PotentEx VivoActivity of Naphthoquine and Methylene Blue against Drug-Resistant Clinical Isolates of Plasmodium falciparum and Plasmodium vivax
Wirjanata G., Sebayang BF., Chalfein F., Prayoga None., Handayuni I., Trianty L., Kenangalem E., Noviyanti R., Campo B., Poespoprodjo JR., Möhrle JJ., Price RN., Marfurt J.
<jats:title>ABSTRACT</jats:title><jats:p>The 4-aminoquinoline naphthoquine (NQ) and the thiazine dye methylene blue (MB) have potent<jats:italic>in vitro</jats:italic>efficacies against<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Plasmodium falciparum</jats:named-content>, but susceptibility data for<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. vivax</jats:named-content>are limited. The species- and stage-specific<jats:italic>ex vivo</jats:italic>activities of NQ and MB were assessed using a modified schizont maturation assay on clinical field isolates from Papua, Indonesia, where multidrug-resistant<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. falciparum</jats:named-content>and<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. vivax</jats:named-content>are prevalent. Both compounds were highly active against<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. falciparum</jats:named-content>(median [range] 50% inhibitory concentration [IC<jats:sub>50</jats:sub>]: NQ, 8.0 nM [2.6 to 71.8 nM]; and MB, 1.6 nM [0.2 to 7.0 nM]) and<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. vivax</jats:named-content>(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 IC<jats:sub>50</jats:sub>s in parasites exposed at the trophozoite stage than at the ring stage for NQ in<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. falciparum</jats:named-content>(26.5 versus 5.1 nM,<jats:italic>P</jats:italic>= 0.021) and<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. vivax</jats:named-content>(341.6 versus 6.5 nM,<jats:italic>P</jats:italic>= 0.021) and for MB in<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. vivax</jats:named-content>(10.1 versus 1.6 nM,<jats:italic>P</jats:italic>= 0.010). The excellent<jats:italic>ex vivo</jats:italic>activities of NQ and MB against both<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. falciparum</jats:named-content>and<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">P. vivax</jats:named-content>highlight their potential utility for the treatment of multidrug-resistant malaria in areas where both species are endemic.</jats:p>