title: World Antimalarial Resistance Network (WARN) II: in vitro antimalarial drug susceptibility.
abstract: Intrinsic resistance of Plasmodium falciparum is clearly a major determinant of the clinical failure of antimalarial drugs. However, complex interactions between the host, the parasite and the drug obscure the ability to define parasite drug resistance in vivo. The in vitro antimalarial drug susceptibility assay determines ex-vivo growth of parasite in the presence of serial drug concentrations and, thus, eliminates host effects, such as drug metabolism and immunity. Although the sensitivity of the parasite to various antimalarials provided by such a test provides an important indicator of intrinsic parasite susceptibility, there are fundamental methodological issues that undermine comparison of in vitro susceptibility both between laboratories and within a single laboratory over time. A network of laboratories is proposed that will agree on the basic parameters of the in vitro test and associated measures of quality control. The aim of the network would be to establish baseline values of sensitivity to commonly used antimalarial agents from key regions of the world, and create a global database, linked to clinical, molecular and pharmacology databases, to support active surveillance to monitor temporal trends in parasite susceptibility. Such a network would facilitate the rapid detection of strains with novel antimalarial resistance profiles and investigate suitable alternative treatments with retained efficacy.
authors.affiliation: Parasitology Program, Naval Medical Research Center Detachment, Lima, Peru. bacon@nmrcd.med.navy.mil
authors.forename: David J
authors.initials: DJ
authors.lastname: Bacon
authors.forename: Ronan
authors.initials: R
authors.lastname: Jambou
authors.forename: Thierry
authors.initials: T
authors.lastname: Fandeur
authors.forename: Jacques
authors.initials: J
authors.lastname: Le Bras
authors.forename: Chansuda
authors.initials: C
authors.lastname: Wongsrichanalai
authors.forename: Mark M
authors.initials: MM
authors.lastname: Fukuda
authors.forename: Pascal
authors.initials: P
authors.lastname: Ringwald
authors.forename: Carol Hopkins
authors.initials: CH
authors.lastname: Sibley
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Kyle
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D019992:Databases as Topic; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D014943:Global Health; D006801:Humans; D020407:Internet; D007753:Laboratories / Q000458:organization & administration; D008288:Malaria / Q000188:drug therapy*; D021261:Parasitic Sensitivity Tests; D012016:Reference Values