Plasmodium malariae and Plasmodium falciparum comparative susceptibility to antimalarial drugs in Mali

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dc.contributor.authorDembele, L.
dc.contributor.authorAniweh, Y.
dc.contributor.authorDiallo, N.
dc.contributor.authorSogore, F.
dc.contributor.authorSangare, C.P.O
dc.contributor.authorHaidara, A.S.
dc.contributor.authorTraore, A.
dc.contributor.authorDiakite´, S.A.S.
dc.contributor.authorDiakite, M.
dc.contributor.authorCampo, B.
dc.contributor.authorAwandare, G.A.
dc.contributor.authorDjimde, A.A.
dc.date.accessioned2021-11-15T13:38:22Z
dc.date.available2021-11-15T13:38:22Z
dc.date.issued2021
dc.descriptionResearch Articleen_US
dc.description.abstractObjectives: To evaluate Plasmodium malariae susceptibility to current and lead candidate antimalarial drugs. Methods: We conducted cross-sectional screening and detection of all Plasmodium species malaria cases, which were nested within a longitudinal prospective study, and an ex vivo assessment of efficacy of a panel of antimalarials against P. malariae and Plasmodium falciparum, both PCR-confirmed mono-infections. Reference compounds tested included chloroquine, lumefantrine, artemether and piperaquine, while candidate antimalarials included the imidazolopiperazine GNF179, a close analogue of KAF156, and the Plasmodium phosphatidylinositol- 4-OH kinase (PI4K)-specific inhibitor KDU691. Results: We report a high frequency (3%–15%) of P. malariae infections with a significant reduction in ex vivo susceptibility to chloroquine, lumefantrine and artemether, which are the current frontline drugs against P. malariae infections. Unlike these compounds, potent inhibition of P. malariae and P. falciparum was observed with piperaquine exposure. Furthermore, we evaluated advanced lead antimalarial compounds. In this regard, we identified strong inhibition of P. malariae using GNF179, a close analogue of KAF156 imidazolopiperazines, which is a novel class of antimalarial drug currently in clinical Phase IIb testing. Finally, in addition to GNF179, we demonstrated that the Plasmodium PI4K-specific inhibitor KDU691 is highly inhibitory against P. malariae and P. falciparum. Conclusions: Our data indicated that chloroquine, lumefantrine and artemether may not be suitable for the treatment of P. malariae infections and the potential of piperaquine, as well as new antimalarials imidazolopiperazines and PI4K-specific inhibitor, for P. malariae cure.en_US
dc.identifier.otherdoi:10.1093/jac/dkab133
dc.identifier.urihttp://ugspace.ug.edu.gh/handle/123456789/37127
dc.language.isoenen_US
dc.publisherJournal of Antimicrobial Chemotherapyen_US
dc.subjectPlasmodiumen_US
dc.subjectPlasmodium malariaeen_US
dc.subjectPlasmodium falciparumen_US
dc.subjectcomparative susceptibilityen_US
dc.subjectantimalarial drugsen_US
dc.subjectMalien_US
dc.titlePlasmodium malariae and Plasmodium falciparum comparative susceptibility to antimalarial drugs in Malien_US
dc.typeArticleen_US

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