Browsing by Author "Dembele, L."
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Item The Pan African Vivax and Ovale Network (PAVON): Refocusing on Plasmodium vivax, ovale and asymptomatic malaria in sub-Saharan Africa(Parasitology International, 2021) Quaye, I.K.; Aleksenko, L.; Oeuvray, C.; Yewhalaw, D.; Duah, N.; Gyan, B.; Haiyambo, D.H.; Dongho, G.B.D.; Torgby, R-A.; Amoah, L.; Hamid, M.A.; Worku, S.; Bahiti, A.A.; Pasquale, H.A.; Bitshi, M.; Troare, I.; Diarra, A.; Njunju, E.; Cisse, M.; Soulama, I.; Savadogo, R.J.; Issifou, S.; Niangaly, A.; Dembele, L.; Greco, B.The recent World Malaria report shows that progress in malaria elimination has stalled. Current data acquisition by NMCPs depend on passive case detection and clinical reports focused mainly on Plasmodium falciparum (Pf). In recent times, several countries in sub-Saharan Africa have reported cases of Plasmodium vivax (Pv) with a considerable number being Duffy negative. The burden of Pv and Plasmodium ovale (Po) appear to be more than acknowledged. Similarly, the contribution of asymptomatic malaria in transmission is hardly considered by NMCPs in Africa. Inclusion of these as targets in malaria elimination agenda is necessary to achieve elimination goal, as these harbor hypnozoites. The Pan African Vivax and Ovale Network (PAVON) is a new consortium of African Scientists working in Africa on the transmission profile of Pv and Po. The group collaborates with African NMCPs to train in Plasmodium molecular diagnostics, microscopy, and interpretation of molecular data from active surveys to translate into policy. Details of the mission, rational and modus operandi of the group are outlined.Item Plasmodium malariae and Plasmodium falciparum comparative susceptibility to antimalarial drugs in Mali(Journal of Antimicrobial Chemotherapy, 2021) Dembele, L.; Aniweh, Y.; Diallo, N.; Sogore, F.; Sangare, C.P.O; Haidara, A.S.; Traore, A.; Diakite´, S.A.S.; Diakite, M.; Campo, B.; Awandare, G.A.; Djimde, A.A.Objectives: 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.