Potent Ex Vivo activity of naphthoquine and methylene blue against drug-resistant clinical isolates of Plasmodium falciparum and Plasmodium vivax

Grennady Wirjanata , Boni Sebayang, Ferryanto Chalfein, P Prayoga, Irene Handayuni, Leily Trianty, Enny Kenangalem, Rintis Noviyanti, Brice Campo, Jeanne Rini Poespoprodjo, Jörg Möhrle, Ric Price, Jutta Marfurt

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    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 multidrugresistant 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.
    Original languageEnglish
    Pages (from-to)6117-6124
    Number of pages8
    JournalAntimicrobial Agents and Chemotherapy
    Volume59
    Issue number10
    DOIs
    Publication statusPublished - Oct 2015

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  • Cite this

    Wirjanata , G., Sebayang, B., Chalfein, F., Prayoga, P., Handayuni, I., Trianty, L., Kenangalem, E., Noviyanti, R., Campo, B., Poespoprodjo, J. R., Möhrle, J., Price, R., & Marfurt, J. (2015). Potent Ex Vivo activity of naphthoquine and methylene blue against drug-resistant clinical isolates of Plasmodium falciparum and Plasmodium vivax. Antimicrobial Agents and Chemotherapy, 59(10), 6117-6124. https://doi.org/10.1128/AAC.00874-15