Abstract Background and objectives The emergence and spread of antimalarial drug resistance threaten malaria control efforts in sub-Saharan Africa. Monitoring the susceptibility of circulating Plasmodium falciparum isolates is essential to inform national treatment guidelines and guide the development of new therapies. To assess the ex vivo susceptibility of P. falciparum field isolates to 14 antimalarials, including withdrawn/unused and currently used drugs, and next-generation agents in Mali. Methods Twenty-six isolates collected from patients with uncomplicated malaria at three endemic sites (Faladje, Kolle and Bougoula-Hameau) were cultured ex vivo under standardized conditions. Parasites were exposed to 14 drugs, including tafenoquine, N-desethyl-amodiaquine, chloroquine, dihydroartemisinin, lumefantrine, pyronaridine, quinine, sulfadoxine, pyrimethamine, amodiaquine, atovaquone, GNF179, KDU691 and cabamiquine. Susceptibility was measured using fluorescence-based assays with SYBR Green I and Mitotracker dyes, and IC50 values were derived from dose–response curves. Results Tafenoquine showed a very low potency (IC50 1500 nM). Chloroquine exhibited marked inter- and intra-site variability (IC50 ∼50–1300 nM), while N-desethyl-amodiaquine potently inhibited isolates (median IC50 20 nM in Faladje and Bougoula-Hameau). Current frontline drugs, dihydroartemisinin (median IC50 6 nM), lumefantrine (median IC50 50 nM) and pyronaridine (median IC50 10 nM), remained highly potent. Quinine showed variable efficacy (IC50 ∼75–1000 nM). Chemoprevention agents sulfadoxine and pyrimethamine displayed high IC50 values (median IC50 1000 and 2000 nM). Atovaquone and amodiaquine consistently inhibited all isolates (IC50 10 nM). Next-generation compounds cabamiquine and GNF179 demonstrated consistently strong activity (IC50 10 nM), while KDU691 showed moderate activity (median IC50 18–22 nM). Conclusions While current frontline therapies remain effective, reduced activity of chemopreventive antimalarials supports the need for continued surveillance to detect early signs of resistance in Mali. The potent activity of next-generation candidates (cabamiquine and GNF179) supports their potential for further clinical development and field deployment.
Maiga et al. (Wed,) studied this question.