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

Simple item page
dc.contributor.authorDembele, Laurent
dc.contributor.authorAniweh, Yaw
dc.contributor.authorDiallo, Nouhoum
dc.date.accessioned2023-04-22T14:17:27Z
dc.date.available2023-04-22T14:17:27Z
dc.date.issued2021-03-16
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 antimalar ials 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 imidazolpiperazines and PI4K-specific inhibitor, for P. malariae cure.en_US
dc.description.sponsorshipACE: Cell Biology of Infectious and Non-Communicable Diseaseen_US
dc.identifier.issn0305-7453
dc.identifier.issn1460-2091
dc.identifier.urihttps://datad.aau.org/handle/123456789/1527
dc.language.isoenen_US
dc.publisherAdvance Access Publicationen_US
dc.relation.ispartofseriesJ Antimicrob Chemother;2021; 76:
dc.subjectFanta Sogoreen_US
dc.subjectCheick Papa Oumar Sangareen_US
dc.subjectAboubecrin Sedhigh Haidaraen_US
dc.subjectAliou Traoreen_US
dc.subjectSeidina A. S. Diakiteen_US
dc.subjectMahamadou Diakiteen_US
dc.subjectBrice Campoen_US
dc.subjectGordon A. Awandareen_US
dc.subjectAbdoulaye A. Djimdeen_US
dc.subjectpolymerase chain reactionen_US
dc.subjectchloroquineen_US
dc.subjectantimalarialsen_US
dc.subjectmalariaen_US
dc.subjectplasmodiumen_US
dc.subjectpiperaquineen_US
dc.subjectlumefantrineen_US
dc.subjectmalariaen_US
dc.subjectplasmodium falciparumen_US
dc.subjectinfectionsen_US
dc.subjectartemetheren_US
dc.subjectWACCBIPen_US
dc.titlePlasmodium malariae and Plasmodium falciparum comparative susceptibility to antimalarial drugs in Malien_US
dc.typeArticleen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Plasmodium malariae and Plasmodium falciparum.pdf
Size:
592.01 KB
Format:
Adobe Portable Document Format
Description:
Main article
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Health