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Potent Ex Vivo Activity of Naphthoquine and Methylene Blue against Drug-Resistant Clinical Isolates of Plasmodium falciparum and Plasmodium vivax

Wirjanata, Grennady, Sebayang, Boni F., Chalfein, Ferryanto, Prayoga, Pak, Handayuni, Irene, Trianty, Leily, Kenangalem, Enny, Noviyanti, Rintis, Campo, Brice, Poespoprodjo, Jeanne R., Mohrle, Jorg J., Price, Ric N. and Marfurt, Jutta (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.

Document type: Journal Article
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IRMA ID 11381xPUB138
NHMRC Grant No. 1023438
1037304
Title Potent Ex Vivo Activity of Naphthoquine and Methylene Blue against Drug-Resistant Clinical Isolates of Plasmodium falciparum and Plasmodium vivax
Author Wirjanata, Grennady
Sebayang, Boni F.
Chalfein, Ferryanto
Prayoga, Pak
Handayuni, Irene
Trianty, Leily
Kenangalem, Enny
Noviyanti, Rintis
Campo, Brice
Poespoprodjo, Jeanne R.
Mohrle, Jorg J.
Price, Ric N.
Marfurt, Jutta
Journal Name Antimicrobial Agents and Chemotherapy
Publication Date 2015
Volume Number 59
Issue Number 10
ISSN 0066-4804   (check CDU catalogue  open catalogue search in new window)
Scopus ID 2-s2.0-84942860129
Start Page 6117
End Page 6124
Total Pages 8
Place of Publication United States of America
Publisher American Society for Microbiology
HERDC Category C1 - Journal Article (DIISR)
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.
DOI http://dx.doi.org/10.1128/AAC.00874-15   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)


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