title: Potent Ex Vivo Activity of Naphthoquine and Methylene Blue against Drug-Resistant Clinical Isolates of Plasmodium falciparum and Plasmodium vivax.
abstract: The 4-aminoquinoline naphthoquine (NQ) and the thiazine dye methylene blue (MB) have potent in vitro efficacies against Plasmodium falciparum, but susceptibility data for P. vivax are limited. The species- and stage-specific ex vivo activities of NQ and MB were assessed using a modified schizont maturation assay on clinical field isolates from Papua, Indonesia, where multidrug-resistant P. falciparum and P. vivax are prevalent. Both compounds were highly active against P. falciparum (median [range] 50% inhibitory concentration [IC50]: NQ, 8.0 nM [2.6 to 71.8 nM]; and MB, 1.6 nM [0.2 to 7.0 nM]) and P. vivax (NQ, 7.8 nM [1.5 to 34.2 nM]; and MB, 1.2 nM [0.4 to 4.3 nM]). Stage-specific drug susceptibility assays revealed significantly greater IC50s in parasites exposed at the trophozoite stage than at the ring stage for NQ in P. falciparum (26.5 versus 5.1 nM, P = 0.021) and P. vivax (341.6 versus 6.5 nM, P = 0.021) and for MB in P. vivax (10.1 versus 1.6 nM, P = 0.010). The excellent ex vivo activities of NQ and MB against both P. falciparum and P. vivax highlight their potential utility for the treatment of multidrug-resistant malaria in areas where both species are endemic.
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia.
authors.forename: Grennady
authors.initials: G
authors.lastname: Wirjanata
authors.affiliation: Eijkman Institute for Molecular Biology, Jakarta, Indonesia.
authors.forename: Boni F
authors.initials: BF
authors.lastname: Sebayang
authors.affiliation: Papuan Health and Community Development Foundation (PHCDF), Timika, Papua, Indonesia.
authors.forename: Ferryanto
authors.initials: F
authors.lastname: Chalfein
authors.affiliation: Papuan Health and Community Development Foundation (PHCDF), Timika, Papua, Indonesia.
authors.lastname: Prayoga
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia.
authors.forename: Irene
authors.initials: I
authors.lastname: Handayuni
authors.affiliation: Eijkman Institute for Molecular Biology, Jakarta, Indonesia.
authors.forename: Leily
authors.initials: L
authors.lastname: Trianty
authors.affiliation: Papuan Health and Community Development Foundation (PHCDF), Timika, Papua, Indonesia District Health Authority, Timika, Papua, Indonesia.
authors.forename: Enny
authors.initials: E
authors.lastname: Kenangalem
authors.affiliation: Eijkman Institute for Molecular Biology, Jakarta, Indonesia.
authors.forename: Rintis
authors.initials: R
authors.lastname: Noviyanti
authors.affiliation: Medicines for Malaria Venture (MMV), Geneva, Switzerland.
authors.forename: Brice
authors.initials: B
authors.lastname: Campo
authors.affiliation: Papuan Health and Community Development Foundation (PHCDF), Timika, Papua, Indonesia.
authors.forename: Jeanne Rini
authors.initials: JR
authors.lastname: Poespoprodjo
authors.affiliation: Medicines for Malaria Venture (MMV), Geneva, Switzerland.
authors.forename: Jörg J
authors.initials: JJ
authors.lastname: Möhrle
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Ric N
authors.initials: RN
authors.lastname: Price
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia jutta.marfurt@menzies.edu.au.
authors.forename: Jutta
authors.initials: J
authors.lastname: Marfurt
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D008751:Methylene Blue / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects*; D010966:Plasmodium vivax / Q000187:drug effects*
chemical_list: D000962:Antimalarials; D008751:Methylene Blue