@article {Wirjanata6117, author = {Wirjanata, Grennady and Sebayang, Boni F. and Chalfein, Ferryanto and Prayoga, and Handayuni, Irene and Trianty, Leily and Kenangalem, Enny and Noviyanti, Rintis and Campo, Brice and Poespoprodjo, Jeanne Rini and M{\"o}hrle, J{\"o}rg J. and Price, Ric N. and Marfurt, Jutta}, title = {Potent Ex Vivo Activity of Naphthoquine and Methylene Blue against Drug-Resistant Clinical Isolates of Plasmodium falciparum and Plasmodium vivax}, volume = {59}, number = {10}, pages = {6117--6124}, year = {2015}, doi = {10.1128/AAC.00874-15}, publisher = {American Society for Microbiology Journals}, 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.}, issn = {0066-4804}, URL = {https://aac.asm.org/content/59/10/6117}, eprint = {https://aac.asm.org/content/59/10/6117.full.pdf}, journal = {Antimicrobial Agents and Chemotherapy} }