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Cross-resistance of the chloroquine-derivative AQ-13 with amodiaquine in Cambodian Plasmodium falciparum isolates

Abstract : Background Expanding resistance to multiple antimalarials, including chloroquine, in South-East Asia (SEA) urges the development of new therapies. AQ-13, a chloroquine derivative, is a new drug candidate for treating malaria caused by Plasmodium falciparum. Objectives Possible cross-resistance between the 4-aminoquinolines amodiaquine, piperaquine and AQ-13 has not been assessed. In vitro parasite growth assays were used to characterize the susceptibility of multidrug-resistant and susceptible P. falciparum patient isolates to AQ-13. Methods A [3H]hypoxanthine uptake assay and a 384-well high content imaging assay were used to assess efficacy of AQ-13 and desethyl-amodiaquine against 38 P. falciparum isolates. Results We observed a strong cross-resistance between the chloroquine derivative amodiaquine and AQ-13 in Cambodian P. falciparum isolates (Pearson correlation coefficient of 0.8621, P < 0.0001). Conclusions In light of the poor efficacy of amodiaquine that we described recently in Cambodia, and its cross resistance with AQ-13, there is a significant risk that similar clinical efficacy of AQ-13-based combinations should be anticipated in areas of amodiaquine resistance.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03480931
Contributor : Benoit Witkowski Connect in order to contact the contributor
Submitted on : Wednesday, December 15, 2021 - 8:22:00 AM
Last modification on : Wednesday, January 19, 2022 - 3:38:02 PM

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Flore Nardella, Mélissa Mairet-Khedim, Camille Roesch, Steven Maher, Sopheakvatey Ke, et al.. Cross-resistance of the chloroquine-derivative AQ-13 with amodiaquine in Cambodian Plasmodium falciparum isolates. Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), 2021, 76 (10), pp.2565-2568. ⟨10.1093/jac/dkab219⟩. ⟨pasteur-03480931⟩

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