK.
authors.forename: Arthur
authors.initials: A
authors.lastname: Talman
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Colin
authors.initials: C
authors.lastname: Sutherland
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Cally
authors.initials: C
authors.lastname: Roper
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK; Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Taane G
authors.initials: TG
authors.lastname: Clark
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK. Electronic address: Susana.campino@lshtm.ac.uk.
authors.forename: Susana
authors.initials: S
authors.lastname: Campino
mesh_terms: D000962:Antimalarials / Q000494:pharmacology; D019295:Computational Biology; D004351:Drug Resistance; D062665:Epidemiological Monitoring; D014644:Genetic Variation; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*
chemical_list: D000962:Antimalarials
keywords: Antimalarial drugs; Drug-resistant mutations; Gene targets; Genetic diversity